








key: cord-022650-phsr10jp
authors: nan
title: Abstracts TPS
date: 2018-08-14
journal: Allergy
DOI: 10.1111/all.13539
sha: 
doc_id: 22650
cord_uid: phsr10jp

nan

(either in men or women) between metabolic syndrome and incident asthma.

Conclusion: This study confirmed the significance of obesity as a risk factor for incident asthma. Moreover, obesity appeared to be a stronger risk factor than metabolic syndrome. 0638 | Relationship between helminth infection, blood eosinophils and asthma symptoms in a rural community from the tropics Peñaranda D; Alvarez L; Sierra N; Lopez J; Zakzuk J; Caraballo L Institute for Immunological Research. University of Cartagena, Cartagena, Colombia Background: Immune response to helminths shares many features with the allergic response. In tropical regions where helminths are highly prevalent, asthma is still a major public health burden. Large clinical cohorts suggest that high blood eosinophils (HBE=>400 cells/ mm 3 ) are associated with asthma exacerbations. However, the association between HBE and asthma severity in rural communities with prevalent helminthic infections is unclear.

Method: Patients with wheezing symptoms in the last year living in a rural tropical community (Santa Catalina, Colombia) where helminths are highly prevalent, were recruited for this study. Blood eosinophils were assessed by complete blood count. Parasitic infection was evaluated with two serial coprological exams (Kato-Katz method) and skin prick tests were conducted to determine reactivity to Ascaris.

Results: Seventy-three patients (mean age: 21; range: 2-64 years old) were recruited in this study. A. lumbricoides and T. trichuria active infection (47.9% and 16.4%, respectively) were not related to age or gender. A positive SPT to Ascaris extract, ABA-1 and D. pteronyssinus was observed in 23%, 18.4% and 34.2%, respectively. Mean eosinophil count was 621 cells/mm 3 ; 43.9% had HBE.

Rate of patients with at least one emergency department visit was 61.9% and hospitalization, 21.9%. Blood eosinophil counts (as a continuous variable) were inversely associated with age (P = 0.03) and higher in helminth infection (P = 0.002). In crude univariate analysis, exacerbations (ER and/or hospitalization) were associated with age (OR: 0.96; 95% CI: 0.93-0.99, P < 0.01) and HBE (OR: 2.9; 95%CI:

1.1-7.8, P = 0.04), but not with helminth infection. For a better definition of asthma, multivariate analysis done in those >7 years old indicated that HBE, helminth infection and positive Ascaris SPT were not associated with asthma exacerbations.

Conclusion: Uncontrolled asthma is common in rural places of the tropics. Since helminth infection influences eosinophilia, the clinical value of HBE to predict exacerbations is limited in helminth-endemic populations.

Castro MC 1 ; Ferreira J 2 ; Sarmento D 2 ; Carvalho C 2 ; Matos A 2 ; Bicho M 2 1 CHLN-Immunoallergy; Lisbon Medical School-Genetic Department, Lisboa, Portugal; 2 Lisbon Medical School-Genetic Department, Lisboa, Portugal Background: The bioavailability of NO and endothelial homeostasis depends on the functional polymorphism of 19-bp Del/Ins within intron-1 of DHFR (Dihydrofolate reductase enzyme) (rs70991108) that could interfere in the regeneration of BH4 (tetrahydrobiopterin) from BH2 (7,8-dihydrobiopterin) and contributes to endothelial dysfunction in asthma.

Method: Asthmatics (n = 123) compared with control group (n = 50).The polymorphism was analyzed by PCR. Control of asthma assessed by (ACQ7 and PAQLQ). Statistical analysis with SPSS 23.0 establishing a significance level of P < 0.05.

Results: There are 80 women and 43 males in asthmatics and 39 women and 11 males in controls (P = 0.137). In asthmatics: age ( x ± SD): 38.26 ± 19.24 ; and in control group: age ( x ± SD):

51.50 ± 13.34. The genotype frequencies in asthmatics are: DD (6.5%); ID (66.7%); II (26.8%); in control group: DD (12.0%); ID (64.0%); II (24.0%); there is no statistical difference between groups (P = 0.478). The allelic frequencies in asthmatics are: allele D (39.8%); allele I (60.2%); in control group: allele D (44%); allele I (56%); there is no statistical difference between groups (P = 0.476).

The genotype frequencies in the uncontrolled asthmatics are: DD (0.0%); ID (61.1%); II (38.9%) ; in the controlled asthmatics are: DD (9.4%); ID (68.2%); II (22.4%); there is statistical difference between groups (P = 0.047). Genotypes ID and II are more frequent in the uncontrolled asthmatics. The allelic frequencies in the uncontrolled asthmatics are: allele D (30.6%); allele I (69.4%); in the controlled asthmatics are: allele D (43.5%); allele I (56.5%); there is a trend to have differences between groups (P = 0.059). Allele I is more frequent among uncontrolled asthmatics.

The uncontrolled asthmatics are older than the controlled asthmatics (P < 0.001). There is no differences in gender distribution (P = 0.903).

The genotype II confers a risk of being uncontrolled asthmatic of 2.950 times when compared with controlled asthmatics and adjusted for age: OR b : 2.950 [1.117-7.789 ]; P = 0.029. physiopathology and the emergence of evidence-based clinical guidelines. However, variation still exists among some diagnostic aspects of asthma in real life. It is unknown to what degree diagnosis is affected by the treating physician's medical specialty. Results: A total of 62 GPs, 239 pediatricians, 364 allergists, 161 pulmonologists and 34 otolaryngologists (ORLs) replied. Although for general application of diagnostic clinical criteria all physicians rated similarly, in general accordance with the MAG suggestions, a third of non-pulmonologist practitioners don't recognize chest discomfort as one of the clue symptoms of asthma, but they erroneously believe crackles are (P = 0.01). We found agreement in almost half of all physicians to erroneously believe that viral illness' induced wheezing in non atopic children predisposes asthma. Conversely, 75-85% are aware that allergic sensitization predisposes to asthma. Most specialists -except pulmonologists (P = 0.02)-incorrectly listed FEV1 as the best parameter to identify airflow obstruction (AO) and FEV1/FVC to assess AO severity. 20% of GPs do not know peak expiratory flow (PEF) measurements could be valuable, and 75% of all specialists are not aware that changes in PEF can also be used to confirm AO reversibility. To classify asthma, only pulmonologists adequately considered the level of control in similar proportion than severity (81% and 83%, respectively), which is uniformly the preferred method by most other specialists.

Conclusion: Although in general many clinical aspects of asthma diagnosis seem to be accurately assessed, there is a wide specialityspecific variation regarding some aspects of phenotyping and classification, diverging from MAG's recommendations. As such, our results can help to detect knowledge-gaps and to guide the development of more focused specialty-specific learning tools to improve clinical impressions, process medical evidence, and apply it to patient care. 0652 | Issues, continuous medical education on treatment of acute asthma, exercise induced asthma and asthma in pregnancy should include, per medical specialty Background: To unify and improve the management of asthma, including asthma exacerbations, the Mexican Guideline on Asthma (25.5%) of 51 employees who stated increased symptoms with flour exposure. Among all workers 9 (5.5%) employees were diagnosed as asthma and 7 (4.3%) workers were diagnosed as BA.

Conclusion: Wheat flour sensitivity is high among workers who are exposed to wheat flour, however the prevalence of BA is similar to the previous data in the literature.

Johnsen CR 1 ; Callesen KT 2 ; Jensen BM 2 ; Poulsen LK 2 1 Clinic of Allergy, Dept. of Dermato-Allergology, Gentofte Hospital, Copenhagen, Denmark; 2 Laboratory of Allergy, Gentofte Hospital, Copenhagen, Denmark

Background: Enzymes are well known as sensitizers and causes of occupational allergy primarily in the industries producing and using the products. We present a case of occupational contact urticaria, rhino-conjunctivitis and asthma in a 32 year male chef who was using a transglutaminase enzyme powder obtained from fermentation of streptomyces mobaraense as meat glue in processing of fine culinary dishes. This transglutaminase has been used for protein food preparation in industrial settings since 1992 to improve the texture of protein rich foods such as surimi or ham. In this case it was used in small scale in a gastronomy restaurant kitchen spraying enzyme powder with a sieve over raw meat without any protective equipment in contrast to the producer's recommendation. The chef was also found allergic to dried, edible mushrooms also forming part of the meat dish prepared with the transglutaminase enzyme powder.

In one occasion he experienced an oral reaction with itching and swelling of the mucosa in the mouth, stridor, angioedema of the face, and urticaria after ingestion of beef meat treated with transglutaminase and rolled in horn of plenty dried mushroom powder.

No other symptoms of food allergy were reported but a known cat allergy was.

Background: Formaldehyde and xylene are occupational skin and respiratory irritant and/or sensitizer, exposure to those may be associated with dermatitis, rhinitis and asthma. Health care workers, as nurses, laboratory technicians, doctors could be exposed in different tasks in operating rooms, endoscopy and in pathology laboratory.

We describe three cases of work-related rhinitis in technicians employed in the same unit of hospital pathology .

First case: A woman of 38 years old underwent medical examination in our occupational allergy unit because allergy respiratory symptoms. She has been working for 8 years in pathology laboratory and was exposed to xylene and formaldehyde. She developed rhinitis, rhinosinusitis, hyposmia and cough with sputum after 5 years started work. She had negative skin prick test for common aeroallergens. Lung function was normal with a FEV1/FVC ratio of 80% of predict. Blood cells count reveled 15% of eosinophils (980/mmc) with 6550 total leucocytes.

Second case: A Woman of 40 years old was affected by moderate persistent allergic rhinitis with positive skin prick tests to house dust mite, dog and cat. In the last year rhinitis symptoms worsened in relation to work and improved during vacation. When she was exposed mostly to formaldehyde during shift at the end of it she usually experienced face skin and conjunctival erythema. She developed work-related symptoms after 14 years of exposure in the pathology unit.

Third case: A woman of 38 years old, who has been working for 14 years in the pathology unit and was exposed to formaldehyde and xylene, in the last year developed moderate-severe persistent rhinitis with hyposmia and chronic cough. She referred to otorhinolaryngologist and an irritant induced rhinitis was diagnosed. She had negative skin prick test for common allergens and normal lung function.

Results and conclusion: The workers experienced respiratory symptoms in relation to work exposure to formaldehyde and xylene.

The suspected causal agents were monitored in the work environment and an exceeding of the recommended limit values was found.

Preventive measure were adopted with a reduction of exposure and symptoms improve only in the second and third case. challenge test with mannitol is considered to be more specific than test with methacholine. Also, duration of procedure is shorter and safer. Therefore the study aim was to compare the usefulness of these two tests in monitoring of SICT.

Method: Four bakery workers with suspicion of OA underwent single-blind, placebo-controlled SICT with workplace allergens accompanied by evaluation of NSBHR with mannitol and methacholine before and after SICT. Clinical examination, spirometry, skin prick tests (SPTs) to common aeroallergens and occupational allergens, serum specific IgE antibodies to occupational aeroallergens were also performed.

Results: Positive SPTs results to occupational aeroallergens were found in all bakery workers, specific IgE to flours were detected only in two subjects.

Three out of the four patients displayed positive SICT reaction (in two cases early spirometric response). In all of these 3 patients, airway response to methacholine increased significantly. In the first two patients also airway reaction to mannitol was significant, whereas in one subject with early reaction there was no increase in NSBR after mannitol inhalation. The patient with negative SICT results did not reveal any changes in NSBR before and after the test, neither to methacholine nor mannitol. 0668 | Rice-induced occupational anaphylaxis and socio-economic impact-case report Method: In this prospective study, a total of 240 students completed a self-administrated questionnaire that comprised different questions and gave information about the participants and their glove use, working habits, signs and symptoms related to these gloves, precautions taken to minimize it, etc. Skin prick test is performed through commercial extract latex gloves (Stallergenes), while patch test is prepared through latex gloves and adhesives. Two types of gloves are used: gloves that contain latex and gloves without latex (vinyl gloves), which are used also as e negative control.

Results: Questionnaire items and diagnostic tests revealed that one-fourth of subjects were suspicious for latex gloves hypersensitivity. Their mean value for skin reactions like irritant or allergic dermatitis or contact urticaria was between 10% and 14%, while for other symptoms the mean value was under 5%. Logistic regression analysis revealed an association between different questionnaire items and positive allergy tests among suspected cases and diagnosed cases of latex allergy. Approximately 20% of people who work with laboratory animals experience some allergic symptoms and about 10% of animal technicians go on to develop serious symptoms of asthma. UK government guidelines state that employers must prevent or adequately control exposure of employees to animal allergens and should undertake monitoring to ensure that suitable controls remain effective. The most widely used monitoring method is personal IOM filters. However, these need to be attached to a pump and carried by the technician which can be cumbersome and awkward. Previous data has demonstrated that allergens from dust mite, cat, dog and pollen could be captured and quantified by a novel type of nasal filter. In this current study, we sought to assess the feasibility of using the nasal filters for the assessment of exposure to mouse allergen in a laboratory facility.

Method: Technicians working in a laboratory animal facility were asked to wear the filters during normal routine work. For comparison, they were also asked to wear an IOM filter for the same duration. Allergen was extracted from nasal and IOM filters by gentle rocking in PBS-Tween for two hours. Levels of the major mouse urinary protein (Mus m 1) were quantified using our multiplex array technology, which is highly sensitive and allows for quantification of Mus m 1 down to 0.01 ng/mL.

Results: Significant levels of Mus m 1 were detected in the nasal filter extracts and these levels correlated with the type of activity that was being performed by the technician, as well as the housing environment of the mice. Levels were compared to the suggested 'safe' limit of allergen exposure of 5 ng/m 3 . We also found that the technicians grew accustomed to the nasal filters quickly and found them far more practical for every day monitoring that wearing the IOM filter and pump.

Conclusion: These data indicate that nasal filters may be considered a simple and easily wearable method for monitoring laboratory animal allergen exposure. Future studies are planned to assess the feasibility of wearing the filters for analysing exposure to other laboratory animal allergens from rat and guinea pig.

Havana University lower CO 2 emission, water and feed consumption and limited waste production.

Insects are currently allowed both for human and animal feeding in some EU countries, including Italy and the risk profile related to production and consumption of insects as food and feed, including risk of allergenicity, is currently under evaluation by EFSA. Both food and feed products derived from insects require multiple manipulations by the breeder and/or by the workers who transform the insect into the commercial products, thus the occupational exposure have to be considered too.

The aim of this work is to evaluate the allergenicity of Tenebrio molitor, one most used species for animal feeding.

Method: T. molitor proteins were extracted from intact dried larvae and from flour of dried larvae. The protein extracts were separated in one-dimensional electrophoresis Conclusion: According to these results, the larva flour seems to be less immunoreactive than the intact counterpart, probably due to the processing that causes the degradation of protein bands over 50 kDa. Working in gastronomy is associated with exposure to many factors with an irritating and allergic potential influencing respiratory system.

Food products and organic dust are the source of inhaled allergens which may cause sensitization during apprenticeship.

The study aim is a prospective observation of incidence of sensitization to selected environmental and occupational allergens among culinary school apprentices and identification of work-related allergic diseases in this group.

Method: The cohort comprised 374 apprentices. They were examined in the first and the second year of education. Questionnaire and allergological tests [(skin prick test) SPT to common and occupational allergens, IgE level evaluation (total and specific for occupational allergens) and pulmonary tests] were performed].

Results: The most frequent symptoms reported by examined apprentices were rhinitis (12.8%), conjunctivitis (7%), skin symptoms (6.7%), dyspnea (5.6%) and cough (2.7%). 10 subjects developed nasal symptoms during the second year of education, while in 6 cases the skin symptoms and in 4 subjects conjunctivitis appeared.

In 7 cases the work-related symptoms were reported.

The most frequent positive results of SPTs were obtained with Dermatophagoides pteronyssinus 24.4%, Dermatophagoides farinae 21.6%, grass pollens 18.6%. Positive SPT to rye and barley flour were found in respectively 2.2% and 1.4% apprentices. 4.1% of apprentices had specific IgE to flours.

The preliminary results indicate that work-related allergy symptoms and hypersensitivity to occupational allergens are rarely found among culinary school apprentices in the first years of education. The further observation will allow to evaluate the trends in incidence of allergy to occupational allergens, as well as the clinical presentation of allergy in that group.

0677 | How multifaceted the clinical presentation and etiology of allergic diseases could be?

Method: The study was done in children from West Georgia randomly and on based of questionnaire of representative cohort. (2014) (2015) (2016) . The cohort was 1500 children, 1-16 years old, risk factors were studied by way of interviewing, clinical-laboratory dates.

For assessing the risk factors, was used 'case control' method. The statistical processing of material was done with computer program sps/sv12. Inclusion criteria for enrolment were: collectors of dust, gender, existence of moisture and mold consuming of Tabasco, atopic dermatitis and seasonality.

Results: The groups, which we have studied, prevalence of acute respiratory viral infection was 61%, bronchitis −29.3%, allergic rhinitis 33.9%, atopic dermatitis 9.1%, food allergy 5.4%. The reliability was high (P < 0.05) in families with bronchial asthma compared with healthy population. Bronchial asthma was detected in 5.7% of population. The hereditary load of allergic diseases in patients with bronchial asthma was 9.7% and in healthy cohort it was 5.7%

(P < 0.001).

Conclusion: Based on the results, we can conclude that, ecological factors and genetic predisposition significantly influences on prevalence of sensibilisation of house dust mite, molds and formation of bronchial asthma.

As the genetic and environmental factors that act on an immune system are better elucidated and their roles established, the implementation of more enduring preventive efforts will be developed.

However, at present, the best approach to the child at high risk for the development of allergies is to institute dietary and environmental control measures early to decrease sensitization, and to recognize and appropriately treat the evolving signs and symptoms of allergic disease. Background: Plantation of road-side avenue trees has become a major part of the urbanization programme in Kolkata metropolis of India for megacity beautification and environmental management.

Due to evergreen habits, Gulmohor (Delonix regia) and Chhatim (Alstonia scholaris) are frequently selected for plantation programme to generate green belts. However, an increasing incidence of seasonal pollinosis was observed among the inhabitants living in close vicinity to these trees suggesting a possible link between the airborne pollen load and the concomitant respiratory hazards. This prompted us to investigate the allergens in the pollen of these two dominant avenue trees.

Method: Aerobiological surveys were conducted at multiple sites of Kolkata for a period of two years using seven-day volumetric Burkard sampler to record the pollen concentration in the outdoor ambient air. Clinical data and residual blood of pollinosis patients were collected from a public hospital. Allergens were detected in the pollen proteome fractionated in 2D gel by IgE-serology. The major IgEreactive proteins were partially purified by ammonium sulphate fractionation followed by ion-exchange chromatography. The allergenic activity of the fractions was tested by histamine release assay.

Results: A clear correlation was observed between the pollinosis related morbidity and the aeropollen load especially during the peak flowering period of these two trees. About 41% and 52% of the patients displayed positive SPT response and IgE-reactivity using pollen extracts of Gulmohor and Chhatim respectively. Immunoproteomic analyses revealed the presence of 7-8 IgE-reactive components in the 2D pollen proteome of these species. Hierarchical cluster analysis with patient immunoblot data identified a 31 kDa and a 25 kDa protein as major allergens of Gulmohor and Chhatim respectively. The purified fractions containing each of these two major allergens induced histamine release from granulocytes within a range between 42 and 77%. Method: Immortalized human keratinocyte cell line (HaCaT) and

primary normal human epidermal keratinocytes (NHEKs) were differentiated with calcium chloride for 1 and 3 days, respectively. Following the differentiation, the cells were treated with IL-4 (100 ng/mL), IL-13 (100 ng/mL), and/or HCHO (4 × 10^-4%) for 2 hours. The mRNA expression of FLG, IVL, LOR, DSG1, DSG3, DSC1, DSC3, as well as TSLP was analyzed using quantitative real-time PCR.

Results: HCHO exposure decreased the mRNA expressions of structural components (FLG, IVL, and LOR) and cell adhesion molecules (DSG1, DSG3, DSC1, and DSC3) in a short-period time of exposure (2 hours). We also found that HCHO exposure significantly enhanced IL-4-and/or IL-13-induced TSLP production in NHEKs as well as HaCaT. Interestingly, exposure to HCHO alone is enough to increase the TSLP mRNA expression in both cells.

Conclusion: Our results suggest that HCHO exposure might synergistically damage the skin barrier function with IL-4 and IL-13 by increasing TSLP expression and decreasing structural components as well as cell adhesion molecules.

0685 | Skin prick test reactivity to aeroallergens in adult allergy clinic in a tertiary hospital: a 12-year retrospective study Results: Five different human sera were screened for specific IgE level against 29 different allergen sources using test methods of three different suppliers.

The sensitivity of the three different methods can be arranged in the ascending order manufacturer A < manufacturer C < manufacturer B. With the test of manufacturer A, 45% of the measurements were below the detection limit (0.35 kU/L), with the test of manufacturer C, 16% of the measurements were below the detection limit, whereas the test of manufacturer B leads to values below the detection limit in 10% of the cases. In terms of variation coefficient, the test system of manufacturer C had the best performance. Test systems of manufacturers A and B exhibited comparable variation coefficients, which were considerably higher than that of manufacturer C.

Conclusion: Based on these test results, only the test of supplier C is recommendable for determination of levels of specific IgE for diagnostics of allergic patients. With the test of manufacturer A, elevated levels of specific IgE antibodies for many allergens cannot be detected due to the poor sensitivity of the test system. The test system of supplier B exhibits a good sensitivity but the coefficient of variation is rather high for a diagnostic test. This drawback could be circumvented by multiple determination of one test parameter.

Although this is an advisable strategy in general, the routine in diagnostic laboratories is incompatible with this approach, since throughput would decrease while costs would increase.

This study is another good example for the need of the implementation of a characterized standard material with known values of sIgE, as demanded by Wojtalewicz et al. Method: CD203c and CD63 expression on basophils were monitored upon exposure of whole blood samples (<24 hours) to anti-IgE and/or allergenic extracts. Staining was conducted on exposed samples using dry room temperature stable antibody panels (DURA Innovations format) coated in 96 well plates, eliminating all antibody pipetting steps from the workflow. Red blood cells were lysed and data was acquired (without further wash steps) on a CytoFlex flow cytometer (Beckman Coulter). Staining and lysing were automated using a Biomek (Beckman Coulter).

Results: The described no-wash preparation protocol, already established for manual preparation mode in tubes, could be trans- Conclusion: The HR-test was significantly less likely to be positive, if a patient suffered from monosymptomatic AE than in AE patients with concomitant urticaria. This could signify a higher likelihood of treatment response to antihistamine and other anti-allergic medication in the latter group. Background: Pathogenetic mechanisms of allergy are polymorphic.

They include IgE-dependent and IgE-independent, allergen-specific granulocyte-mediated and lymphocytic reactions, as well as nonspecific hypersensitivity, which are realized through a variety of mediators: histamine, tryptase, etc.

Allergen bucal challenge mimics the natural situation and is useful for understanding the mechanisms of allergic airway inflammation and airway hyperresponsiveness (AHR).Saliva used as a non-invasive readily available bio-sample for diagnosis instead of blood. Biomarkers in saliva are associated with the pathogenesis and clinical outcome of allergic diseases Method: Aim: to examine mediators for AHR with buccal(mucosal) challenge tests. We examined 14 patients with allergic asthma(the history, positive skin prick test, serum specific IgE) and 12 healthy volunteers. Saliva were collected. Then, both groups were subjected to buccal(mucosal) allergen challenge by a water-salt solution of the mite allergen Dermatophagoides pteronyssinus. Saliva was recollected in 30 minutes and 24 hours after the provocation. The level of myeloperoxidase, elastase, tryptase in saliva were determined by the ELISA. That provocative test did not cause clinical symptoms development or reduction in nasal bronchial patency in any patient.

Results: In patients with allergopathology, an initially increased level of myeloperoxidase and tryptase in 30 minutes after the provocation, elastase increased in 24 hours (Table 1) .

Tryptase in saliva after 30 minutes increased till 0.07 (0.04; 0.19) (Me, pg/mL (LQ;UQ)), P = 0.0006. Increased tryptase is presence of increased cellular inflammation, e.g. mast cells. Its IgE-dependent hypersensitivity, because there was the correlation between the elevated level of tryptase and positive prick tests.

Elevated levels of myeloperoxidase and elastase in saliva may be the criteria for the neutrophil hypersensitivity and IgE-independent reactions.

In healthy volunteers this increase was not observed.

The identification of tryptase, myeloperoxidase, elastase can be used for diagnosis of types of AHR. Tryptase is a mediator of early (immediate) response to allergen.

Increased myeloperoxidase and elastase indicates the involvement of the eosinophils and neutrophils in the oral mucous membrane in the allergic process. These mediators have additional roles in the late phase response. Elevated levels of myeloperoxidase and elastase in saliva may be the criteria for the neutrophil hypersensitivity.

Conclusion: Safe and acute in vitro methods allow to conduct early etiological diagnosis of allergy, which contributes to the effectiveness of therapy; the detection of polyvalent sensitization dictates the need for molecular diagnostics to single allergens, which has a higher prognostic level and the clinical significance of predicting the appropriateness and effectiveness of allergen-specific therapy; laboratory diagnostics of the allergy allows to reveal sensitization at the 0 (0, 0) 0 (0, 0) 0 (0, 7.28) *P = 0.002; **P = 0.008; ***P = 0.038.

subclinical level, which increases early diagnosis and identify persons with a predisposition to allergy; the establishment of causal aller- Background: Antibacterial chemicals like parabens and triclosan have been associated with allergic disease in children. Parabens are also suspected to affect metabolic functions, possibly due to their weak endocrine disrupting properties. Furthermore, a possible link has been suggested for eczema and adiposity, and thus, how body burden of chemical exposures affect both of these outcomes are of interest. We aimed to describe the association between exposure to parabens and eczema and body mass index (BMI) in an adult population in Norway.

Method: Urine biomarkers of butyl-, ethyl-, methyl-and propylparabens were quantified by mass-spectrometry in 496 adult participants (median age=29 years) from the RHINESSA study in Bergen, Norway. Linear regression models adjusted for gender, age and BMI (for eczema outcomes) and with clustering for siblings, were applied to model possible association between specific gravity standardized urine biomarker concentrations of parabens with BMI and eczema.

Results: Propyl-(PPB) and methyl-parabens (MPB) were detected in 95% of the urine samples; ethyl (EPB) in 62% and butyl (BPB) in 38% of the samples. In women, EPB and BPB were detectable in 73% and 61%, respectively. Participants with current eczema (15%) had lower level of several parabens compared to those without eczema (BPB for both genders; EPB in women only and sum of all parabens in men only). Body burden of EPB (geometric mean (GM)) was 6.7 μg/L in women with current eczema compared to 22.3 μg/L in women without eczema (P = 0.03). Body burden of parabens (MPB and EPB) were inversely associated with obesity (BMI>30, (11.4%) ), as compared to normal range BMI (BMI=18. 5-25 (56.4%)) in both men and women. The concentration of MPB for obese women was GM=2213 μg/L compared to 11503 μg/L in women with normal range BMI. For men, the GM for MPB was 35.3 μg/L in obese compared to 134.4 μg/L in normal weight men (P = 0.03).

Conclusion: Person with eczema or obesity had lower paraben levels in urine. We speculate that these chemicals might be stored in adipose tissue, and therefore excreted in urine in lower levels among the obese. Eczema and obesity was not strongly associated in the current study. Method: We retrospectively analysed medical records of 75

patients who were patch-tested with our dental screening series of 23 substances. Adverse reactions to dental materials were suspected based on subjective complaints in the oral cavity and/or objective conditions of the oral mucosa. Square plastic chambers on hypoallergenic tape were used. Patch tests were applied to the upper back and removed by the patient after 48 hours. Readings were performed 3 and 7 days after application (D3 and D7). Results were evaluated according to the International Contact Dermatitis Research Group guidelines. Positive patch test reactions fulfilled the criteria of at least a one plus (+) reaction on D3 and/or D7. The term »contact allergy« is usually used for such reactions. We prefer the term »contact sensitization«. Clinical relevance of positive reactions to dental materials was not systematically assessed in this analysis. Conclusion: We report a high frequency of positive reactions on D7 that were not seen on D3. This finding demonstrates the importance of an additional late patch test reading in patients with suspected contact allergy to dental materials. Background: Psoriasis is a chronic inflammatory skin disease. Its etiopathogenesis is not exactly known. It is believed that the disease occurs in people with genetic tendency with the effect of a triggering factor. In some studies it is observed that contact dermatitis in psoriasis is increased with respect to normal population. For this reason it is proposed that allergen materials could trigger psoriasis. In this study it is aimed to determine contact allergy frequency in psoriasis cases using patch test. Results: 62 of the cases were plaque, 5 of them were guttate, 10 of them were palmoplantar and 3 of them were inverse type. More positivity rate is observed in psoriasis cases (26.25%) than control (12%). The positively responsed materials with respect to decreasing number of patients are found as follows: Nickel sulphate (16.25%), thimerosal (7.5%), peru balsam(5%), p-phenylenediamine(2.5%), colophony(2.5%), n-isopropyl-n-fenil-4-fenilendiamin(2.5%), mercaptobenzothiazole(2.5%), benzocaine(2.5%), Most frequently plaque type and following guttate type positive responses are observed in evaluations with respect to clinical types. No statistical significance is found between patch test results and PASI values in psoriasis cases.

Conclusion: Patients with psoriasis should be carefully evaluated.

Sometimes some materials may trigger psoriasis. The composition of the pigments that professional tattooists use are varied inorganic salts of metals or organic vegetable pigments. Red tattoos, especially those that contain mercury, are the most common cause of late reactions.

Method: 35 year-old male patient with no previous allergy history known, who gets a tattoo on his right leg and develops within months, cutaneous erythema and pruritus on the same location as the tattoo.

TRUE TEST ® for skin allergy patch epicutaneous testing is performed.

Results: 48 and 96 hours reading: showed positiveness for mercury ++, with no late positive reactions after that.

Conclusion: As allergists we should be familiar with the different types of tattoos available, and know the possible cutaneous complications that each of these decorative techniques can present.

It is our responsibility to be able to diagnose any complications at an early stage, establish the most appropriate treatment and, if possible, prevent them by informing the possible users. Background: Within otorhinolaryngological pathology chronic eczematous otitis externa is one of the most common, usually treated with topical medication successfully; however, there are cases in which the poor response to treatment, or the recurrence thereof, may be due to causes secondary to the medication itself, as observed in cases of allergic contact dermatitis caused by these drugs.

Case Report: We present a 68-year-old male patient without relevant pathological antecedents or known allergies, who consulted the otorhinolaryngology service of our center for otorrhea of 15 days of evolution, bilateral external otitis is diagnosed and a topical otological combination is recommended (beclomethasone dipropionate 0.025% and clioquinol 1%, excipient: macrogol) with improvement.

However, during the following 3 years the patient presents exacerbations and remissions of the condition, with negative or inconclusive microbiological studies. During all that time he was using the prior topical treatment and other combination treatments of topical antibiotics, corticosteroids and local antiseptics. More aggressive causes of external otitis such as malignant external otitis were ruled out.

During the third year of follow-up, a clear relationship of exacerbations was observed with the use of the first combination of topical drugs, so it was decided to investigate allergic sensitization.

Material and Methods: We perform patch tests using True Test ® , standard spanish series (GEIDAC -Spanish group for investigation of contact allergy dermatitis), topical corticosteroid battery, antiseptic, as well as topical medications used by the patient.

Results: From the first reading on day two, positivity was observed for: Mixture of quinolines ++ patient's otological combination ++ and Chlorquinaldol ++; being confirmed in the reading at day four.

Eczematous external chronic otitis is diagnosed with allergic sensitization to quinolines (clioquinol, chlorquinaldol).

We conclude that in the case of chronic external otitis, allergic contact dermatitis should also be investigated as a possible cause, and it is important to perform epicutaneous tests with the patient's own products to evaluate non-common or hidden allergens that may be relevant to their current pathology. 

most common causes of ACD. It is important to distinguish local findings of infection from ACD caused by topical antibiotic treatments.

Here we present a patient with ACD with topical use of bacitracin and neomycin combination therapy due to recurrent blepharitis.

An 11-year-old male patient presented with the complaints of itching, redness, swelling of the eyelids and facial edema. He had used various topical ophthalmic antibiotherapy and eye shampoo for 7 years due to recurrent blepharitis. Five days ago, due to the redness of the eyelids, burning sensation in the eye, itching of the eyes;

he was examined by an ophthalmologist. The eyelids and eyelashes were scaly and dry. The patient was treated with warm water soaked cloth dressing, mechanical eyelash cleaning and topical antibiotherapy (neomycin-simple combination therapy). After the second day of treatment, the patient's topical ophthalmic antibiotherapy was discontinued due to an augmentation of the redness in the eye- 0723 | Contact allergy after exposure to ivy (Hedera Helix L) potent steroid treatment associated with systemic antihistamines, but with no improvement.

On dermatological examination a small, well delineated, eczema-like plaque was noticed on a digital finger, as a new finding striking with her old burn scars. She denied any symptoms and was in good health condition. A 4 mm punch biopsy was performed and histological report established the diagnosis of squamous cell carcinoma. The patient was transferred to Oncology Department for further investigation and treatment.

Conclusion: Early diagnosis and prompt surgical therapy are recommended to all patients with chronic wounds and scars who develop malignant transformation.

*Written informed consent for the publication of potentially identifiable personal details of patient (gender, age, illness, location) was obtained.

**In relation to this presentation, I declare that there are no conflicts of interest.

Ertugrul A; Hizli Demirkale Z; Bostanci I Dr Sami Ulus Maternity and Children Training and Research Hospital, Ankara, Turkey

Introduction: The incidence of contact sensitization among adolescent has been increasing. Nickel is one of the important causes of allergic contact dermatitis (ACD) in this age group. Increased exposure to nickel and deterioration of the skin barrier are among the important risk factors in children. The gold standard for diagnosis is skin patch test. We report here an adolescent patient who has allergic sensitization to nickel and cobalt.

Case: A 17-year-old female patient admitted in our clinic with a complaint of edema on her face. The patient had applied chickpea water to her face at least once a day for one week because of her acnes. Her medical history revealed that she had experienced similar edema on her face after applications of clay mask one year ago. She was diagnosed with cellulitis and she had been treated with antibiotics for five days. On her physical examination, angioedema was observed on her face, especially on the glabellar region. Eosinophilia was not found on her laboratory data. C-reactive protein (CRP), C4

and C1 esterase inhibitor protein levels were also normal. The skin prick test was performed with aeroallergens, chickpea, lentil, bean and nuts, and no reaction had been observed. The patch test was performed with 'Thin-Layer-Rapid-Use-Epicutaneous' (T.R.U.E) test and chickpea. The patient had positive reactions to nickel and cobalt.

Detailed questioning disclosed that the patient was preparing the chickpea water in a metal pot.

Result: Chickpea water and clay mask contain varying amounts of nickel. It was thought that the edema of the patient is due to nickel allergic contact sensitization. An increased exposure to nickel and cobalt raises the frequency of sensitization. Nickel allergy can cause different clinics ranging from localized lesions to systemic reactions.

We want to emphasize that a detailed medical history and the patch test would enable clinicians to demonstrate hidden allergens and then make a correct diagnosis. Case report: Autoimmune progesterone dermatitis is a condition of hypersensitivity to progestogens. It is not an easy diagnosis given the variety of clinical presentations it may have, ranging from eczema, urticaria, erythema multiforme, folliculitis, to angioedema or even anaphylaxis. Manifestations are cyclical, occurring when the levels of progesterone are higher, this is, at the luteal phase of the menstrual cycle, and disappear during menses, with the physiological decrease of the hormone. It can also be triggered by exposure to exogenous progestins. We report the case of a 49-year-old woman with a cyclical erythematous and violaceous rash related to the menstrual period. The symptoms typically began 4-6 days before the onset of menses and ended 1-2 days before. The diagnosis was based in the clinical history and intradermal skin tests: skin prick testing with levonorgestrel and medroxyprogesterone were negative, but the intradermal skin test with medroxyprogesterone was positive at a concentration of 50 mg/mL. We performed intradermal testing with the same concentration in three other women with no symptoms to exclude an irritative reaction, which were negative. Autoimmune progesterone dermatitis is, perhaps, not so rare, but rather poorly recognized and reported, and thus, underdiagnosed. Clinicians should be aware and include always this condition in the differential diagnosis, especially in cases of atypical or intractable skin eruptions. Case report: A 46 year old male was referred to a community allergy clinic for assessment of chronic urticaria (CU). Allergy assessments for foods, inhalant and inducible physical triggers revealed no

association. An autoimmune workup followed, with treatment consisting of standard dose antihistamines (H1 and H2). Blood work revealed a persistently low hemoglobin with low-normal Ferritin.

Hematology consulted and followed attempted iron replacement to no avail. Skin biopsy revealed neutrophilic rich urticaria with the presence of eosinophils. Serum protein electrophoresis (SPEP) revealed a monoclonal gammopathy with elevated IgM, felt to be of undetermined significance (MGUS). C-Reactive Protein (CRP) was consistently elevated (183, 256) in conjunction with anemia.

Rheumatology consulted and cleared of any evidence of vasculitis.

Hematology considered the anemia to be of chronic disease linked to CU.

The CU was resistant to treatment including high dose antihistami- Background: Isolated head and neck angioedema (AE) can be mediated by bradykinin (Bk) or histamin (Hi) . The objective of our study was to determine which etiology was most frequent in cases of death by asphyxiating AE in France.

We sought all cases of death by isolated asphyxiating AE reported in France between 2000 and 2014 via death certificates and/or the national pharmacovigilance database.

Results: The overall mortality by asphyxiating AE for all causes was 0.36 / million inhabitants. The death rate of BkAE per million inhabitants was 0.14 and lethality of 0.27 per thousand patients per year.

The death rate of HiAE per million inhabitants was 0.09 and lethality of 0.006 per thousand patients per year. We found a 45 times higher risk of death in case of BkAE than HiAE.

Conclusion: Consequently, particularly severe episodes must be initially considered as bradykinin mediated and quickly reassess any first-line treatment that is inappropriate. Case report: We present the case of a 72-year-old man who suffered recurrent abdominal pain since age of eight, leading to 3 unnecessary emergency surgical interventions and 5 endoscopies before hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) was diagnosed at the age of 70. Rare subcutaneous swellings were considered allergic reactions preventing proper diagnosis. Family history, positive for recurrent abdominal pain and swellings was totally neglected until diagnosis of C1-INH-HAE type I was established through appearance of severe oro-facial symptoms in the propositus' grandson. The diagnosis was suggested by the boy's mother, directed by educational materials available in the international HAE patients' association website (www.haei.org). This report highlights and emphasizes the importance of accurately evaluated personal and family history to suspect condition that are scarcely known to the majority of physicians.

Highlights: Diagnostic delay in HAE and iatrogenic procedures are an underestimated problem, hiding undefined consequences, possibly destructing an entire lifetime. Correct, publically available information provided by patients' associations raise awareness about the disease and could put the milestone of establishing correct diagnosis.

De Luque V 1 ; Lara P 1 ; Guardia P 1 ; Jimenez AR 2 1 Virgen Macarena Hospital, Seville, Spain; 2 Hospital Virgen Macarena Sevilla, Seville, Spain Background: In the protocol for the study of patients who consult for recurrent acute angioedema with facial involvement, the contactant battery is included (epicutaneous test). We review the results in our patients with facial angioedema to evaluate the contactants to which these patients present sensitization, some of them coexisting with contact dermatitis clinic.

We reviewed the patients referred to the clinic for recurrent acute angioedema with facial involvement and to whom a standard battery epicutaneous test was requested. In all these patients, other habitual triggers included in the diagnostic protocol (food, medications, autoimmune diseases, bradyinergic AEA/complement deficit …) were ruled out. Conclusion: It seems to be profitable to continue including in the diagnostic battery of patients who consult for AEA with facial affectation, study of epicutaneous with standard battery. It is a small sample, but the data correlate with what has been published, being more frequent the sensitization to contactants in women and the contactant more frequently involved nickel sulphate.

0734 | Ace inhibitor-related angioedema-the value of history taking Background: Angioedema is a well-recognized side effect of angiotensin-converting enzyme (ACE) inhibitor therapy. Although it occurs in <1% of the patients who take these drugs, it seems to be responsible for 40% of the episodes of angioedema. This entity is underdiagnosed and failure to recognize it leads to recurrence of episodes, with an impact on morbidity and increased risk of serious reactions.

Our objective is to analyze the clinical, therapeutic and orientation approach of patients diagnosed with ACE inhibitor-related angioedema, evaluated at the outpatient consultation (OA) of Immunoallergology (IA).

A 3-year retrospective study was performed by analyzing the clinical files of all patients diagnosed with angioedema observed in OA of IA. The following variables were analyzed: gender; age; clinical data; evaluation in emergency department (ED); therapy in the episode; evolution and orientation. The Chi-square test was used to study the association between categorical variables: "established therapy"/"disease evolution" and "place of reference"/"withdrawal of ACE inhibitor".

Results: Review of 62 cases of patients referred for angioedema.

Only in 29% the final diagnosis was "ACE inhibitor-related angioedema". The mean age of the patients was 63.7 years and 67% were male. The location of angioedema occurred in the tongue in 33% and in the remaining sites (lip, hemiface, tongue and hemiface, tongue and lip) appeared in the same frequency, 17%. None of the patients had airway obstruction. During the episode of angioedema, 22% of patients were not referred to ED and the therapeutic approach was done with antihistamines in 75%. In patients who were referred to ED (78%), antihistamines and corticosteroids medications were administered in 85%. Regarding the evolution, it was verified that the duration of the episode was independent of the established therapy (P > 0.05). Regarding the place of reference, 60% of the patients were referred form Hospital (EC or ED) and, in these, the ACE inhibitor was suspended in 73%. In patients referred from General Practitioners (40%), in none of them the ACE inhibitor had been withdrawal.

A causal association between the use of ACE inhibitors and the episode of angioedema becomes crucial, since drug withdrawal is indicated. A reference for AI OA should be weighed.

Therapy with antihistamines and corticosteroids has no proven efficacy.

Hereditary Angioedema (HAE) seen by physicians belonging to the HAE scientific committee of the AAAeIC Background: Patients with C1-INH-HAE frequently suffer from anxiety and stress. The impact of prophylactic treatment on anxiety and stress in C1-INH-HAE patients is largely unknown. Here, we analyzed data from the ApeX-1 study, a phase II study that investigated the effects of the oral kallikrein inhibitor BCX7353.

Method: C1-INH-HAE patients with a history of at least 2 HAE attacks per month were randomized to receive four different doses (350, 250, 125, 62.5 mg) of BCX7353 or placebo for 28 days. The depression anxiety stress scale (DASS) was administered at Baseline and at Day 29. The DASS consists of three self-reported scales designed to measure the negative emotional states of anxiety and stress. Subjects used a 4-point severity/frequency scale to rate the extent to which they have experienced each state.

Results: Baseline DASS total scores as well as anxiety and stress domain mean (SD) scores for the 125 mg treatment arm (N = 13) were 20.9 (23.7), 5.0 (5.9), and 8.9 (9.1) points respectively. Placebo scores were generally similar or slightly lower at baseline than for the 125 mg treatment arm. The DASS questionnaire data showed statistically significant improvements in total score vs. placebo at day 29 (−11.4 Method: A two-phase mixed methods approach was used to develop the HAE-RT Tool including: Phase 1: Delphi study [HAE specialists (N = 9) and National Patient Advocacy Group Members (N = 3)] was conducted to reach consensus (80% agreement) on predictor variables to include in the Tool. Phase 2: Retrospective chart review was conducted to assess the predictive findings of the decided variables. A convenient patient sample presenting with angioedema (with and without HAE) between January 2012-January 2017 were included in the study.

Results: Nine of 12 invited experts (75%) participated in the Delphi study. Of 8 HAE-specific predictive variables, 4 reached consensuses including: (i) recurrent angioedema; (ii) absence of urticaria; (iii) recurrent abdominal pain/swelling; (iv) lack of response to allergic therapy.

The retrospective study included 85 patients (N = 46 with HAE; N = 39 non-HAE; overall 72% female). HAE patients were significantly more likely to have a family history of HAE (72% vs 0%; P < 0.0001); previous recurrent angioedema (96%; P < 0.009); present with no hives (91%; P < 0.036); previous recurrent abdominal pain (80%; P < 0.0001); and 2% responded to allergy treatments (P < 0.0001). A regression analysis categorized observed frequencies (actual patient outcomes from chart review) versus predicted (by model); plotted on a 2 by 2 table and calculated the sensitivity and specificity of the HAE-RT which resulted in one hundred percent for both.

Conclusion: Our study demonstrated that expert involvement led to the identification and prioritization of variables that when included an HAE-RT tool, were associated with a high level of sensitivity and specificity when applied to known patients. The next step is to observe the effect of the HAE-RT tool on patient care in the ED. Method: Evaluation of cardiovascular manifestation included morphology, serum level of troponin T, electrocardiography (ECG) and echocardiography. Evaluation of pulmonary manifestation included spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) and evaluation for mastocytosis included bone marrow biopsy and serum total tryptase measurements.

Results: In the study there were 55 patients -35 women and 20 men between 21 and 71 years old (the average age was 45). There were 7 (12.73%) patients with MPCM, 4 (7.28%) with BMM, 42 (76.36%) with ISM and 2 (3.64%) with SSM. The average level of serum tryptase was 45.1 μg/L (6.9-270) . Troponin levels was within the normal range in all patients. One patient had lowered the ejection fraction (EFLV=23%). No one patient had restriction. The average value of a forced lung capacity was 3.33 L (104%) and a total Here, we describe a case series of twelve MIS patients seen at our Department over a 3-year period and report how many of these patients have SM. common phenotypical manifestations of acute HAE1 episodes in this region, to review therapeutic challenges in a rural setting in comparison with world standards, and lastly to evaluate the socio-economic burden inflicted by the disease.

Method: A sample of 13 individuals from a total of 28. The exclusion criteria was the inability to attend booked appointments more than 3 times in 1 year (2017). The following methods were used: An interview to formulate a family tree identifying affected individuals in 4 contiguous generations, and review of the acute presentations in the past year (2017) . A questionnaire to obtain the relevant HAE1 associated socio-economic burdens. A chart review to identify the therapeutic strategies in this region. C1INH levels, and Complement C4 to confirm the diagnosis.

Results: Polygamy as a local culture was found to be an important factor that perpetuated the genetic burden of the disease. C1INH

and C4 levels confirmed HAE1 in all participants individually. Clinical features during acute attacks included swelling of extremities (100%), facial swelling (69%), neck swelling (23%), and laryngeal swelling (8%). Therapeutic strategies for acute attacks included Fresh

Frozen Plasma or Fresh Dried Plasma. Danazol was used for prophylaxis. HAE1 has had a significant negative impact upon the socioeconomic status of the affected individuals.

Conclusion: HAE1 is a newly identified disorder in the broad spectrum of Allergy Medicine in KwaZulu-Natal. The diagnosis is simple to confirm but requires an initial high index of suspicion, and therapeutic management still poses a challenge in this region due to lack of resources. Genetic counselling is of paramount importance during intervention since polygamy forms part of most cultures in this region. A support strategy is highly recommended in order to help alleviate the socio-economic burden posed by the disease in this region. The socio-economic burden secondary to HAE1 (10 participants/5 identical questions each)

Question 1 (0-5 POINTS) 3

Question 2 (0-3 points) 2

Question 3 (0-3 points) 1

Question 4 (0-3 points) 1

Question 5 (0-1 point) 1 Method: A total of 172 medical faculty senior year students were included to study on a voluntary basis. Students are divided into two groups. One group was given visual user guide that has not been modified, and a visual user guide on which we have modified to the other group ( Figure 1 ). Then they were asked to show how to use the inhaler spacer.

Results: The mean age of the volunteers was 25.3 ± 126 years and 104 (60.5%) were male. There were 82 students in the group without modification of the visual user guide and 90 students in the other group with modified the visual user guide. Sixty-four per cent of the modified user guide group showed correct use of the inhaler spacer, while 15% of the unmodified group showed correct use (P = 0.001). The group that given modified visual user guide was more successful in all of the display steps of the inhaler spacer.

Conclusion: Modification of the currently available visual user guide of inhaler spacer in our country will increase the correct usage rate. Results: Mean FEV1, FVC, FEV1/FVC z-score were 1.8 (1.1-3.9), 1.7 (0.9-3.7), 0.9 (0.8-0.9), respectively. Restriction had 31 (57.4%) and obturation 3(5.3%) patients. FEV1 (P < 0.001, r 2 = 0.37) and FVC (P = 0.001, r 2 = 0.38) decreased with age (%PV and z-score). Background: Children who were treated for leukemia are known to have developed long term impairment of lung function.

The reasons that complication are only partially known. The aim of this study was to asses pulmonary function in children treated 

The lower DLCO is the most frequent abnormality in childhood leukemic survivors. HSCT and pulmonary infection (in particular CMV pneumonia) is a strong risk factor for impairment of DLCO in children. Clinical manifestation of DLCO impairment is poor exercise tolerance. A screening for respiratory abnormalities in survivors following treatment for childhood haematologic malignancies, seems to be of significant importance. 0746 | Phenotyping allergic respiratory diseases: An unsupervised classification using latent class analysis allergen groups was significantly associated to UAwI (aOR[95% CI]:2.1 [1.3-3.6] ), compared to UAsI. Results: 80.8% of BR and 49% of PY were women, median age was 32 years, 35% BR and 52% PY reported having more than four years of training. Although they recognized the main symptoms of AR, 26% BR and 100% PY never asked whether the patient had a medical diagnosis of AR; 20.5% BR and 100.0% PY did not ask whether the symptoms occurred when close to animals or allergens;

55% BR and 76% of PY did not ask if the patient had a medical diagnosis of asthma; 59% BR and 70% PY did not ask if rhinitis worsens asthma symptoms and 51.3% BR and 84.3% PY did not ask whether symptoms of rhinitis interfere with their daily activities. Results: There was a predominance of female (BR: 73%, PY 50.4%, UY: 70%) median age 31 years old, 124/235 worked in the community and 75/127 in the emergency departments, 34% of the BR had more than 10 years of education, 67% from PY had between 1 and 5 years, and 82% from UY had been graduated for less than 1 year.

BR/UY recognize the main symptoms of AR, however 67% of those from Uy do not ask: if the patient has physician diagnosis of AR, 72% present shortness of breath, and 93% a medical diagnosis of asthma, 94% if rhinitis worsens asthma symptoms and 90% if symptoms of rhinitis interfere with the patient's daily activities. The prescribed treatment varied a lot, the intranasal corticosteroid use rate was: BD: 78%, PD: 92% and UD: 54%.

100% of doctors in PY, 73.4% in BR and 78% of UY never refer the patient to the specialist. 22.9% of PCD of BR, 62% of PY and 6.0%

of UY are aware of ARIA guideline.

Conclusion: Although AR is largely attended by PCP, recognition of symptoms and their impact on asthma, as well as the knowledge about ARIA Guide is low and treatment is not always prescribed according to best practice. Allergy education programs, with an emphasis on AR and ARIA guide, need to be directed to PCP in LA for the better assistance of AR patients.

0749 | Assessing knowledge of allergic rhinitis among final year medical and pharmacy students in Croatia-Curriculum change necessity? The two factor structured questionnaire was formed by the authors regarding the topics mentioned. T-test was used for statistical analysis.

The global results were formed as composites of (1) AR general characteristics, (2) AR treatment approach, and (3) the participants' overall knowledge. Of the 201 respondents, 143 (71.1%) were female and 58 (28.9%) were male (P < .0001). Medical students had a median score of 6 of 10 correct answers on (1), 4 of 10 on (2), and 10 of 20 on (3), whereas pharmacy students had median score of 7 of 10 correct answers on (1), 4 of 10 on (2), and 10 of 20 on (3). There were no significant differences in knowledge between two student groups.

The results indicate an inadequate level of knowledge of AR in both groups, especially regarding the therapy approach.

Since general practitioners and community pharmacists have a major role in providing treatment to patients suffering from AR, it is important to develop advanced knowledge on this topic during medical and pharmacy degree courses. Despite a relatively small study population, it would be advisable to introduce change by improving the core curriculum regarding AR with more emphasis on treatment, but additional research on this topic is necessary.

Tan R 1 ; Cvetkovski B 1 ; Kritikos V 1 ; Price D 2 ; Yan K 3 ; Smith P 4 ; Bosnic-Anticevich S 5 1 Woolcock Institute of Medical Research; University of Sydney, Sydney, Australia; 2 Observational Pragmatic Research Institute Pte Ltd, Singapore, Singapore; 3 Royal Prince Alfred Hospital, Sydney, Australia; 4 Clinical Medicine, Southport, Australia; 5 Griffith University, Sydney, Australia Background: People with allergic rhinitis symptoms frequently selfselect over-the-counter medications from community pharmacies without seeking advice from a health care professional. This increases the incidence of complications due to delayed diagnosis and suboptimal treatment. This study aims to (i) compare the demographics, clinical characteristics and medication selected, between pharmacy customers who choose to self-select and those who interacted with a pharmacist when purchasing medication for allergic rhinitis symptoms, and (ii) identify the key factors associated with allergic rhinitis patients' medication self-selection behaviour.

A cross-sectional observational study was conducted in a convenience sample of community pharmacies from the Sydney metropolitan area. Data were collected using a researcher administered questionnaire that included: demographics, pattern of allergic rhinitis symptoms, their impact on quality of life, factors triggering allergic rhinitis symptoms and medication(s) selected. Logistic regression was used to identify key factors associated with participants' medication self-selection behaviour.

Results: Of the 296 recruited participants, 202 were identified with allergic rhinitis, of which 67.8% were female, 54.5% were aged more than 40 years old, 64.9% had a diagnosis of allergic rhinitis, and 69.3% self-selected medication(s). Significant differences were noted in allergic rhinitis symptoms, impact of allergic rhinitis on quality of life and medication(s) selected between participants who chose to self-select and those who interacted with a pharmacist. Participants who experienced moderate-severe wheeze were 4 times more likely to self-select allergic rhinitis medication(s), and those who had allergic rhinitis symptoms impacting on their quality of life were 0.4 times less likely to self-select allergic rhinitis medication(s).

Conclusion: There is a high incidence of self-selection of over-thecounter treatments for allergic rhinitis symptoms in community pharmacy, with the majority of allergic rhinitis sufferers failing to seek pharmacist advice. This research identified predictors of medication self-selection behaviour in community pharmacy among people with allergic rhinitis, which can inform the design of tools/strategies and targeted interventions, aimed at improving pharmacist engagement and future practice in optimising allergic rhinitis management. The Weir Family Health Clinic, Cork, Ireland; 2 University College, Cork, Ireland Background: Allergic rhinitis is a common condition that is predominantly managed in primary care. The incidence of allergic rhinitis is increasing. It is frequently under diagnosed, misdiagnosed and mistreated. It has a significant impact on patients' health related quality of life and represents a huge cost both to healthcare systems and society. The aim of this study was to implement appropriate guidelines regarding the management of allergic rhinitis in primary care and evaluate the effect on patients' health related quality of life.

Method: Patients with a history of allergic rhinitis were selected from three general practice bases in West Cork, Ireland and quality of life of patients was assessed initially in year one and followed up one year later in a general practice setting using the standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and appropriate prescribing were implemented during this year and patient education and structured follow up was arranged in the intervention group.

This was compared with the control group who received usual care.

Results: 93 valid responses were received, 34 from the control group and 59 from the intervention group. The study demonstrated a statistically significant difference in quality of life in the intervention group. In the adult intervention group the quality of life score decreased between 2015 and 2016 representing an improvement in their quality of life, (t = 4.13; df=56; P < 0.01). The difference in the score between the control and intervention groups in 2016 was also statistically significant.(t = 6.11; df=54; P < 0.01). The numbers in the adolescent groups and paediatric group also demonstrated an improvement in quality of life but the sample size was too small to demonstrate a statistically significant difference.

Conclusion: As the majority of patients rely on their general practitioners for treatment and diagnosis of allergic rhinitis, primary care represents an important area to target in the management of allergic rhinitis to improve patients' quality of life. The implementation of guidelines has been shown to improve patients' quality of life. This study demonstrates this care can be delivered in a primary care setting with an improvement in patients quality of life but substantial investment in education and resources available to primary care physicians is needed. 0752 | The predictive value of allergy tests in the diagnosis of peanut allergy in adults Rey-Garcia H; Gunawardana N; Wheeler K; Scadding G; Durham S; Skypala I Royal Brompton Hospital, London, United Kingdom Background: Adults presenting with either new-onset symptoms attributed to peanuts or with early-onset peanut allergy, often wish to know whether they should continue to avoid peanuts. Clinical history and standard tests may be sufficient to provide an answer, but for many the tests are inconclusive and an oral food challenge is required. This review was undertaken to determine the most accurate tests. Conclusion: These data suggests that peanut SPT and Ara h 2 provide the most accurate prediction of the outcome of oral food challenge in adults. Should components not be available, then SPT would be the test of choice being more accurate in all aspects than SIgE.

Combining SPT and SIgE improves the sensitivity and negative predictive value of SPT alone. However, the best combination is SPT and Ara h 2, which increases the overall accuracy to 87%. Further studies are needed before it can be determined whether peanut diagnostic tests can replace the oral food challenge in adult patients. Method: Retrospective chart review was carried out in a community allergy clinic. Patients with RAP, bloating and altered stools who underwent BT were characterized by age, gender and atopic status.

A separate study to assess patients' outcome post-dietary counselling was carried out to determine impact on symptom management.

Results: Thirty-four patients were assessed for FI from January 2014 to December 2017. Female gender predominated (31/34, 91%) with an average age of 31 years at presentation. Results of FI were positive in 15/34 (44%), borderline in 2/34 (6%) and negative in 17/ 34 (50%). The average age of patients with a positive, borderline and negative tests were 30, 20 and 34, respectively. Of the patients who tested positive for FI, 5 (33.3%) had comorbid inhalant allergies alone, 1 (6.7%) had comorbid (unrelated) food allergies alone, 2 (13.3%) had inhalant and food (unrelated) allergies, and 7 (46.7%) were non-atopic. Of the patients who tested negative for FI, 7 (41.1%) had comorbid inhalant allergies alone, 0 (0%) had comorbid (unrelated) food allergies alone, 1 (5.9%) had inhalant and food (unrelated) allergies, and 9 (53.0%) were non-atopic.

Conclusion: Patients investigated for carbohydrate intolerance with RAP, bloating and altered stools were predominantly female (91%). FI was confirmed in half. Atopic status did not help differentiate between the FI positive or negative groups. Results of a FOD-MAP elimination diet are separately reported. Conclusion: Post-BT, 88% of patients reported symptom improvement. Patients who implemented fructose or FODMAP avoidance reported symptom improvement. One patient who tested negative for FI reported symptom improvement with a low FODMAP diet.

Patients suspected as being fructose intolerant may benefit from a fructose restriction or FODMAP diet, while awaiting BT confirmation. This form of dietary intervention may assist and shorten the natural history of non-specific chronic GI symptoms.

Inappropriate referrals to a UK paediatric tertiary allergy clinic demonstrate lack of allergy education and knowledge in primary care Marriage DE Bristol Royal Hospital for Children, Bristol, United Kingdom Background: Up to 8% of children have a food allergy. Allergy has become an explanation for all manner of nebulous symptoms and self-diagnosis is common. Sham allergy tests are easily available giving incorrect results and resulting in unnecessary, potentially harmful ABSTRACTS | 423 parentally-imposed dietary exclusions. There are 100 million allergyrelated Google searches per year. The rising prevalence of perceived allergic disease has led to an increase in health service utilisation, including increased referrals to secondary care. Clinic waiting lists are long and children with severe food allergies have to wait longer than necessary to be seen Method: UK paediatric tertiary allergy clinic referrals were prospectively reviewed over three months. Five inappropriate referrals deemed most reflective of poor knowledge in Primary Care were selected as case summaries to highlight this gap in knowledge.

Results: 1: Schoolchild referred for investigation of allergic cause for a red, watery eye after splashing juice in her eye whilst cutting a kiwi, despite having a co-existent dendritic ulcer.

2: Schoolchild referred for peanut allergy testing after inhaling a peanut and developing wheeze, with all respiratory symptoms resolving following peanut removal.

3: Young child referred for peanut allergy testing after developing a rash on leg following skin contact with faeces 24 hours after ingestion of peanut butter. 4: Teenage boy referred for investigation of likely peanut allergy despite eating peanut butter and tree nuts almost every day. The family were concerned he was allergic to peanut butter. 5: Toddler referred for milk allergy investigation after developing urticaria lasting 24 hours 15 minutes after drinking a bottle of milk.

The child had consumed cow's milk formula since birth, and continued to consume milk daily for a further five months following the episode of urticaria.

Conclusion: Provision of allergy services in the UK is poor and lack of investment in allergy services has led to suboptimal recognition and management of food allergy in primary care. Allergy education provision for primary care practitioners is inadequate and fails to empower healthcare professionals to discern between allergy requiring full investigation and management, parentally-diagnosed allergy or symptoms which clearly have no association with allergy. Progress to improve primary care training for allergy needs to be optimised to prevent further unnecessary referrals and lengthening clinic waiting lists. Background: In case of allergic reactions to food or insect venom, quick and adequate treatment, based on clear instruction for use of emergency medication and calling for help, is necessary. However, daily practice shows that patients do not use the prescribed emergency medication because they are afraid to use the epinephrine auto-injector or they do not know how to use it. Information and instruction offered by a reliable app could be a useful aid. We aim to develop an app for adult patients and children older than 12 years with allergy to food or insect venom, which offers a step-wise approach to support patients, their relatives or acquaintances in case of an allergic reaction.

Method: First, the content of the app, including a step-wise approach to treat the allergic reaction has been determined, based on literature, a survey about needs of patients and on consultations of healthcare professionals. Subsequently, a web-based prototype has been developed with an adult profile and children profile. The content and flow of this prototype was tested by the project group, as well as by selected healthcare professionals and patients and improved according to the test results. Next, the revised prototype was submitted to representatives of patient and professional organizations for final approval. Currently the procedure for CE approval is ongoing. Finally, the app will be built and offered to the market for iOS and Android.

Results: A web-based prototype of the Allergy App is available with two profiles: adult and older children. The app is useful for patients with a doctor's diagnosed allergy to food or insect venom, who received emergency medication and instructions to use prescribed medication in case of an allergic reaction. Based on severity of complaints, the user is informed about the steps to treat the allergic reaction. In case of a moderate to severe reaction, the patient is advised to use an epinephrine auto-injector, to call the emergency number and, if prescribed, to use medication such as antihistamines, prednisone or inhaler. Besides that, the app provides links to websites of expertise centres and patient organisations and includes instructions how to use the epinephrine auto-injector.

Conclusion: The Allergy App will help patients, their relatives or acquaintances to adequately treat an allergic reaction to food or insect venom. Involving patients and professionals in the development of the app will contribute to its acceptability and usability. 0757 | Electronic documentation of drug allergies in a tertiary hospital in Singapore: are we relying too much on it?

Choo KJL; Garuna Murthee K; Naing CS Singapore General Hospital, Singapore, Singapore

Background: Singapore has 26 hospitals shared between public and private healthcare system. Its healthcare system, ranked #6 in the world by WHO in 2010 serves a multi-racial population of 5.2 million of which 9% are above 65 years old. Drug allergy alert cards (Medik Awas) were started in 1970s by Singapore Medical Association to improve patient safety. Work on computerisation of drug allergy and medical alerts started in the 80s, a precursor to today's Critical Medical Information System (CMIS). CMIS serves as a platform across all public hospitals in Singapore. It promotes uniform reporting of drug allergy and notification of adverse drug events to the Health Science Authority.

Yet, we found that there is a lack of awareness of one's own drug allergies.

Method: All patients admitted to ward 73 (general medicine ward) at Singapore General Hospital from 17 July to 31 Oct 2017 were screen for any previously documented drug allergies. Consenting patients who had previously documented drug allergies on CMIS were interviewed to document their demographics, education level, current medications, knowledge of their own drug allergies and possession of a drug medication alert card. The answers were then compared with their electronic documentation of drug allergies for accuracy.

We interviewed 192 patients aged 20-94 with documented drug allergies during the recruitment period. 74% had secondary school education or higher. The majority (76%) spoke English and (58.5%) Mandarin. Almost half had medical problems and are on long term medications (mean 5.17 medications); hypertension and diabetes being the top two common diseases. 48% of the patients could accurately relay their drug allergies; antibiotics and analgesia being the most labelled. Only 24% had a drug allergy alert card while the rest both rely on the hospital's electronic documentation and/or their caregivers to record and relay their allergies to future prescribers. About 21% received prescription from multiple healthcare sites in both the public and private healthcare system.

We found patients' knowledge of their own drug allergies dismal. The CMIS electronic documentation provided a false sense of security. Unfortunately, the CMIS platform is not available to all private hospitals, increasing the risk of mis-prescription due to the lack of information. Unless this is made available nationally, patients with drug allergies should be given some written documentation, either a letter or Medik Awas.

How frequent are they and how are they treated? Method: For this cross-sectional study, participants were recruited in the waiting rooms of local doctors in the rural Bavarian Forest region of Southern Germany (Q1/2017). A paper questionnaire was handed out to the participants, asking for allergies (pollen, animal hair, bee and wasp venom, drugs, food, house dust mites, contact allergies and other allergies) and how or rather by whom (e.g. general practitioner, specialist, self-treatment) these allergies are treated.

Results: 718 participants with a mean age of 50.61 years (SD=15.15) and 59% women were included in this study. 38.2% indicated to have at least one allergy, including pollen allergy most frequently (17.4%). Women had significantly more often at least one allergy than men (RR= 1.552; CI [1.243;1.937] ) and for almost all examined allergies a significant higher risk of disease. Younger age groups indicated more often to have at least one allergy (18- [.506;1.151 ]) seemed to be affected less. Participants indicated most frequently that their allergy was treated by a general practitioner (37.5%), except of the 18-29-yearold young adults who indicated "no treatment" most frequently (28.2%).

Conclusion: There is a high self-reported prevalence of allergies in the examined rural Bavarian region, that increases with decreasing age and is significantly higher among women. Moreover, the data on the absence of an appropriated treatment for allergies is alarming.

Therefore, medical care needs to be improved in rural regions to lower the burden of allergies. 0759 | The prevalence of the burnout syndrome among medical professionals involved in allergology education programmes Astafieva N 1 ; Kobzev D 2 ; Gamova I 1 ; Perfilova I 1 ; Udovichenko E 1 ; Skuchaeva L 1 ; Michailova I 1 1 ≥10) and RPA (Low ≥0-11, subscales were calculated and analyzed.

Results: On average students demonstrated: moderate/high EE scores (24-26); moderate/high DP scores (9-12) and moderate RPA scores (17); higher RPA scores were common (41.4%) among junior students, which is also linked with their levels of engagement, and lower (28%) among senior students.

Junior specialist (starting specialization) had very low scores in all 3 subscales and expressed a very high motivation in their course and new profession.

Clinical allergologists with significant experience demonstrated moderate / high EE scores (22-26); low DP (1) (2) (3) (4) (5) and RPA (below 10) scores. High EE scores associated with pressures of service were compensated by a substantial loyalty to their profession and positive assessment of the outcomes of their work. Clinical academics demonstrated the highest level of EE scores (29 + among 70 + % of the group) with low to moderate DP and RPA scores, the latter being associated with a loyalty to their profession. It was also possible to identify a correlation between engagement in research activities and lower RPA scores.

Conclusion: Burnout is a complex and multifaceted phenomena, which requires further investigation. However, this research identified that students and junior specialists involved in allergology and clinical immunology programmes with higher levels of engagement and motivation to acquire new specialist knowledge had lower levels of EE, while loyalty to the profession and positive assessment of the outcomes of clinical and research work allows to compensate high levels of EE among experienced practitioners and clinical academics and to reduce burnout effects overall. 0760 | APPEAL (Allergy to Peanuts ImPacting Emotions And Life): the first pan-European study to evaluate the psychosocial burden of living with peanut allergy Deutscher Allergie-und Asthmabund (DAAB)/German Allergy and Asthma Association, Mönchengladbach, Germany; 8 Food Allergy Italia, Padua, Italy; 9 AEPNAA Asociación Española de Personas con Alergia a Alimentos y Látex, Madrid, Spain; 10 AFPRAL Association Pour La Prevention Des Allergies, Paris, France; 11 Asthma-Allergy Denmark, Roskilde, Denmark; 12 Anaphylaxis Campaign Ireland, Cork, Ireland; 13 Brainsell Ltd, London, United Kingdom; 14 Aimmune Therapeutics, London, United Kingdom Background: Peanut allergy, one of the most common and rapidly growing food allergies, is most frequently a lifelong condition. Current management is limited to avoidance and symptomatic treatment of allergic reactions when accidental exposures occur. Peanut allergy can affect the quality of life (QoL) of individuals and also that of parents/caregivers and family members. APPEAL was designed to assess the impact of peanut allergy on QoL in peanut-allergic individuals and their parents/caregivers and families.

Method: The first, quantitative part of APPEAL is described here and consisted of a pan-European, cross-sectional online survey of approximately 30 minutes in length. The study was conducted in the UK, Republic of Ireland, France, Spain, Germany, Italy, the Netherlands and Denmark. Over 1800 participants were recruited via patient advocacy groups or directly through a specialist survey recruitment panel. Ethics committee approval was obtained and all participants provided their informed consent. Eligible participants were: (1) parents or caregivers of a child/adult with peanut allergy;

(2) parents or caregivers responding as a proxy for a child aged under 18; (3) adults. All allergic subjects had self-reported diagnosed peanut allergy.

After several screening questions, eligible participants answered a set of clinical questions about their (or their child's) allergies and other conditions, details on the peanut allergy diagnosis, contact with healthcare professionals, worst allergic reaction to date and use of emergency medicine.

Depending on whether they were an allergic adult, a parent responding on behalf of the child, or a parent/caregiver recounting their own experience, they then answered specific questions on restrictions on life choices, coping strategies and the impact of peanut allergy on feelings and emotions of families, friends and other people. Sociodemographic questions completed the questionnaire.

The results of the survey are being summarized using descriptive statistics and the data are being analysed on a pan-European level, by country, and according to the participant's perspective (parent, caregiver or individual).

Conclusion: This comprehensive, pan-European online survey has been specifically designed to uncover the psychosocial burden and effect on QoL of peanut allergy in terms of individuals' lives and those of their families. Results: 246 pediatric patients were included in the study. 65.9%

(n = 162) were male. The median age of onset of symptoms (interquartile range) was 4 months (2-6).The median age (interquartile range) of diagnosis was 6 months (4-7). Initial reactions associated with CMPA were observed in 95.8% of patients before 12 months old. Patients' diagnoses were atopic dermatitis (39%), urticariaangioedema (24%), anaphylaxis (12.2%), proctocolitis (10.2%), atopic dermatitis and urticaria (8.9%), food protein induced enterocolitis (4.9%) and eosinophilic esophagitis (0.4% Method: The study involved 147 patients, who are two years old (and above), diagnosed with cow milk allergy and are observed for at least six months in our hospital. Socio-demographic features of the patients, their symptoms, symptom-start ages, age of diagnosis, clinical findings at diagnosis and during observation were recorded in data collection questionnaires.

Results: The samples were 91 (61.9%) boys. The average symptomstart age was observed to be 5 months , average diagnosis age 6 months (1-54) and average age of final check 36 months . When symptoms at entry were observed, 85.7% of the patients had dermal system, 25.2% gastrointestinal system, respiratory system disorders, and 15% were detected to have developed anaphylaxis. Among the patients diagnosed with cow milk allergy, 31.3% showed food reaction to nutrients with lgE agents, 51.7% to mixed types, and 17% to nutrients with non-lgE agents. It was also observed that, in the end of 30.4 ± 19.8-month observations, sensitivity to cow milk was observed to continue in 34 (23.1%) of our patients. When tolerance improvement rates among the patients were compared, anaphylaxis (P < 0.001) during entry were observed to be influential in continued allergic state. 5 (3.4%) patients were able to consume yoghurt, 10 (6.8%) patients could consume dairy products and 19 (12.9%) patients could not consume dairy products.

Conclusion: In the end of our investigation, it was observed that 57 (50.5%) of the 113 patients developed cow milk tolerance before the age of 2. When the factors enabling the continuation of sensitivity in cow milk allergy were investigated, anaphylaxis during entry, entry specific lgE and pasteurized milk antigen as well as high skinprick test results were detected to be significant. 0765 | Initial lower threshold was a risk factor of severe adverse reaction during oral immunotherapy for cow's milk anaphylaxis Results: Before OIT, median age was 5.7 years old, median threshold to induce initial reaction was 2.1 mL, to induce anaphylaxis was 14.6 mL of CM and median milk specific IgE was 56.4 kU/L. Twentyseven subjects (24%) dropped out from the protocol, 69 subjects 0766 | Investigation of heat and matrix effect on milk proteins' allergenicity and the development of hypoallergenic food products reduce some milk proteins' allergenicity (ß-lactoglobulin) . In this project we aimed to investigate the effect of heat and matrix on different milk protein fractions through Maillard reaction and eventually develop hypoallergenic food products that have milk protein with low reaction risk.

Method: Milk cake matrix is prepared in different flour/sugar (F/S) ratio (2F/1S, 1F/1S, 0.5F/1S) and baked 30 minutes at 180°C. Proteins that cake contains are separated using SDS PAGE and stained with coomassie blue to check total protein. In parallel specific proteins are detected by western blotting using pooled sera from patients with milk specific IgE>60kU/L for incubation Results: In normal milk cake recipe (2F/1S) ß-lactoglobulin bands are disappeared but casein bands did not differ in size. In order to investigate the matrix effect F/S ratio is changed and it is found that when this ratio decreases, with the affect of heat and maillard reaction, milk casein bands' intensities also decrease in SDS gel coomassie staining. In western blot experiments it is also shown that milk specific IgE bound weakly to casein bands in low F/S ratio cake (0.5F/1S) whereas in cakes that have high F/S (2F/1S) ratio it bound significantly higher.

and ß-lactoglobulin proteins' structure and lower the milk specific IgE bindings to milk proteins in low F/S ratio cake through Maillard reaction.

0767 | Extensively hydrolyzed formulas for the management of cow's milk protein allergy in infants: is extensive hydrolysis sufficient to guarantee success? Method: To better understand the range of eHFs, we aimed to analyse samples of commercially available eHFs from 11 countries and various manufacturers, with a focus on suitability for CMPA management.

Samples were de-identified and coded for the analyses. Molecular weight (MW) distribution of hydrolysates and residual proteins and peptide profiling were assessed with SDS-PAGE gel and size exclusion-high-performance liquid chromatography (SE-HPLC), as they reflect both the design of the formula and the quality management applied during production. Osmolarity, nitrogen fractions, lactose content, total and free amino acids, β-lactoglobulin, and casein content were quantified and β-lactoglobulin residual allergenicity was assessed.

Results: Peptide MW distribution displayed significant variation, with the percentage of peptides with MW >1.2 kDa varying from 1% to 36%. MW distribution was shown to be positively correlated with β-lactoglobulin specific in vitro degranulation.

Twenty % of samples had non-measurable β-lactoglobulin content (smaller than or at the limit of quantification (LoQ): 0.010 mg/kg); however, 80% of samples had β-lactoglobulin content greater than the LoQ, with high variability from 0.020 to 36 mg/kg. Surprisingly, even in samples featuring a high degree of hydrolysis, significant levels of residual β-lactoglobulin were quantified.

Conclusion: Lack of consensus over the definition of 'extensively hydrolysed' is reflected in the wide range of degree of hydrolysis in commercially available eHFs, and can result in products that are mislabelled as 'extensively hydrolysed' and may be high-risk or even unsuitable for the management of CMPA. Results of these analyses also highlight that degree of hydrolysis alone is not sensitive enough to characterise eHFs, and that whilst a high degree of hydrolysis is desirable, further quality control measures are essential to ensure clinically safe and suitable products. Actionable guidelines to better define hypoallergenic formulas based on extensively hydrolysed milk proteins are warranted. Background: Assessing the effect of baked milk products on accelerating unheated milk tolerance in patients with cow's milk allergy.

Method: A randomized clinical trial was done on 84 patients (6 months-3 years old) divided randomly to case and control groups matched for age and sex. Baked milk in form of muffin for

6 months followed by baked cheese in form of pizza for next 6 months was given to the patients in case group. Skin prick test and serum IgE (sIgE) levels (ImmunoCAP) of milk, casein and betalactoglobulin were measured before and after the study. The ones having milk sIgE less than 3 kU/L and being asymptomatic during the study underwent oral food challenge test for evaluating unheated milk tolerance. Chualalongkorn University, Bangkok, Thailand; 8 KK Women's and Children's Hospital, Singapore, Singapore; 9 University of the Philippines, Philippine General Hospital, Manila, Philippines Background: Problems in recognising cow's milk allergy (CMA) and lactose intolerance (LI) in infancy may lead to a delayed or incorrect diagnosis, as well as inappropriate dietary interventions.

Method: Between January and November 2017, a survey was conducted online in China, India, Singapore, Thailand, Mexico, Kuwait, United Kingdom, Australia, and paper-based in the Philippines. The survey consisted of 12 multiple-choice questions on CMA and LI in infants aged under 12 months, two case scenarios (non-IgE CMA and anaphylaxis) and 10 questions on educational needs (Likert scale [1] [2] [3] [4] [5] . Data on the type of medical practitioner and clinical setting were collected. Responses were summarised as percentages and categorised by country.

Results: 1663 responses were received from general practitioners (22.2%), paediatricians (39.7%), paediatric allergists (6.9%), paediatric gastroenterologists (11.2%) and other specialities (20.0%). There were significant misconceptions about the clinical importance of primary LI in infancy. While primary LI rarely manifests before 3 years of age, 73.7% of participants felt it was a significant clinical problem in the first year of life. Regarding secondary LI, 44% of respondents recommended lactose restriction for viral gastroenteritis, and 36% for cow's milk protein-induced enteropathy. While the management of IgE CMA was relatively well understood, there were greater knowledge gaps for non-IgE CMA. 59% of practitioners appropriately identified extensively hydrolysed formula (EHF) as first-line treatment of CMA in formula-fed infants. However, the distinction between lactose-free and lactose-containing EHF appeared to be an area of uncertainty. In India, 34.4% used soy-based formulas as first- Results: Patch tests were positive in 62 (79.5%) and negative in others. Positivity to milk was seen in 29 patients (37.2%), to soy in 41 (52.6%), to egg white in 7/72 (9.7%), to wheat in 12/66 (18%), to potatoes 6/48 (12.5%), to corn (maize) in 3/38 (7.9%), to rice in 1/2, and to peanut in 3/37 (8.1%).

Patients were requested to withdraw the suspected food(s) from their diets during a 4 months period. Preliminary follow-up data show the improvement of one or more symptom in 19/20 patients (gastroesophageal reflux in 10, appetite in 5, stool consistency in 1, respiratory symptoms in 10, pain in 3, eczema in 1).

Conclusion: Patch tests are informative, easy to use tools in order to identify potential causes of common lasting symptoms in children with negative or weak RAST results and introduce beneficial changes in the daily diet. Longer follow-up is necessary in order to refine and assess the benefit of such strategy. Background: Currently in the US, 1 in 13 children suffer from food allergies. At present, there is no cure and strict avoidance of the relevant foods is the only way to prevent allergic reactions. Elimination diets put infants and children at risk for nutritional deficiencies and impaired growth. We examined the role of the registered dietitian (RD) in advising patients and families of food allergic children.

Method: A retrospective review of clinical notes was performed for the first 13 consecutive children who required a dietetic consultation in a dedicated food allergy clinic. We examined common questions from parents that were addressed by the dietician during the consultation.

Results: Patients were aged 10 months -9 years (median: 16 months) and were diagnosed with the following food allergies:

Cow's milk: 69.2%, Egg: 62%, Tree Nut: 54%, Peanut: 39%, Wheat: 31%, Soy: 31%, Fruit/Vegetable: 15%, Legume: 8%, Fish: 8%, Sesame: 8%.

The most common questions for the dietitian included: ways to meet nutritional needs following a prescribed allergen-restricted diet (31%), meeting vitamin D and calcium requirements on a milk protein-free diet (23%), suitable oral supplements and recommended serving sizes (14%), appropriate order of solid foods introduction in food protein-induced enterocolitis syndrome (FPIES) (14%), cautionary food ingredient statements (7%), baked milk protein introduction (7%), cross-reactivity risk of milk protein with soy (7%) and crossreactivity of nuts in retail bakeries (7%).

Conclusion: Parents of children with food allergies have multiple questions with regards to nutrition. Dietetic input in the food allergy clinic addresses important issues for children and families including successful avoidance of allergen-containing foods while ensuring optimal nutrition, decreased exposure to high-risk situations and avoidance of allergen cross-contamination. 0773 | Multicenter prospective study of a stepwise single dose oral food challenge of egg Background: Oral food challenges (OFCs) are necessary for allergy management. We previously reported that a low-dose OFC can avoid complete elimination, even if patients react to higher doses of causative foods. Nevertheless, this approach has only been validated in a retrospective single-center trial. We have previously reported that the median time for initial symptom onset is 50 minutes for egg OFC using a single exposure. Therefore, this study aimed to confirm the safety and effectiveness of a stepwise single-dose OFC in a multicenter, prospective study. who showed a positive reaction to low-dose OFC, only 1 patient (2%) showed a severe reaction: barking cough immediately improved with adrenaline inhalation. Among 8 patients with a positive reaction to medium-dose OFC, none had a severe reaction. The median times to symptom onset were 60 and 50 minutes following low-dose and medium-dose OFC, respectively. Patients in the three groups, divided according to threshold doses, differed significantly in sIgE levels against egg white and ovomucoid.

Conclusion: This multicenter prospective study confirmed that stepwise single-dose OFC to egg will help to clarify the severity of egg allergy, and will contribute to improved food allergy manage- Method: The study design was a retrospective cohort study extracting data from the electronic chart of children older than 4 years who visited our out-patient clinic for egg or milk allergy and who underwent an oral food challenge test (OFC) twice within 24 months between November 2013 and December 2017. The patients were divided into five groups according to their treatment schedule, which consisted of those who: a) Started from 1/10 of the first OFC reaction threshold and maintained 1/10 till the end of OIT; b) Started from 1/100 of the threshold and maintained 1/10; c) Started from 1/10 000 of the threshold and maintained 1/10, d);

Conventional slow OIT (started from just below the first OFC reaction and increased 1.2-1.5 times every few weeks); or e) Continued elimination. We determined the presence or absence of an increase in threshold reacted to the allergen, any adverse events during OIT, and food-specific IgE reduction.

Results: The number of participants was 217 and their median age was 6 years. The number of patients in groups a, b, c, d, and e was 17, 51, 33, 95, and 21, respectively. The percentage of patients in groups a, b and c showing an increase in reaction threshold to the allergen was higher than that in group e (P < 0.05), and that in group b was higher than that in group d (P < 0.001). The number (percentage) for group a, b, c, d, and e was 12 (70.6%), 43 (84.3%), 23 (69.7%), 54 (56.9%), and 5 (23.8%), respectively. There was a significant difference in the frequency of adverse events during OIT between group a-c and d, which was as follows: 5 (29.4%), 9 (17.6%), 8 (24.2%), and 67 (70.5%), for the respective groups (P < 0.0001). There was no significant difference in the percentage of patients showing a decrease in food-specific IgE in each group.

Conclusion: The regimen starting from 1/100 of the OFC reaction threshold and maintaining the dose at 1/10 was safer and more effective for increasing the threshold reacted to the allergen than the 'conventional slow OIT' regimen. Elimination continuation was not effective for increasing the threshold reacted to the allergen.

Legumes allergy was presented in different clinical features; urticaria and angioedema in 32 (50%) patients, anaphylaxis in 23 (35.9%) patients, atopic dermatitis in 5 (7.8%) patients, eosinophilic esophagitis in 3 (7.8%) patients and as food-related enterocolitis in 1 (1.5%) patient. Thirteen (35.1%) of the patients had asthma, 9 (24.3%) had allergic rhinitis. Fourteen (58.3%) of the 24 patients with single legume allergy showed improvement. The patients who developed tolerance, of these 7 (29.1%) had peanut allergy, 4 (16.6%) had lentil allergy and 3 (12.5%) had chickpea allergy. Two of 13 patients with multiple legumes allergies, it developed tolerance to all the legumes they are allergic.

Conclusion: Peanut and lentils were the most frequent legumes that displayed allergic reactions in our study. In these patients the rate of allergy to non-legumes food is high. In patients who were allergic to single legumes, the symptoms were ameliorated in 58.3%. Conclusion: Cashew nut is a potent allergen and can cause quite severe reactions. Avoidance of pistachio nut and other related allergens should be advised to patients after allergologic investigation. In the majority of the patients, presence of atopic dermatitis with food allergy is noteworthy. Therefore, it would be useful to investigate these patients for cashew and other tree nut allergy before they present with a serious clinical reaction. and jellyfish sting. Serum allergen-specific IgE test was negative; skin prick test was positive for Natto and pork. We performed an oral food challenge with Natto, pork, crustaceans, and wheat, and she developed a general itchy rash after 7 hours of eating Natto. H1blocker was administered and she recovered soon. However, the general itchy rash relapsed after 4 hours. Hence, we intramuscularly injected epinephrine, H1-blocker, and steroids; then, her symptoms did not relapse. Based on these findings, we inferred that anaphylaxis caused by Natto could be associated with a jellyfish sting.

Discussion: Although association between Japanese fermented soybeans (Natto) allergy and jellyfish sting has been previously reported, its anaphylaxis is a rare event. In this case, we suggest that anaphylaxis was caused by Natto allergy, which was perhaps related to jellyfish sting. Hence, further investigation is essential to elucidate the association between fermented soybeans allergy and jellyfish sting. Introduction: Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extra intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease (CD) or wheat allergy (WA).Once the gluten-containing foodstuff is removed from the diet, the patients will have relief of their symptoms.

Case: A 6-year-old girl was referred by his General Practitioner with history of occasional constipation and abdominal pain (especially after main meals and defecation), short stature and low weight. The growth indices were proper for her age till she was 5. Then after there was a stunting. She had short stature and low weight. Despite different types of supplementation, there was no improvement in growth indices, so she was referred to a pediatric endocrinologist for GH therapy. Primary investigations and anti-TTG, IgA, anti-EMA all were normal. After a consultation with a pediatric gastroenterologist, a genetic study of HLADQ2 and 8 were done because of the highly suspicion of celiac disease. The results were also negative. At last she was referred to immunology-allergy clinic for evaluation of probable food allergy. IgE level was checked and a prick test was performed which they were not indicative of any suggestive food allergy.

Because of the history of the abdominal pain and constipation which was more prominent after meals, negative results of genetic study, SPT to wheat, and serologic markers, a gluten free diet was suggested for her with the suspicious of non celiac gluten sensitivity. A significant improvement in her symptoms was noticed within 2 weeks of starting gluten free diet. She has 2Kg of weight gain and height improved from 116 cm to 120 cm in 4 months. She continued to improve on a GFD and when seen in the follow-up clinic 6 months later reported complete resolution of symptoms and another 2 cm and 1 Kg gain in her height and weight.

Conclusion: Non-celiac gluten sensitivity syndrome is a diagnosis made by excluding celiac disease and wheat allergy. It should be taken into consideration especially in patients who have the suspicious symptoms of celiac without supporting lab data, and also negative SPT to wheat. The young man in question along with his parents were keen to proceed, so with some hesitation we proceeded to a hazelnut oral provocation challenge, having very carefully explained the risks of undertaking such a challenge.

He successfully completed the challenge and experienced no allergic symptoms and is now able to have hazelnuts in his everyday diet.

Discussion: This young man wanted to confirm if indeed he was allergic to hazelnuts. Not being hazelnut allergic would mean that he would be no longer allergic to any nut and would not have to take precautions prior eating products.

Positive results to both Cor a 9 and Cor a 14, hazelnut storage proteins are associated with the patient possibly experiencing systemic reactions, at a higher risk of experiencing anaphylaxis it they were to ingest hazelnut. These facts in conjunction with his specific IgE to hazelnut would have prevented us from proceeding to challenge was it not for this young man's persistence that he wanted to proceed to challenge despite the risks.

Conclusion: Appearances are deceptive, as this case demonstrates; allergen-specific IgE and component testing can only predict the probability of an allergic reaction, the final test in the diagnostic process is the oral provocation challenge.

The patient and his family were happy for me to share the above with other health care professionals. Method: We present the case of a female of 29 years old diagnosed of ACU with poor control of the symptoms at maximum doses of antihistamines. We decided to associate Omalizumab treatment.

The patient had a good control of the symptoms with Omalizumab at dose of 300 mg/4 weeks, but in the 6th month she presented an erythematous, raised and pruritic lesion in the area of injection together with localized abdominal edema at 12 hours of the administration, with two weeks of evolution without symptomatic treatment. We decided to discontinue Omalizumab alter a second episode with half doses.

Results: We performed a skin biopsy of the lesion and epicutaneous tests with the drug. Immediate hypersensitivity tests were not taking due to the impossibility of stopping antihistamines.

Skin biopsy showed a perivascular lymphocytic inflammation of the superficial and deep dermis with frequent presence of perivascular and interstitial eosinophils, suggestive of a hypersensitivity reaction. RESULTS: Nine months before presentation at our clinic, the patient had been hospitalized and treated with imipenem and TMP/SMX for pulmonary nocardiosis. Once discharged, she had been prescribed oral TMP/SMX alone, according to antimicrobial susceptibility. At our first evaluation, the patient presented with fever, macular erythematous non-pruritic (vasculitic-like) skin lesions on the upper limbs, polyarthralgia and bilateral ankle arthritis. TMP/SMX was transiently stopped. After four days, there was a dramatic improvement, with resolution of all signs and symptoms. She was tentatively diagnosed with a viral infection and thus TMP/SMX was started again. However, after three days, the symptoms (fever, arthritis and skin lesions) recurred. Laboratory investigations showed increased levels of inflammatory markers. Complete blood count with differential, serum creatinine, urinary sediment, liver enzymes, rheumatoid factor, antinuclear antibody, C3, C4, immune complexes, serology for Rickettsia, Borrelia and Coxiella were all negative. Hence, TMP/SMX was stopped again and cutaneous lesions, fever and arthritis resolved spontaneously in five days. CONCLUSION: Given the clinical course and the resolution after the withdrawal of TMP/SMX, we diagnosed a SSLR due to sulfonamides.

To the best of our knowledge, this is the first case of SSLR occurring after a nine-month therapy with TMP/SMX and allergists/immunologists should be aware of the possibility of such a reaction even after months. Case report: * We received written informed consent for publication of these clinical details and/or clinical images included in my abstract was obtained from the patient.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse cutaneous reaction that usually appears 2-6 weeks after treatment with the causative drug. This syndrome is characterized by severe dermal rash, fever, eosinophilia, and internal organ involvement, and clinically, diffuse maculopapular eruption, exfoliative dermatitis, and facial edema are often observed.

We performed blood tests and laryngeal fiberscopy for the diagnosis of the patient. Intradermal test with delayed reading and patch test were performed 2 months after the end of treatment.

A 53-year-old man had begun treatment with carbamazepine for epilepsy. After 4 weeks of treatment, he observed skin rash with pruritus on both lower extremities, and after 6 weeks, his skin lesions had begun to spread over his whole body, and he complained of several new symptoms, including hoarseness, dyspnea at rest, and dysphagia. An examination revealed maculopapular rash, facial edema, and bilateral cervical lymphadenopathy. Laryngeal fiberscopy revealed both arytenoid and epiglottic swelling. Laboratory studies revealed eosinophil counts of 2100 /μL and increase in alanine aminotransferase level to 65 U/L. A diagnosis of DRESS syndrome was definite according to the RegiSCAR group criteria. Carbamazepine, the suspected culprit drug, was withdrawn, and systemic corticosteroid was initiated. The patient experienced rapid improvements in hoarseness, dyspnea, and dysphagia. After 5 days of treatment, laryngeal fiberscopy revealed complete resolution of both arytenoid and epiglottic swelling.

To the best of our knowledge, our case is the first reported case of DRESS syndrome to manifest with laryngeal edema. Case report: Bortezomib (Velcade Ⓡ ), a targeted therapy works by blocking the action of proteasomes in side cells, is commonly used to treat newly diagnosed as well as relapsed/refractory myeloma.

Bortezomib has been reported to have gastrointestinal symptoms, peripheral neuropathy, neuropathic pain and thrombocytopenia as its most common side-effects. Although several cases of skin lesion caused by bortezomib have been reported, severe cutaneous adverse reaction (SCAR) such as Stevens-Johnson syndrome (SJS) is very rare. We here report a case of bortezomib induced SJS.

A 71-year-old female patient, who was diagnosed with multiple myeloma, received bortezomib and melphalan /dexamethasone therapy.

After the 4th dose of bortezomib, she presented with fever and maculopapular skin rashes spreading from face to the trunk. Erosive lesions in the oral mucosa and corneal ulceration with conjuntival injection were observed. She was diagnosed as SJS. The symptoms of SJS improved after bortezomib was discontinued and systemic steroids and intravenous immunoglobulin were administered. Drug patch test was performed, the result was positive in bortezomib. This is the first case report of bortezomib induced SJS in this country, which was diagnosed by a patch test. Although the SCAR by bortezomib is generally considered very rare, we suggest that clinicians be aware of potential adverse reactions, including SJS. Case report: We report the case of a healthy 46-year-old woman with history of red erythematous macules in both hands, one hour after taking a fluconazole (150 mg) tab for a vaginal candidiasis. It faded spontaneously. She didn't recall if she had ever taken that medicine, but denied known drug allergies. Although FDE is primarily a clinical diagnosis, we conducted an oral challenge test with fluconazole (150 mg). Two hours after intake of the drug the patient started complaints of pain and erythema in both hands and the challenge was stopped. Two days after the challenge, she developed red painful erythematous macules on the same sites of the first episode. Due to the specificity of the challenge, local patch testing was not performed. Introduction: The classic form of a fixed drug eruption is one or more anular or oval erythematous patches as a result of systemic exposure to a drug. These skin lesions normally resolve with hyperpigmentation and may recur in the same location with re-exposure to the drug.

Other types of fixed drug eruptions have been described, being fixed drug urticaria a rare form of presentation. (1, 2) Case Report: In the last 2 years, a 48 year old woman has developed more than 15 episodes of a wheal in the right supraciliary region 5 minutes after taking 600 mg of oral Ibuprofen. The symptoms resolved in less than 6 hours without treatment and without leaving residual lesion.

After the last episode, she refers good tolerance to 1 g of oral Paracetamol. She denies local traumas.

She also refers mild spring rhinoconjunctivitis well controlled with antihistamine, and sneezing with house dust. A 37-year-old-M patient had psoriasis vulgaris for 15 years, and had been using methotrexate at intervals of 4 years. Despite the addition of phototherapy, he underwent a new treatment with biological agent (antitumor-necrosis-factor; anti-TNF), since the disease control was insufficient. Before anti-TNF, preventive treatment against latent tuberculosis (TB) activation was indicated with positivity in tuberculin skin test (20 mm). He was given INH 300 mg/day, and at the 20th day of treatment, desquamation, erythema, and subsequent exfoliation developed in his hands and foots dorsum. INH was withdrawn. In order to distinguish the lesions from psoriasis attack, skin biopsy was performed and reported as erythema multiforme-like dermatitis with no relation to psoriasis. The lesions were completely improved at 3 weeks of topical steroids, and INH was re-initiated at the same dose. A week after the initiation of the drug, skin lesions similar to previous reoccurred with more severity and progression from distal to proximal extremities. Cell counts, renal and hepatic function tests, and hepatitis markers in blood were in normal limits.

Skin lesions were retracted after 4 weeks of topical steroids, and withdrawal of INH. There was positivity in skin patch test with INH at 72 hours. Finally, for TB prevention an alternative drug rifampicin (10 mg/kg/day) was given, and the patient successfully completed with no adverse event. His psoriasis lesions were improved with anti-TNF which was started after 1 month of TB prevention with rifampicin.

In these days which the use of biologic agents is increasingly widespread, INH use will be more prevalent than the past. Even tough, it is effective and safe in most of the patients, its adverse event dermatitis may be a reason to withdraw in patients with dermatological diseases. In this case, diagnostic drug allergy evaluation should be performed to optimize the second-line treatment of TB infection, in addition to early withdrawal of the culprit drugs. Background: Around 50% of cancer patients will receive radiotherapy (ionizing radiations) as a treatment, either as a single therapy or as an adjuvant to chemotherapy and surgery.

Several side effects have been described due to radiotherapy, of which we can mention Erythema Multiforme and Stevens Johnson Syndrome, but in lower prevalence. Erythema Multiforme can be described as an acute skin condition and may be present within a wide spectrum of severity. Erythema multiforme minor represents a localized eruption of the skin with minimal or no mucosal involvement. The papules evolve into pathognomonic target or iris lesions that appear within a 72-hour period and begin on the extremities (see the following image).

Lesions remain in a fixed location for at least 7 days and then begin to heal.

It is considered to be a type IV hypersensitivity reaction associated with certain infections, medications, and other various triggers Precipitating factors and complex interactions may trigger the appearance of signs and symptoms. These include especially recurrent herpes simplex virus (HSV), Epstein-Barr virus (EBV), histoplasmosis, alcohol, systemic diseases and immunological factors.

Method: 69-year-old male diagnosed with Prostate Adenocarcinoma who underwent transurethral resection and was taking Trinomia (Ramipril, Atorvastatin, Acetyl-salicylic Acid)

After his 8th RTE external radiotherapy session, he presented erythematous maculo-papular lesions in the suprapubic area with some vesicles. Therefore, withdrawal of treatment was decided and the performance of a skin biopsy.

15 days later, regarding the improvement of the lesions, RTE was continued, presenting incipient exacerbations of the lesions but it allowed us to end the cycle of treatment.

Results: Skin biopsy results (Anatomical Pathology): basal keratinocytes, which blur the dermoepidermal interface, with lymphocyte exocytosis at this level, associated with isolated images of spongiosis.

The dermis shows a superficial perivascular lymphocytic inflammatory infiltrate of moderate intensity. Compatible with erythema multiforme.

Conclusion: Radiotherapy is a technique of increasing use, so it is important to recognize the associated cutaneous lesions that appear less frequently and are sometimes underdiagnosed.

Diagnosis is both clinic and pathological and is usually late in most cases so it is vital to take into account this skin disease complication in order to be properly managed. including Chinese herbal medicine is usually considered to be without any allergic and adverse reaction.

Method: Visits were made to pharmacies in Hong Kong and Luoyang, China and a martial art monastery/temple in Dengfeng, China. Some CAM were found to have ingredients with potential allergic and adverse reaction.

Results: Three CAM, one from Hong Kong (1), one from Shaolin martial art monastery/temple in Dengfeng (2) and one from Luoyang

(3), China were found to contain Chinese herbal medicine with potential allergic and adverse reaction.

(1) Cordyceps Ling-Zhi Complex Ingredients: Cordyceps sinensis "caterpillar fungus", Tremella fuciformis "snow fungus", Ganoderma lucidum (Ling-Zhi) "Reishi mushroom" and others 30 years old female patient who has ulcers in oral mucosa and purple, itchy lesions on her right hand palmar area, little finger, index finger, on her left hand palmar area, pollex finger. In her history, she has relapsing vaginal yeast and she hasn't any hypersensitivity reaction with fluconazole before 1 month ago she started to take fluconazole because of vaginal candidiasis. After using fluconazole she started to itch from described areas and dark redpurple eruptions appeared. She was prescribed oral methylprednisolone and topical pomade which included corticosteroid for four days but she didn't aware of fluconazole related drug reaction. Lastly four days ago she took fluconazole and metronidazole for severe vaginal yeast.

12 hours later pruritus, same eruption appear on the same area, lip and tongue angioedema than she had dyspnea, dizziness, hypotension, arrhythmia and consciousness. She had admitted to the emergency department and performed adrenalin. After a day bullae and ulcers came into existence in her oral mucosa.

In her blood analysis there was mild increase in white blood cell count (13.300 /mm 3 ), eosinophil count was normal (300 /mm 3 ), biochemistry parameters were in normal limits, CRP and sedimentation rate were in normal limits, total IgE was 439 IU/L. Introduction: Tuberculosis is a disease that most commonly affects the lungs, which is transmitted by the respiratory tract and drugs are the most important factor in the treatment. Non-resistant tuberculosis infection is usually treated with HRZE. In rare cases, a hypersensitivity reaction may develop against one or more of the drugs during treatment.

Case: A 37-year-old female patient was diagnosed with culturepositive pulmonary tuberculosis and HREZ treatment was started by the related department. Seven days later she referred to the policlinic with edema and itchy erythematous lesions which are common in her extremities, which developed after 6 hours of taking her medication.

Liver and kidney function tests and eosinophil count were normal.

Drug eruption was considered with current physical examination findings. The treatment was interrupted, short time systemic corticosteroids and antihistamine treatment started. Desensitization planned. There was no feature in the prick and patch tests with drugs. Desensitization was performed with isoniazid, no reaction was observed during the procedure. Six hours after the procedure, the patient applied to the emergency department with painful edema and pruritic erythematous lesions in the extremities. Desensitization procedures with rifampicin, ethambutol, pyrazinamide were performed without any problems after the lesions were regressed. isoniazid was withdrawn from the treatment protocol.

Outcome: We would like to present on this case that drug eruption may develop in the form of maculopapular rash after desensitization. This study aims to compare ethmoid mucosa and nasal polyp regarding density of tissue eosinophil and its sensitivity, specificity, and correlation with clinical characteristics for diagnosing ECRS.

Method: Patients with CRS with polyps scheduled for endoscopic sinus surgery were enrolled. Specimens were collected from polyp apex, polyp pedicle and ethmoid mucosa. Tissue eosinophil from these three sites in the same patient were compared. Using eosinophilic mucin as a reference, sensitivity, and specificity of each site for diagnosing ECRS was assessed. Correlations between tissue eosinophilia (defined as greater than 10/ HPF) and clinical characteristics of ECRS including asthma, serum eosinophilia, and eosinophilic mucin were analyzed using each site of specimens.

Results: Thirty patients with CRS with polyps were enrolled. Polyp apex, polyp pedicle and ethmoid mucosa gave similar results regarding tissue eosinophilia in 16 patients (53.3%). Eleven (36.7%) patients were ECRS (having tissue eosinophilia at all sites) and five (16.6%) were non ECRS (no tissue eosinophilia at any sites). Median tissue eosinophil was significantly greater in polyp apex (84, and polyp pedicle (96, IQR: 80-320) than ethmoid mucosa (21, IQR: 10-220), P = 0.04. Sensitivity of polyp apex, polyp pedicle and ethmoid mucosa for diagnosing ECRS were 100%, 60% and 80% respectively. Specificity were 36%, 40% and 48% respectively. Correlations between tissue eosinophilia and asthma were significant when assessing ethmoid mucosa (P = 0.04), and polyp pedicle (P = 0.05) but not polyp apex (P = 0.21). Correlations with serum eosinophilia, and eosinophilic mucin were not significant (P > 0.05) when assessing any specimens. gov/pubmed/) was performed using the following key words: "Obstructive sleep apnea syndrome"; "allergy rhinitis"; "hypoxia"; "intermittent hypoxia"; "fluctuating hypoxia"; "cyclic hypoxia"; and "HIF-1α"

Results: OSAS may affect the prognosis of AR patients based on the following evidence: 1) AR is thought to be a cause of OSAS.

2) Exposure to hypoxia could mediate immune activation in AR and affect the response to treatment.

3) HIF-1α expression may be a risk factor for AR. 4) Intermittent hypoxia can induce robust expression of HIF-1α.

Conclusion: First, improvement of ventilation during sleep represents an efficient strategy for treating AR. Therefore, continuous positive airway pressure or nasal surgery to resolve a nasal obstruction could be added to AR treatment. Finally, medications that target HIF-1α, such as digoxin, can be tested as adjuvant therapy. Method: Forty patients diagnosed with allergic rhinitis and olfactory dysfunction were recruited in current study in the Group 1 and 2. Patients of Group 1 were administered with no treatment and patients administered with the traditional Chinese acupuncture therapy were incorporated into the Group 2. Before the treatment, all of them underwent T&T olfactory testing, nasal sinus computer tomography scanning and visual analog scale (VAS; 0-100), and repeated the assessment after four-week treatment.

Results: Improved total T&T olfactory testing scoring averages and VAS Scoring averages was observed in eleven patients treated with traditional Chinese acupuncture compared with four patients in the observation group. No side effect was found. No significant differences in olfaction recovery were found according to age, gender, or duration of disease between the two groups. The observation group underwent nasal endoscopic sinus surgery and the control group underwent external approach surgery, and the therapeutic effect of the two groups were investigated.

Results: The total effective rate was 94% in observation group and 74% in control group, the total effective rate of observation group is significantly higher than control group (P < 0.05). The recurrence rate was 3% in observation group and 24% in control group, the recurrence rate of observation group is significantly lower than control group (P < 0.05). Complication occurrence rate of observation group was 6% which is significantly lower than control group 24% (P < 0.05).

The therapeutic effects of endoscopic sinus surgery on chronic sinusitis in geriatric patients are better than conventional external approach surgery which is worth clinical application. Results: (descriptive).

The eQUICK app is user-friendly even for VKC patients with sub-optimal reading ability. Home use between clinic appointments allows responsive temporal data gathering of QoL, symptoms, medication scores and impact of medical interventions. eQUICK may be used in future as a research tool in gathering outcome data following interventions for VKC. Ectoine, a substance deriving from halophilic micro-organisms, is a strong water structure forming solute exerting cell protective antiinflammatory and antiallergic properties.

Method: Purpose of our study was to assess the efficacy of the preventive administration of 2% Ectoine eye-drops (3 times a day for 6 months) to shorten the duration of VKC relapses (which begin, in our country, very early in Spring and usually end in October), or to mitigate the attacks, which are only controlled by topical corticosteroids or cyclosporine resulting in an important burden of side-effects.

In this retrospective study, we included 192 children of both sexes (148 males and 44 females), under the age of 10 years (mean age 7.8 years), affected by VKC from more than 3 years/seasons and treated for more than 4 months during a year, with cyclosporine eye-drops.

These patients underwent, from February to September 2017, the additional-to-the-usual protocol treatment with 2% Ectoine eyedrops.

Results: 8% of the included subjects astonishingly had no relapse of VKC, 38% needed topical CS or CYC treatment but it was started 2 months later compared to previous years, 29% needed the topical drugs 3 months later and 25% had a similar to previous years course (no Ectoine efficacy).

The treatment was well tolerated and only 1 child had to stop it because of local allergy to the eye-drops.

The preventive administration of 2% Ectoine eyedrops was able to stabilize and to delay VKC attacks in more than 50% of the selected patients showing the importance of anti-inflammatory and anti-allergic properties of this product. Following international criteria we considered normal levels of vitamin D the levels between 50 nmol/L (20 ng/mL) and 125 nmol/L (50 ng/mL), a potential deficiency between 30 nmol/L and 50 nmol/L and a severe deficiency less than 30 nmol/L. Results: 58.8% (30 children) of AKC group patients presented vitamin D low levels, among them 18 children showed a potential deficiency and 12 a severe deficiency. 24.3% (18 subjects) of VKC patients suffered a deficiency in vitamin D which was mild in 13 and severe in 5 patients.

40.3% (25 children) of SAC group showed a deficiency in vitamin D which was potential in 17 and severe in 8 subjects.

Conclusion: Our study shows that in different forms of allergic conjunctivitis many children are suffering a Vit. D deficiency and it can be supposed that a correlation between the severity of the allergic form and the level of vit. D deficiency exists.

We recommend allergists and ophthalmologists to check Vit. D levels in children suffering from allergic conjunctivitis because its deficiency is very common and many are unaware of it; in case of a vit. D insufficiency it is fundamental to give a vit. D suitable-to-the-case supplementation. Method: 83 children (57 males and 26 females, mean age 7.3 ± 5 months) affected by VKC and allergic rhinitis from more than 2 years were treated with mometasone furoate nasal spray 1 spray bid × 2 weeks in a month, for 3 consecutive months as a co-seasonal treatment at the beginning of eye allergic symptoms.

Other systemic or topical treatments did not vary compared to the previous 2 years.

Results: A quick questionnaire administered to children and their care-givers showed that nasal symptoms regressed after a mean period of 9.2 days from their beginning but, impressively, in more than 30% of them, these patients did not show a VKC typical relapse along the 3 months of mometasone treatment, moreover the following summer period was milder in subjective ocular symptoms in more than 25% of the patients.

Our experience pointed out that INCS adjunctive treatment was positively associated with a regression of eye and nose symptoms in children suffering from VKC, confirming previous literature data which concern milder forms (seasonal allergic conjunctivitis or allergic rhino-conjunctivitis) compared to the severe forms (like VKC) we analyzed in our work. One of the involved mechanisms of action can be the alleged effect on the reduction of substance P in tears; it is supposed to reflect the neuropeptides levels in ocular tissues. 0816 | Patient response to MP-AzeFlu in an allergen exposure chamber onset of action (OOA) timing may impact treatment adherence. MP-AzeFlu, intranasal azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single device, has proven to have greater efficacy and faster OOA than a combination of oral loratadine and intranasal FP (LORA/INFP), but the clinical relevance for patients is unclear.

This single-center (Ontario, Canada), randomized, double-blind, double-dummy, three-period crossover trial examined by which extent MP-AzeFlu provides clinically relevant symptom improvements according to different efficacy parameters.

Method: AR symptoms were induced in asymptomatic, ragweedsensitive patients via ragweed pollen challenge in an environmental exposure chamber. Patients received a single dose of MP-AzeFlu, LORA/INFP, or placebo and were monitored for 4 hours. Symptoms were assessed using total nasal symptom score (TNSS) and total ocular symptom score. Responder analyses included the number of patients to achieve relevant response (RR) to therapy (30% or 50% reduction in TNSS), time to RR (ie, first time point at which RR was reached), and minimal clinically important difference (MCID) in OOA. Background: Nasal allergen provocation test (NAPT) is a standardized diagnostic tool indicated in the diagnosis of allergic rhinitis, to design and monitoring allergen immunotherapy, and to study the pathophysiology of airway allergy. Unfortunately, until now very few studies have evaluated its reproducibility and safety.

In this study we wanted to analyse the safety and reproducibility of NAPT in a large group of rhinitis patients and healthy controls.

Unit until December 2017. A bilateral saline challenge followed by a bilateral NAPT were performed in symptoms-free individuals. The response was assessed by nasal-ocular symptoms and acoustic rhinometry. All subjects signed a written informed consent.

The safety of NAPT was checked by the occurrence of extra-nasal/ ocular reactions (ENOR), severe adverse events (SAE), and use of rescue medication (RM). ENOR was assessed by clinical symptoms, physical examination, cardiopulmonary auscultation, spirometry, and oxygen saturation. The reproducibility of NAPT was tested by comparison of the results in 2 or more sessions with≥1-month interval. Background: Nasal hyperreactivity (NHR) is self-reported by a majority of patients with allergic rhinitis (AR) and is likely mediated by neural-immune interactions. The combination of fluticasone propionate (FP) and azelastine (AZE) hydrochloride administered in a single spray (MP-AzeFlu) has been shown to be superior to FP or AZE alone in patients with seasonal AR (SAR). We hypothesize MP-Aze-Flu may reduce neuro-immune mediators in AR with NHR. In a post hoc analysis of three pivotal studies of MP-AzeFlu, we analyzed the efficacy of MP-AzeFlu, FP, and AZE in patients with AR with and without nonallergic triggers.

Method: In three randomized, double-blind, controlled trials, patients with SAR were randomized 1:1:1:1 to MP-AzeFlu, FP, AZE, or placebo (PBO). Patients self-reported sensitivity to nonallergic triggers. Change from baseline in total nasal symptom score (TNSS) and treatment differences between active agents and PBO were calculated.

Results: Across 3412 patients in three studies, mean age was 36.3 years and mean age at AR symptom onset was 15.6 years.

Overall, 89% reported ≥1 nonallergic trigger, which included sudden temperature/humidity change (72%), tobacco smoke (61%), perfumes/fragrances (57%), incense/candles (38%), and cleaning products (38%). Change from baseline in TNSS for patients with AR and nonallergic triggers was greater with MP-AzeFlu than with FP or AZE (Table) , and patients with nonallergic triggers improved slightly less than patients without nonallergic triggers in both the MP-AzeFlu and FP groups. Background: In low-income countries (LICs), assessment of phenotypes, prevalence and risk factors for allergy-related diseases (ARDs) using allergen-specific IgE may be complicated by environmental exposures such as helminths. These exposures may also induce cross-reactive carbohydrate-specific IgE profiles that could inhibit allergic effector responses. We sought to elucidate the molecular basis of IgE sensitisation among individuals in Uganda, using a component-resolved approach to IgE measurement.

We employed the ISAC ® allergen microarray to assess plasma IgE reactivity to 112 purified natural and recombinant allergen components in participants of three studies: a trial of intensive versus standard anthelminthic treatment in the rural helminth-endemic Lake Victoria islands (n = 126), a parallel urban survey of allergy outcomes in a lower helminth exposure community (n = 60) and a study on asthma risk factors in children from the urban setting and from nearby rural schools (n = 100). Data on sensitisation to crude allergen extracts were obtained by skin prick testing (SPT) with cockroach and house dust mites (HDM), and by ImmunoCAP IgE testing (cockroach, HDM, and peanut).

Results: The rural setting was characterised by high prevalence (≥34%) of sensitisation to crude extracts (ImmunoCAP IgE>0.35 kU/ L) but low sensitisation to the major, established, allergenic components on the microarray (≤2%, IgE>0.30 ISU). However, sensitisation to cross-reactive carbohydrate determinant (CCD)-bearing components and venoms was more common in rural (up to 14%) versus urban (up to 8%) individuals, and was associated with helminth infection. Urban individuals mounted higher responses to allergenic components of dust mites but responses to other components were similar between the two settings. Sensitisation to allergenic components was higher among asthmatics and SPT+ children but CCD sensitisation profiles were similar between asthmatics and nonasthmatics, and between SPT+ and SPT-school children.

Conclusion: We show that, in LICs, IgE to crude allergen extracts (detected in standard ImmunoCAP assays) reflects sensitisation to a myriad of environmental exposures (absent in more developed countries), such as CCDs expressed by helminths, and may not accurately define ARD phenotypes in this setting. However, our data does not seem to indicate that CCD-specific IgE detected by ISAC ® microarray protects against ARDs. considered minor allergens. Due to their sequence homology and conserved structure, they show a high cross-reactivity. The objectives were to study the IgE/IgG binding properties of polcalcin in relation to the calcium ions, and the IgE cross-reactivity between purified polcalcin from Olea europea (Ole e 3) and two recombinant polcalcins (rPhl p 7 and rBet v 4).

Method: Ole e 3 was purified by immune-affinity chromatography using polyclonal antibodies anti-rChe a 3. Serum samples were obtained from 6 patients allergic to grasses recruited at Hospital de Guadalajara (Spain), all of them positive to Phl p 7 with sIgE values ranging from 12.1 to 92.6 kU/L. Equal volumes of all sera were used to prepare a pool. Calcium binding assay was performed either by addition or not, or depletion of Ca 2+ . Ole e 3 was incubated with 0.1 mM CaCl 2 or with 1 mM EGTA pH 7.5 (Ca 2+ chelator agent) at the same time as the antibody in immunoblot or ELISA assays with the pool of sera or with anti-Che a 3 polyclonal antibody. Crossreactivity assay was performed by ImmunoCAP inhibition. Aliquots of the pool of sera were previously incubated with amounts of Ole e 3 ranging from 0.02 to 12.5 ng. The same dilution of the pool of sera without Ole e 3 was used as a control. After 2 hours of incubation, sIgE (kU/L) binding to rBet v 4 or rPhl p 7 was determined.

Results: A 9 kDa protein was purified from the O. europea extract and identified by LC/MS-MS as Ole e 3. In the calcium binding assay there were no differences between the samples with or without Ca 2+ . However, the addition of EGTA to the reaction completely inhibited the binding of the polyclonal antibody by immunoblot and also produced a 32.3% reduction of IgE binding by ELISA. In the cross-reactivity assay, a 50% inhibition of IgE binding was obtained with 2.8 ng of Ole e 3 for rBet v 4 and 3.9 ng for rPhl p 7. The maximum rate of achieved inhibition was 68.6% for rBet v 4 and 61.6% for rPhl p 7.

Conclusion: Native purified Ole e 3 contains the Ca 2+ necessary to bind to the specific antibodies and the depletion of Ca 2+ inhibited this binding.

High cross-reactivity of Ole e 3 with rPhl p 7 and rBet v 4 was demonstrated.

0826 | Effect of Glutathione-S-transferase pi on the cysteine protease activity of the house dust mite allergen Der p 1 Background: Environmental proteases have been proposed to be involved in the pathogenesis of allergic disorders via different mechanisms, such as the disruption of epithelial tight junctions, the cleavage of surface proteins, the activation of damage and pathogen-associated molecular patterns receptors, and the alteration of redox status. Der p 1 from house dust mite is one of the most clinically relevant indoor allergens worldwide, which exhibits cysteine protease activity and has been linked to allergenic rhinitis and asthma. However, it is unknown whether the host microenvironment could regulate Der p 1 activity once it reaches the mucosal surface.

Glutathione-S-transferase pi (GSTpi) is an anti-oxidant and detoxification enzyme. GSTpi is the predominant GST in human lung epithelial cells, where it is expressed in high levels. Polymorphic variants of GSTpi have been associated to various inflammatory lung disorders such as allergic asthma. More recently, GSTpi has been identified as a redox regulator through protein S-glutathionylation, a post-translational modification where glutathione (GSH) is conjugated to cysteine residues.

Method: This work aimed at determining if GSTpi affects the cysteine-protease activity of Der p 1, compared to GSTmu -a different GST isoform-by using different in vitro approaches.

Results: We found that GSTpi increased Der p 1-activity, but not GSTmu.

Our results suggested a potential role of GSTpi in upregulating the protease activity of Der p 1 allergen. However, the clinical implications of these findings in allergic airway diseases needs for further investigations. 0827 | Cari p 1, a novel polygalacturonase allergen from papaya acting as respiratory and food sensitizer Biswas Sarkar M; Sircar G; Ghosh N; das AK; Jana K; Dasgupta A; Gupta Bhattacharya S Bose Institute, Kolkata, India Background: Papaya was globally reported to elicit IgE-mediated hypersensitivity. Certain papaya sensitive patients with food allergic symptoms were found to experience recurrent respiratory distresses at peak flowering period of papaya even after quitting the consumption of papaya fruits.

The immunoreactive protein present both in pollen and fruit proteome was detected by IgE-serology and identified by mass spectrometry. One such allergen, designated as Cari p 1 was cloned, and purified as recombinant protein. The IgE-reactivity of rCari p 1 was examined by immunoblot using patient sera. The allergenic activity of rCari p 1 was evaluated by histamine release assay from IgE-sensitized granulocytes. The aggregation and folding pattern of rCari p 1 was assessed by size exclusion chromatography and circular dichroism spectroscopy respectively. The presence of Cari p 1 in papaya fruit was searched by IgG-immunoblot using allergen-specific rabbit antisera. A mouse model of papaya allergy was established to study the role of rCari p 1in eliciting respiratory and food hypersensitivity.

Results: A 55 kDa IgE reactive protein commonly present in pollen and fruit proteome of papaya was identified as endopolygalacturonase. Recombinant Cari p 1 remained monomer and the CD-spectra revealed predominantly β-sheet characters. The melting curve of the allergen showed partial refolding from a fully denatured state indicating the possible presence of conformational IgE-epitopes in addition to the linear IgE-epitopes of food allergens. 7 out of 7 papaya allergic patients displayed IgE reactivity to rCari p 1. rCari p 1 at 1 μg/mL, induced histamine release from challenged granulocytes within a range of 30% to 72% (i.e. 50 ± 9.2%; n = 4 patients).

Expression of Cari p 1 was detected in the peel and pulp tissues of papaya fruits at two edible stages of fruit maturation. In mouse model, rCari p 1 exhibited a comparable level of eosinophil infiltration and goblet cell hyperplasia in lung and duodenum histology.

Conclusion: Cari p 1 the first major allergen reported from papaya with a dual role in respiratory sensitization via pollen inhalation and sensitization of gut mucosa via fruit consumption. The recombinant allergen can be used as marker allergen for molecular diagnosis and immunotherapeutic management of papaya allergy. Background: Lipids can be potent stimulators of the immune system, and their role in allergy is highly investigated and debated.

Since many allergens bind lipids, one question that arises is the relative importance of the lipids versus the lipid-allergen complex in eliciting the immune response. Also of interest is an evaluation of the importance of the allergen-lipid complex. In our characterization of the structure of the cockroach allergen Bla g 1, we discovered that it could promiscuously bind a variety of lipids in a large central cavity. This suggested that Bla g 1 could be used as a prototypical allergen and lipid delivery vehicle to test in various models of sensitization.

Method: CD spectroscopy. NMR spectroscopy. Molecular modeling.

We have developed an HPLC procedure to strip the phospholipids derived from the E. coli-based expression system, and reconstitute the allergen with a variety of lipids. Using CD spectroscopy and NMR, we have verified that the protein conformation is highly similar in the presence and absence of lipids. Temperature dependent CD spectroscopy revealed that unloaded Bla g 1 is the least stable, and the melting temperature increased with increasing fatty acid chain length up to C20. Similar CD melting experiments revealed that Bla g 1 could bind lipoteichoic acid (LTA) from Gram positive bacteria, but did not interact with lipopolysaccharide (LPS) from Gram negative bacteria. Molecular modeling studies have suggested that the stoichiometry of phospholipid binding is likely 4 phospholipids per Bla g 1 and give insight as to the different binding characteristics that would allow Bla g 1 to bind LTA but exclude

Conclusion: These biophysical studies will allow the design of Bla g 1-lipid systems to test a variety of sensitization models. 0829 | Sal k 7, a new allergen from Salsola kali Sola JP; Pedreño Y; Fernández J; Cerezo A; Peñalver M Probelte Pharma, Murcia, Spain Background: The polcalcin from Salsola kali was identified and sequenced (GenBank KT254655) and the recombinant protein was characterized as a minor allergen with a prevalence of 40% of patients with a SPT positive to S. kali. The objective of this study was to purify the polcalcin from S. kali pollen and to include the allergen in the website for the systematic allergen nomenclature (www.allergen.org).

Method: The native polcalcin from S. kali (nPSk) has been purified from pollen after a first step of protein extraction and then diverse chromatographic steps: a size exclusion chromatography to remove particles minor than 5 kDa, an ionic exchange chromatography, a hydrophobic interaction chromatography and a final step of size exclusion chromatography to obtain the purified sample of polcalcin.

The purity of the nPSk has been determined by SDS-PAGE and the binding capacity to a specific polcalcin antibody from rabbit serum was tested by immunoblot. The specific antibody had previously been obtained by immunization with the recombinant polcalcin from S. kali. The allergenicity of the nPSk has been assayed by immunoblot with a pool of sera of patients sensitized to S. kali. The identity of the purified nPSk has been analyzed by peptide footprint in HPLC-MS/MS after digestion with trypsin. All the information about the polcalcin from S. kali was sent to WHO/IUIS Allergen Nomenclature Sub-Committee.

The nPSk showed a high purity in SDS-PAGE with a molecular weight of approximately 9 kDa and this purified protein reacted with the specific polcalcin antibody from rabbit serum. The IgE binding capacity of the nPSk was confirmed by immunoblot using a pool of sera from patients sensitized to S. kali. The analysis of peptide footprint confirmed that the purified protein is a polcalcin. The WHO/IUIS Allergen Nomenclature Sub-committee included the polcalcin from S. kali in the website for the systematic allergen nomenclature as a new minor allergen named Sal k 7.

Conclusion: The polcalcin from S. kali has been purified from pollen and tested for its IgE binding. It is included in the website for the systematic allergen nomenclature as the new allergen Sal k 7. Background: Alt a 1 protein is the major allergen from the fungus Alternaria alternata and responsible for chronic asthma, yet little is known about its physiological role and immunological activity. Our main purpose was to investigate the mechanism through which Alt a 1 induces an allergic response in bronchial epithelium.

Method: Although Alt a 1 has a unique topology, we studied the structural relationship by in silico procedures consisting of three distinct structural alignment methods in order to understand its nature. The immunological properties of the allergen were investigated by using monocyte cell line THP1 and human peripheral blood mononuclear cells.

Results: Its crystal structure has been recently reported and claimed to be exclusively in fungi without equivalent in the Protein Data Bank.

Data obtained in silico show that this allergen shows some structural relationships with a number of other β-barrel proteins such as human lipocalin 2 (LCN2). Besides, our experimental data demonstrate that Alt a 1 is also able to interact with LCN2, human lipocalin. In this way, the results obtained from several immunological assays showed that Alt a 1 is able to produce a response of the immune system through different immune innate receptor pathway inducing the Th2 cytokines. Background: Increasing evidence of cross reactivity syndromes between pollen grains and fruits, with immediate or delayed reactions, has been reported. While some syndromes such as the birch pollen/apple syndrome are well documented, some other such as the cypress pollen/peach syndrome remain to be understood. For the latter, significant progress has recently been made with the discovery of a new allergen family, the gibberellin regulated proteins (GRPs), which has been shown to be responsible for the observed cross reactivity i.e. Pru p 7 and BP14 (1, 2) for the peach and the cypress pollen respectively. GRPs are small cationic proteins with anti-microbial properties and have been shown to be over produced in response to a stress. Herein, the case of a patient, born and raised in the south of France but currently living in Paris, has been studied. This patient has been suffering since childhood from allergic rhinoconjunctivitis to cypress pollen and from some oral symptoms to peach and other fruits (including pomegranate).

Method: In addition to the clinical exploration and cutaneous tests, a very thorough biological characterization of the patient samples has been performed through various specific IgE quantitation techniques, western blotting after one and two-dimensional gel electrophoresis and flow cytometry based basophil activation testing (BAT).

Results: Specific IgEs to cypress pollen, birch pollen, peach, orange and apple have been found. PR10 allergenic proteins are recognized by IgEs but no LTPs. The presence of specific IgEs to cypress pollen BP14, peach peamaclein (Pru p 7) and a cationic 14 kDa protein from pomegranate has been shown through western blotting after gel electrophoresis separation of the protein extracts. The use of BAT finally enabled to demonstrate that the basophils of this patient were, ex vivo, strongly activated with protein extracted from orange and cypress pollen and also with purified proteins such as BP14 and Pru p 7.

Conclusion: These results unambiguously show that the cypress pollen GRP, BP14, is clinically relevant, similarly to its homologous protein in peach, Pru p 7. It can be proposed that these two allergens are at the basis of the observed cross-reactivity syndrome. The search for new cross-reactive allergenic GRPs in pollen, fruits or vegetables may enable to better understand other pollen/food associated syndromes that still remain unexplained. Background: Nine allergens of Phleum pratense have been described until now (IUIS database) and classified into groups based on their function and cross-reactivity. Group 1 and 5 allergens are considered the most immunodominant, due both to their greater IgE-binding capacity and the number of patients IgE-reactive to them. Previously published studies have estimated that group 1 is recognized by almost 95% of grass pollen-allergic patients, and group 5 by 80%. However, until now a comparative of the ability of these allergens to provoke an immune response has not been performed.

The objective was to study the immunogenicity of the major allergens Phl p 1 and Phl p 5, by analyzing the ability of the recombinant forms (rPhl p 1 and rPhl p 5a) to induce a humoral immune response.

Method: Five mice were immunized with the same amount of each recombinant protein: rPhl p 1 and rPhl p 5a (Indoor Biotechnologies) (60 μg plus two boosters of 30 μg). The specific IgG antibodies produced by each mouse were tested against the recombinant proteins by direct ELISA and the title of each of them was determined by optical density (O.D.). Additionally, the recognition of both allergens in native and depigmented-polymerized (Dpg-Pol) extracts of P. pratense was studied by direct ELISA using these generated antibodies.

Results: Preimmune sera were negative. All mice produced antibodies against the corresponding recombinant protein. The immune response (sIgG) was statistically significant higher in mice immunized with rPhl p 5 than in those immunized with rPhl p 1; it was needed 8 times more rPhl p 1 serum than rPhl p 5a serum to obtain the same O.D. values. The difference in responses was higher in the group of mice immunized with rPhl p 1 than with rPhl p 5a.

Differences in the recognition of Phl p1 and Phl p 5 in native and depigmented-polymerized extracts of Phleum pratense was also observed. It was necessary 8 times more rPhl p 1 serum to produce the same signal than rPhl p 5a serum in native extract and it was necessary 4 times more rPhl p 1 serum to produce the same signal than rPhl p 5a serum in Dpg-Pol extract.

Conclusion: rPhl p 5a is more immunogenic than rPhl p 1, which was also probed with native and Dpg-Pol extracts. Background: Glioblastoma (GBM) is an incurable primary malignant brain tumour with a median life span of less than 15 months despite multimodal treatments. Therefore, there is a serious need for the development of innovative medications. Several epidemiological studies underlined an inverse correlation between pre-existing IgEmediated allergy and GBM risk, where having such an allergy decreased the odds of developing GBM by 20 to 40%. We aim to delineate the intrinsic immuno-biological and molecular mechanisms that can be responsible for these correlations, based on the hypothesis that allergies may promote a state of increased immuno-surveillance in the brain through the presence of immunological factors such as immunoglobulins, cytokines and cells involved in Th2-driven allergic reactions. We consider that as the major immune cell type of the brain, microglia should be implicated in this beneficial association and may favour the elimination of the nascent tumour in brain parenchyma in an allergic context.

We implemented a long term allergic airway inflammation by repeated nasal instillation of house dust mite (HDM) extract in a syngeneic orthotropic mouse model of GBM. We followed animal survival and the tumour growth by MRI. In addition, we purified microglia from allergic vs non-allergic mice in order to assess their cytotoxic function against the GBM cell line ex vivo and their secretory capacities. Finally, we investigated immunoglobulin reactivity against GBM antigens in the context of allergic reactions by reverse phase protein array (RPPA).

We demonstrated an increase of the animal survival that was correlated with a delayed tumour engraftment and a reduced tumour growth. These phenotypes were associated with functional modification of microglia from sensitized mice. Indeed, these microglia showed a rise in the production of IL-6 and TNF-a as well as an increase in cytotoxic functions against a GBM cell line ex vivo. In parallel, we observed an increase in serum IgG1 reactivity against GBM antigens in mice sensitized with HDM compared to control mice. Results: In 23 patients (48%) with CVID we recorded at least one temporary platelet count decrease below 150 × 10 9 /L compared to only 1 patient (10%) with XLA (P = 0.024). More importantly in 18 patients (38%) with CVID this decrease was observed in a period longer than 6 months compared to 1 patient (10%) with XLA (P = 0.077). In 10 patients (21%) with CVID we recorded at least one temporary platelet count decrease below 100 × 10 9 /L and only in 3 patients (6.5%) with CVID this decrease was observed in a period longer than 6 months. We did not record any platelet count decrease bellow 100 × 10 9 /L in patients with XLA however the difference with CVID did not reach statistical significance. No thrombocyte count decrease bellow 50 × 10 9 /L was observed in either group. None of patients required immunosuppressive treatment for immune thrombocytopenia (ITP).

Conclusion: Although the statistical significance was documented only in temporary platelet count decrease below 150 × 10 9 /L it is obvious that numbers of thrombocytes commonly fluctuate in some patients with CVID. The mechanism leading to these temporary decreases is unclear. Monitoring of complete blood count is a basic follow-up investigation in patients with CVID. Introduction: Wegener's granulomatosis (WG) is a systemic disease that may affect all organs, most frequently the ears, noses, throats, sinuses, lungs and kidneys. It is a rare autoimmune disease, also called granulomatosis with polyangiitis, and characterized by necrotizing granulomatous inflammation in small and medium sized blood vessels. Anti-neutrophil cytoplasmic antibody against to proteinase 3(c-ANCA) is thought to be responsible for autoimmune inflammation. The coexistence of WG and common variable immunodeficiency (CVID) is extremely rare. In this report, we describe a patient with WG and CVID who was treated with immunosuppressive drugs and intravenous immunoglobin concomitantly.

Case report: A twenty-four-year-old male patient was referred to our clinic for immunological evaluation due to recurrent infections, fever of unknown origin and neutropenia. The patient had been diagnosed with WG and taking immunosuppressive therapy for three years. He had chronic renal failure due to WG and had also been on peritoneal dialysis for three years. Serum IgG, IgA levels, peripheral blood CD19 + B cell percentage and absolute count of the patients were found to be low according to reference limits. He was diagnosed with CVID after excluding secondary reasons for hypogammaglobulinemia and he started to receive 600 mg/kg intravenous immunoglobulin (IVIG) therapy once in a month. Also, the treatment that consists of mycophenolate mofetil (MMF) and glucocorticoids was continued to decrease c-ANCA levels in serum. He has been accepted as a candidate for kidney transplantation, and prepare for this purpose.

Discussion: The management of the patient with CVID and WG may be complicated. It is considerably difficult and needs competency and courage. Moreover, the cases similar to ours, are extremely rare. Therefore, the authors should share their own experiences on CVID and discuss them by comparing the data obtained from other cases. Background: Leukocyte adhesion deficiencies (LADs) are a group of three genetic disorders leading to defective leukocyte adhesion to the endothelium and as a consequence decreased leukocyte recruitment and immune defense. LAD-I is caused by mutations in the gene encoding the ß2-integrin CD18 on chromosome 21.LAD-III is a rare primary immunodeficiency syndrome, characterized by homozygous mutations in the KINDLIN-3 gene (official symbol FERMT3). We have aimed to evaluate our patients who were followed up with LAD for the last 15 years, retrospectively.

Method: All data of the cases were obtained from the file records of age at diagnosis.

Results: Seven patients from separate 6 families were included in the study. Four patients were LAD-III and 3 patients were LAD-I.

The female to male rate was 2/5. The age of diagnosis is ranged from 16 days to 4 years. The median umbilical cord detachment was 21 days (7 -53 days groups: up to 6 times (6 people) and from 6 to 12 times (6 people).

10 healthy donors were examined as a control. Flow cytofluorometry method was used to study peripheral blood and assess the parameters of innate and adaptive immunity

Results: It was found that at a frequency of edema up to 6 times a

year there are changes in the T-system of adaptive immunity, which are shown by a decrease in the expression of late activation markers (CD3 + HLADR+ 3.46 ± 0.60%, in control 8.04 ± 0.14%), an increase in the number of CD3 + CD8 + cytotoxic lymphocytes (0.60 ± 0.17x10 9 /L, in control 0.39 ± 0.01x10 9 /L) and as an increase in their functional activity (CD8 + Gr+ 0.53 ± 0.02x10 9 /L, in control 0.16 ± 0.01x10 9 /L). The nature of disorders of cellular factors of the innate immunity is manifested by decrease in the adaptive resources of neutrophils (KstNBT 1.62 ± 0.13u.e., in control 2.15 ± 0.02u.e.).

Patients with HAE with a frequency of edema up to 12 times a year, we observed the disorders of the humoral link of adaptive immunity, which consist in an increase in the number of circulating B lymphocytes (0.27 ± 0.11x10 9 /L, in control 0.11 ± 0.01x10 9 /L). In addition, with the strengthening of the HAE clinic, changes in the system of innate immunity progressed very fast and consisted in increasing the amount (CD16 + 0.37 ± 0.05x10 9 /L, in control 0.21 ± 0.01x10 9 /L), and functional activity (CD16 + Gr+ 0.32 ± 0.16x10 9 /L, in control 0.14 ± 0.0210 9 /L) of natural killer cells Results: We included 261 children, mostly males (54%), aged between 1 month and 16 years. 37.5% of patients (n = 98/261) showed abnormal absolute results of lymphocyte count for age. We found more patients evaluated in the age group of 2 to 5 years (31.8%), followed by 5-10 years (24.5%), Lymphopenia was found in 15.4% of patients. B lymphocyte deficiency was the most common pattern (37%) followed, in decreasing order, by low CD4, T CD3, TCD8 and NK. Many patients have more than one affected population (12.6%) . Some patients were affected in all three series (4.2%). The CD4 / CD8 ratio decreased in 28.7% of the patients.

The majority of the children were males between the ages of 1 month and 16 years. 37.5% of patients showed abnormal absolute lymphocyte count for age. B-cell deficiency was the most common pattern followed, in decreasing order, by low CD4, T CD3, TCD8 and NK. Many patients have more than one affected population.

0847 | Indicators of the humoral immunity in the mechanical jaundice of benign genesis The aim of the investigation was to study the indices of humoral immunity in patients with benign MJ, depending on the level of bilirubin.

Method: 62 patients with MJ and 125 practically healthy volunteers were examined. Patients with a level of bilirubin less than 60 μmol / l -9, with a bilirubin level of 60-200 μmol / l -37 and with a bilirubin level of more than 200 μmol / l -16 patients. The concentration of immunoglobulin classes A, M, E and G in serum was determined by enzyme immunoassay. The statistical significance of the differences was determined using the ranked Mann-Whitney test.

The critical level of significance in checking statistical hypotheses was assumed to be P < 0.05. Results: Of the contacted dermatologists, 136 participated (53 women, 83 men; mean age 53.2 ± 8.5) which results in a response rate of 27.3%. The guideline compliant prescription rate of biologicals in patients with CSU was 6.9%. The most prevalent barriers in the prescription were the high cost of the treatment (64.7%), low reimbursement for doctors (62.5%) and the fear of a recourse claim (52.9%).

However, a lack of evidence or an insufficient efficiency were not con- Case report: Eosinophil associated gastrointestinal disorders (EGIDs) including eosinophilic colitis are commonly associated with atopy. Aeroallergen sensitization may accompany food allergy in these patients. A case with eosinophilic colitis responsive to anti-IgE monoclonal antibody (Omalizumab) treatment is presented.

An eleven-year-old boy had bloody diarrhea lasting nearly one month in autumn for last 3 years. This year diarrhea lasted more than 3 months. Colonoscopic biopsy revealed lymphoplasmacytic inflammatory cells including eosinophils leading to a diagnosis of ulcerative colitis. Corticosteroid and mesalazine treatment was started with a good clinical response. Recurrence of diarrhea during corticosteroid dose reduction suggested corticosteroid dependent ulcerative colitis. Eosinophilic/allergic colitis was an alternative diagnosis when seasonal recurrence, lack of weight loss, eosinophils in biopsy and high serum IgE level were considered. Colonoscopy done after cessation of therapy for one month, revealed exudative ulcerous lesions, lacerations, loss of haustration compatible with colitis (inflammatory/allergic?). Presence of significant mucosa associated lymphoid tissue in biopsy supported any inflammatory, reactive process.

He had recurrent bronchiolitis until age six and allergic rhinitis in spring for three years. Total IgE and mix aeroallergen specific IgE were high (518 IU/mL, 56.1 kUA/L), absolute eosinophil count was normal (210/mm3). Food skin prick and patch tests were negative.

He had positive skin reactions with dermatophagoides, grass and olea pollens (induration diameter: 9, 10, 6 mm, respectively). Pulmonary function test was normal.

He was considered as eosinophilic/allergic colitis and Omalizumab was started according to manufacturer's dosing table (300 mg/ 2 weeks). Rectal bleeding decreased after first dose and ceased after the second dose. Early colonoscopy examination after 3rd month of therapy showed that exudations disappeared and haustrations became evident. Microscopy revealed mild nonspecific colitis.

Few patients with eosinophilic colitis improved with Omalizumab were reported before. IgE-mediated processes are responsible from eosinophilic inflammation in EGIDs, making Anti-IgE therapy as a promising treatment option. 0859 | Design of liposomal carriers modified by glycoconjugates for liver cell delivery of nucleic acids used. The surface of liposomal nanoparticles can be modified to increase the selectivity of intracellular delivery. It is well known that asialoglycoprotein receptors of hepatocytes have a strong affinity to galactose carbohydrate. Therefore, the aim of this study was to assess the effect of the modification of the liposome surface by glycoconjugates on the selectivity of intracellular transport of nucleic acids into the liver cells.

Method: Liposomes based on OrnOrnGlu(C 16 ) 2 were chosen previously as the effective nucleic acid delivery system. We modified liposomes with novel lactose-based derivatives. Every of four glycoconjugates was added to OrnOrnGlu(C 16 ) 2 in an amount of 5, 10 and 15%. As a result, 12 variants of modified liposomes were obtained. To determine the cytotoxicity, an MTT test was used.

Using luciferase test, the selectivity of penetration was evaluated on nonspecific 293T (human embryonic kidney) and specific HepG2 (human liver cells) cell lines.

Results: Modified liposomal compositions OrnOrnGlu(C 16 ) 2 -4 + LacC 16 (5%) and OrnOrnGlu(C 16 ) 2 -4 + LacGGG16 (15%) had the lowest cytotoxicity similar to that for unmodified OrnOrnGlu(C 16 ) 2 .

The IC 50 , calculated based on the data of MTT test, was 0.14 and 0.26, vs. 0.16 mg/mL, respectively. OrnOrnGlu(C 16 ) 2 -4 + LacGGG16 (15%) showed a 1.5-fold increase in transfection activity on the nonspecific 293T cells, compared to unmodified OrnOrnGlu(C 16 ) 2 , whereas the modification of OrnOrnGlu(C 16 ) 2 -4 + LacC16 (5%) resulted in a 6-fold decrease in transfection activity. However, the ability of these variants to penetrate the specific liver HepG2 cell was significantly higher by 15 and 25 times, respectively, than for unmodified OrnOrnGlu(C 16 ) 2 . Results: The greatest inhibitory effect of SBFHD was observed in MDM infected with HIV-1 Bal: 90% and 50% suppression of HIV replication was achieved at concentrations of 1.5 μg/mL and 0.4 μg/ mL, respectively. The activity in PBMC and DC was less pronounced (the respective IC90 values were 5.8 μg/mL and 19.7 μg/mL). Studies in endometrial HEC-1A cells demonstrated that SBFHD suppressed CD4-independent entry of HIV-1 (10 3 TCID 50 /mL) by 33%, 54%, and 98%, respectively, at 1, 10, and 100 μg/mL. The effect was also observed after increasing the dose of the virus. At 10 4 TCID 50 /mL, SBFHD suppressed HIV infection by 45% (10 μg/mL) and 97%

(100 μg/mL). The cytotoxicity of SBFHD in this system was low. Similar results were obtained with colorectal Caco-2 cells. SBFHD exhibited no spermicidal activity at concentrations of up to 3 mg/mL.

Combining within a single microbicide two agents that target distinct steps of HIV life cycle will maximize its efficacy (via synergistic effects and/or interference with multiple stages of the transmission).

We therefore explored the synergistic potential of combinations of SBFHD and AZT, the classical nucleoside RT inhibitor. In these experiments, 50% suppression of HIV infection was reached at concentrations of SBFHD and AZT, which were significantly lower than the respective IC50 values of each component (determined in parallel experiments). The synergistic effect was most pronounced for the combination of 0.1 μg/mL SBFHD (which is 60 times less than the IC50) and 0.16 nM AZT (which is 45 times less than its IC50). CD80 expression was increased after the co-culture with Reishi, Shiitake and Boletus mushrooms (C -5.6(1.4-9.2)%; PMA -60.5 (27.2-70.9)%; )%; Shiitake -9.6(4.3-15.5)%; Boletus -16.6 (14.0-24.0)%). Method: the study included 38 men (mean age 34 ± 5.9 years) before and immediately after staying in countries with a hot climate. Results: The development of lymphopenia observed In the first week of observation. This was accompanied by a decrease in the number CD3 + lymphocytes expressing the markers of late activation (CD3 + HLADR+ 4.8 ± 1.09x10 9 /л и 3.2 ± 2.04x10 9 /л).

Revealed significant decrease of CD4 + CD25 + Foxp3 + regulatory cells in the first week after returning from the area of adverse climatic conditions, as well as a significant sustained decrease in the number CD3 + CD8 + HLADR+(P < 0.05). Change of the effector link of innate immunity was determined in significant reliable decrease in relative (CD16 + 13.2 ± 2% and 4.6 ± 2.1%, respectively, P < 0.05) and absolute (CD16 + 0.3 ± 0.02 x109/L and 0.1 ± 0.03%, respectively, P < 0.05) in the number of a population of natural killer cells in the first week of observation. In the context of acute stress marked a significant increase in relative and absolute numbers of B lymphocytes (8 ± 1.16% (0.15 ± 0.04 × 109/L) before a trip to countries with a hot climate and 19 ± 3.1% (0.4 ± 0.07 × 109/L) in the first week after returning, P < 0.05). The activity is the production of antibodies was not changed. (AST) which is the intramuscular injection of patients own serum, is a promising therapy with a substantial efficiency on CIU patients. In this study we aim to assess the efficacy of AST on chronic urticaria patients by DLQI questionnaire.

Method: This was a single-blind randomized clinical trial which evaluated the efficacy of autologous serum therapy compared to oral antihistamines in patients with CIU. 49 CIU patients received the AST. Every session 5 cc of each patient's blood was centrifuged at the speed of 2000 rpm for 10 minutes and 2.5 cc of the serum was injected intramuscular into the patient's deltoid muscle weekly for 9 weeks. The control group consisted of 51 CIU patients took 10 mg of Cetirizine daily for 9 weeks. Patients answered the DLQI questionnaire at the first session of treatment as baseline and 7 weeks after the last session(week 16) as response to treatment.

The mean baseline score of DLQI for AST group was Conclusion: Pharmacotherapeutic and inpatient costs for patients with prevalent AR and asthma were lower in those prescribed AIT than in those not prescribed AIT in all years, both with and without including the cost of AIT itself. This indicates that treatment with AIT is associated with lower cost burden for health services. Background: Immunotherapy with peptides rather than conventional whole allergens is being developed to improve the benefit/risk balance of subcutaneous immunotherapy (SCIT). Lolium perenne peptides (LPP) demonstrated reduced allergenicity following ex-vivo analyses, allowing higher doses to be given over a shorter period to improve treatment adherence and compliance. Such treatment resulted in significant reduction in symptoms and rescue medication intake during the grass pollen season. Here we report the safety of LPP immunotherapy in adults. Background: A new allergoid from Alternaria alternata was characterized to determine its reduced allergenicity in vitro. The objective of this study was to determine the skin response to the allergoid and to evaluate the clinical tolerance of the immunotherapy with the allergoid product using a rush schedule.

Method: To assess the skin response (SR) two groups of patients were included: group 1 with patients sensitized to A. alternata and with respiratory disease caused by this mold; group 2 (control) with patients sensitized to others allergens and non-atopic patients. The SR was determined by SPT using three concentrations of the allergoid: P1 (lowest concentration), P2 (four times higher than P1) and P3 (estimated to obtain a wheal area similar to histamine 10 mg/mL).

In SPT was also used a native extract of A. alternata (N) and histamine 10 mg/mL (H). All products were tested in duplicate in all patients and the SR was evaluated by comparing the median of the wheal area produced by different products. To evaluate the clinical tolerance to immunotherapy the patients of group 1 were treated with the allergoid product using a rush schedule consisting in a dose of 0.2 + 0.3 mL the first day and 0.5 mL after one month (maintenance dose). The clinical tolerance was determined as the percentage of adverse reactions (AR) to the treatment and the classification of AR was established according to EAACI.

The number of patients included to evaluate the SR was 46 (group 1: 25; group 2: 21, 16 atopic and 5 non-atopic) with an average age of 34.8 (range . The SPT data from group 1 were expressed as median and interquartile range of wheal area (mm 2 ): H:

19.58 (15.3-25.2); N: 22.71 (11.1-33.1); P1: 0.99 (0-5.7); P2: 6.44 (0-12.5); P3: 19.78 (12.0-30.4 ). It was determined that SR of allergoid was reduced in 87% respect to the native. The products N, P1, P2 and P3 did not produce any response in patients of group 2. To evaluate clinical tolerance, 21 patients of group 1 were treated with the allergoid product with a rush schedule and only two AR were registered (3.2% of doses). These were retarded local reactions with a wheal diameter higher than 5 cm. No systemic reactions were registered and all patients continued the treatment.

The allergoid from A. alternata produces a significant reduced response to SPT due to its reduced allergenicity. The treatment with an allergoid product in a rush schedule is safety and clinically well tolerated. Background: In our study we aim to determine the more effective, The total cost of 3 years of patients using SCIT was 15665 TL per person whereas the total cost of 3 years of patients using SLIT was 15271 TL per person. When we compare the total cost data of both groups, we found that they are close to each other. While the greatest portion of the cost data of patients with SCIT treatment was direct costs associated with the treatment itself (72%); The remaining part of the total cost was indirect (16%) with non-medical expenses such as transportation (12%). In the SLIT group, direct costs including drug expenditures have a larger percentage (92%) and it was significantly more costly compared to the direct costs of the SCIT group (72%). Transportation costs were found to be more costly in the SCIT group (12%) when compared to the SLIT group (4%). Similarly loss of parent work days in the SCIT group(%16) was found to be significantly more expensive compared with SLIT group (4%).

Our study results show that SLIT is a similar treatment for clinically and laboratorially and has a similar efficacy to SCIT to reduce the patients' complaints and to the need for medication. For cost-effectiveness however medicines for treatment of SCIT are less costly; when long term total treatment costs are calculated SLIT and SCIT treatment are economically close treatments. 

The protein content of the new ACD was 182.28 μg/mg and the protein profile in SDS-PAGE and SEC-HPLC confirmed the presence of proteins with high molecular weight and the absence of smaller proteins. The content of free lysine in ACD, involved in glutaraldehyde modification, was reduced in 91.96% respect to NCD and it can be considered as the polymerization degree. Regarding to the allergenic profile, through ELISA inhibition was determined a reduction of 18 times in the capacity to bind IgE of the proteins in ACD respect to NCD, whilst the IgG binding capacity was maintained. In immunoblot there was no reaction of ACD proteins to specific IgE from sera. The analysis by peptide footprint determined the presence of Fel d 1 and others allergens in ACD. The content of major allergen Fel d 1 in ACD was determined as 11.9 μg/mg.

The new developed and characterized allergoid from cat dander has an excellent safety profile and will allow a safer immunotherapy to treat the allergy to Felis domesticus. Results: The protein content of the new AAA was 65.6 μg/mg and the protein profile in SDS-PAGE and SEC-HPLC confirmed the presence of proteins with high molecular weight and the absence of smaller proteins. The content of free lysine in AAA, involved in glutaraldehyde modification, was reduced more than 85% respect to NAA and it can be considered as the polymerization degree. Regarding to the allergenic profile, in immunoblot there was no reaction of AAA proteins to specific IgE from sera and by ELISA inhibition was determined a reduction of 91% in the capacity to bind IgE of the proteins in AAA respect to NAA. The IgG binding capacity in AAA was maintained. The analysis by peptide footprint determined the presence of Alt a 1 and others allergens in AAA. The content of major allergen Alt a 1 in AAA was determined as 2.4 μg/mg.

A. alternata shows an excellent safety profile and allows a safer immunotherapy to treat the allergy to this mold. She was an otherwise healthy woman: she took no drugs and she did not have any remarkable concomitant diseases. The distribution and appearance of the remaining body hair was normal and the hormonal level profiles (LH, FSH, estrogens, progesterone and testosterone) did not show any significant alteration according to her age.

A 30 year old woman with allergic rhinitis underwent sq glutaraldehyde-modified AIT to house dust mites (D pteronyssinus and G domesticus) without any incidences and complete tolerance to maintenance dose without local reactions during a 5 year period.

Two years after AIT discontinuation, patient first experienced a local urticarial reaction with multiple hives at previous sq AIT injection sites 40 minutes after 600 mg of ibuprofen intake. These symptoms recurred at least in seven occasions when patient was exposed to ibuprofen (in five) and metamizol (in two).

Results: Case 1: Dermatologist diagnoses localized hypertrichosis.

Case 2: A single blind, placebo controlled oral challenge (SBPCOC) with ibuprofen 600 mg was performed and elicited multiples hives in the circumscribed area in the arm where AIT was conducted. Subsequently, SBPCOC with aspirin was carried out showing the same reaction although a controlled challenge with celecoxib was negative.

Conclusion: Local hypertrichosis is a very rare injection-disease associated with injected allergen vaccine treatment. We also firstly described a recall urticaria phenomenon after allergen immunotherapy which has been only elicited after different NSAIDs intake. Results: There were included 47 patients, in five Spanish hospitals.

Following ARIA 2010 guidelines, 95.7% of patients were diagnosed of persistent moderate/severe rhinitis. The mean age was 37.7 ± 11.8 years, being 59.6% female. Moreover, 57.4% of the patients had concomitant mild/moderated asthma. The period between the diagnosis of rhino-conjunctivitis and the informed consent signing was 9.8 ± 7.5 years.

According to International 2006 Guidelines, eight systemic reactions were registered, representing 1.9% of the administered doses: five reactions grade 0, (described as nonspecific ocular pruritus, nasal herpes, general discomfort, localized non-specific pruritus plus nausea and non-specific pruritus in throat), a grade I reaction described as rhinoconjunctivitis and two reactions grade II, registered as generalized urticaria and asthma. All reactions were classified of mild or moderate intensity and only two required symptomatic treatment.

There were five clinically significant delayed local reactions, which were higher than 10 cm or involved modifications in next dose.

Regarding efficacy parameters, Immunoglobulin titers between baseline and final visit according to specific IgG and IgG4 significantly increased. Cutaneous reactivity also decreased significantly in the dose response skin prick test. Results: 47 patients were included, 24 to accelerated and 23 to polymerized cluster group schedules. According to ARIA criteria, 89.4% of patients presented persistent moderate/severe rhinitis. The mean age was 31.1 ± 9.9 years, being 40.4% male. Moreover, 61.7% had concomitant mild/moderated asthma. Immunoglobulin titers Method: The quantification of total proteins in the products was carried out by means of a colorimetric technique using the Bradford reagent (Sigma-Aldrich™, US) in accordance with the manufacturer's instructions. The absorbances of each standard and samples were obtained in a Scinco™ S-3100 spectrophotometer (Seoul, Korea) at 595 nm. All samples were analyzed in duplicate. The electrophoretic profile of the proteins in the tested allergens was obtained according to the procedure described by Laemmli, under denaturing conditions in a polyacrylamide gel at 12.5% concentration and stained in silver.

In each lane approximately 30 μg of total proteins were applied.

Commercial extracts of the main allergens marketed in Mexico were obtained, Rossel ® , ALK ® , Alerquin ® , Alergomex ® , Allerstan ® , IPI ASAC ® ; and they were assigned randomly with the numbers 1, 2, 3, 4, 5 and 6.

Results: The following protein concentrations were found in the various extracts analyzed: see table 1 Conclusion: Differences were found in the protein profiles ana- Background: A new allergoid from cat dander was developed and characterized to determine its reduced allergenicity in a 95% and the maintenance of IgG binding capacity. The objective of this study was to develop an immunogenicity assay in mice with the new allergoid and a native extract from cat dander.

The study included 24 female Balb/c mice separated in three groups of 8 mice each: group 1, immunized with a mold allergen extract (control); group 2, immunized with a native extract from cat dander with a Fel d 1 content of 0.525 μg per dose; group 3, immunized with the new allergoid from cat dander with a Fel d 1 content of 2.36 μg per dose. All mice were immunized four times by subcutaneous injections with a volume corresponding to 1/10 of the recommended human maintenance dose with an interval between injections of 2 weeks. One week after the last injection the mice were sacrificed and the serum was obtained. To determine the specific antibody title indirect ELISA were performed using a cat dander extract as antigen, sera from mice as primary antibody and antimouse IgG or IgG1 as secondary antibody. ELISA assays were performed using serial dilutions of sera or a simple dilution by duplicate to determine the specific antibody title as arbitrary units/mL (AU/mL). The data were analyzed by one-way ANOVA and Tukey HSD test to compare the averages of specific antibodies in each group.

Results: The immunization with both the native extract and the allergoid from cat dander produces specific IgG and IgG1. Regarding to IgG, a higher title was observed in group 3 respect to group 2 in a curve obtained after ELISA with serial dilutions of sera. The specific IgG title obtained in terms of AU/mL was 18.6 ± 2.6 in group 1,

105.0 ± 15.0 in group 2 and 139.9 ± 16.6 in group 3. Concerning to IgG1 the AU/mL obtained was 5.7 ± 0.4 in group 1, 73.5 ± 16.8 in group 2 and 97.5 ± 18.8 in group 3. The increase of specific IgG or IgG1 in mice from group 3 respect to mice from group 2 and control group was statistically significant (p ˂ 0.01).

The safety profile of the allergoid from cat dander allows a treatment with higher dose of allergens to produce a greater response to immunotherapy to induce formation of specific 

This was an open, multicenter clinical trial, in patients aged between 18 to 60 years with rhinoconjunctivitis with or without concomitant mild asthma sensitized to house dust mites (HDM).

The aim was to evaluate the safety and tolerability of the vaccine.

Secondary endpoints included were: changes in immunoglobulin levels (specific IgE, IgG and IgG4) versus D. pteronyssinus and D. farinae and changes in cutaneous reactivity. Patients were under study treatment for 17 weeks: five for the induction phase (weekly injections) and 12 for the maintenance phase (monthly injections).

Results: 42 patients were included. There were 6 withdrawals from the trial; no one was related to treatment. The patients mean age was 33.6 years, being 50% female. 71.4% were diagnosed of persistent moderate/severe rhinitis according to ARIA guidelines and 31.0% presented concomitant mild asthma. Regarding to safety results, 22 systemic adverse reactions were registered which corresponded to 7.9% from a total of 277 administered doses. The most of systemic reactions were grade I, (5.4%) described as rhinitis or urticaria, grade 0 or nonspecific (2.2%) and 1 reaction (0.3%), was grade II. All of them were mild or moderate and only 4 needed treatment. Among local reactions, 21 (7.6%) were clinically relevant late local reactions, meaning a wheal at injection site >10 cm and /or requiring a dose readjustment in the next administration; 6 (2.2%) were clinically relevant immediate local reactions meaning a wheal >5 cm. Concerning the efficacy parameters, cutaneous reactivity at the final visit versus baseline was, in average, significantly decreased, and specific titers of IgG and IgG4 against tested HDM increased significantly at final visit. 162 patients completed the study. Mean values in RQLQ questionnaire (total score) decreased from 2.56 to 1.24 points (51.6% score reduction) in final visit, reflecting a statistically significant improvement (P < 0.01). Annual episodes of rhinoconjunctivitis decreased from 13.7 to 9.7 (P < 0.01). 43.8% of patients improved from persistent to intermittent rhinoconjunctivitis (P < 0.01) and 46.9% from moderate/severe to mild intensity (ARIA) (P < 0.01). Moreover, 16 .1% of asthmatic patients at baseline, did not have any bronchial symptoms after 1-year treatment (P < 0.01). Mean value of treatment satisfaction was 7.2 (SD=1.8) and 7.2 (SD=1.7) for patients and physicians respectively. 0884 | Evaluation of safety and tolerability of "Allergovac Poliplus" in polysensitized patients with allergic rhinitis-rhinoconjunctivitis with or without asthma: An observational prospective study (APOLO) Background: The objetive of this study was the safety and tolerance assessment of "Allergovac Poliplus" SCIT treatment, with 2 allergen combination-mixtures in polysensitized patients, as well as the evaluation of the clinical improvement and patients' satisfaction after treatment.

Method: This is a prospective observational clinical study. Allergovac Poliplus treatment is being administered in a "1-day" or in an abbreviated schedule. Polysensitized patients (to pollens or mites), with rhinitis or rhinoconjunctivitis, with or without asthma, and between 5-60 years have been included. All adverse events are being recorded. Visual analog scales (VASs) are being used to evaluate clinical improvement, tolerance and satisfaction after treatment (10 months).

Results: A total of 147 patients have been included, with an aver- Results: In all groups prevailed severe forms of the disease and the phenotype of frequent exacerbations. Groups were comparable in age composition and structure of severity. Observations in the group of vaccinated PCV13 continue the dynamics of decreased dyspnea up to 1.66 (1.11;2.21) Results: Of a total of 631 pts under SCAIT, 110 were excluded due to data unavailability, and 521 included (♀283 (54%), mean age 32 ± 13 years (minutes: 7 max 73 Md30), age range [18-30] being most prevalent (40%). The most frequent diagnosis was rhinitis/rhinosinusitis (97%), followed by asthma (43%), diagnosis coexisting in ABSTRACTS | 479 214 pts (41%). Other diagnosis such as conjunctivitis (24%), atopic eczema (15%) and food allergy (9%) were also found. Mite sensitization occurred in 422 patients (81%) of which 199 (47%) were monosensitized. The pollen sensitization was verified in 288 (55%) with 88 monosensitized pts (31%). The double sensitization mitespollens was displayed in 189 (36%). Sensitization to epithelia and fungi occurred respectively in 100 (19%) and 42 pts (8%). It was found that 20 pts (4%) presented sensitization to the 4 groups of allergens (mites, pollens, fungi, dander). An average of 58 ± 23 pts started this treatment per year. Prescription included 10 laboratories with the following %: A-39.6; B-29.3; C-13.2; D-5.4; E-4.7; F-4.2; G-2.5; H-0.9; I-0.1; J-0.1. Option for extract of physical modification (5%), physical-chemical (16%) and chemical (79%). Table 1 shows the frequency of distribution of SCAIT composition.

Conclusion: In this population sensitization to mites was predominant being the most prescribed SCAIT followed thru sensitization to grasses with the respective SCAIT. The majority of the population was polysensitized. However, in composition preference the choice of 1 group of allergens prevailed and only 5% had more than one sort of pollen and 4% pollen+mites. Polysensitization is a reality, nonetheless the choice of AIT composition should be guided thru scientific criteria and not through the availability of mixtures encouraged by laboratories. Background: Allergen immunotherapy (AIT) has been proven to be an effective treatment of allergic diseases in numerous studies. However, its use in seniors remains limited and questionable, due to common comorbidities and limited evidence of efficacy and safety of AIT in aging population.

The aim of presented study was to assess the safety of AIT in patients over 55 years of age undergoing subcutaneous immunotherapy (SCIT) and analyze the potential risk factors of adverse reactions in this population, compared to younger adults.

We followed subcutaneous immunotherapy in a group of 1302 patients treated in the outpatient clinic of Medical University of Lodz, of whom 163 were aged 55 and older (118 between the age of 55-60, 31 aged 61-65 and 14 patients above the age of 65).

We recorded detailed information of each administration and corresponding adverse reactions over the period of 2 years. We compiled results of our observations with patients' medical records to compile a database, which we then analyzed using statistical software. Method: A total of 46 cases with seasonal allergic rhinitis undergoing pre-seasonal immunotherapy and 28 cases followed with conventional drug treatment were included in the study. Immunotherapy and control groups were divided into monosensitized (only pollen) and polysensitized (at least 1 additional allergen except pollens) patient groups according to skin prick test reactivity. All patients were followed between March-September 2013 with symptom and medication scores, and visual analogue scale (VAS). The quality of life was assessed using the Mini-RQLQ questionnaire. Phleum pratense (Phl p) specific IgE and specific IgG4 (UNI-CAP 100, Phadia) measurements were performed before and after 7 weeks of immunotherapy in all patients. Gramineae pollens were counted during the grass pollen seasons.

Results: Mean age was 34.9 ± 10.6 and 34.2 ± 12 years, female/ male ratio was 29/17 and 17/11, the number of monosensitized/polysensitized patients were 37/9 and 20/8 in immunotherapy and control groups, respectively. In the immunotherapy group, June-July symptom scores, May-June-July-August VAS scores and June combined symptom-medication scores were lower than the control group (P = 0.005). Furthermore, improvements in activities-practical problems and other quality of life scores were significantly different between two groups (P < 0.05). In immunotherapy group, Phl p specific IgE and Phl p specific IgG4 levels measured after immunotherapy were significantly higher compared to those before immunotherapy (P < 0.001, P < 0.001, respectively). Phl p specific IgG4 levels measured after immunotherapy were also significantly higher in the immunotherapy group than in the control group (P < 0.001). There was no difference in terms of clinical and immunologic parameters in monosensitized and polysensitized patients (P > 0.05).

Conclusion: Clinical improvement with pre-seasonal allergoid immunotherapy is accompanied by an important increase in specific IgG4 blocking antibodies despite short-term injections. Our findings show that pre-seasonal allergoid immunotherapy has similar clinical efficacy and B cell response in polysensitized subjects compared to monosensitized patients. 0891 | The safety trial of sequential sublingual immunotherapy with Japanese cedar droplet and house dust mite tablet Matsuoka T 1 ; Kuroda Y 1 ; Igarashi S 1 ; Fukano C 2 ; Natsui K 2 ; Ohashi-Doi K 2 ; Masuyama K 1 1 University of Yamanashi, Yamanashi, Yamanashi, Japan; 2 Torii Pharmaceutical Co. Ltd., Tokyo, Japan Background: Sublingual immunotherapy (SLIT) is recognized as the only treatment option with the potential to provide long-term posttreatment benefits. In Japan, the prevalence of Japanese cedar (JC) pollinosis is very high, about 30% of the population, of which the majority are co-sensitized to HDM. SLIT is now well established, safe and convenient treatment form for allergic disease, and recently, JC SLIT-droplet and HDM SLIT-tablet products were approved in Japan for treatment of JC and HDM induced allergic rhinitis, respectively.

However, the safety of sequential JC SLIT-droplet and HDM SLITtablet has not yet been investigated. Therefore, we investigated the safety trial on SLIT combined with JC droplet and HDM tablet in allergic patients.

Method: Eleven subjects with JC pollinosis and HDM rhinitis were enrolled. Patients were treated once-daily with JC SLIT-drops for 4 weeks, followed by 24 weeks of sequential SLIT treatment where the JC SLIT-drops and the HDM SLIT-tablets were administered daily with a 5 minute interval (1st: JC-SLIT drops, 2nd: HDM SLIT-tablet).

The primary endpoint was the frequency and severity of adverse events (AEs) during sequential SLIT by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and SLIT grading system. Serum antibodies were measured as the secondary endpoint.

Results: Eleven patients were recruited. AEs after JC SLIT-drops administration were found in 9 patients out of 11 cases (82%). AEs after sequential SLIT were found in 8 patients out of 10 cases (80%). All AEs were graded 1 or 2. No severe AEs were observed during the study period. The levels of JC-and HDM-specific IgE and IgG4 in serum were increased during treatment.

Conclusion: Sequential-administration of JC SLIT-drops and HDM SLIT-tablets was well tolerated by patients suffering from both JC pollinosis and HDM rhinitis. Background: According to the EMA guideline on the clinical development of products for specific immunotherapy products should be tested in phase II at different doses in several study-arms to establish a dose-response relationship for clinical efficacy before confirmatory trials can be initiated. Allergen exposure in an AEC may be used as primary endpoint.

The study was a single-center, randomized, double blind, placebo-controlled, phase II trial, treatment duration 10 months. 168 grass pollen allergic patients (18-65 years of age) with seasonal rhinitis/rhinoconjunctivitis (ARC) with (mild, GINA I) or without concomitant asthma were randomized to three different dosages of a liquid Phase III study is in preparation. As part of an effort to prepare the analysis plan using the CSMS as primary endpoint, the grass pollen data of the European Aeroallergen Network (EAN) was used to identify the window within the grass pollen season (GPS) with optimal correlation between the grass pollen counts and the CSMS.

Method: EAN currently includes information from more than 400 active and 300 historical pollen-monitoring stations in Europe including 39 countries. The EAN database used for analysis included grass pollen data collected during 2009-2016. The daily allergy symptoms and medication were recorded spontaneously using an APP questionnaire on the subject's smart phone. The CSMS was re-calculated using the EAN database, using the recorded symptom scores with estimation of the medication score using similar methods as recently published. The correlation between the daily grass pollen count and the daily CSMS was analyzed with a mixed effects model accounting for patient-specific correlations and symptom levels. Conclusion: These results confirm a statistically significant correlation between grass pollen counts and the CSMS. Importantly, these findings suggest that the optimal window to observe treatment effects after immunotherapy may be a short interval after start of the GPS and during the peak GPS, due to generally higher CSMS values. This provides sufficient basis to consider additional sensitivity analyses to evaluate the treatment effect of grass MATA MPL SCIT on the primary CSMS endpoint during a shortened window after the start of the GPS and to consider excluding the overlapping period between the BPS and GPS from the primary analysis. 0894 | Combo-VAS as a tool to assess efficacy of allergen immunotherapy Ciprandi G 1 ; Silvestri M 2 ; Olcese R 2 ; Tosca MA 2 1 Ospedale Policlinico San Martino, Genoa, Italy; 2 Istituto G. Gaslini, Genoa, Italy Background: Allergen Immunotherapy (AIT) is at present the unique cure for respiratory and venom allergy. Usually, AIT lasts for some years, but its efficacy is longstanding. Criteria for assessing AIT efficacy are mainly based on symptom severity improvement and saving of symptomatic medications. In this regard, there are different score grading for both measuring symptom severity and drug use.

Visual analogue scale (VAS) is a well-defined and validated method widely used in many diseases, including allergic disorders. VAS is a psychometric tool measuring the patient's perception of symptoms, emotions, pain, drug use, etc.

Recently, it has been published an EAACI position paper concerning the recommendations for the standardization of clinical outcomes used in AIT trials for allergic rhinoconjunctivitis, but it is complex. So we would propose a simpler way to measure AIT efficacy by VAS, in particular a combo-VAS based on one VAS for symptom and one for medications.

Results: Globally 150 patients were retrospectively evaluated. All of them were treated with a 3-year AIT course: 120 were defined as responders and 30 as non-responders. In Responders group the Combo-VAS mean value was 14 (IQR 12-15) at baseline and 4 (IQR 3-6) after AIT treatment. In Non-Responders group Combo-VAS mean value was 13 at baseline and 11 (IQR 9-12.5) at the end of AIT. The difference was significant (P = 0.012). The D Combo-VAS was −66.67% in Responder Group and −10% in Non-Responders group (P < 0.0001).

Conclusion: Combo-VAS, i.e. the sum of VAS for symptoms and medications, could be an easy and quick tool for assessing AIT efficacy and reflects the patient's perception. Therefore, it could be very fruitful in clinical practice. 0895 | Rapid up-dosing in sublingual specific immunotherapy is safe, well-tolerated and effective in patients suffering from tree pollen allergic rhinitis Background: An optimised up-dosing period of specific immunotherapy (SIT) is desirable for better patient compliance because a long or complicated up-dosing scheme is sensitive to disruption. The aim of this study was to compare the safety, tolerability and effectiveness of an optimised up-dosing scheme with two preexisting schemes of sublingual SIT (SLIT) in patients under standard medical care.

Method: This was a prospective, open, active controlled, multi-center non-interventional study in Germany and Austria to document the treatment of children and adults with allergic rhinoconjunctivitis and/or allergic asthma treated with a SLIT containing purified, aqueous extracts of birch, alder and hazel pollen. The investigators were free to select an up-dosing scheme for included patients: scheme A consisted of an up-dosing period of up to 12 days at the patient's home using three different solution strengths to reach the maximum dose; ultra-rush scheme B performed only with the highest solution strength at the physician's office within 2 hours, and the optimised scheme C which was initiated at the physician′s office and continued at home using exclusively the highest solution strength within 2 (long-term) or 4 (pre-seasonal) days. Data on up-dosing and maintenance treatments were documented by physicians during 5 patient visits and by patient diaries. The study was approved by ethic committees, and all patients or parents gave their informed consent.

Results: In total, 164 patients aged 3-76 years were included into this study. Scheme A was applied by 90 patients, 29 patients decided on regimen B, and 45 patients on the optimised scheme C. Conclusion: One-day UR-SCIT conducted in an outpatient clinic was safe and well-tolerated in patients with AD sensitized to HDM. UR-SCIT can be a safe and useful option to start a subcutaneous allergen immunotherapy for AD. 0899 | Factors affecting on adherence to allergen specific immunotherapy Results: Among 1162 enrolled patients, 228 (19.6%) patients failed to complete at least 3 years of AIT, which were regarded to be nonadherent in this study. Univariate analysis revealed that male, younger age group less than 40 years, cluster and ultra-rush schedules, atopic dermatitis, the absence of associated diseases, and follow up of other department were found to be associated with nonadherence to AIT. In multivariate analysis, younger age group less than 40 years (OR 2.31, 95% CI 1.55-3.45), cluster (2.37, 1.56-3.60) and ultra-rush schedules (6.03, 3.18-11.42) , and absence of follow up of other department (2.11, 1.31-3.40) were independently associated with non-adherence to AIT. No association was found in gender, diagnosis of allergic diseases, kind of allergen extracts, and patients' distance from hospital.

Conclusion: Various factors are related with AIT non-adherence to interfere the effectiveness of immunotherapy. Clinicians need to be aware of the factors associated with non-adherence to AIT and consider them when choose to maximize AIT adherence. 0900 | Cost-effectiveness of allergen immunotherapy to grass in patients with allergic rhino-conjunctivitis and asthma Background: Allergen Immunotherapy (AIT) has been shown to reduce symptoms and medication use in subjects with rhino-conjunctivitis and asthma. However, long-term cost effectiveness of this therapy needs to be evaluated. Our aim was to assess cost effective of AIT, both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), vs. pharmacotherapy alone in subjects with rhino-conjunctivitis, with or without allergic asthma, to grass pollens.

Method: A Markov cohort state-transition model with a time horizon of 9 years was used to assess the costs and effects of 3-year AIT in adults. Relative efficacy of the treatments expressed as standardized mean difference was estimated using an indirect comparison on symptom and medication score extracted from available meta-analyses. The Rhinitis Symptom Utility Index was used as a proxy to estimate utility values for symptom score. The societal perspective, through the Human Capital technique, was used to estimate indirect costs, to represent the scenario of a country with nationalized medicine. Data on drug and other medical costs were derived from published sources as well as AIT duration and asthma occurrence. Additional sensitivity analyses were performed to test the robustness of our results.

Results: In the base case analysis, using Italy clinical practice patients with moderate-to severe allergic rhino-conjunctivitis (SS ranging from 6 to 15 points) and a mean age at entry of 21 years, both SCIT and SLIT were associated with increased cost but superior efficacy compared to pharmacotherapy alone. The results were most sensitive to variation in efficacy estimates and AIT persistence rates.

Conclusion: This analysis suggests that AIT is cost effective relative to pharmacotherapy alone. SCIT, despite significantly higher indirect cost burden, seems to be the most cost effective option.

The results should be interpreted in the context of the data input and modelling assumption used. 0901 | iELISA as a tool to measure IgE binding towards single modified peanut allergens Background: Immunotherapy has shown to be a potential treatment for food allergies but needs further research to improve safety.

Modification of peanut allergens to reduce their allergenicity is a promising approach to develop a safe and effective immunotherapy as shown by the successful completion of a first-in-human safety and tolerability study using HAL-MPE1 in adult patients with peanut allergy (EudraCT 2013-004238-13) . In order to assess the impact of modification on individual peanut allergens and to assess its impact on IgE binding by individual patient sera, we have developed peanut allergen-specific inhibition ELISAs. With this methodology we are able to identify patients with residual IgE binding to modified peanut allergens.

Method: IgE inhibition ELISAs (iELISAs) were developed and performed to test IgE binding towards purified Ara h2 and Ara h6 and their reduced and alkylated (modified) versions, using the individual responses of single patient sera.

Results: Ara h6-specific iELISAs showed that modification of Ara h6 results in >95% reduction in IgE-binding for all individual sera tested. Ara h2-specific iELISAs showed that modification of Ara h2 also results in >95% reduced IgE-binding for most of the sera, but some sera were identified which showed residual, 10%-20% IgE binding to mAra h 2. In some of the latter sera, the presence of IgE binding to a linear hydroxyproline-containing peptide could be confirmed as a possible source for the residual IgE binding to mAra h2.

We have developed a methodology to assess residual IgE binding to modified peanut allergens. The sensitivity of the allergen-specific iELISAs allowed us to discriminate between patient sera in which IgE binding to mAra h2 and to mAra h6 was virtually completely absent and sera in which 10-20% residual IgE binding to Ara h2 was observed. The clinical importance of these observations is yet unknown. Future clinical studies will need to reveal whether the patient-specific IgE binding profiles to individual modified peanut allergens do correlate with the adverse events profile of immunotherapy with modified peanut extract. 0902 | Design of a phase II allergen immunotherapy study to determine the optimally effective and safe dose of subcutaneously administered tyrosine adsorbed modified grass allergen+MPL (MPL) adjuvants for the treatment of allergic rhinoconjunctivitis (ARC) due to grass pollen.

There is increasing evidence that the effectiveness of allergy immunotherapy to control ARC symptoms is related to the cumulative allergen (or allergoid) dose administered. Previously, two clinical studies have been conducted using a conjunctival provocation test (CPT) as primary efficacy measure for a similar SCIT MATA MPL product for birch allergy [EudraCT 2012-004336-28 and 2015-000984-15] . These studies showed a 5.5 fold increase in cumulative dose to achieve~50% increase in efficacy, with a relative reduction in total symptom score (TSS) of 32.3% compared to placebo and no safety signals of concern. The shape of the dose response curve was curvilinear, where this high dose almost reached plateau.

Method: This is a multi-center (~47 clinical study centers across Europe), randomized, double-blind, placebo-controlled, parallel-group study in~440 adult patients with moderate to severe seasonal ARC with or without mild asthma. A positive CPT is to be achieved at screening and verified prior to randomization. The primary outcome is the post-treatment TSS following CPT. A wide range of cumulative dose regimens is used (5100, 14400, 27600 and 35600 SU) applied over 6 weekly injections to establish the shape of the dose response to support dose selection for Phase III.

The design of the current Phase II grass allergoid SCIT study will be discussed, including the rational of using 4 cumulative dose regimens and placebo and the pre-selected shapes of the dose response curves. In addition, the number of patients screened and randomized will be presented by country, gender and/or age category and screen failures will be categorized.

Conclusion: This Phase II study was initiated to establish the dose response of a grass MATA MPL SCIT product, using CPT to measure the effect of a wide range of cumulative dose regimens. The achievement of its aim will be an important milestone in the development of an efficacious and safe state-of-the-art grass SCIT. Conclusion: We observed that the specific nasal challenge with house dust mite generates an inflammatory response within the first hours, but we did not demonstrate any correlation with the response to immunotherapy after six months. 0905 | Tolerability of a two week rush updosing with modified allergens in pollen allergic subjects in the day-to-day practice Background: In two Phase IV studies the tolerability of a subcutaneous Rush up-dosing, using three injections in two weeks, has been tested and proven to be save in adults. In the course of a non-interventional study (NIS) now the tolerability of this treatment scheme was tested in the day-to-day practice. Conclusion: Over 97% of the patients could reach the highest dose of 0.5 mL. The overall tolerability is very good. The data from daily practice confirm the data that were previously obtained in two Phase IV studies. sIgEs from 40 patients, evaluated during the 1st semester of 2017 at an outpatient clinic. All patients presented persistent moderatesevere allergic rhinitis, in pollen season and had not been submitted to IT. All patients had positive SPT for grasses (grass) and olive (olea). sIgE-tot for Phleum pratense and Olea europaea and some sIgE-CRD (rPhl p 1, rPhl p 5, rPhl p 7, rPhl p 12, rOle1 and nOle7) were determined. Physicians were divided into 2 groups (group 1 if <10 years of practice and group 2 if≥10 years of practice) and were asked to choose which IT to prescribe for each patient (none, only grass, only olive or both grass and olive), according to SPT and sIgE results.

Results: Fifteen physicians (60% with ≥10 years of practice) participated in the survey. Considering only the sIgE-tot results, the IT choice (group 1/2) was: no vaccine in 10%/3%; grass vaccine 50%/ 58%; olive vaccine 5%/10% and both grass and olive vaccines in 35%/30% of the patients (P = 0.42), the intergroup agreement was 70% (kappa 0.612). According to the sIgE-CRD results the physicians chose (group1/2): no vaccine at 10%/13%; grass vaccine in 63%/60%; olive vaccine in 10%/5% and both vaccines in 18%/23% of patients However, data on control of allergic rhinitis (AR) after discontinuation of therapy are insufficient. The aim of our study was to assess sustained control of AR in three consecutive years after Grass-pollen SLIT discontinuation.

Method: A total number of 35 patients [24 (68.57%) males; mean age 32 years, age range 15-56] well-controlled after a three-year course of SLIT with grass pollen extract were prospectively evaluated in three consecutive years after discontinuation of therapy. Conclusion: A three-year course of Grass-pollen SLIT seemed to have a long-term effect on control of symptoms in patients with AR.

The authors declare no conflict of interest. Results: All patients showed a positive sensitization profile by skin prick test to either Betula and/or Alnus. In 40% of patients this profile was furtherly confirmed with serum specific IgE levels to Betv1, (mean 13.56 kU/L). Allergic symptoms in patients with birch/alnus pollen allergy after ingestion of certain food can result from crossreactivity of Bet-v1-specific IgE to homologous pathogenesis-related proteins, particularly the PR-10 protein.

Conclusion: Within the allergy history we emphasize on focusing on SAO symptoms as many patients under-recognize them. Among the sensitization profile of these patients it is quite important to highlight cross reactivity between Bet v1 and Alnus. The other patient suffered from anaphylaxis(GRADE II) induced by minimum amount of lettuce consumption without co-factors. Both patients suffered from oral allergy syndrome to peach and allergic rhinitis.

SPTs to foods and pollens were performed with commercial extracts, prick-through-prick with fresh plant foods, while specific IgE was determined accordingly. LTP syndrome was defined as a sensitization to Pru p 3 and symptoms elicited by at least 2 unrelated plant foods.

Co-factors were also investigated.

Results: The first patient was sensitized to lettuce, peanut, hazelnut, sunflower's seed, peach and banana, and plane tree, olive tree, grasses, parietaria and mugwort. sIgE to lettuce was 2.04KUA/L, to Pru p 3 was 20.8KUA/L and total IgE was 703.4U/mL. Co-factors, such as exercise, were involved. The second patient was sensitized to peanut, walnut, hazelnut, almond, sunflower's seed, cashew, lettuce and peach, and, plane tree, olive tree, grasses, parietaria, mugwort and willow. sIgE to lettuce was 27.6kUA/L, to Pru p 3 was 37 and total IgE was 1705.9kU/L. No co-factors were identified. Background: Garlic (Allium sativum) is a vegetable that belongs to Amaryllidaceae's family. Hypersensitivity to garlic is not very common. It has been mainly reported in occupational allergy but it also may cause contact dermatitis, rhinoconjunctivitis, asthma, urticaria, gastrointestinal symptoms and anaphylaxis after its ingestion. Some studies have identified Alliin lyase, a 56 kDa protein, as a major garlic allergen and it seems to be a heat-sensitive allergen.

We report on a 9-month-old infant who presented, 15 minutes after an accidental ingestion of garlic sauce, generalized erythema and cough. She was still breastfeeding and she had never ABSTRACTS | 491 eaten garlic before (although the mother usually consumed garlic).

The patient had never tasted other vegetables belonging to Amarylidaceae's family either but zucchini, with good tolerance. We performed skin tests and specific IgE (sIgE) to different vegetables. A raw garlic extract was also carried out and analysed in the patient by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Results: Prick by prick with garlic was positive (10 mm) and negative to onion, leek, asparagus, zucchini and saffron. Skin prick tests to commercial extracts of mugwort, grass pollen, peach LTP and profilin were negative as well. Specific IgE to garlic was 3.15 KU/L (out from a total IgE 32 kU/L) and 0 kU/L to onion and asparagus. SDS-PAGE immunoblotting assay with patient′s serum revealed IgE reactivity with proteins of 6 kDa and 8 kDa.

Conclusion: We report a garlic IgE-mediated anaphylaxis case in an infant with proteins of 6 and 8 kDa as the relevant allergens. The mechanism of sensitization in the present case remains unclear. The authors hypothesized that breastfeeding, cutaneous contact or inhalation might be possible mechanisms involved.

Chong KW 1 ; Saffari SE 2 ; Chan N 3 ; Seah R 3 ; Tan CH 3 ; Goh SH 1 ; Goh A 1 ; Loh W 1 1 Allergy Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore; 2 Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Medical School, Singapore, Singapore; 3 Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Background: The predictive decision points for both peanut skin prick test (SPT) wheal size and serum IgE concentrations, in peanutsensitized children, have not been evaluated in Singapore. We aim to assess these for purposes of risk stratification and prediction of oral food challenge (OFC)s' outcomes by means of a retrospective chart review. Results: The number of patients evaluated was 328, of which 269 had clinical diagnosis of peanut allergy based on recent immediate reaction to peanut (PA group) and 59 were tolerating peanuts regularly (PT group). The mean age of both groups were similar, 3.9 ± 3.2 and 3.7 ± 3.3 years in PA and PT groups respectively.

There was a high prevalence of atopic diseases in both groups, with atopic dermatitis (75.8% in PA, 79.7% in PT), and other food allergies (55.4% in PA, 44.1% in PT). Presence of rhinitis was statistically higher in the PA group compared to the PT group, with odds ratio of 2.52 (95% CI: 1.42-4.47) . A wheal size of ≥8 mm and a peanutspecific IgE of ≥6 kU/L provided for a 95% positive predictive value.

The larger the wheal size on SPT, the higher the probability of a clinical reaction to peanuts.

The results will help us in deriving preliminary cut-off values when conducting future prospective studies with OFCs in our peanut-sensitized cohort (whom had no prior peanut exposure), and to eventually reduce the need for expensive and potentially risky food challenges. 0913 | Ginger: flavory, spicy …allergenic? A report of four patients with allergy to ginger Background: Ginger (Zingiber officinale) belongs to the family Zingiberoidae, along with cardamom and turmeric. The edible portion is the horizontal rhizome, and it is very appreciated for its aroma and spicy flavor. It also presents great interest for its therapeutic and culinary use. Hypersensitivity to ginger is rare and has been scarcely reported. We report 4 cases (P1, P2, P3, P4) of adverse reactions to ginger after its ingestion and with good tolerance to cardamom and turmeric.

Method: Skin prick tests (SPT) to environmental allergens and prick-by-prick with ginger were carried out. Total IgE, and specific IgE to ginger were also determined. A raw ginger extract was prepared. This extract was analyzed in all the patients by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Background: Food allergy is divided into 3 groups according to pathophysiology: IgE-mediated, IgE-and non-IgE (mixed type), and non-IgE (cellular type). However, in clinical practice, patients who fall under more than one group may be observed.

Method: Patients who were diagnosed with food allergy at our clinic from January 2012 to December 2016 were included in the study. The medical files of patients were retrospectively evaluated, their symptoms and findings after consumption of foods were recorded, and they were categorized into 3 groups (IgE-mediated type, non-IgE type, and mixed type) according to their symptoms and findings.

Results: A total of 587 patients (63.5% male) with food allergies were included in the study. According to categorization via symptoms and findings, the distribution of patients was as follows: 140 (23.8%) IgE-mediated type, 44 (7.5%) non-IgE type, 195 (33.2%) mixed type. The remaining 208 (35%) patients were found to show various combinations of symptoms and findings that fit more than one group.

In this study, we observed that food allergy symptoms and findings were distributed in a broad range which caused difficulties in the categorization of more than one-third of our patients. Background: Fish allergic patients suffer a lifetime of strict dietary restrictions. Crocodile meat is a nutritious alternative choice in many countries around the world; however, it has recently been reported to also trigger severe allergic reactions. In these two case reports from 2017 pediatric patients were sensitised to the major fish allergen parvalbumin (PV), a potential cross-allergen. Bony fish contain predominantly PVs of the β-lineage, which are the most common trigger of allergic reactions in fish allergic patients. In most other vertebrates, PVs of the α-lineage are most abundant, which have been reported as a causal allergen in frog, cartilaginous fish, and chicken allergies. We aimed to evaluate the allergenicity of crocodile meat in fish allergic children, with focus on PV.

Method: Over 70 children with clinical history of IgE-mediated fish allergy were identified, skin tested to commonly consumed fish species using commercial and in-house preparations, and serum samples were collected. A sub-cohort was skin tested to crocodile using heat-treated tail muscle tissue from Saltwater crocodile (Crocodylus porosus). Extracted proteins and purified PVs were analysed by SDS-PAGE, immunoblotting, and mass spectrometry. Serum from all fish allergic children was analysed for IgE reactivity to the crocodile PV.

This reactivity was compared to those of raw and heated crocodile protein extracts as well as protein extracts and purified PVs from frequently consumed fish species.

Results: More than 5 fish allergic children were positive on skin testing to crocodile (wheal size>3 mm), demonstrating its clinical reactivity. In vitro analyses revealed IgE reactivity to crocodile PV in serum from more than half of all patients. Two βand one α-crocodile-PV isoforms were identified. PVs constituted approximately 90% of total proteins in heated crocodile extracts, with β-PV (11 kDa) being 10 times less abundant, but up to 500 times more IgE-reactive than α-PV (13 kDa). αand β-PVs from crocodilians, including alligators and crocodiles, share more than 96% and 74% of their amino acid sequence, respectively.

Conclusion: Crocodile PV is a new allergen as per the IUIS guidelines. Fish allergic patients may be at risk of severe allergic reactions upon ingestion of crocodile meat due to strong IgE cross-reactivity of β-PVs. This study suggests that fish allergic individuals and health professionals need to be aware of potential allergic reactions to meat from crocodilians, termed 'fish-crocodile syndrome'. Background: We present a 39-year-old nonatopic woman that in December 2016 after eating a seafood paella with green pepper presented asthenia, nasal obstruction, incoercible vomiting and diarrhea.

Later she ate a grilled loin sandwich in a bar and she had the same symptoms (she asked the waiter at the bar and the chef had cooked her sandwich in the same pan where he had cooked green pepper just before). After that, she suffered from abdominal pain, nausea, abdominal distension without diarrhea two hours after she ate an omelet sandwich with certain flavor of green pepper. At present even the casual smell of pepper causes her nausea. The woman eats everything including spices and just avoids pepper.

Method: Skin prick tests were performed using extracts from food (nuts, fish, mollusk, fruits, vegetables, legumes), aeroallergens (mites, ABSTRACTS | 493 pollens and epithelia) and purified proteins (Pru p 3, profilin, polcalcin, alfalactoalbumin, betalactoglobuline, casein). We also performed prick by prick to raw and cooked green pepper.

SDS-PAGE immunoblotting according to Laemli under reducing conditions (with 2-mercaptoethanol) was performed to study the molecular mass of the IgE-reactive proteins. Extracts from green pepper and green pepper seed were used.

The prick tests were all negative and the prick by prick test to raw and cooked green pepper was positive in both cases. Blond was taken from all patients to specify the levels of allergenspecific IgE against 112 allergen components of ImmunoCAP ISAC test, the result≥0.30 ISU-E was assumed as positive.

Results: In the study group, in 12 patients (24%) specific antibodies against LTP were detected, the ISU-E level range 0.3-34 average 5.26 ISU-E On average, in patients with detected LTP IgE was detected for 3.5 components belonging to the LTP, however the highest number 41% patients were detected IgE only for 1 LTP. In 9 subjects (75% of respondents with detected LTP), IgE was detected against Art v 3 and this is the only LTP component whose occurrence was statistically significant (P = 0.044). In 6 patients IgE was detected against Pru p 3, Jug r 3, Pla a 3,; 5 patients IgE to Ara h 9; 4 patients Cor a 8; 3 patients Ole e 7, 2 patients Tri a 14, and in 1 person Para j 2. Background: The birch pollen-associated oral allergy syndrome (OAS), an IgE-mediated local allergic reaction, is the most common manifestation of pollen-associated food allergies. Its origin is explained by cross-reactions between birch pollen-and food-allergens belonging to the pathogenesis-related protein subfamily 10 (PR-10). [1] So far, there is no marker available for its detection and no standardized test established to evaluate objectively the subjective feelings experienced by OAS. The diagnosis is based on a characteristic history and on detecting the sensitization to triggering allergens in skin prick test (SPT) and laboratory examination.

Method: The aim of this study was to evaluate whether the food skin prick test could be a helpful marker in the diagnosis of a birch pollen-associated OAS.

For this exploratory study, data from 2016-2017 was collected retrospectively at the dermatological outpatient department of the Ordensklinikum Linz Elisabethinen.

Patients with positive SPT results for birch pollen were included.

The variables age, gender, tree pollen-(birch, alder, hazel) and food-SPT, laboratory tests (IgE, Bet v 1, Bet v 2, Gly m 4) and symptoms (OAS, rhinoconjunctivitis allergica, atopic dermatitis, anaphylaxis) for statistical analysis.

Results: There was an association between food-SPT and OAS but also between the negative OAS patients and food-SPT (P = 0.9-0.1).

All of the Bet v 1 sensitized patients with positive Gly m 4 results had also a positive food-SPT result.

Conclusion: There was no evidence for a possible role of food-SPT as helpful markers in the diagnosis of birch pollen associated OAS.

Maybe Gly m 4 could be a helpful marker, but more data are needed. Bet v 1 seems to be the cause of birch-pollen associated OAS, due to the dominant sensitization pattern to major allergens in Austria. Background: Eggs are among the foods most frequently causing allergy. The most common one is hen egg, although we may consume other bird's eggs such as duck's, those of goose, quails and seagulls. Clinical and serological crossreactivity between hen egg proteins and those of other birds eggs have been described.

Allergy to other species eggs are less frequent and are usually described in patients allergic to hen eggs. We report a case of food allergy after ingestion of duck egg in an adult patient without hen egg allergy.

The patient was a 50 year-old man who had symptoms of generalized itching, swelling uvula, erythema neck and deglutition difficulty immediately after he ate eggs from duck and hen. He claimed to have eaten hen eggs almost daily without clinical symptoms and he had not previously ingested duck egg. He denied allergic reactions to any other food but did complain of seasonal allergic rhinoconjunctivitis in the spring. We performed skin prick test with extracts of egg and feathers, prick by prick test with cooked and fresh yolk and white from duck and hen egg and oral challenge with hen eggs. Specific serum IgE was measured to hen proteins and we carried out a western blot with the proteins of allergenic extracts from different eggs (white and yolk of quail, chicken, goose and duck) and an inhibition of western blot with ovalbumin as inhibitor allergen.

Results: Skin test with extracts of eggs and feathers, cooked and fresh hen and duck eggs were positive. Total serum IgE was 29.2 KU/L. Specific IgE to hen's egg was class two for hen egg white, ovoalbumin and class one for yolk and ovomucoid. Oral challenge with heated egg yolk negative and with egg white was positive.

The patient's serum recognized mainly and intensely several proteins of white and egg yolk of quail and duck with a molecular mass around 45 to 50 kDa respectively. On the other hand a protein around 45 and 50-52 kDa was unique recognized in white eggs of hen and goose. The Western blot inhibition revealed ovalbumin inhibited the protein recognized in the egg white but not egg yolk involved in. Background: Management of tree nut allergy is usually based on the avoidance of the suspected tree nut (TN), as well as peanuts and seeds, either because of the risk of cross-reactivity and/or contamination, or due to the clinical severity.

Objective: To assess the sensitization pattern and clinical reactivity patterns to different TN, peanut and sesame seeds (SS) in patients with a history of reaction to at least one of these foods. Results: A total of 47 patients with confirmed nut allergy were included; 70% female, median age [interquartile range] of 28 years; 72% were atopic. The most frequently involved foods were walnuts (53%), hazelnuts (40%), almonds (32%) and peanuts (38%).

Anaphylaxis was the clinical presentation in 51% of the patients.

In those with a history of reaction to only one nut (24), the most prevalent was peanut (42%). In the 23 patients that reacted to more than one nut, the most frequent combinations were walnut/hazelnut (15), walnut/almond (12) and almond/ hazelnut (10). Of these patients, 5 tolerated other nuts. Two had sesame seed allergy, one reacted only to SS. Nine patients (19%) were sensitized to foods that they tolerated. Fourteen (30%) patients were sensitized to LTP and 8 of them reacted to more than one nut.

Conclusion: These data concur with the existence of different sensitization profiles (primary, concomitant or cross-reactive), which may predict different clinical reactivity patterns and therefore, influence dietary recommendations. Background: Buckwheat (Fagopyrum esculentum) is a Polygonaceae weed, not a cereal, which is increasingly been consumed and used as an alternative food in the diet of celiac patients. Despite its wide use, allergy to buckwheat has unfrequently been reported in our setting.

Method: Two female patients, aged 37 and 58, suffered an immediate severe allergic reaction after eating a bread and a pancake containing buckwheat among its ingredients. The first patient presented generalized urticaria, palpebral angioedema and pharyngeal occupation. The second one showed those same symptoms, as well as abdominal pain, nausea, dyspnea, dizziness, hypotension and loss of consciousness.

Skin tests and specific IgE determination to aeroallergens and food allergens were carried out, including prick-prick test with buckwheat and all other components contained in the food involved. Buckwheat allergens were studied by SDS-PAGE and IgE-Immunoblotting of one of the patients.

Results: Prick-prick tests yielded strongly positive results to the food itself and buckwheat, and negative to the remaining food components in both cases. CAP was positive to buckwheat (11.30 kU/L and >100 kU/L, respectively). Basal serum tryptase levels were normal. Both patients were not sensitized to cereals, LTPs, profilins or PR-10 proteins. For the first patient, the skin tests were negative for other foods, seeds and nuts. The CAP was negative for LTPs, profilins and storage proteins of peanut and other nuts. The second patient who had the most severe reaction, was also sensitized to hazelnut(CAP 13.7 kU/L), pistachio (1.44kU/L), almond(0.66kU/L), walnut(29.7kU/L) and sesame(4.47kU/L), which were not included in the pancake. The buckwheat Immunoblot of the first case, under non-denaturing conditions, revealed a IgE-binding protein of 60-kDa.

IgE-immunoblotting under reducing condition showed protein bands of 30, 20, 17 and 14 kDa in the buckwheat extract.

Conclusion: Two cases of anaphylaxis by buckwheat flour contained in two frequently consumed foods are presented. The absence of sensitization to LTPs, together with the pattern of specific IgE binding in the immunoblot in one of the cases suggests that the responsible allergen could correspond to a storage protein of buckwheat, without cross-reactivity with other seed and nut allergens. Buckwheat must be taken into account as an unsuspected food allergen capable of causing severe allergic reactions. Background: Allergy to linseed (Linum usitatissimum) has infrequently been reported despite of its wide use in bread and in a range of "health food" products. Linseed contains potent allergens which have not yet been characterized.

We studied three patients who presented allergic reaction after eating different foods which contain linseed. Two of them (Patient P1 and patient P2) had anaphylaxis and the third one (patient P3) had oral syndrome, abdominal pain and diarrhoea. P2 was also allergic to mustard and P3 to sesame seed. All of them tolerated the remaining seeds, nuts and food. Baseline tryptase levels were in normal range in all patients.

Skin tests and specific IgE determination to inhalants and food allergens were carried out. Linseed allergens were studied by SDS-PAGE and IgE-immunoblotting.

Skin tests: Patient 1: Prick tests were positive to pollens and Linseed, and negative to LTP, profilin, nuts, seed and the remaining food; Patient 2: Prick tests were positive to linseed and mustard and negative to other food and inhalants; Patient 3: Prick tests were positive to linseed, pollens, sesame and nuts (peanut, hazelnut, almond, pistachio). 

We present three cases of severe allergic reactions to linseed. The pattern of specific IgE binding in the immunoblot seems to lead to storage proteins as the responsible allergens. 0925 | PR-10 sensitization-looking it up in food allergy Background: PR-10 protein group sensitization is found in patients with respiratory allergy, mainly in areas inhabited by trees of the Betulacea or Fagacea families. Its role in food allergy is, however, more frequently described in the context of cross reactivity.

Our aim was to characterize the pattern of molecular sensitization of food allergic patients sensitized to PR-10 protein group with Immu-noCap ISAC ® (ISAC). The remaining patients, with more severe reactions, were all co-sensitized to either LTP and/or Storage Proteins (SP). Only 2 of the 7 patients without PFA were co-sensitized to LTP or SP versus 7 of 9 with PFA (P < 0.05).

Conclusion: PR-10 sensitization is rare in our population. Approximately half of the patients had allergy to plant foods, but the majority were co-sensitized to LTP and/or SP. The few patients only sensitized to PR-10 had minor reactions. Among the patients without plant food allergy, co-sensitization to LTP and SP was significantly less common. According to these results, in our population, PR-10 seems to be less relevant to food allergy, when compared to reported results from other European countries.

Gür Çetinkaya P; Uysal Soyer Ö; Esenboga S; sahiner ÜM; sekerel BE Hacettepe medical school, Ankara, Turkey Background: Pistachio is a tree nut belonging to "Anacardiacea" family, and constitutes 7% of tree nut allergies. This nut most often ABSTRACTS | 497 cross-reacts up to 95% with cashew which is located in the same family. Pistachio allergy is mostly seen in Iran, Turkey, the United States, and China where this tree nut is frequently consumed. In this study, we analyzed age and cut-off values for development of tolerance to pistachio.

Method: Children who had reported allergic reactions with pistachio, and who have not consumed pistachio, but had positive SPT and/or specific IgE levels were enrolled into the study. SPT and specific IgE levels were measured in all patients. Oral provocation(OP) tests with pistachio were performed by 82 patients, and 21 of them had positive test result. The median age of tolerance development was 60 months (IQR: 48.0-89.0 months). The most commonly involved systems during OP tests were skin (90%, n = 19), gastrointestinal system (33%, n = 7), and lower respiratory tract (24%, n = 5). Concomitant allergic diseases were atopic dermatitis (70%), asthma (40%) and allergic rhinitis (17%). There was a positive correlation between skin prick test diameter (SPT) and specific IgE levels (spIgE) (r = 0.331, P = 0.001). SPT of≥8.25 mm to pistachio nut was found as highly predictive of clinical allergy (AUC: 0.83, 95%CI: 0.73-0.94, P < 0.001). Any relation was not determined between eosinophil, basophil counts, triptase levels, and OP test positivity.

Conclusion: Pistachio allergy is one of the frequently seen nut allergies in Turkey which may cause serious allergic reactions including anaphylaxis. OP test showed that tolerance was achieved by the median age of 60 months, and a cut-off level of 8.25 mm was best predictor for positive reaction. In an oral challenge test, the patient responded with generalized urticaria, swelling of the lips and difficulty breathing at a cumulative dose of 0.1 g peanut protein, however, without blood pressure drop.

(Grade 2, Moderate Symptoms). The patient was treated with anti-IgE for 3 months (with 450 mg every 4 weeks sc). Oral desensitization began with ingestion of 500 μg peanut, escalating to 500 mg, on the first day and escalating weekly doses of peanut from 500 mg to 4000 mg (8 peanuts). Then anti-IgE was discontinued while the patient ingested 8 peanuts every day. We have followed the patient's sensitivity to peanuts from before anti-IgE treatment to after anti-IgE washout with basophil testing.

Results: The patient completed desensitization without side effects, and continues to ingest 8 peanuts a day. Basophil sensitivity was reduced 13-fold by anti-IgE treatment, but returned to baseline levels after anti-IgE washout.

Conclusion: Anti-IgE allows rapid desensitisation of peanut allergic subjects with peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after anti-IgE is discontinued.

Additional studies will help clarify which patients would benefit most from this approach. The return of basophil response to pre-treatment levels suggests that the patient is desensitised, and depends on the daily ingestion of allergen.

What do we (not) know?

Background: The use of biologic prosthesis is a well-established surgical procedure. Acute and delayed complications may occur, but accurate epidemiologic data about allergic reaction to graft tissue is lacking.

Methods: A 9 years old boy referred to our Unit for urticaria and gastrointestinal symptoms which developed a few years before. He received a biologic porcine vascular duct during a cardiovascular surgery at 20 days of life. At the age of 5 urticarial episodes occurred, and a diagnosis of beef allergy was made. After the exclusion of beef meat from the diet, most symptoms resolved, but the child began to complain about occasional episodes of vomit and diarrhoea.

Results: Skin prick tests confirmed the beef meat sensitization and prick-prick test resulted positive against raw pork meat but not against cooked pork meat. In vitro tests demonstrated the presence of pork meat specific IgEs (14.1 kUA/L). Component-resolved diagnostic tests revealed allergy sensitization toward Bos d 6 (bovine serum albumin, BSA; porcine serum albumin was not tested due to lack of a specific test). After accurate exclusion of pork meat from diet, a complete remission was achieved, and the diagnosis of pork meat allergy was confirmed.

Conclusion: BSA is a major beef allergen, responsible for the raw beef-cow milk cross-reactivity but with a scarce importance in milk allergy. It is highly homologous with human serum albumin and other mammalian serum albumins, including porcine albumin. Porcine albumin is also highly homologous with cat serum albumin and therefore responsible for cross-reactivity in patients affected by cat-pork syndrome. We hypothesize that the implanted porcine tissue was the trigger for pork meat allergy in our patient, as this condition is exceptional in childhood and that our patient never owned a cat.

Few cases of pork allergy due to porcine tissue implantation have been reported so far. Of interest, pig sensitization was recognized as a rare but possible cause of blood-culture negative endocarditis in patients with porcine bioprosthesis according with anamnesis, increased IgE level against pork, tissue eosinophilia during autopsy. Background: Desensitization to foods is assuming a new paradigm in food allergy. This technique is becoming widespread especially for patients with egg and milk allergy, but the effect of desensitization on the consumption of similar but not identical foods is still uncertain.

Material and Methods: We describe the case of a 16-year-old patient, with a history of chicken egg allergy, who had been successfully desensitized tolerating cooked and raw chicken eggs for a year.

The patient came to the office after presenting an episode of anaphylaxis immediately after eating fried quail eggs. An immunological study was carried out. We performed skin prick test with chicken egg′s proteins (white, yolk, ovoalbumin and ovomucoid). An

Immunoblotting to detect specific IgE to egg proteins was also performed. For this purpose, the following extracts were used: chicken egg white and yolk (Commercial extract form ALK) and quail egg white and yolk prepared following a similar procedure (extracted in 10% phosphate buffer (w/v)). Conclusion: We present the case of a patient with specific allergy to quail egg white and yolk, probably through ovotransferin, but not to chicken egg. The desensitization against chicken eggs does not allow the consumption of eggs of other species of birds, such as quail eggs, and this indication must be made specifically to patients after a protocol of desensitization against chicken′s eggs. Case Report: Seven years ago we presented the case of a 32year-old male, who suffered two acute episodes of oral pruritus, lip angioedema, epigastric pain, generalized urticaria and dizziness after ingesting lettuce. He previously tolerated salads (including lettuce).

He was later diagnosed with non-LTP-dependent lettuce anaphylaxis and an Aspartyl protease was identified as a new lettuce allergen with cross-reactivity with other members of the Compositae family.

Since the diagnosis he has avoided lettuce and all the other Compositae. We present the patient's curious outcome after 7 years of follow up.

Methods: Total IgE, basal tryptase, specific IgE to lettuce by Immu-noCAP, prick-prick and oral challenge tests with lettuce and other

Compositae. SDS-page, Immunoblotting and molecular characterization of IgE binding bands by mass spectrometry. Skin prick tests and specific IgE to lettuce were repeated on several occasions in the following years. After 7 years an oral challenge test with lettuce was carried out.

Results: Prick-prick test was positive to fresh lettuce (11 × 15 mm) and to other Compositae (raw endive, chicory, thistle, artichoke and chamomile). Prick-prick test was negative with these boiled Compositae. Basal tryptase was 7.07 μg/L. Total IgE in serum was 189 Ul/mL. Specific IgE by ImmunoCAP was positive to lettuce (7.35 kU/L) and negative to profilin, LTPs and thaumatin. Oral challenge test with endive was positive and negative with cooked Compositae (artichokes and thistle). SDS-page and Immunoblotting detected an intensely binding IgE band about 46 kDa, common for endive and chicory, which was identified by mass spectrometry as an Aspartyl protease. No bands were detected at LTP (9 kDa) and profilin (16 kDa) . In the first two years after the diagnosis, prick-prick test and specific IgE to lettuce remained positive (CAP 1.91 kU/L and 0.44 kU/L, respectively). After 7 years, prick-prick test and specific IgE to lettuce became negative (CAP 0.08 kU/L). With this findings a new oral challenge test with lettuce was carried out which result turned out negative.

We report the first case of spontaneous tolerance to lettuce in a patient who previously presented lettuce anaphylaxis and identify an Aspartyl protease as the causative allergen.

Introduction: Eosinophilic esophagitis (EoE) is an emergent allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Recently, it has been seen that EoE develops in up to 2.7% of patients with IgE-mediated food allergy undergoing oral Immunotherapy (OIT). Ingestion of baked milk and egg was associated with increased development of tolerance to regular milk and Immunologic changes have been reported in subjects ingesting baked milk and egg, similar to those seen in food Oral Immunotherapy studies.

Case description: We present the case of a 13-year-old girl, with history of IgE mediated Cow′s milk allergy and rhino conjunctival and bronchial asthma symptoms. Prick test against milk proteins showed: milk 6 mm, alpha-lactalbumin 6 mm, casein 3 mm and to beta-lactoglobulin: negative. Total IgE: 469 KU/L. Specific IgE to milk: 3, 15 alpha-lactalbumin: 3, 16 KU/L; casein: 2 KU/L and beta-lactoglobulin: 0.10 KU/L. We performed an oral food challenge with baked milk which was well tolerated. Then, we performed an oral food challenge with fresh milk and she presented facial urticaria and pharyngeal pruritus. After 3 months eating baked milk every day, she had symptoms of dysphagia and esophageal food impaction. For this reason, we performed an Esophagogastroduodenoscopy (EGD) and biopsies which showed white exudates and vertical furrows. The histological study showed eosinophil count>20 per high-power field.

Eosinophilic esophagitis was diagnosed and she started treatment with Esomeprazole 20 mg. The EGD was repeated 8 weeks later with similar results in the biopsy. She was treated with a comprehensive diet free of cow′s milk proteins. After 8 weeks she was asymptomatic and endoscopy and biopsy findings were normal.

We report the case of a Cow′s milk allergic patient who developed EoE after introduction baked Cow′s milk which apparently was tolerated in her diet. The avoidance proved efficacy in inducing the remission of EoE. Method: We examined 87 bottle-feeding infants with food allergy aged from 1 to 12 months. Serum vitamin levels were measured by immunoassay methods (retinol binding protein (RBP), vitamin B6, 25hydroxy vitamin D), biochemistry methods (vitamin C, vitamin E) and microbiology methods (vitamin B1, vitamin B2). As criteria for complete sufficiency standards adopted in the Russian Federation were used (the lower limit of normal levels: RBP -0.52 μmol/L; B6-8 ng/mL; 25-hydroxy vitamin D-15 ng/mL; vitamin C -0.4 mg/dL, vitamin E -0.8 mg/dL; vitamin B1 -28 μg/mL; vitamin B2 -6 ng/ mL).

Results: Complete sufficiency were observed in 21 infants (25.9% cases), one vitamin deficiency in 33 infants (40.7%), two vitamins deficiency in 23 infants (28.4%), three and more vitamins deficiency in 6 infants (7.4%).

should be used after vitamin status asses, mainly using monovitamin medication. Results: Patients were followed with the diagnoses of CMA and asthma. Age at the beginning of symptoms and start of OIT were in the range of 3-6 months and 4-19 years, respectively. They had high total IgE (139-843 IU/mL), milk spIgE (2.9-418 kUA/L), casein spIgE Background: Food allergies may affect up to 6% of school-aged children. It has been shown that approximately 20% of all anaphylactic reactions caused by food allergy are firstly presented at (pre) school. Therefore, it is of high importance that (pre)schools have a policy on food allergy management and the use of an epinephrine auto-injector (EAI). To our knowledge, limited is known on the policies of food allergy management at (pre)schools. The aim of this study was to investigate the policy on food allergy management in preschools and primary schools in the Northern part of the Netherlands. Results: We included 87 preschools and 110 primary schools in this study. We showed that 80.5% of the preschools and 73.6% of the primary schools had a child(ren) with food allergy. Only 13.8% of the participating preschools and 27.2% of the primary schools had a policy on allergen avoidance and only 35.6% of the preschools and 35.8% of the primary schools had a policy for the use of an EAI.

The majority of the pre-and primary schools in the Northern part of the Netherlands have children with food allergy.

However, only a limited number of (pre)schools do have written guidelines for food allergy management in (pre)schools. Additionally, there is limited experience how to use an EAI at (pre)schools. Therefore, an evidence-based policy on food allergy management in (pre) schools is needed. Background: Food allergies are the most common cause of anaphylaxis in childhood. Here we present 3 cases had anaphylaxis due to cow 's milk allergy, and treated with specific oral tolerance induction (SOTİ) to cow' s milk.

Method: SOTI protocol was administered according to previously published by Longo et al. Skin prick test were performed according to standard methods with allergens. Cow's milk specific IgE was investigated with immunoCAP system. In all cases, the wheal size of the cow's milk in skin prick tests or the specific IgE levels was higher than level of positive predictive value of 95%.

Results: Case 1: A 7 years old male patient who had 3 anaphylaxis after milk consumption. SOTI treatment was started one year ago.

There was no complications during the dose increasing phase. However, he had two episodes of anaphylaxis during the maintenance phase. In the final visit, we observed that he could drink 200 mL milk and could consume dairy products.

Case 2: Eight-year-old male patient has an intensive care-of-hospitalization story due to anaphylaxis three times after milk consumption.

His accordance to strict diet was bad, and had frequent asthma attack. Anaphylaxis developed 2 times during the dose increasing phase in SOTI protocol. After SOTI treatment, he could consume 200 mL cow's milk and dairy products without problems.

Case 3: A 7-year-old male patient followed-up for asthma and cow's milk allergy. It was learned that anaphylaxis developed 2 times after milk consumption. He was fed in accordance with the milk-free diet.

He has used fluticasone nebules, montelukast, mometasone nasal spray, and cetirizine. Anaphylaxis developed 4 times during the dose increase phase of SOTI administration. There were many mild to moderate anaphylactic episodes during the maintaining phase. After the SOTI treatment, he could consume 150 mL milk and dairy products. Background: Cow's milk protein allergy (CMPA) is one of the most common food allergies in early childhood. Small dietetic group sessions for parents of infant with non-IgE mediated CMPA were held to meet increasing demands and reduce waiting times. Parents were given information on CMPA, advice on weaning and milk reintroduction using a locally designed milk ladder. Parents were also advised to contact the dietitians via telephone if they had further questions.

We aim to evaluate the sustained effectiveness and patient satisfaction of the group sessions.

Method: Parents and carers who attended the group dietetic sessions held between November 2015 and July 2016 were included in the survey. Feedback were obtained via a self-designed questionnaire using a Likert-type scale, rating several questions from 1 (least satisfied) to 5 (most satisfied). Initial feedback was obtained directly after the session. We followed these patients up a year after the initial session via telephone and postal questionnaire.

Results: Overall attendance rate of the 9 group sessions held was 58% (n = 40). During the initial survey, participants found the group session useful (mean score 4.7 out of 5) and felt more confident in managing CMPA (mean score 4.8).

We successfully obtained follow up feedback from 13 participants.

Majority agreed that the group sessions have been informative (mean score 4.8). They also said they felt confident weaning their child on milk-free diet (mean score 4.8), and in reintroduction of cow's milk in diet (mean score 4.3).

30% (n = 4) said that they would have preferred an individual session. 38% (n = 5) have contacted the dieticians via telephone after the initial session, and 15% (n = 2) had requested individual consultations. 69% (n = 9) have attempted reintroduction of cow's milk in their child's diet using our local milk reintroduction guide. The mean age at first challenge was 14 months (age range 6 to 26 months), with average of two attempts. 31% (n = 4) have been successfully challenged and are managing well on a normal diet.

We recognised the limitation in obtaining feedback via telephone and postal questionnaire, which resulted in the poor follow-up response rate.

Overall, parents felt more confident in managing CMPA and the positive responses were sustained a year on, highlighting the success of these group sessions. Follow up opt-in sessions could be offered to provide additional support and allay parental anxiety in challenging their child with cow's milk at an appropriate age. Results: Goats and rabbits were immunized with specific allergoids, the allergoid-specific IgG titer determined and sera pools produced.

The allergoid reference material was comprehensively characterized.

While IgE reactivity of the allergoids was not detectable anymore, IgG reactivity was maintained. Allergoid-specific assay parameters as serum dilution, reference dilution and sample dilution factor to obtain at least six data points within the pseudo-linear range of the inhibition curve were determined. With these set parameters the evaluation of the analytical method was performed. The assay showed very good results in terms of linearity, accuracy, precision, reproducibility and robustness for all investigated allergoids as well as aluminum-adsorbed allergoid-preparations.

Conclusion: With the developed immunological inhibition assay, it is possible to determine the specific IgG reactivity of allergoids in different preparations. The performance of the analytical method met all pre-defined acceptance criteria, which will be confirmed in the next step by a validation procedure according to ICH-guidelines. Case report: We present the case of a 32-year-old patient, diagnosed with rhinitis and asthma due to sensitization to pollens, as well as dyshidrosis and allergic contact dermatitis to Cobalt.

The patient presented a cutaneous pattern consisting of erythematous papules, some scaly, very pruritic, of initial appearance in the upper limbs 2-3 days after initiation of administration of specific immunotherapy extract (DEPIGOID forte grasses, Leti ® ). Subsequently generalize lower limbs and neck. She presented them repeatedly and late after 2-3 days of the first 3 doses administered. She referred partial control of pruritus with oral antihistamines, without total resolution of lesions for weeks. Immunotherapy was suspended persisting the skin lesions for 3 more weeks.

According to the personal history of sensitization to metals, and the clinic presented in a temporal relationship with the use of an extract of immunotherapy with aluminum hydroxide, a study was requested with epicutaneous tests with aluminum hydroxide as well as with epicutaneous tests with immunotherapy extract.

Aluminium hydroxide and Depìgoid Forte grasses extract epicutaneous test were negative. In subsequent visits the patient reported that coinciding with the start of immunotherapy, presented at home and mainly in her bedroom a plague of Cimex lectularius, popularly known as bedbugs, proving that they had been the cause of bites on their skin, and later skin reaction. Patient reported that with the elimination of said pest the skin lesions disappeared. The administration of its immunotherapy extract was tolerated.

Cimex lectularius, commonly known as bed bugs, is a hemiptera insect of the family Cimicidae. The clinical picture usually corresponds to multiple pruriginous lesions from the prurigo type, to multiple erythematous plaques, some infiltrated and others with a urticarial appearance, or even bullous. The lesions last for 3 to 6 weeks without treatment, and while the older ones heal, new ones may appear. In our patient it was not considered as an initial diagnosis, having considered immunotherapy as an etiological factor, but we must not forget that although in our country it is not a reason for frequent consultation, either due to underdiagnosis, because of the transitory nature of the pathology or because of scarce number of causative agents, it is important to consider insect bites in the differential diagnosis of dermatosis.

Di Cara G; Salvatori C; Testa I; Pacitto A; Bizzarri I; Isidori C; Tarsia M; Esposito S Università degli Studi di Perugia-Dipartimento di Scienze Chirurgiche e Biomediche, Perugia, Italy Background: House dust mites (HDM) are one of the most important allergens involved in childhood respiratory diseases, and the most frequently prescribed extract for sublingual immunotherapy in children (SLIT).

Despite the improvement of standardization methods for the production of SLIT, the differences in cultivation and purification processes used to produce raw materials for specific immunotherapy extracts may still impact on the final composition of mite allergen extracts.

Our study investigated the total protein and main allergen content of five commercial HDM sublingual immunotherapy extracts using SDS-PAGE and immunoblotting. Recombinant allergens of group 1 and group 2 major allergens were used to test the immunogenicity of such extracts.

Method: HDM SLIT extracts were purchased from five Italian suppliers (ALK-Abellò, Allergy Therapeutics, Anallergo, Lofarma, Stallergenes).

The protein composition of extracts was evaluated analysing equal volumes (15 mL/lane) by SDS-PAGE (12% separating gel) and subsequent immunoblotting. For identification of allergens in the extracts, western blot analyses were performed with rabbit monoclonal antibodies (RayBiotech) against Der p 1 and Der p2.

The total protein content in the five tested commercial extracts showed a relevant variability. The protein contents ranged from 32.9 to 44.2 μg/mg for what concerns Der p1, while Der p2 showed a greater variability, ranging from 4.2 to 14.6 μg/mg. SDS-PAGE showed a similar pattern of distribution in 3 of the tested extracts, which showed protein bands of comparable intensity, while 2 extracts showed a lower total protein count. Extract 2 showed a higher intensity band corresponding to the molecular weight of tropomyosin.

Western-blotting showed a similar concentration of Der p 1 in most extracts, while Der p2 was more variable.

Conclusion: Our analysis of five commercial extracts commonly used for sublingual specific immunotherapy against HDM showed important variations in term of total protein content. A less evident but still relevant difference was also evidenced when testing the major allergen content, with up to 25% variation in Der p1 and up to a 3-fold variation in Der p2 concentration. This differences, likely related to the different production and extraction methods, could still be responsible of a different immunological response in children who underwent SLIT. Method: We evaluated 29 children who had completed their immunotherapy treatment. Along with demographic data we were able to record skin prick test (SPT) results and mRQLQ at start and end of treatment. We only included patients who had completed pre and post treatment questionnaires in the study to allow a comparison. The scores were evaluated using a student T test.

Results: Patients' starting age ranged from 6 to 17 years (mean 11 years). 29 of the 48 children had completed pre and post treatment questionnaires. All 29 had grass pollen allergy confirmed on SPT at the start of treatment. 10 patients (34%) had isolated grass pollen allergy on SPT and 19 (66%) had multiple allergies. Mean start treatment score for all patients was 37 on mRQLQ. Mean score at end of treatment was 24, indicating a 35% reduction in total mRQLQ score (P value <0.05). For those with multiple allergies the mean total mRQLQ scores were 33 at start of treatment and 25 at end of treatment, indicating a 27% reduction (P value 0.16). For those with isolated grass pollen allergy scores were 44 at start of treatment and 23 at end of treatment indicating a 50% reduction (P value <0.05).

Conclusion: For children with uncontrolled symptoms of allergic rhinoconjunctivitis, grass pollen immunotherapy is associated with statistically significant improvement in quality of life. This improvement is most beneficial for patients with isolated grass-pollen sensitivity on SPT. Those with multiple aeroallergen sensitivities on SPT did show an improvement (not statistically significant) post-treatment. Grass-pollen immunotherapy is an effective treatment for rhinoconjunctivitis to offer patients in a rural DGH setting.

Background: Allergic asthma is a common clinical refractory disease, most patients with asthma are accompanied by varying degrees of allergy. In clinical practice, treatment of this disease using specific immunotherapy has proven effective. In the current study, we examined the effectiveness of specific immunotherapy in a total of 99 patients admitted to our hospital from 2015 to 2016.

Method: To investigate the clinical efficacy of allergic asthma-specific immunotherapy. 99 patients were selected, of which 49 were males, aged 22 to 61 years, 50 females, aged between 23 to 64 years old, all patients were clinically diagnosed only as allergic asthma. The 99 patients were randomly divided into two groups, including the observation group containing 50 cases, the control group of 49 cases. All patients were first treated with conventional basic treatment. The observation group was subsequently treated with specific immunotherapy. Both groups were followed-up and the treatment efficiency were analyzed.

Results: After treatment, both two groups of patients showed improvement, in the observation group, the effective rate was 93%, while for the control group, the effective rate was 75%. Observation group showed significantly better outcomes than the control group.

Conclusion: In allergic asthma treatment, adding specific immunotherapy on the basis of routine treatment is beneficial and could be widely used in clinic. Case report: Atopic dermatitis(AD)is the most common itchy dermatosis that affects millions of children and adults. During recent years, diagnosis and treatment based on component resolved diagnostics (CRD)is recommended. We report a 9-year-old boy with severe Atopic dermatitis. He had positive family history of atopy. The atopic dermatitis was developed since infancy. He was referred to our clinic when he was 5 years old. He had generalized xerosis with ulcerative eczematous lesions on his neck, popliteal and antecubital areas. He had mild eosinophilia and his serum total IgE level was 590 IU/mL. Daily bleach bath, moisturizing agents, topical steroids and systemic antibiotics in addition to antihistamine were prescribed.

He had multiple food and aeroallergen sensitization in skin prick test (SPT). He started to eliminate some foods according to the SPT results. He was suffering from recurrent relapse even after strict food avoidance; so treatment with cyclosporine was initiated for him, with partial response. CRD showed sensitization to Alternaria alternata (Alt a1 specific IgE:10.97 kU/L). Allergen immunotherapy by Alternaria alternata was started. After accomplishment of buildup phase, he had significant improvement and we were successful to taper and finally discontinue cyclosporine. Now he is on maintenance phase of immunotherapy, his skin is in optimal condition only by hydration and moisturization. Result: A 15-year-old Thai girl is a known case of severe asthma since one year old. Her asthma was uncontrolled asthma even treatment with high dose combination of inhaled corticosteroid and long acting beta agonist (ICS/LABA), montelukast and Omalizumab.

Spirometry revealed the force expiratory volume in one second (FEV1): 34% predicted, FEV1/forced vital capacity (FVC): 48% predicted and 14% improvement of FEV1 after salbutamol 400 ug inhalation. Allergic sensitization showed specific IgE to cat: 2.04 KUA/L. SLIT with cat allergen started at the dose of 450 AU per month and increased to 1500 AU per month (SCIT dose is 1000 AU per month) for three-year-and-six-month course. After SLIT, her asthma symptom improved significantly. She can exercise without exacerbation and plays sport at school. Her last episode of asthma exacerbation was 1.5 year ago. Her FEV1 (% predicted) was improved from 34% predicted to 48% and the FEV1 bronchodilator response decreased from 14% to 6%.

Conclusion: An improvement of pulmonary function and asthmatic symptoms of the presenting case would support the efficacy of SLIT of cat allergen in a patient with severe asthma.

RA developed during pollen SCIT in this case might be related with immunomodulation effect of immunotherapy. Background: We report a case of 20-year-old woman with allergic rhinoconjunctivitis and mild persistent asthma due to sensitisation to seasonal pollens and molds with bad clinical evolution and not response to conventional drug therapy.

We decided to start subcutaneous allergen specific immunotherapy with Alternaria extract in our Immunotherapy Unit in accordance with the guidelines of the European Academy of Allergology and Clinical Immunology (EAACI) and we used a cluster regimen.

The immunotherapy was not well tolerated: the patient had two grade 2 systemic reactions with the first dose in two attempts.

Method: Sensitisation was diagnosed through skin prick test with aeroallergens standard panel and serum specific IgE by ELISA.

Due to the bad tolerance to immunotherapy, molds molecular diagnosis by ImmunoCAP, study of the molecular weight to specific IgE binding proteins by SDS-PAGE IgE immunoblotting, and cross-reactivity study by means of Immunoblotting-inhibition assay were performed. A. fumigatus extract was able to produce a total IgE binding inhibition on the 38 kDa band of A. alternata extract when IgE Immunoblotting assay was performed.

Conclusion: Respiratory allergic disease due to Alternaria is difficult to control, the use of subcutaneous specific immunotherapy could be of significant benefit.

Most of the allergic patients to A. alternata are sensitized to Alt a1, major allergen from A. alternata. However, our patient is sensitized to a 38 kDa Alternaria protein due to cross-reactivity with A. fumigatus allergens, this sensitization could explain the bad tolerance to the Alternaria immunotherapy. Background: The association between natural pollen exposure, clinical symptoms as well as allergen-specific immune responses has not been investigated at a molecular level. Our aim was to monitor the effect of seasonal birch and grass pollen exposure on clinical symptoms as well as specific B cell and T cell responses to defined allergen molecules in sensitized subjects during two consecutive years.

Method: Grass pollen sensitized (n = 10) and birch pollen sensitized (n = 13) subjects were included in this study and were followed for two consecutive years (2013) (2014) . Subjects were taking part in a clinical trial for the recombinant grass pollen vaccine (BM32) but did not receive immunotherapy for the allergen they were sensitized to. Before, during and after the respective seasons IgE and IgG levels as well as T cell responses to the major birch pollen allergen Bet v 1 and the major grass pollen allergens Phl p 1, 2, 5 and 6 were measured. Pollen counts were recorded throughout the year and patients kept a daily diary including symptom medication score (SMS) and visual analogue scale (VAS).

Results: We noted that IgE levels specific for Bet v 1 and the grass pollen allergens increased most in the seasons in which patients experienced the highest peak symptoms according to VAS and SMS but not depending on cumulative pollen counts. Increases in allergen-specific T cell responses were observed in the pollen seasons as compared to shortly before the pollen seasons in the grass pollenallergic patients also in association with VAS and SMS but not in the birch pollen allergic subjects. No relevant changes of allergen-specific IgG levels were observed during the two years observation in grass and birch pollen allergic patients.

We found an association of increases of allergen-specific IgE increases shortly after the pollen season with clinical symptoms in the pollen season as reflected by VAS and SMS which was not necessarily reflected by cumulative pollen counts in the season.

These results may be important for the analysis of allergen-specific immunotherapy trials. Background: The morbidity and mortality of severe asthma is much higher than that of mild to moderate asthma. This study was performed to understand the clinical characteristics of severe asthma in Korea. Results: Data from the questionnaire showed that bronchial asthma was diagnosed before pregnancy only in 193 women (4.83%). 43 patients (1.1%) were diagnosed with chronic bronchitis at the pregestation stage. Asthma attacks were experienced repeatedly during a lifetime in 4.2% of patients, 12.7% of patients noted long periods of dry cough at night, among them 8.1% had wheezing. The cold did not precede the wheezing breathing in 5.1% of patients. Difficulty in breathing on waking was noted in 2.6% of patients, at night-4.3%.

After examination, the diagnosis of asthma was confirmed in 14.65% of the respondents (586 people). Symptoms of rhinitis are noted in 58% of women surveyed, 18% of rhinitis was allergic. Before examination, the diagnosis of AR was only in 3.5% of patients.

The incidence of symptoms of asthma and AR in pregnant women is significantly higher than the reported cases of these diseases, which leads to untimely initiation of treatment. Method: A total of 117 nonsmoker asthmatic patients without concomitant pulmonary pathology are recruited to our study. All patients underwent spirometry tests, measurement of fraction of exhaled nitric oxide and sputum induction to asses sputum cell counts, demographic features and current medications were recorded. Using the variables of age at onset, BMI, allergy status, FEV1%, FEV1/FVC, asthma severity and induced sputum cytology cluster analysis is performed.

Results: 4 clusters are identified. Cluster1: (n = 43) Early onset atopic asthma, consists of mild asthmatics with a good asthma control and lower BMI. Cluster 2: (n = 14) Severe atopic asthma, consists of lowest spirometry measurements with a least ACT scores. Induced sputum cytology shows a neutrophilic character, while having also the highest percentage of eosinophils. Cluster 3 (n = 27) Late onset obese asthma, nonatopic asthmatics having high spirometry measurements, with a lower ACT scores. Cluster4 (n = 33) Nonatopic mild asthma, consists of patients with the best respiratory functions and least inflammation in means of lowest total IgE, FeNO, sputum cell counts.

Conclusion: Identification of asthma phenotypes in different countries will improve our understanding on the heterogeneity of the disease among the different geographies. Results: Results and discussion. In the course of analysis, obesity was more common in children with bronchial asthma −25% than in the comparison group-in 9.3%. Obesity of the 1st degree was diagnosed in 10 patients of the main group, II degree-in 8, and III degree-5 and IV degree-in 2 patients e diagnosis of obesity, the SDS indices of body mass index (BMI) were determined. Obesitymore than +2.0 (I degree: SDS BMI 2.0-2.5, II degree: SDS BMI 2.6-3.0, III degree: SDS BMI 3.1-3.9, IV degree: SDS BMI ≥4.0).

Conclusion: Thus, the results obtained indicate a high prevalence of constitutional-exogenous obesity in children with bronchial asthma and precedes the formation of the underlying disease e diagnosis of obesity, the SDS indices of body mass index (BMI) were determined. Obesity-more than +2.0 (I degree: SDS BMI 2.0-2.5, II degree: SDS BMI 2.6-3.0, III degree: SDS BMI 3.1-3.9, IV degree: Method: Postal questionnaires were distributed to an unselected group of asthma patients (n = 190). Healthy non-asthmatic volunteers were recruited amongst university and hospital co-workers (n = 53). The presence of self-reported NHR, the type of triggers evoking nasal symptoms, asthma phenotype, medication use and environmental factors were evaluated.

Results: 114 patients and 53 controls completed the questionnaire (responder rate of 60% and 100% respectively). NHR was reported in 71% of asthma patients and 22% in non-asthmatic controls (P < 0.0001), with changes in temperature being the most important inducer of nasal symptoms (74% of asthmatics), followed by strong odours (62%) and cigarette smoke (61%). Interestingly, NHR was more prevalent in patients with severe (79%) compared to mild (50%) asthma symptoms (P = 0.015), and more prevalent in atopic (77%) compared to non-atopic (55%) asthmatics (P = 0.028). Most asthma patients reported more than one trigger evoking nasal symptoms, with 44% of patients reporting 3 or more triggers evoking nasal symptoms. Results: The mean score of CBCL questionnaire in case group with 28.12 ± 2.06 was significantly higher than in comparison with a control group with 17.33 ± 9.7 (P = 0.01). The mean scores of the subscales of social isolation (the case group: 5.83 vs control: 1.18, P = 0.006), anxiety-depression (4.99 vs 2, P = 0.22), intellectual problems (4.8 vs 2.3, P = 0.000), and aggressive behaviors (5.1 vs 2.3, P = 0.003) were significantly higher in children with asthma than in healthy children. The study showed a significant correlation between the mean duration of asthma and a general score of CBCL (P = 0.012, CC=0.8). Moreover, there was also a significant correlation between asthma severity and CBCL scoring (P = 0/001, CC=0.03).

Conclusion: Behavioral disorders in children with asthma are significantly more than healthy children. The duration of asthma and the severity of asthma, are related to and can predict behavioral disorders in children with asthma. Background: Assessment of asthma control is an integral part of the management of asthma. Whilst Asthma Control Test (ACT) is a commonly used questionnaire to assess symptom control, its utility in predicting long term risk of exacerbation has not been well studied.

Aim: To analyze the factors associated with uncontrolled asthma symptoms using ACT and its impact on predicting future exacerbation.

Method: Severe asthma patients on at least

Step 4 Background: Most of the asthma-scoring tools detect the asthma severity from patients' symptoms but there is no scoring tool using parameters to define risk of asthma exacerbation. Thus, this study use factor analysis to evaluate the relationship of parameters in childhood asthma.

Method: The descriptive study using factor analysis in asthmatic children aged less than 15 years old, who attended Thammasat University, the center of excellence for allergy, asthma and pulmonary diseases, Thailand. The participants or caregivers were inter- 

The factors which have the major impact on asthma control are changing bed sheets less than once per month and using dust mite-proof bed sheets. This study is supporting non-pharmacological strategies but further studies are needed to create a more efficient asthmatic symptom checker. were not different between the controlled and uncontrolled group.

The ACT score in the controlled group was significantly higher than the uncontrolled group (P < 0.001). The study showed that cigarette smoke is one of the significant factors that can trigger asthma exacerbation (P < 0.001) and mosquito repellent coil smoke is also significantly associated with asthma exacerbation (P < 0.03 Background: Experimental studies have demonstrated that tumor necrosis factor family member 14 (TNFSF14/LIGHT) plays an important role in airway remodeling. There is little data available concerning in vivo regulation of TNFSF14/LIGHT expression in humans. The aim of this study was to evaluate serum concentration of TNFSF14/ LIGHT in different subsets of asthmatic patients.

The study was performed on 36 nonsmoking asthmatic patients (A), including 24 mild-moderate-severe asthmatics controlled on inhaled corticosteroids (AICS) and 12 asthmatics evaluated twice during asthma exacerbation (AEX) and during subsequent remission (AREM). In addition age and sex matched 24 nonsmoking healthy controls were included (HC). Serum TNFSF14/LIGHT concentration was evaluated using ELISA method. In asthmatic patients lung function tests, exhaled nitric oxide concentration (FeNO), serum total IgE concentration (t-IgE), allergen-specific IgE concentration (s-IgE) and

peripheral blood eosinophilia were evaluated.

(250 + /-134 pg/mL) was significantly greater than that in HC (72 + / -32 pg/mL; P < 0.001). Among all asthmatic patients studied the greatest TNFSF14/LIGHT serum concentration was demonstrated in AEX (357 + /-79 pg/mL), which was significantly greater than that in AICS (194 + /-123 pg/mL P < 0.001). During resolution of asthma exacerbation a significant decrease in serum TNFSF14/LIGHT concentration (118 + /-70 pg/mL; P < 0.001) was demonstrated. In AREM the mean serum TNFSF14/LIGHT concentration was comparable to that seen in AICS (P = 0.06) but was still significantly greater than in HC (P < 0.01). No significant correlation could be demonstrated between serum TNFSF14/LIGHT concentration and baseline lung function parameters, exhaled nitric oxide concentration, serum t-IgE or s-IgE concentration or peripheral blood eosinophilia.

Conclusion: Enhanced production of TNFSF14/LIGHT seen in asthmatic patients, which is further upregulated during asthma exacerbations may play an important role in asthma pathogenesis. Method: Two models of Aspergillus fumigatus-induced allergic airway inflammation were used in the study: long terms (4 weeks) and

short terms (2 weeks Background: Chalcone 4 is identified as an inhibitor of the interaction between CXCR4 or CXCR7 and their ligand CXCL12. Therefore it is called a neutraligand. The chemokine CXCL12, interacting with the CXC-receptor4 (CXCR4) can play a role in the progression and development of bronchial asthma. Asthma is defined as a chronic disease characterized by episodes of obstructive events which affects about 300 million people over the world. The aim of this study is to approach the mechanism of the anti-inflammatory effect of the CXCL12 neutraligand chalcone 4 and also to assess its impact on the migration of dendritic cells in a murine model of allergic airway inflammation.

Method: Chalcone 4 is administered intranasally to BALB/c ovalbumin (OVA) asthma mice and control groups as well.

Our results indicate that the CXCL12 neutraligand chalcone 4 can modify the inflammatory reaction in an airway allergic hypereosinophilia model. Furthermore, found out that CXCL12 neutraligand chalcone 4 prevents DC migration to the airways and airway JNC ganglia during allergic airway inflammation.

The detection of the CXCR4-CXCL12 pathway and its role in the pathophysiological actions of asthma offers a promising target for allergic diseases treatments.

Method: Four groups of Balb/c mice were defined: control and asthmatic, with and without treatment. Asthmatic groups were sensi- Overexpression of PTGDR in pulmonary cells associated to a generalized increase of cytokine expression.

Conclusion: In a mouse model we confirmed the involvement of PTGDR in allergic asthma by the increase of its expression levels after ovalbumin sensitization. We also identified a reduction of PTGDR levels in response to dexamethasone treatment. The in vitro model suggests that PTGDR induces an inflammatory response, increasing the cytokines levels. 0979 | Immune imbalance between transcription factor t-bet/gata3 and allergic asthma Results: T-bet mRNA expression of peripheral blood lymphocytes in patients with allergic asthma was lower than that of the normal control group, and the expression level of GATA-3 mRNA was higher than that of the normal control group (P < 0.05). The Th1 percentage of peripheral blood lymphocyte subsets was lower than that of the normal control group (P < 0.05), the percentage of Th2 cells was significantly higher than that of the normal control group (P < 0.05), and the changes in T-bet/GATA3 expression and Th1/Th2 ratio was highly correlated. Our objectives were to assess the changes of BMP4 and BMP7 serum levels in the response to allergen and methacholine challenge tests and the correlation between BMP4 and BMP7 serum levels and FEV1 before and after allergen and methacholine challenge tests.

Method: Study group consisted of 59 patients with asthma and 48 healthy volunteers. Spirometry, skin prick tests, allergen and methacholine challenge tests were performed in compliance with EAACI, ERS and ATS guidelines. Personalized clinic surveys including ACT ™ were performed. Venous blood was collected before and after 1 hour, and 24 hours afterwards the provocation to EDTA-KE-filled test tubes. Evaluation of BMP4 and BMP7 serum protein levels was performed using specific ELISA immunoassay kits according to the manufacturer's protocol.

Results: The increase in BMP4 and BMP7 serum level 24 hours after provocation test correlates significantly with the concentration methacholine during provocation time (P < 0.05).

BMP7 serum level before the provocation, 1 hour and 24 hours after provocation, correlates negatively with FEV1 change (P < 0.05).

The median BMP7 level 24 hours after provocation was significantly lower in patients with negative methacholine challenge test compared to the control group (P = 0.03).

The median BMP4 level 24 hours after provocation was higher in patients with positive allergen provocation test than in patients with negative test results (P = 0.03).

The BMP7 serum level 24 hours after positive methacholine test is lower and correlates inversely with FEV1 change in every time point, which could indicate that serum level of BMP7 is a predictive factor of FEV1 change. The higher BMP7 serum level, the lower FEV1 change was observed. This could suggest the protective influence of BMP7 in patients with obstructive pulmonary disease, i.e. asthma. The higher BMP4 serum level 24 hours after positive allergen provocation test result shows that the BMP4 could be an indicator of the response to a specific trigger. Background: Inflammation and coagulation are closely linked events. Thrombin is the key enzyme in coagulation system. Besides its well-known functions in hemostasis, thrombin plays a role in inflammation. The aim of our study was to evaluate thrombin generation in children with mild asthma and demonstrate associations between thrombin levels and control of asthma.

Method: Forty-two children with mild asthma and forty-nine healthy children included in the study. Asthmatic children had no asthma exacerbation during the last 6 months. Patients (n = 27) who had mild persistent asthma, were using either inhaled steroid or montelukast. All patients performed spirometry. Thrombin levels were measured by thrombin generation test. Thrombin peak levels, endogenous thrombin potential, thrombin lag time, time to thrombin peak and thrombin tail time were recorded.

Results: Thrombin lag time was significantly longer in children with asthma (3.98 ± 1.2) compared to those in control group (3.29 ± 0.6) (P < 0.01). Children with asthma also had longer thrombin tail time compared to control group (19.5 ± 8.9 vs 16.7 ± 2.9, P = 0.02). Thrombin peak was inversely correlated with FEF 25-75 (-0.41, P < 0.01). Thrombin lag time was inversely correlated with FEF 25-75 (-0.39, P < 0.01).

Thrombin generation parameters did not show difference according to asthma control treatment, asthma control scores and having atopy.

Conclusion: Coagulation/anticoagulation balance is disturbed in mild asthma but this disturbance may not be as strong as to increase thrombin levels. Factors increasing inflammation may cause an increase in lag time, and increase in inflammation and excessive fibrin deposition may contribute to airway narrowing. Background: Cytokines represent key mediators in the onset and persistence of inflammatory process, in both asthma and COPD. IL-31, which belongs to IL-6 family, it might act in a similar way with IL-6 at the beginning of the inflammatory process. Its role in atopic skin diseases has already been demonstrated, but there are conflicting results related to its role in respiratory allergic diseases.

The aim of the study was the evaluation of IL-31 plasmatic level in patients with asthma and COPD and the its correlation with clinical and lung function parameters.

Method: Fifty consecutive patients with bronchoobstructive diseases were included in the study. Thirty-two patients presented asthma and 18 patients had COPD. The evaluation included: number of exacerbation in the last year, disease's severity, spirometry. Plasmatic levels of IL-31 and IL-10 were determined in all patients.

Results: The mean age was higher in patients with COPD Dermatophagoides pteronyssinus [house duste mite (HDM), 100ug/ mouse] were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49 . AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52.

Results: AT inhibited HDM-induced total cells (P < 0.001), eosinophils (P < 0.01), neutrophils (P < 0.01) and lymphocytes (P < 0.01) in bronchoalveolar lavage (BAL), and eosinophils (P < 0.01), neutrophils (P < 0.01) and lymphocytes (P < 0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (P < 0.001), IL-5 (P < 0.001), IL-13 (P < 0.001), CXCL1 (P < 0.01), IL-17 (P < 0.01), IL-23 (P < 0.05), IL-33 (P < 0.05), while increased IL-10 (P < 0.05). Airway collagen fibers (P < 0.01), elastic fibers P < 0.01) and mucin (P < 0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6.25 mg/mL (P < 0.01), 12.5 mg/mL (P < 0.01), 25 mg/mL (P < 0.01) and 50 mg/mL (P < 0.01). Mechanistically, AT reduced the expression of STAT6 (P < 0.05), STAT3 (P < 0.001), STAT5 (P < 0.01) and JAK2 (P < 0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (P < 0.001) was upregulated in leukocytes and in airway epithelial cells, SOCS2 (P < 0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (P < 0.05) and in airway epithelial cells (P < 0.001).

Conclusion: AT reduces asthma phenotype which is followed by positive modulation of SOCS-JAK-STAT signaling in peribronchial leukocytes and in airway epithelial cells.

Rodolfo A 1 ; Paciência I 2 ; Rama T 1 ; Leão L 1 ; Silva D 3 ; Rufo J 2 ; Mendes F 4 ; Padrão P 5 ; Oliveira Fernandes E 6 ; Moreira P 7 ; Delgado L 8 ; Moreira A 9 Porto, Portugal; potentially irritating chemicals that may have a cutaneous drying side effect. This study aimed to evaluate if skin barrier function, as measured by transepidermal water loss (TEWL), is affected by a training session in swimmers compared with football players.

Environment Impact on the Human Respiratory Health (ClinicalTrials.gov Identifier: NCT03017976) and football players were invited to participate.

Due to the lack of prior information no sample size calculation was possible and all athletes that provided informed consent were included in the analysis (n = 58, 29 females, aged 12 to 21 years). TEWL was measured using the Tewameter ® TM 300 before, immediately after, and 30 minutes after a 2 hours training session. The probe was held on the dorsum of hand, the volar forearm and the antecubital flexure for 60 s. The average of two consecutive measurements was recorded. Non-parametric statistic was used were appropriate. Ethical approval was obtained from the University Clinical Research Ethics Committee and informed consent provided.

Results: Mann-Whitney U Test showed significantly higher baseline median TEWL level on football players hand's dorsum compared with swimmers, median (P25-P75) respectively 17.1 (14.7 to 21.7) and 13.7 (11.9 to 16.2); P = .001. Friedman test revealed a significant effect of swimming on TEWL on the hand's dorsum, volar forearm and antecubital flexure (P < .001) while football training affected only the hand's dorsum (P = .008). Differences in changes after swimming and football training were significant only for TEWL in volar forearm (P = .028).

In conclusion, our exploratory findings do not provide support for a specific deleterious effect of swimming, compared with football training, on the training induced changes in TEWL. Background: Exercise-induced bronchoconstriction (EIB) is defined as transient, reversible airway narrowing occurring during or after exercise, is common among elite athletes and associated with epithelial damage.

However, little is known about the existence of EIB in young athletes.

The goal of this study is to investigate the presence and to evaluate potential (bio)markers of EIB in young high-school elite athletes in different sport disciplines versus age-matched control subjects.

Method: High-school selected elite athletes (12-13 years) from different sport disciplines: basketball (n = 26), football (n = 44) and swimming (n = 47) performing at least 12 hours of sport per week (median=13 h) and 17 control subjects (performing less than 6 hours of sport per week) were recruited. The eucapnic voluntary hyperventilation (EVH) test was performed according to ATS guidelines and adapted for this age group.

Lung function was measured before, immediately after and 5, 10, 15 minutes after the EVH test. The test was considered positive if a maximal fall in FEV1 of 10% was measured on at least one time point and exhaustion was excluded. A blood sample was obtained at baseline.

Sputum induction and skin prick test for the most common allergens were performed after the EVH test.

Results: Fifteen swimmers had a positive EVH test (33.3%), which is higher than in basketball players (18.2%), football players (17.95%) and controls (17.65%). 40.4% of the swimmers were atopic which is also higher than in basketball players (23.1%), football players (31.8%) and controls (23.5%). Serum Clara cell secretory protein (CC16) levels are significantly higher in swimmers (7.6 ± 2.5 ng/mL) compared to indoor athletes (5.1 ± 2.2 ng/mL) and controls (5.2 ± 1.2 ng/mL). A significant positive correlation was found between the magnitude of maximal fall in Conclusion: Young elite swimmers have a higher prevalence of EIB compared to basketball and football players. Atopy and/or chlorine is a risk factor for the development of EIB in young elite athletes.

CC16 levels and sputum uric acid levels are increased in athletes compared to control subjects suggesting the presence of epithelial damage already at young age. This is especially observed in young elite swimmers, pointing to a probable role of exposure to chlorineby-products in combination with intensive exercise. Results: Data from 237 subjects (134 females, 56.5%) were analyzed. FRAST was positive in 97 (40.9%) patients (55 females, median age of 14 years (IQR 11-18)). In this group, 55 (56.7%) had a previous diagnosis of asthma, 27 (27.8%) practiced federated sports, 18 (18.6%) had smoke cigarette exposition and 3 (3.1%) had a BMI >30 kg/m 2 . 82.5% of patients showed a ΔFEV1% >10% in the first 5 minutes after finishing the challenge. Median FEV1 reduction was 13.4% ) and 390 mL .

FRAST was more frequently positive in patients with previous diagnosis of asthma (P < 0.01). There were no differences related to Conclusion: FRAST is an important tool to diagnose exerciseinduced bronchospasm without asthma (EIB wa ), as well as to diagnose asthma. In our study, FRAST was fundamental to access EIB wa in 28% of patients with RSEE, and confirmed asthma diagnosis in 53% of cases with previous asthma diagnosis and negative SBT. There was no difference in the prevalence of atopy between patients with positive and negative FRAST.

Patients older than 9 years-old presented higher ΔFEV1% compared to younger patients (P = 0.04).

Higher levels of FENO were observed in patients with positive FRAST (P = 0.032, P = 0.045), both in patients with and without previous diagnosis of asthma.

A positive correlation was observed between FENO levels and ΔFEV1% in the whole sample (r = 027, P = 0.009); when these data were analyzed considering a previous diagnosis of asthma, only patients with this condition showed a positive correlation of FENO and ΔFEV1% (r = 0.29, P = 0.031).

Conclusion: Our results evidenced that higher FENO was associated with atopy and a positive FRAST, both in patients with and without previous diagnosis of asthma. Higher FENO seems to correlate with ΔFEV1% in patients with previous diagnosis of asthma. Background: Specific immunotherapy is the casual treatment for allergic rhinitis.

A 28 year old professional footballer suffer from severe allergic rhinitis since two years. During May, June and July his level of playing, concentration and durability decreased about 20%. Patient was complaining of runny nose, nasal blockage, each eyes, sneezing, tearing.

Method: We did skin prick tests -which showed greatest allergy to grass pollen. We confirmed the allergy by specific IgE and nasal provocation tests. Spirometry was done-FEV1 116%. The patient was qualified to undergo specific immunotherapy. However, because of his profession, it was hard to find a day without trainings to get the vaccine. After long discussion, patient decided to start specific immunotherapy-SCIT.

Results: The patient start the immunotherapy. He was attuning very irregularly, because of matches, injuries, trips, trainings, and lack of time. Several times we had to call the patient to remind him about the immunotherapy. After one year of SCIT the patient felt big improvement. During grass pollen season he suffered from mild allergic symptoms, and just for few days. After next year of immunotherapy, the patient had no symptoms of allergic rhinitis during the grass pollen season. However, it was the reason for him, to stop SIT, before 3rd year of immunotherapy.

Conclusion: Such a treatment-specific immunotherapy-is a burdensome method for both, for professional athletes and doctors.

Such a patients need to be on special observation, and cooperation with trainers must be obtained, if we want to see results. To improve compliance we have to keep in touch with patients, to remind them about next visit.

Gherasim A 1 ; Choual I 1 ; Radu C 2 ; Khayath N 2 ; Beck N 1 ; Jacob A 1 ; Schoettel F 1 ; Domis N 1 ; De Blay F 2 1 ALYATEC, Strasbourg, France; 2 Hôpitaux Universitaires de Strasbourg, Strasbourg, France Background: Late allergic response (LAR) is a good asthma model. It has been shown, in individual challenge tests that mite allergen induces more frequently late allergic responses (LAR) than cat allergen.

The aim of this study is to compare the frequency of LAR in asthmatic subjects allergic to mite with asthmatic subjects allergic to cat.

Method: 24 asthmatic subjects allergic to mite were compared to 21 subjects allergic to cat (GINA 1 or 2). The subjects had prick tests≥5 mm compared to the negative controls and specific IgE ≥ 0.70 KU/L. The dose selected for the mite and cat allergen was the airborne allergen concentration inducing the most frequently early asthmatic response (EAR) (a 20% drop in FEV1) and LAR (a 15% drop in FEV1).

Results: The frequency of LAR with mite allergens was 66.6% and 20% with cat allergens (P = 0.007). The frequency of EAR for mites was 78.2%; of 91.3% for EAR or LAR, and 50% for EAR and LAR. In contrast, with cat allergens, 55% of patients had an EAR, 60% had EAR or LAR and 25% had an EAR and LAR. No significant differences was observed between cat and mite allergen regarding the severity and the time necessary to obtain an EAR and LAR. No significant differences was observed between cat and mite allergen regarding the severity and the time necessary to obtain an EAR and LAR.

The frequency of LAR in asthmatic subjects allergic to dust mite exposed in ALYATEC ® EEC was higher than in asthmatics sensitized to cats. Our results confirmed previous results with individual bronchial challenge. Therefore, it appears that the mite model is more interesting in the study of asthma.

Exposure Chamber in Strasbourg (ALYATEC ® ) in asthmatic patients allergic to cat allergens Gherasim A 1 ; Choual I 1 ; Radu C 2 ; Khayath N 2 ; Beck N 1 ; Jacob A 1 ; Schoettel F 1 ; Domis N 1 ; De Blay F 1 1 ALYATEC, Strasbourg, France; 2 Hôpitaux Universitaires de Strasbourg, Strasbourg, France Background: As recommended by the Task Force on Environmental Exposure Chamber (EEC), allergenic and non-allergenic exposure must be better controlled in EEC. It is the aim of ALYATEC's EEC.

The aim of the study is to validate ALYATEC's EEC by determining the concentration of Fel d1 inducing 50% of early asthmatic response (EAR) and/or late phase asthmatic response (LAR) in subjects sensitized to cat.

Method: It was a randomized, double blind, cross-over study including group A:20 asthmatic subjects allergic to cat and group B:10 asthmatic subjects allergic to another allergen. All subjects were first exposed to placebo. Group A was exposed to 2 Fel d1 concentrations. The number and size of particles were recorded online during the exposure. Group B was exposed to the concentration of Fel d1 which fulfills the objective of the study.

The mean age of subjects was 29 years (±8). For the 2 concentrations of Fel d1, we obtained more than 50% EAR and/or LAR. The mean time necessary to obtain an EAR was: 59.7 ± 8 minutes and 138.6 ± 90 minutes for the LAR. The mean fall in FEV1 during EAR and LAR was −29.22% and −17.64% respectively. We didn't observe any severe reaction. No subjects in group B experienced any symptoms during exposure.

We have validated ALYATEC's EEC in asthmatic subjects allergic to cat allergens. We also demonstrated its specificity. Background: The best test and strategy for diagnosing asthma especially in those patients with negative bronchodilator reversibility tests still remains unclear. In this study we aimed to investigate the diagnostic yield of peak expiratory flow (PEF) variability for the patients with symptoms suggesting asthma but negative bronchodilator reversibility tests.

Method: Subjects referred to our outpatient clinic with suspicion of asthma were enrolled in this study. Demographics and referral symptoms were recorded, asthma control test (ACT) scores and health related quality-of-life scores (AQLQ, SF36) were calculated.

Monitoring of PEF variability during 2-weeks and bronchial challenge test with methacholine (BPT) were analyzed. Asthma was diagnosed by having PEF variability ≥20% and/or positive BPT.

Results: Thirty out of 50 enrolled patients were diagnosed as having asthma. When we compare asthmatic patients with nonspecific respiratory symptomatic subjects there were statistically-significant differences regarding to wheezing (P = 0.020), activity limitation (P = 0.058), total symptom score (P = 0.028) and basal FEF (P = 0.050) in the favor of asthma cases. Multiple logistic regression analysis revealed that lower basal FEF 25-75 was an independent predictive factor of asthma diagnosis (P = 0.05). When the BPT positivity was assessed as gold standard for the diagnosis of asthma, the sensitivity and specificity of PEF variability for different cut-offvalues (≥20%, >15% and >%10) were 61.5-83.3%, 88.5-62.5% ve 100-16.7%, respectively.

Conclusion: FEF 25-75 is an important diagnostic parameter for asthma. Although current guidelines recommend PEF variability of 10% for the diagnosis of asthma in general, this cut off level may not be appropriate for this defined group of subjects. Our results suggest to use a cutoff level of >15% while excluding asthma and ≥20% while confirming the diagnosis of asthma for patients with asthma suspicion but without shown reversibility.

De Barayazarra S

Background: In recent years obesity has been considered as a factor that contributes to the development of asthma, increases exacerbations and leads to poor control of it due to resistance to drugs to control this pathology. It is known that obesity produces chronic systemic inflammation; one of the markers that are affected is the levels of C-reactive protein (CRP), which are increased.

Objective: Evaluate, lung function, the use of medications to control asthma and systemic inflammation, after bariatric surgery. Results: 15 obese asthmatic patients with surgery, 15 non-asthmatic obese patients with surgery, 16 obese asthmatic patients without surgery.

A significant difference was found between the severity of obesity and forced expiratory volume in patients with asthma and without asthma of 1 second (FEV1) before surgery with an average of 87.9% at the beginning of the study and 105.5% at 12 months (P:0.0004).

In the non-operated group, FEV 1 at the beginning was 69% and 83.04% at 12 months (P: 0.0018).

The CRP, before surgery in all operated patients had CRP: 9, at 12 months after surgery they became negative, CRP: 0 (P: 0.004).

In obese asthmatics with surgery at the beginning, 100% used medication, and at 12 months only 20% In obese asthmatic patients without surgery, 93.75% used the medication at the beginning, at 12 months 62.5% (P:0.0006). Method: 20 patients with asthma aged 18 to 80 and a predetermined positive methacholine Pc20 were recruited and underwent a single challenge to cause bronchoconstriction of~20% comparing the outcome of the device with spirometry. The subjects were monitored at baseline, after a~20% fall in FEV 1 and after bronchodilation back to baseline.

The study protocol allowed for an interim analysis of the initial 8 subjects at which point the sensor was calibrated to optimise sensitivity. A further 12 subjects were studied using the optimised sensor.

Results: All 20 subjects successfully completed the study. The device was found to be straightforward to use by both operator and subject with no concerns regarding safety. The initial sensitivity of the device was found to be suboptimal in the first eight patients to reliably detect changes in lung function.

After adjustment to the device the tests results of the remaining 12 subjects were analysed. 66.6% of subjects were female. The mean age of all subjects was 45.8 years. An average baseline FEV 1 value of 2.575 (S.D. 0.881) was observed.

Changes in lung function were detected in 100% of subjects. A baseline value, drop in lung function and reversal were measured in 66% of subjects. The mean percentage drop observed in 66% of subjects using the investigational device was 13.04 %. The mean percentage increase observed using the investigational from drop to reversal was 25.36 %.

The device (using EBC 1 ) was able to detect changes in lung function tracked using FEV 1 . This provided proof of concept that the device could potentially be used to monitor lung function more effectively in the home than peak flow and supports further development to optimise the device and demonstrate functionality in clinical asthma. Method: Ninety four patients under 18 years of age seen in the Allergy Department due to common asthma symptoms (wheezing, dyspnea, cough, chest tightness) with normal spirometry and negative bronchodilator response, underwent MCT during 2016 and 2017. The variables studied were: sex, age, body mass index (BMI), asthma symptoms, exercise symptoms, rhinoconjunctivitis, family history of atopy, sensitization to respiratory allergens, spirometric data and fractional exhaled nitric oxide (FeNO).

Results: Of the total sample, half were women (51.06%) and the other half were males (48.94%). Mean age was 11.8 years. BMI was normal in most of them (with an average of 19.55 Kg/m 2 ). The most common symptom among the patients with positive MCT was cough (79.8%), followed by dyspnea (62.76%), wheezing (34%) and chest tightness (11.7%). 43.6% had symptoms of asthma with exercise and 70.2% had rhinoconjunctivitis. 37.23% had a family history of atopy.

74.4% were sensitized to aeroallergens, mainly to pollens (grass and olive tree). 75.5% of the MCT′s were positives, with a mean PC 20 of 1.89 mg/mL. 62.7% had a moderate-severe result (PC 20 ≤4 mg/mL), 7.4% mild (PC 20 4-6 mg/mL) and 5.3% bordering (PC 20 6-8 mg/mL).

The mean FeNO was 19.62 ppb.

Conclusion: In our series, the completion of a test of HRB was decisive to confirm the diagnosis of asthma in most patients of a pediatric population with symptoms of suspicion (cough, mainly), normal spirometry and negative bronchodilator response (with normal FeNO in most of them). Therefore, we consider it important to include in the routine clinical practice HRB tests in the pediatric population with suggestive symptoms of asthma, despite normal functional and/or inflammation tests. 1000 | Cut-points of the ′Control of allergic rhinitis and asthma test′ (CARAT) asthma subscale based on an international survey patients with asthma) in Kashan, Iran. The data collection tool was a questionnaire with 38 questions, designed to gather information on demographic asthma patients, the current use of mobile functionalities, and the willingness to use these functionalities to receive selfmanagement services, which was distributed among patients with informed consent. The collected data were analyzed by descriptive statistics method using SPSS software.

Results: The most use of patients from mobile phone functionalities was to receive information about asthma symptoms and allergens and irritants via mobile internet (42.1%). Patients were most likely to use social networking (31.7%) in comparison with other mobile phone functionalities, to receive reminders about appointments and medication. The respondents were most likely to use social networks through mobile phone functionalities, to receive asthma self-management information (53.1%), to communicate with other patients (55.9%), to receive reminders about medication use, and to perform a peak flow meter test (52.4%) and to get an alert when the asthma is not controlled (53.1%).

The findings show that asthma patients are currently using the internet search for educational information and they have a tendency to use social networks to receive asthma-related services.

Patients believe that mobile health is an appropriate intervention for providing educational information, reminders, and alerts and communication with other patients.

1002 | Concordance between the determination of asthma control through the GINA 2015 guidelines and the ACT questionnaire-Results of the EFIMERA study Background: The exacerbation of asthma, progressive worsening of acute episodes, is one of the most frequent attending reasons at hospital emergency unit 1 . Several factors causing poor control of asthma, such as inadequate therapy, have been described. In the present study, estimations of asthma severity by researchers were assessed by comparing the concordance between the assessment of asthma control through the GINA 2015 guidelines and the ACT questionnaire Method: Cross-sectional observational study on the evaluation of factors related to treatment that influence the poor control of asthma was assessed through the GINA guidelines and the ACT questionnaire. Patients referred to a pneumologist or allergist by a primary care for the first time were evaluated. Two variables were collected for the assessment of asthma control: one derived from the GINA 2015 guidelines and another derived from the ACT questionnaire. Regarding the GINA assessment, researchers' evaluations guidelines were compared with the scoring calculated from the variables registered in the CRD. Both measures were compared in terms of sensitivity-specificity to determine their ability to classify patients.

The patients included in this study (n = 1682) had a mean age of 45 ± 17 years, with a 64% of women and an average disease evolution of 14.9 ± 14.1. The control of asthma according to "GINA Results: Pts were reasonably representative of those in SLS Asthma (at SLS baseline: 43.8% male; mean age 48.4 yrs; mean Asthma Control Test [ACT] score 16.5) . The most frequently reported symptoms during SLS Asthma for these pts were cough/ breathlessness, followed by wheeze, phlegm and chest tightness; breathlessness and wheeze were perceived as the biggest impactors on pts' lives. The aspects of daily life most impacted by asthma were reported as walking at a hurried pace, strenuous physical activity, and asthma-related frustration. Since SLS began, 50% of pts in this subset reported improvements in overall asthma (44% no change; 6% worsening). Perceived changes in symptoms are shown (Table) .

Most pts (66.0%) reported avoiding places with dust, smoke or fumes. Most pts (57.5%) perceived no change in overall QoL; 36.3% reported improvement.

Being an ACT responder during SLS (total ACT score ≥20 or ≥3 change at end of SLS) was associated with reported improvements in overall asthma symptoms, lower impact of asthma on QoL, and higher perceived confidence/control in managing asthma. More pts (65.8%) in the FF/VI arm reported an overall improvement in asthma vs UC (34.3%); the most evident differences between treatment groups were for breathlessness, wheezing and chest tightness.

Improvements in confidence/control in managing asthma were reported by 53.8%/49.3% of pts (FF/VI) vs 31.3%/25.3% (UC).

Conclusion: Breathlessness and wheezing were key symptoms in SLS Asthma and had the biggest impact on pts' daily lives. This patient-centred study enriches the findings of SLS Asthma.

Funding: GSK (study 204500) 1004 | Asthma and COPD treatment adherence and breach using TAI questionnaire Suarez-Vergara M; Fuentes-Soltero F; Garcia-Nunez I; Ignacio-Garcia J

Background: Adherence is defined as medication (inhalator) intake following the dosage and schedule prescribed. Adherence mistakes are a public healthy problem according to the big morbi-mortality presented in patients with an incorrect intake. Our aim is to evaluate the adherence level and fulfillment in patients with asthma or COPD using TAI (Inhalators Adherence Test) questionnaire.

Method: Patients with a diagnosis of persistent asthma or COPD were selected. We used to size adherence and breach type the TAI questionnaire. Adherence is defined as good when patient′s test reaches 50 points, medium (46-49 points) and bad (less than 45 points). Breach type is defined as erratic when points between questions 1 to 5 are less than 25, deliberate when questions 6 to 10 are less than 25, and unconscious when questions 11 and 12 are less than 4 points.

A correct fulfillment is defined when questionnaire reaches 50 points plus 4 points of conscious fulfillment.

Results: Fifty-five patients more than 14 years old (mean age 50.61 years and 50.9% males) were selected. A 67.27% of them were asthmatics, 30.9% COPD and 1.81% a mix phenotype. A 21.81% presented a correct fulfillment with conscious fulfillment, and the other 78.18% presented good, medium or bad adherence with a breach type.

According to adherence level, a medium adherence was defined in 16 patients (29.09%), with an erratic mistake in 8 patients (50%).

Bad adherence was seen in 21 patients (38.14%) , with the three breach types in 9 patients (40%). Good adherence with unconscious breach type was defined in 6 patients (10.9%).

Conclusion: TAI questionnaire confirms a good adherence and fulfillment in less than 30% patients.

An erratic mistake is the most frequent breach type defined in our patients.

Educational protocols should be applied to improve adherence and fulfillment.

1005 | What is adhesion to treatment of asthmatic patients like in Argentina according to the TAI questionnaire? Background: Asthma is a chronic inflammatory disease of the airways, which requires an adequate treatment and control.

The adhesion of a patient to an asthma treatment is a critical factor in order to achieve and maintain control. This adherence arises from a consensual agreement of the doctor-patient relationship; it is a complex multifactorial variable in which the variability in human behaviour in relation to its environment influences. Background: The association between ambient pollen and asthma has been studied intensively with inconsistent results, attributed to differences in study population, geographic factors (geoclimatic features), data sources, measurement of pollen (different types of traps), and different outcome occurrence (hospitalizations or emergency department visits). We investigated the associations between daily sales of short-acting β2-agonists (SABA) and outdoor pollen concentrations in the central France area.

The relationship between daily changes in pollen concentrations and daily SABA sales obtained from the social security database was analysed with generalized additive models, taking into account confounding factors such as air pollution, weather conditions, and day of the week.

Results: The daily SABA sales (mean, SD) rose from 46. 5 (23.6) Conclusion: This study indicates that outdoor pollens contribute to asthma morbidity in the general population. It confirms the highly allergenic role of Fraxinus, Betula and Quercus pollens, but also shows a relatively unknown association between treated asthma and Carpinus and Platanus pollens, despite their counts being less than 1% of overall pollen concentration. Results: Of 15 437 asthma patients (mean age 47.8 years, female 62.6%), regular OCS use was identified for 223 patients (1.4%), periodic OCS use for 3054 patients (19.7%), and no OCS use for 12 160 patients (78.7%) 1-year post-index. Regular OCS users had a greater mean age, were more often male, and had greater eosinophil counts, lower lung function, and greater prevalence of comorbidities than did the periodic and no OCS users (P < 0.001). Total yearly cost was greatest for the regular OCS users (€ 5509), followed by periodic OCS users (€ 2892) and no OCS users (€ 2042) (P < 0.001). Among regular OCS users, hospital admissions were the main cost driver (41.5% of total cost), while GP consultations were driving the total cost in periodic and no OCS users (48.0% and 52.9% of total cost, respectively).

Conclusion: In this sample of patients with asthma in Sweden, the total yearly cost of health care resource utilization for a regular OCS user is twice as high as for a patient with no OCS use, demonstrating substantial economic and clinical burden in asthma patients on regular oral steroid treatment. Method: Children with physician-diagnosed asthma who attended to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to recent GINA guidelines. Laboratory investigations including skin prick tests, complete blood counts with differential, total IgE levels, serum periostin levels and pulmonary function tests were performed.

Results: A total of 158 children (125 with asthma and 33 age and sex-matched control subjects) with a median age of 10.2 years (range 5.9-17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%) and severe in 21 (16.8%) children.

Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL; P < 0.001). The mean serum periostin levels of children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (P < 0.001). Serum periostin levels were found to be significantly correlated with asthma severity (Spearman's rho [r]=.41, P < 0.001). Analysis using ROC curves identified the role of periostin levels in determining children with severe asthma (AUC: 0.77, 95% CI: 0.67-0.87, P < 0.001].

Conclusion: Serum levels of periostin, a novel asthma biomarker, were higher in asthmatic children, and were associated with asthma severity.

Adam I 1 ; Selevestru R 1 ; Rogut V 2 ; Sciuca S 1 Background: Nowadays, data from several epidemiological studies confirm the important role of fungi in respiratory disease in the indoor as well as in the outdoor environment. In general, exposure to fungi occurs via inhalation, skin contact, or ingestion. Alternaria alternata is one of the most common fungi associated with presence asthma and persistence and severity of asthma. Although exposure to A. alternata is also may represent a risk factor for development of asthma. In Ukraine has been an increase in the number of the mold sensitized children for the last few years. At the same time we can see increasing frequency BA at the children of pre-school age.

Method: Thirty five children aged 3-7 years with allergic rhinitis and high level of asthma predictive index (API) sensitized to A. alternata were included in a 2-year cohort study of the efficacy and safety of SLIT (Diater Laboratories, Spain) using standardized sublingual extracts containing molds (Alternaria alternata). Treatment efficacy was analyzed using the score of symptoms such as difficulty in nasal breathing, rhinorrhea, sneezing, itching of the nasal mucosa (upper palate) and discharge from the nose and recurring wheezing. We also have analyzed the level API during the period investigation.

Symptoms were measured before starting treatment, and at 4, 12

and 24 months after starting immunotherapy.

Results: SLIT significantly reduced both symptoms and medication score: nasal symptoms (38% vs. control group) and the use of rescue medications (38% vs. control group), and improved FEV1 (in children aged≥5 years). In the SLIT group, API decreased by 15% for the first year, by 31% for the second year. No patient had a systemic reaction during therapy.

Our results have shown that SLIT is an effective treatment in pediatric patients suffering from allergic rhinitis and high API with significantly improved clinical outcomes (less symptoms and less medication intake) in comparison with children treated with symptomatic drugs only. In this study, large and statistically significant differences in symptom and medication scores were demonstrated in patients receiving SLIT compared to control group. Sublingual immunotherapy is effective for allergic rhinitis in children especially early age and is generally advantageous because of the convenient administration and safety profile and ensure prevention of developed BA.

Bednarek A Background: The classification of asthma based on the severity of its clinical course has been recommended by GINA since 2008. This division is useful for the patient's initial assessment when asthma is being diagnosed and essential decisions concerning an appropriate therapy are made. The objective of the work is to evaluate the influence of a clinical form of asthma on vaccine immunity in preschoolers following three years after the programme of mandatory vaccination has been realised.

The study encompassed 172 preschool children (mean age of 5.22 ± 0.34 years old) with asthma being newly diagnosed, including 140 patients with mild asthma and 32 ones with moderate asthma, whose vaccine immunity (IgG specific antibody titer) was assessed after the mandatory early childhood vaccines had been administered. Monovalent vaccines (HBV+IPV+Hib) along with a three-component combined vaccine (DTwP) were given to 86 children while a six-component vaccine (DTaP+IPV+Hib+HBV) was given to the remaining 86 children. The vaccine doses were consistent with the Polish Immunisation Programme and manufacturers' recommendations. The ELISA immunoenzymatic method was applied to assess titer of specific antibodies to diphtheria, tetanus, pertussis, poliomyelitis and H. influenza type B. The level of HBV antibodies was measured chemiluminescently. The immunity class for particular vaccinations was assessed according to the test manufacturers' instructions.

Results: Children suffering from mild asthma had considerably more frequently vaccinations on time (P < 0.001) and the type of vaccines (monovalent, highly-combined) administered to them did not have a significant influence on a clinical form of asthma in the children examined (P > 0.6951). Apart from the vaccines against hepatitis B and rubella where considerably more frequently a high antibody titer occurred in children with mild asthma, the titers of antibodies to other vaccines, namely diphtheria, tetanus, pertussis, Hib and mumps, were not associated with a clinical form of asthma.

The protective antibody titers in the children with asthma were found in 100% after vaccinating them against poliomyelitis (≥12U/ mL) and measles (≥300 mL U/mL). Significantly higher current weight was solely found in the children with mild asthma (M = 20.80, SD=3.77; P < 0.05). Conclusion: There are some clinical and cultural differences among the four southern Chinese cities within the Canton province. This study identifies potentially modifiable environmental and treatment factors associated with poor asthma control and QoL for healthcare interventions. Having a smoker in the family is independently associated with poor asthma control and QoL. were classified into two groups (levocetirizine group (L) and montelukast group (M)) and we treated each group for another 10 week.

To evaluate the therapeutic effectiveness, we used symptom score (SS) and EBC leukotriene E4 (LTE4). EBC samples were collected with RTube. Each parameter was checked at 0, 2, 12 week therapeutic period.

Results: Most AR patient showed clinically improvement with 2 and 12 week fluticasone therapy (0 wk SS=6.6, 2 wk SS=3.2, 12 wk SS=1.9 P < 0.01 in L group; 0 wk SS=6.8, 2 wk SS=3.6, 12 wk SS=2.0 P < 0.01 in M group). LTE4 levels of AR were higher than control (0 wk 77 vs. 12 pg/mL), and were reduced after 2 week fluti- MiC were: MD allergic rhinitis, wheezing apart from colds, eosinophilia ≥4%.

Outcome was defined as MD asthma and at least 1 episode of asthma during the previous year or more than 3 episodes of wheezing during the 12 months regardless of asthma diagnosis.

Results: From a total of 144 of parents approached, 86 (58%) agreed to participate in a phone interview. 18 (21%) children were diagnosed with asthma. The age at the time of admission (mean, ABSTRACTS | 533 (SD)) was 27.0 (9.9), at the time of phone survey 77.6 (10.9) months, respectively.

Positive loose API at 2-3 years of age had sensitivity of 77.8%, specificity 75%, positive predictive value (PPV) 45.2%, negative predictive value (NPV) 92.7%.

Positive stringent API at 2-3 years of age had sensitivity of 50%, specificity 91%, PPV 64.3%, NPV 85%. Background: Asthma is the most common chronic airway disease in childhood, with a high unmet need for new treatments due to insufficient symptom control in a relevant percentage of patients.

Ethics and resource factors limit the feasibility of large, long pediatric trials required to assess outcomes such as exacerbations and symptoms. For diseases like asthma, where the disease process is largely similar in children and adults, with the same expected therapy outcome, the International Council for Harmonisation advise extrapolating adult data to those of a younger age, reducing unnecessary pediatric trials. Here we assess the partial extrapolation used in the clinical development of tiotropium.

Phase 3 trials in adults (aged 18-75), adolescents (aged 12-17) and children (aged 6-11) with symptomatic severe (PrimoTinA-/Pensie-TinA-/VivaTinA-asthma) or moderate asthma (MezzoTinA-/RubaTinA-/ CanoTinA-asthma), respectively. Trials lasted 12-48 weeks, all with tiotropium Respimat 5 μg add-on vs placebo as two puffs once daily.

Results: In adult trials, lung function, symptoms and exacerbation endpoints were evaluated in a confirmatory manner: tiotropium significantly improves lung function and asthma control, and reduces risk of exacerbation, vs placebo ( Conclusion: Based on similarities in disease profile and magnitude of treatment responses between age groups, it is reasonable to expect tiotropium add-on to produce clinically meaningful improvements in exacerbation and symptom endpoints in children and adolescents, as in adults. The robust tiotropium clinical program supports using a partial extrapolation to avoid overly long and large trials in pediatrics.

1019 | Clinical state of treatment and examination during last 3 years before remission about asthmatic children in long-term remission cases Method: Remission cases (no symptom and no therapy) for 3 years of asthmatic children were studied. Clinical background and treatment (drugs) was studied during last 3 years before remission annually.

Acetylcholine inhalation test by standard method was performed, and respiratory threshold of acetylcholine (RT-Ach) was obtained.

FEV1%, and serum IgE also examined. These data were compared before remission with 3 years after remission.

Results: Mean age of 25 cases at 3 year before remission was 9.2 years old. Male to female ratio was 1.3.

Severity of asthma was all mild type, and number of attack was 2 to 8 times in a year. There was no admitted case during this study.

The long-term therapeutic drugs were leukotriene receptor antagonist (Anti LT) in 20 cases, and/or inhaled corticosteroids (ICS) in 12 cases, but 5 cases had no treatment for the control.

Geometric mean of RT-Ach (after then: 3 years before and after remission) was 2900 μg/mL and 5800 μg/mL. The mean FEV1% was 83% and 90%. Geometric mean of serum IgE level was 360 IU/L and 410 IU/L. Complicated cases of atopic dermatitis decreased after remission, but the incidence of allergic rhinitis increased slightly.

Conclusion: Characteristics of asthmatic children during last 3 years before remission were mild type, had several times of attack in a year, and the treatment was mainly Anti LT and/or ICS. FEV1% was within normal range, and serum IgE level was not changed after remission. RT-Ach had the tendency to improve during 3 years before and after remission. These data is supposed that airway hyperresponsiveness is one of the indicators for quitting treatment.

1020 | Clinical aspects of polyvalent mechanic bacterial lysate (PMBL) treatment in children with uncontrolled asthma 

Our results indicate that long-term treatment with Omalizumab in children can help to achieve better asthma control and reduce the amount doses of basic therapy. Method: Allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) diagnosed-patients' demographic information, accompanying-asthma, the allergic history of the family, the onset of symptoms, types of aeroallergens sensitivity were noted from patients' files in our hospital's pediatric allergy clinic.

Results: In this study, 675 patients were evaluated. The mean age of the patients were 11.65 ± 3.85 years and 61% (n = 412) were male. 452 (67%) patients had AR and 223 (33%) patients had ARC. Background: Allergic rhinitis (AR) is a disease characterized by symptoms of nasal discharge/congestion, sneezing, and pruritus, and is caused by an IgE-mediated immunological response to inhaled allergens. We aimed to evaluate pollen season and out of pollen season pulmonary function tests (SFT) of patients with AR in our study.

Method: In our study, the demographic characteristics and aeroallergens were recorded from patients' files with AR diagnosed. In addition, pollen season and out of pollen season SFTs were evaluated and compared. Conclusion: In patients with AR, FEV1 and FVC values are seen to be lower during the season even though there is no lower respiratory symptom. Therefore, SFTs of patients with AR should be evaluated during pollen season. Results: Among the clinical manifestations, the most common combination of allergic rhinitis (AR) and conjunctivitis (AC) is noted in 83.80% of adults and 55.11% of children, but in children aged 3-7, the combination of AR and AC is observed only in 48.40%, among 8-12 years old-51.25%, while in the remaining age groups it is encountered in more than 80%. Higher percentage of isolated AR is also observed among young children-17.55%, and those of the Results: Allergic rhinitis was a main symptom in 69.8% of children with pollen-food sensitization. In all of them concomitant allergic disorders were noticed: bronchial asthma (77.7%), atopic dermatitis (77.8%). Only in 26.7% temporal association between ingestion of pollen-related foods and nasal symptoms was observed (mainly apple and peanuts); occurring also outside the pollen period. The simultaneously sensitization to animal origin food allergens was stated in 63.3% of children with SAR, but only in two of them milk and white egg proteins were an additional exacerbation factor of nasal symptoms. In 18.5% anaphylactic reactions to food allergens were registered. 36.7% of children were asymptomatic despite pollen-food sensitization. The statistically significant differences were noticed in comparison to the control group.

Conclusion: 1. Allergic rhinitis in children, similar to adults, is a common manifestation of pollen-food syndrome and this type of sensitization should be taken into account regardless to age.

2. Children with pollen-related food allergy have the predisposition to multiorgan clinical manifestation.

3. The lack of association of symptoms with plant-origin foods in the majority of cases and the asymptomatic course of food sensitization in more than one third of patients indicate the need for follow-up.

1026 | Clinical benefit of the screening of suspected food allergen using multiple allergen simultaneous test in the patient with pollen-food allergy syndrome (PFAS) Background: The quantitative Fluoresce Enzyme Immunoassay ImmunoCAP (IC) system has been widely used for detection of allergen-specific IgE for the diagnosis of allergy. However, the system can only detect IgE against a single allergen, the multiple antigen simultaneous tests has been developed such as the Fluorescence Enzyme Immunoassay View Allergy 39 (VA) or Chemiluminescent Enzyme Assay MAST IV (MA) and both assay detect more than 39 allergen-specific IgE. In this study we examined the diagnostic capability of these two systems for screening test in the patient with PFAS.

Method: Total number of participants are 37 (Male/Female: 20/17), aged 12.0 ± 3.9 (range 3~20) years old. All the patients showed oral allergy syndrome (OAS) to Rosaceae family plants (apple, peach) and/ or kiwi and/or banana, also showed tree pollen allergy. Specific IgE assay were performed using IC, MA or VA. Results of greater than Class 1 were to be regarded as positive, and the concordance rates between the assays were assessed.

Results: The correlation of sensitivity between PR-10 (rBet v1, rMal d1, rPru p1, measured by IC) and specific IgE to apple (measured by VA), specific IgE to peach (measured by MA) in 27 OAS patients to Rosaceae family plants were assessed. rBet v1, rMal d1, rPru p1 were found to be 96.0%, 96.3%, 92.6% positive measured by IC while the specific IgE to apple (supposed to be including PR-10) were found to be 100% positive measured by VA. On the other hand, the specific IgE to peach (supposed to be including PR-10) were found to be only 33.3% positive measured by MA, this detection rate was lower than that of VA (P < 0.0001). Also, the correlation of sensitivity between PR-10 (rAct d8, measured by IC) and specific IgE to kiwi in 17 patients with OAS to Kiwi were assessed. rAct d8 were found to be 76.5% positive measured by IC while the specific IgE to kiwi (supposed to be including PR-10) were found to be 64.7% and 17.6% measured by VA and MA, respectively (P < 0.005). Additionally, all the 3 OAS patients to banana found to be positive for the specific IgE to banana measured by VA, but only 1 patient was detected as positive measured by MA.

Conclusion: In this study, we found that VA showed better agreement of sensitivity and specificity with IC compared to MA in the OAS patients to Rosaceae family plants, kiwi, or banana. Therefore, it may be clinically useful for screening of allergen specific Background: The hygiene hypothesis for autoimmune and allergic diseases, which exists nowadays, shows that human immune system is dependent on various environment factors. We consider the effects of humic substances (HS) to be important in understanding the hygiene hypothesis. Due to urbanization, the amount of human interaction with HS found in soil has significantly dropped. The goal of our work was to study allergenic potential and antimicrobial activ- Conclusion: HS appear to be exogenous immunocorrectors, and also to have an ability of suppressing propagation of allergic reactions and sensibilization, which leads to conclusion that they seem to play a major role in hygiene hypothesis. Moreover, HS selectively interact with bacterial cell wall, and this effect could be used in order to create antimicrobial drugs based on HS. Background: Peach tree pollen has been identified as having relevant allergens (the third most prevalent after olive tree and grass pollen) in areas of high cultivars (Murcia, East-Spain). When analyzing molecular components in sensitized patients, along with Pru p 3, we have identified other relevant inhalant allergens one of which was named Pru p X.

Because pollen of different species share allergens and with plantderived food, we have also studied Peach tree pollen sensitization in a non-exposed population (Madrid, Central-Spain).

The aim was to study the association between Peach Tree Pollen and several panallergens, as well as the relevance of Pru p X in our area (Madrid).

Method: A total of 328 patients who came to our Allergy Unit In those patients with positive SPT to at least one pollen we also performed Peach tree pollen SPT. If positive, we tested Pru p 3, Pho d 2, Pho d 3 and Pru p X.

To study the clinical relevance of these findings, we also performed Nasal Provocation test (NPT) with Peach tree pollen and Pru p X.

Results: A total of 57 patients were sensitized to Peach tree pollen.

From these, 33% had also positive SPT to Pru p 3 and none of them to Pru p X. Positive SPT to Polcalcin were found in the 33% of the cases and to Profilin in the 13%.

In 7 patients sensitized to Peach tree pollen NPT was performed being 4 cases positive to Peach tree pollen and none to Pru p X.

Conclusion: Peach tree pollen sensitization in non-exposed patients with allergy to other pollens is high although primary sensitization is unlikely. These patients present clinical response when exposed to that pollen that needs further evaluation. In our study, one third of the patients were also sensitized to Polcalcin and Pru p 3 and none to Pru p X. We have not found clinical response to this new inhalant allergen identified in highly exposed Peach tree pollen population. Results: The Bet v 1 ELISA 2.0-EP complete kit format (including pre-coated plates and all buffers and reagents) allowed for the consistent measurement of Bet v 1 in birch pollen extracts within the same lab (IntraLab CV=5.5%) and between different labs (InterLab CV=13.5%). The average recovery from matrix spiked samples (CRS in birch pollen extracts) ranged from 75-112%, with an average recovery of 91% (n = 10). Assay time was reduced from several days to two hours compared to the original method.

The performance of the Bet v 1 ELISA 2.0-EP kit was comparable to that of the Stallergenes Greer candidate standard method and has been successfully cross-validated. This will enable allergen manufacturers and regulatory authorities to adopt a standard method for Bet v 1 determination, which, ultimately, may be included in the European Pharmacopoeia. The development of a certified ELISA represents a major step forward in the standardization and quality control of allergen products.

1031 | An isoform of the Ole e 7 allergen assembled by proteomics could explain the cross-reactivity with pollen and food nsLTPs Results: A total of 457 peptides were obtained by de novo sequencing. Ten of them allowed the completion of the full-length amino acid sequence of the allergen. After purification, rOle e 7 was obtained with a yield of 1.5 mg/L of cell culture. Immunological assays confirmed that the recombinant isoform of Ole e 7 shared most of the allergenic and antigenic properties of the natural allergen. Moreover, we observed its implication in cross-reactivity with pollen extracts, and plant-derived food extracts.

Conclusion: These results suggest that the presence of this isoform in the olive pollen could explain the co-sensitization observed in some allergic patients between Ole e 7 and nsLTPs from foodderived extracts and might be used for a more effective clinical diagnosis of olive pollen sensitized patients. Background: Penicillium oxalicum, one of the prevalent airborne fungi in India, was selected to detect its spores as potential source of allergens and also to identify and characterise its major IgE-reactive component.

The airborne spores of Penicillium oxalicum was detected by Andersen 2-stage air sampler at different parts of West Bengal.

The allergenic potency of P.oxalicum was tested by SPT, ELISA and immunoblotting. Total protein was resolved in 1-D and 2-D gel electrophoresis and allergens were identified by 1-D and 2-D immunoblots. Identification of major IgE-reactive protein spots was made by mass spectrometry based MALDI-TOF-TOF. Major allergen was partially purified by ion exchange chromatography.

Results: Aerobiological investigation clearly indicated the predominance of P. oxalicum spores (56 CFU m −3 ) in the air of West Bengal, India. Sensitivity of patients to spore antigens was highly correlated with rhinitis. In SDS-PAGE, 80 bands were detected with molecular weight range of 16-180 kDa. The allergenic potency of spores was confirmed by skin-prick test, ELISA and dot-blotting. Eleven IgE-reactive proteins were detected as allergens by 1-D and 2-D immunoblots, of which 43% patients were sensitized to 22 kDa allergen. This 22 kDa protein was found to be the major allergen which was further characterized by mass spectrometry based MALDI-TOF-TOF. This major allergen (pI 6.08) was partially purified by ion exchange chromatography.

The eleven allergens were identified from spore of Penicillium oxalicum fungi for the first time from India. Immuno-proteomic identification of major IgE-reactive protein (22 kDa Background: Airway epithelium (AE) is one of the largest cellular surfaces exposed to the environment. AE constitutes a physical barrier due to the presence of intercellular apical junctional complexes between neighboring cells. In the past years evidence indicates an association between epithelial airway dysfunctionality and allergic asthma. It is still unclear if an impaired epithelial barrier could be the cause of allergy development as opposed to the consequence. One of the most common comorbidities of asthma is house dust mite (HDM) allergy. It has been shown that HDM allergen Der p 1 can disrupt the epithelial airway due to its protease action against cellular apical junction complexes damaging the epithelial monolayer. In the last decade, metabolomics has been successfully employed as a new approach to describe metabolic changes in biological systems.

Metabolomics focuses on describing and identifying small molecules to explain complex biological processes. We theorized that metabolomics could be used as a new tool to detect damage of epithelial barrier in vitro after Der p 1 exposure.

Method: Human cell line Calu-3 cultured at air-liquid interphase (ALI) was used as an in vitro model of bronchial epithelium. ALI culture system allows establishing 2 different compartments, mimicking the conditions found in the human airways: a basolateral compartment in which basolateral surface of the cells is in contact with the culture medium, and an apical compartment where the apical cellsurface is exposed to air. After 7 days in ALI, the cells were exposed to either Der p 1 or PBS as a control in the apical side for 24 hours.

Then, apical and basolateral media were collected and processed for metabolomics analyses.

Results: Metabolic profiles from samples were obtained, these were composed by 248 and 397 features for apical and basolateral media, respectively. Of these, using Mann-Whitney unpaired test as statistical analysis, 108 and 15 features were found changed within the apical and basolateral compartments, respectively. Specifically, in the apical compartment there were 104 signals significantly increased and 4 decreased after Der p 1 exposure; whereas for the basolateral compartment, 11 signals were found to be significantly decreased and 4 increased after exposure. Background: Mites are one of the major causes of allergies. It is known that allergen concentration varies depending on the species of mites and the degree of allergy induction is different, but the difference in microbiota according to mite species is not known. In addition to allergen, endotoxin or bacterial DNA, adjuvants of allergen derived from the microbiota in the mites, are also present in the feces. Bacterial endotoxin is found in gram-negative bacteria, acting on TLR4 and acting as an adjuvant to allergies.

Method: Three species of mites (D. farinae, D. pteronyssinus, and T. putrescentiae), known to cause allergies, are cultured in same condition(autoclaved media, 80%RH, 25°C)and analyzed for microbiota of each species. Using the next generation sequencing that complements the existing Sanger sequencing, we analyze the difference of microbiome according to the dust mite species and measure the level of endotoxin. Method: Six hundred and thirty five patients (51.8% males and 48.2% females, mean age 30.2 years old, range 3 to 82 years old) were included.

All of them referred respiratory symptoms (Rhinitis, conjunctivitis or bronchial asthma) and had skin prick tests positive with any pollen.

Patients were skin prick tested with a battery of common pollens in our area, including three species of Chenopodiaceae: Chenopodium album, Salsola kali and Salsola oppositifolia.

Results: Three hundred and forty tree (54%) patients were sensitised to pollen of any Chenopidaceae species: 255 (40.2%) to Chenopodium album, 245 (38.6%) to Salsola kali and 220 (34.6%) to Salsola oppositifolia.

The prevalence of skin sensitisation to pollen of Salsola oppositifolia was 34.6% in the population studied and 64.1% in patients sensi- Results: In patients aged 1-60 years of age in 80.5% of the cases IgE reactivity was at least to one allergen tested. The majority of patients (more than 2/3) had a complex sensitization profile and reacted on average to more than 5 allergens. The highest frequency of sensitization in Ukraine among patients who turned to the clinic among adults was found Phl p1 (34.1%), Amb a1(33.3%), Fel d1 (33.3%), Bet v1 (30.2%) and children (29.2%, 34.6%, 38.5%, 36.9%), respectively. When analyzing the results of tests for the source of the allergen, most often among house dust mites (HDM) allergens in adults and children is sensitization to Fel d1 (35.9%), as well as to HDM: in adults (Der f2-15.1% Der p2 −15.1%, Der f1-12.7%, Der p1-11.9%) and in children (12.3%, 13.1%, 9.2%, 10 .8%), respectively.

Among fungal allergens the most common is sensitization to Alt a1 and varies from 2.4% in adults to 26.9% in children. Among pollen allergens in adults is sensitization to Phl p1 (34.1%), Amb a1 (33.3%), Bet v1 (30.2%), Cynd1 (23.8%), Art v1 (22.2%), Bet v2 (11.1%) and in children (29.2%, 34.6%, 36.9%, 19.2%, 16.9%, 21.5%), respectively. Tests for food allergens in adults and children are more common on PR-10 proteins. In children, sensitization to milk and egg proteins is more common than in adults.

Conclusion: Most patients who came to the clinic have a complex IgE reactivity profile in which pollen sensitization predominates.

Among HDM allergens, more than 1/3 of the examined have sensitization to the cat's proteins. Sensitization to mold Alternaria alternata in children occurs 10 times more often than in adults. Results: Total 130 children were examined, aged 1-16 years (median 5 years). 72% children were sensible to two and more components 57.7%to 5 and more components. The frequency of sensitization to inhalation components was 65.4%, to food ABSTRACTS | 545 components-33.1%. Among the most frequent inhalation components were Feld 1-39%, Betv1-37%, Amba1-35%, Phlp1-29%, Alta1-27%, the sensitization to house dust mites (HDM) was most often observed to Der p2-13%. However, the analysis of these protein by the level of ISU showed that the highest levels were for Der f1median 19 (IQR 9.4-47.0), whereas for Fel d1-6.9 (IQR 2.6-15.0).

Among food allergens, sensitization was most commonly observed to PR-10 proteins -42%. Children sensitized to PR-10 proteins were in most cases sensitized to -Mal d1(28%), Cor a1.0401(27%), Pru p1 (22%).This co-sensitization was accompanied by a high correlation of ISU levels among these components. Sensitization to celery and kiwi was less common, the level of these proteins was also low. The frequency of sensitization to storage proteins was 38%, among which the highest level of ISU was in Ara h6 median 13 . Sensitization to LTP proteins was detected in 22% of children, among which the most commonly detected Pru p3 protein was 9.2%. The sensitization to profilins, which was evaluated at the level of Bet v2, was found in 21% of children, but the levels of these proteins were not high. Among the food products of animal origin, the most frequent was sensitization to egg component Gal d2 −13.1%, however, ISU levels were the highest to milk component Bos d4 −9.8 (IQR 1.2-21.0).

The most frequent causative inhalation allergens were epidermal allergens and weed pollen, however, the highest level of ISU was to HDM and mould. Among food allergens, the most commonly observed sensitization was to PR-10 proteins. Hypereosinophilia of peripheral blood was observed in 87 children under study, which was 50% (4.7%). As a result of testing patients with a wide panel of allergens, 98% of the patients had diagnostic levels of antibodies to allergens sIgEd1, 91.2%to allergens sIgEd2.

In 50% of cases, a significant level of antibodies to plantain allergens sIgE w8 was detected, 30.8% to dandelion allergens sIgE w9, 35.7% to evergreen trees sIgE t23, to maple sIgE t11 to 33.3%, to allergens of olive tree sIgE t9 -40%, to the banana allergens sIgE f92 -63.6%, to the egg protein sIgE f1 in 24.5%, in 34% to the milk allergens sIgE f2, to the food mixture sIgE f x5 -37.7%, to allergens of mold fungi mx2 −17.8%. Among the leading household allergens were registered in the 1st group and in the 2nd group of the investigated children -D pteronyssinus (80.3%, 97.8%), and D. farinae Results: The prevalence results are expressed in the Table 1 .

We have not observed any significant association in allergic rhinitis patients group with any LTP or PR-10 molecules. For atopic dermatitis only rAra h 9 (OR with 95% CI -10.2 (1.9-54.6) and nJug r 3 (OR with 95% CI -6.7 (1.6-29.5)) were associated significantly. For asthma, the most important molecules were rBet v 1, rAln g 1, rCor a 1.0101, rCor a 1.0401, rMal d 1, rPru p 1 and rApi g 1 (P-values for OR less than 0.05).

Conclusion: Future studies focusing on the evaluation the association of cross-reactive molecules with allergy phenotype should be done. Background: The fuzzy/green kiwifruit (Actinidia deliciosa), widely grown commercially, contains various pulp allergenic molecules, including the major allergen cysteine protease actinidin.

Methods. This case report is about a 40-year-old male patient with house dust mite allergic persistent rhinitis and intermittent asthma, presenting a convincing history of anaphylaxis immediately after eating a kiwifruit on empty stomach, followed, a few months later, by a severe oral allergy syndrome after licking a slice of raw kiwi. Previously, the patient ate kiwi without any problems and had no manifestations of pollen or latex allergy. Skin prick testing was done with commercial allergen extracts, while prick-prick testing was performed with raw kiwifruit, avocado and banana. Molecular approach consisted in assessment of serum specific IgE to native extracts and molecular allergen components using patient-friendly allergen nanobead array multiplex test and singleplex capsule-enclosed activated cellulose solid phase fluorescence enzyme immunoassay.

Results. Regarding kiwifruit allergy, the patient presented positive prick-prick tests with raw edible kiwifruit components: outer pericarp and inner pericarp (each 15 mm wheal) and columella/core (19 mm wheal) and negative with kiwifruit whole seeds, avocado and banana, and pollen extracts. Serum specific IgE to kiwifruit were detected (0.5 kU/L), but specific IgE values were negative (≤0.01 FIU/mL) for actinidin Act d 1, thaumatin Act d 2, kiwellin Act d 5, nsLTP type 1 Act d 10, Bet v 1-like major latex/ripening-related protein Act c 11, Act c chitinase_IV, Act d 9 cross-reactive profilins Bet v 2 (birch pollen profilin) and Hev b 8 (latex profilin), and also negative (<0.1 kU/ L) for PR-10 rAct d 8. Moreover, specific IgE to avocado were nor found (≤0,01 FIU/mL). Although IgE against seed proteins cupin/11S globulin Act d 12 and 2S albumin Act d 13 were not determined, this was not considered of great importance since allergic symptoms were also induced by licking kiwi pulp, in which abundantly expressed actinidin enzymatically degrades seed storage proteins, and prick-prick test was negative to kiwifruit seeds.

Conclusion: In a patient with anaphylaxis to kiwifruit, positive skin tests to its pulp and detectable serum specific IgE to Actinidia deliciosa, a detailed molecular allergy diagnosis is necessary, including assessment for Act d 3 glycoallergen or other molecules, not performed in this patient.

1049 | Is PR-10 sensitization a Portuguese phenomenon as well? Background: Bet v 1, a major allergen found in birch pollen, belongs to the PR-10 protein group. In our practice, some Bet v 1 sensitized patients have been identified, residing in areas without this tree genus in its flora.

Our aim was to characterize a Portuguese patient population with PR10 sensitization.

Method: A group of patients in whom ImmunoCap ISAC ® (ISAC) study was performed, between January 2009 and June 2017, were analyzed. All subjects with one or more PR-10 sensitizations were selected, and their clinical records reviewed. A sequential sample of the last subjects (n = 80) who underwent ISAC study, was then used for comparison.

Results: Out of 234 ISAC studies performed, only 16 were positive for PR-10 protein group. Median age was 18.3 years, 68% (n = 11) were male. PR-10 sensitized individuals were more likely to live in Portalegre district compared to the control group (7/16 vs 1/80; P < 0.001). 15 patients were positive for PR-10 family pollens (93.7%), frequently Bet v 1 (n = 13), followed by Aln g 1 (n = 10) and Cor a 1 (n = 8). 14 out of the 16 patients were sensitized to PR-10 foods, mostly Cor a 1.0401 (n = 13) and Mal d 1 (n = 12). Skin prick tests revealed birch as the main sensitizing pollen as well (14/ 16). Moreover, only four patients were skin prick tested for Fagaceae trees which were positive for oak (4), chestnut tree (3) and cork tree (1) . All patients were co-sensitized to other pollens, namely grass and all had respiratory allergy. Nine patients were food allergic, although seven of them were co-sensitized to other cross reactive (LTP/profilin) or species specific proteins.

Conclusion: Although PR-10 sensitization is known to be rare in our population, mostly Alto Alentejo inhabitants showed sensitization to this protein family in our sample, either by in vitro and/or in vivo methods. This phenomenon is consistent with the native plant species of this region, which should be taken into account when studying the allergic profile of these patients. In our sample, all PR-10 sensitized patients had respiratory allergy while this protein didn't seem to be relevant when it comes to food allergy. Further studies are needed to characterize which plant species belonging to this protein family are more significant for our country's aerobiology context and to determine its clinical relevance. included. Allergic asthma, rhinitis, conjunctivitis and eczema allergic symptoms were diagnosed. All patients were tested by ImmunoCAP with mugwort pollen extract and the natural components nArt v 1, nArt ar 2, nArt v 3, and nArt an 7.

Results: The positive frequency and sIgE levels of the four components in the Artemisia allergic patients from Southwestern China were significantly lower than that from the north. Art v 1 and Art an 7 were the highest recognized allergens, followed by Art v 3 and Art ar 2. Patients from Northern China were more likely to have ABSTRACTS | 549 asthma (50%) than patients from Southwestern China (3%), and being sensitized to more than two allergens increased the risk of asthma. Sensitization to Art v 1, Art v 3 and Art an 7 played a significant role in the development of asthma.

Artemisia pollen allergic patients is helpful to assess the potential risk of asthma. Conclusion: A small but significant part of the population react to ragweed pollen extract and are not identified as disease-positive by standard sIgE tests. There is a need for targeted tests towards a larger spectrum of allergen molecules.

In ragweed allergic individuals, this allergy can be the main cause of overall sIgE levels and also of in vivo reactions (tested by SPT).

1052 | Molecular profile of pollen sensitization of Tashkent residents with respiratory allergy Background: In paediatric cohorts, a correlation between specific IgE (sIgE) levels to house dust mite extract or allergen components and the occurrence of asthma has been shown. Higher levels of sIgE to mite extract were associated with a higher risk of wheezing.

Moreover, asthmatic children recognized more allergens and had higher sIgE levels to nDer p 1 as well as rDer p 2, 5 and 23. We sought to investigate potential differences in sIgE levels or sensitization patterns between asthmatic and non-asthmatic patients in a mixed paediatric and adult house dust mite allergic cohort.

Method: Total IgE and specific IgE against house dust mite extracts (Dermatophagoides pteronyssinus and farinae) and allergen components (rDer p 1, 2, 10, and 23) were determined in 190 house dust mite allergic patients. 35 patients had diagnosed asthma ("asthmatic", 54% females, mean age 27 ± 15 years, 31% younger than 18 years), whereas 155 had rhinitis (and conjunctivitis) without respiratory symptoms ("non-asthmatic", 54% females, mean age 28 ± 15 years, 29% younger than 18 years).

Results: Total IgE levels were markedly higher in asthmatic compared to non-asthmatic patients (315 vs. 144 kU/L, P = 0.022). Positivity to rDer p 1 (71 vs. 52%, P = 0.039) as well as rDer p 10 (9 vs.

1%, P = 0.044) differed between both groups. Specific IgE levels to house dust mite extracts and allergen components (rDer p 1, 2, 10, and 23) and positivity to rDer p 2 and 23 did not differ between both groups.

Conclusion: In contrast to previously published data, sIgE levels to house dust mite extracts or allergen components were not statistically different between asthmatic and non-asthmatic patients in our mixed paediatric and adult house dust mite allergic cohort. Only higher total IgE levels and a higher reactivity to rDer p 1 and 10 were found in asthmatic patients. However, larger studies are needed to confirm clinical relevance of these findings. Results: Prior treatments reported at Baseline (BSL) included:

17.3% of pts were receiving 1 or more second-generation H 1 -AH at approved dose (recommended first-line), 23.9% were receiving them at increased dose (second-line); 8.5% were receiving omalizumab (third-line); 29.9% had no treatment. The majority of pts (78.2%) had uncontrolled CSU (UCT<12) at BSL (Table) . Treatment changes were most evident at the BSL visit, with an increase in pts receiving omalizumab (21.4%) and a decrease in those receiving no treatment (12.8%) vs. prior therapy. These changes were associated with improvements in rates of hives and/or angioedema, UCT and QoL scores at Month 3, but only modest improvements thereafter (Table) .

A sub-analysis of 528 pts with UCT<12 and who were receiving the approved (36.9%) or increased dose H 1 -AH (63.1%), revealed that few pts had recommended escalation from the approved to increased dose H 1 -AH (0.0-6.7%) or from increased dose H 1 -AH to omalizumab (0.0-11.1%) (Table) .

Conclusion: Poor physician adherence to guidelines was evident throughout AWARE. Initial improvements in disease activity and QoL plateaued after Month 3, possibly owing to fewer changes to recommended therapies. Greater physician adherence to guidelines is needed for better symptom control in pts with uncontrolled CSU. Results: We revealed that in Russians urticaria is associated with rs20541*Arg/Gln genotype of the IL13 gene (P = 0.02) and rs5743794*CC genotype of TLR6 (P = 0.0011) gene polymorphism.

In Tatars the association with disease development was shown for rs5743571*TT genotype of TLR1 gene SNP (P = 0.0054). The rs5743794*C allele of TLR6 gene polymorphism is associated with acute and chronic forms of urticaria (P = 0.0209 and P = 0.0063, respectively) and rs2243250*C allele of IL4 gene polymorphismwith acute urticaria (P = 0.0247). Method: 100 CSU patients from the URTICA cohort (ClinicalTtrials.gov number: NCT01940393) participated in the study. A questionnaire was carried out evaluating the triggers identified by the patients, the comorbidities and the treatments received. Patients with a self-report of skin exacerbation by foods, nonsteroidal antiinflammatory drug (NSAID) or physical triggers were subjected to a controlled provocation test with the suspect food, medication or physical stimuli report by the patient. the levels of anti-TPO IgE were measured during a period of clinical control and during two exacerbations in all patients.

Results: 30% of the patients had at less one inducible urticaria demonstrated by provocation tests (24% dermographism, 10% cold, 8% pressure). Self-reported exacerbation for a food (60%) or medication (30%) were high, but positive provocation tests were low (1% and 14% respectively). 30 patients had (+) anti-TPO IgE during the baseline period. Among them, 60% presented a significant elevation of anti-TPO IgE during at less one of the two exacerbations. 18.5% of patients (n = 13) with (−) anti-TPO IgE, presented elevation of anti-TPO IgE one of the two exacerbations.

Conclusion: Foods, drugs and physical triggers must be verified by challenge tests to avoid unnecessary lifestyle restrictions in patients with CSU, nevertheless self-report is usually greater than positive provocation tests. Increase concentrations of Anti-TPO IgE seems to be implicated in urticaria exacerbations in some patients with CSU.

Brzoza Z 1 ; Adamczyk K 2 ; Wcislo-Dziadecka D 3 ; Zbiciak-Nylec M 2 ; Brzezinska-Wcislo L 2 adipokines. The aim of the study was to evaluate the possible contribution of leptin to chronic spontaneous urticaria pathophysiology.

The study included 48 chronic spontaneous urticaria patients and 41 healthy subjects. The leptin level in both examined groups was measured.

Results: No statistically significant difference in leptin level was determined between the studied subgroups.

We are among the first to present the effects of exploration aimed at assessment of the possible role of adipokines in chronic spontaneous urticaria pathogenesis. In this study we did not prove any difference in leptin level. In our opinion it is valuable to perform further studies in this area. The microorganisms were inactivated with phenol, and the concentration was adjusted to 1 000 000 microbial cells/mL (labeled as a 1/ 1). Dilutions 1/2 and 1/4 were made from the product labeled 1/1.

The Dot blot technique was used to detect the presence of specific IgE to the different microbial antigens and controls (anti IgE 1/1 and 2 fold dilution ½ and ¼). The Dot blot images were processed with a documentation system (Gel Doc ez, Bio-rad), and the different microbial antigens in different dilutions were compared with the positive anti-IgE controls.

Results: All patients have specific anti IgE to microbial antigens (see table below).

The presence of microorganism-specific IgE could explain, the relationship between the infections and / or microorganisms in CIU, as well, the urticaria control by Omalizumab, even when it has not been detected IgE sensitizations to common allergens.

Finally, these findings, showed that the bacterial allergy could be one line of research to understand the unresolved etiology of urticaria. Background: Dermographism is the most common form of inducible urticaria. It shows itself as hives made by scratching or rubbing on the surface where it has been produced and with the same morphology. The pathogenesis has not been clarified nor has it been associated until now with the sensitization to allergens.

We have studied the relationship between the presence of dermographism and domestic mites sensitization.

We have selected 95 patients older than 14 years old. All of them had symptoms compatible with dermographism at the moment of medical evaluation. At least one third of patients additionally showed rhinitis and/or asthma symptoms.

We performed:: -Skin prick tests with our basic neumoalergens (mites D. Pteronyssinus y Lepidoglyphus Destructor, pollen, molds, dog, cat and horse dander, latex and anisakis simplex).

-Determination of specific IgE levels for Dermatophagoides pteronyssinus, Lepidoglyphus destructor, and anisakis were measured in serum by using the ImmunoCAP (Thermo Fisher Scientific).

-Blood count, serum immunoglobulins, antithyroid antibodies, serine tryptase and proteinogram.

Results: Blood count, serum immunoglobulins, antithyroid antibodies, serine tryptase and proteinogram were normal.

We divided patient in different groups. Background: Urticaria results from the appearance of pruritic papules and/or erythematous plaques caused by substances from mastocytes present in the skin, notably histamine. Chronic urticaria is defined as flare-ups that occur at least two or three days per week over a six-week period. In addition, affected subjects are often prone to an atopic or auto-immune profile that promotes urticaria [1] .

The association of polyphenols (ambora, green tea) and the soothing active ingredients slow down the itching biological process from the outset by reducing the release of pruritic mediators (e.g. histamine, cytokines, etc.) of immune cells such as mastocytes and lymphocytes, involved in urticaria.

In this context, the purpose of the study was to evaluate the efficacy and the tolerance of an anti-pruritic spray containing the polyphenols and the soothing ingredient. The tested product aims to quickly calm the itching in subjects with chronic urticaria. Results: On average, the product was applied 2.3 times per day with a significant decrease of 5D-pruritus scale (-35%) and sensations of itching (-58%) between D0 and D21. In terms of quality of life, a significant decrease of the Skindex score was observed (-48%).

The product soothed the pruritus within 60 seconds for all subjects and the anti-pruritic effect lasts at least 2 hours for 80% of subjects.

The product also showed very good cosmetic properties and was well tolerated; no intolerance case was reported. showed near complete remission. In the week before omalizumab and for a few days after, her urticaria flared but on 3 of 4 weeks she was largely asymptomatic (UAS7 0-5). After 3 years of successful treatment she reported an increase in csu activity. No trigger factors could be identified. Add-on treatment with cyclosporine was refused, montelukast showed no, and prednisolone only transient benefit. Over a period of 2 months wheals occurred almost daily and a maximal score of 42 was achieved on UAS7. We replaced omalizumab with cyclosporine but this was subsequently discontinued due to side effects.

3 months later the patients' csu remained poorly controlled with up to 100 wheals occurring almost daily despite rupatadine 40 mg/d. Due to the good initial response to omalizumab and lack of good treatment alternatives, a trial of re-treatment was considered.

Results: Within 1 week of re-commencing omalizumab she once again achieved near complete remission of csu with UAS7 ≤ 3 on 3 of 4 weeks.

The mechanism of action of omalizumab and the development of resistance to it in csu, are incompletely understood.

Our case shows that some csu patients developing resistance to omalizumab may benefit from a subsequent trial of re-treatment, particularly if treatment alternatives are poorly tolerated. manipulate and store data by electronic means. This includes e-mail, SMS text messaging, video chat and online social media as well as all the different computing devices that perform a wide range of communication and information functions. A rapid increase in the use ICTs in recent decades is an enormous contributing factor in the development of a number of novel clinical and public health intervention strategies.

The aim of the present study is to assess the level of ICT use and to examine patterns of preferences among patients with chronic urticaria (CU).

Method: We will conduct an anonymous multicentre cross-sectional study, starting from January 2018, to investigate the use of ICTs in patients with CU, using a questionnaire as a survey method. This questionnaire will assess the frequency of use of social media and ICTs in patients, and their preferences for receiving and asking disease-related information. The survey will consist of 20 items, evaluating demographical information, time with disease, medication currently used, and additional aspects of social network use.

Results: We will use a chi-squared test to assess the association between Internet access or owning a cell or smartphone, and age, gender, type of urticaria, educational level and number of years since diagnosis. We will employ the same test to assess the association between the independent variables previously introduced and the frequency of use of each ICT type (short messaging service [SMS], Facebook, Twitter, YouTube, Email, Internet, LinkedIn and Skype) as well as agreement in receiving and seeking information (i.e. asking questions to the practitioner) through such ICTs. We will perform adjusted regression analyses between categories of age, gender, educational level, type of urticaria, years since diagnosis and the use and level of interest shown in communicating through ICTs. Our aim is to report on remarkable findings from a registry of a large sample of patients, potentially providing clues for its approach and Results: 285 patients with a median length of 14 months suffering from urticaria were registered, being 71% women; mean age 35.9 years. In 72% of patients no causal agent was identified.

Parasites were found in 9.3% and Thyroid Peroxidase Antibodies in 8.9%, while Autologous Serum Skin Test was positive in 47% and IgG to Mycoplasma in 42% of evaluations.

Two thirds of patients reported wheals on UAS7, with just 1/4 having concomitant angioedema. Almost 2/3 reported significant affection on quality of life because of itch by CU-Q2oL.

Just 14% of patients achieved total control on first anti-histamines provided, and less than half had good control of urticaria. Cetirizine was the first choice in 44%, followed by fexofenadine (15%) and first generation anti-histamines (16%). Method: Cases at 18-65 years of age which were being followedup in our clinic with diagnosis of chronic urticaria and were not receiving any antihistaminic medication for last one month were included in the study. CU-Q2ol, UAS-7, PSQI and PSG results of the patients were evaluated. Correlation of data with each other in regard to sleep disturbances was evaluated.

Results: 21 patients were included in the study. Patients' mean total score in CU-Q2ol was 36.25 ± 13.23. Patients' mean UAS-7 value was 16.71 ± 9.41. Mean total PSQI was 9.75 ± 3.92, the ratio of total scores ≥5 and those with poor quality of sleep was 87.5%.

Mean Epworth sleepiness scale (ESS) score was 9.71 ± 2.05, with total score ≥10 in 52.4%. In PSG, mean apnea-hypopnea index (AHI) was 11.93 ± 12.6, with 44.4% of the patients having AHI ≥5. When patients having AHI<5 were compared with patients having AHI ≥5, no significant difference was determined in regard to total CU-Q2ol score, mean score for questions concerning status of sleep, UAS-7 and PSQI. When correlation analysis was performed between CU-Q2ol and total score for questions concerning status of sleep, a positive correlation was determined with PSQI (P = 0.037).

Conclusion: It was demonstrated in our study that patients with chronic urticaria had poor quality of sleep and this disturbance was independent from AHI. Omalizumab was discontinued due to absence of improvement in CSU symptoms after three consecutive doses. The plasmapheresis without intravenous immunoglobulin replacement was initiated.

Results: The symptoms were relieved during the first procedure and the disease improved shortly thereafter. The following weeks the symptoms still occurred but with lower intensity and severity.

(angioedema was gone). The second attempt with omalizumab was successful after this course (5 procedures of plasmapheresis). Case report: Rosacea is a chronic skin disorder associated with flushing, erythema, dryness, burning and stinging, and inflammatory papules and pustules. New treatments available or in development target the inflammatory and erythematous components of the disease. These agents include the selective alpha-2 receptor agonist brimonidine. Allergic contact dermatitis to brimonidine is an unusual condition. In addition to this, urticarias due to brimonidine are rarely reported. We report on a 35-year-old woman who, immediately after apply a thin layer of brimonidine gel as preparation for a rosacea treatment on her face developed facial urticaria, which reverted in approximately four hours with systemic steroids. She had previously tolerated this product without any problems, but has not use it again ever since. Skin prick-tests with brimonidine (0.03 mg/mL) and latex were realized in the patient. Skin prick-tests with brimonidine were realized in eleven healthy control subjects.

Results: Skin prick-tests with latex was negative in the patient. Skin prick-tests with brimonidine were positive in the patient (9x5 mm).

The prick-test with brimonidine was negative in teen healthy control subjects.

We report on a case of immediate urticaria due to brimonidine and triggered by an immediate, probably IgE-mediated, hypersensitivity mechanism. We highlight this case because it is the only case described in the literature with a positive prick-test. Method: The study was in accordance with the Helsinki Declaration and was previously approved by the National Comity of Ethics.

This was a one dose study conducted on 16 fasting young healthy volunteers, of which 11 were females and five males. The mean age was 21 ± 1 years old and the body weight 61. 13 + 9.44 Background: Cetirizine is a potent H1-receptor antagonist indicated in the treatment of allergic rhinitis and urticaria. Cetirizine is widely used due to its potent antihistaminic effects in yielding strong and fast relief of itchy sensation, sneezy and rhinorrhea and its unlikely probability to manifest anticholinergic side effects in therapeutic doses. Histamine flare and wheal inhibition by anti-H1 are widely used as a standard to test and compare the effect intensity and duration. Our study aimed to test these effects of Cetirizine in young healthy adults.

Method: This was a double-blind, single dose study in healthy young adults, previously approved by the National Comity of Ethics.

Eleven females and five males with a mean age 21 ± 1 years participated in this study. Histamine skin pricks were tested before and after they received a tablet of 10 mg Cetirizine as previously scheduled. Twenty minutes after each test flare and wheal were drawn in a transparent paper which was then scanned and measured with a software. Wilcoxon Signed Ranks Test two-sided with significance at 5% level was used to analyze the differences. claims that the preparation relieves itch within 60 seconds of its application. We performed a simple study to verify this claim.

We used IRP in 20 consecutive subjects, 15 males, median age 12, range 6-49 years, whose workup implied AST. Their preliminary diagnoses were "asthma" (6 subjects), "allergic rhinitis" (10 subjects), "atopic dermatitis" (2 subjects) and "food allergy" (2 subjects). All of them had refrained from systemic antihistamines for at least one week. Standard skin prick tests (SPT) were applied as appropriate, including histamine controls to assess the level of their skin sensitivity. Subjects were asked to mark their sense of itch in the area of the skin to be tested on 100 mm visual-analogue scales (VAS) starting from "0"-"no itch" to "100"-"unbearable itch". VAS assessments were repeated 20 minutes after AST was done; then IRP was applied according to the manufacturer's instructions, and the VAS assessments were repeated after 60 seconds and 20 minutes.

Results: There VAS assessments are shown in table format: Table 1 IRP did not affect the wheal and flare of the histamine control, nor did it abolish positive SPT. No differences were outlined between subjects with different diagnoses.

The commercially available itch relieving preparation not containing defined pharmacological antihistamine is effecting in relieving itch associated with allergen skin testing.

Before AST (1) 4.9 ± 2.6 vs (2) P < 0. represent the first-line treatment for osteoporosis-related mastocytosis. We report a case of SM with bone pain and with an area of osteolysis in the femur as first sign and symptom. We had to consider the risk of adverse reaction when we decided to treat the patient with BP, but the patient was under antihistaminic treatment and also we made a premedication to reduce the risk. 

The PK/PD model available was informed by data from 12 clinical trials. The PD endpoint data was available from two studies and used to characterize the effect of bilastine on wheal and flare. Moreover, food effect had been characterized in 2 PK studies and the data was used to model the effect of food in the PK of bilastine. The PK parameters relative to the fed state were then used to simulate the temporal evolution of the wheal effect using the PK/ PD model. All analyses were conducted by nonlinear mixed effect modeling (NONMEM v 7.2). Using the PK model developed (food effect model) and the PK/PD model already available, Monte-Carlo simulations for plasma concentrations and PD over time were performed for both the fed and the fasting states.

Results: . A reduced bioavailability (F) and a slow absorption constant characterized the PK of bilastine when administered concomitantly with food (F = 77% relative to the fasting state and Ka = 0.51 hour −1 , a 3-fold reduction compared to fasting conditions).

The rest of the PK parameters remained unchanged. Onset of action was 1 hour for bilastine both in fed and fasted conditions. Maximum wheal inhibition occurred at 3.5 hours (fasted 78% and fed 77%).

From 2 to 12 hours, the percentage reduction with bilastine for both fasted and fed was between 75% and 86% after the third day of treatment. A 50% inhibition in wheal effect was maintained during 23 hours for both conditions after the third day. The results of the simulations show that even if the PK is altered with food, the PD is maintained unchanged.

Conclusion: Even if a significant food effect was described for bilastine at a PK level, the difference is not translated directly into the PD. Therefore, the antihistaminic effect of bilastine remains unaffected by the concomitant administration with food. The results of these simulations will be further confirmed in a dedicated clinical trial. Results: We also found no correlation between the different TGT parameters and other clinical and analytical parameters associated with UC (Table 1) Results: Both cetirizine products have no differences in respect to the pharmacodynamic and pharmacokinetic parameters analyzed.

The 95% confidence interval of the mean ratios of the AUC 0-24 , AUC 0-inf , Cmax, AUCE 0-24 , and E max , between the test and the reference, were within the bioequivalence ranges (80%-125%) in both cases. No statistical difference was revealed when comparing the respective T max and TE max too.

The two cetirizine products tested were bioequivalent.

The bioequivalence was evident even when tested with the pharmacodynamic parameters. There is strong evidence that supports the use of Histamine Skin Prick test for the bioequivalence evaluation of different cetirizine products.

1089 | Bradykinin-mediated angioedema associated with combination of angiotensinconverting enzyme and dipeptidyl peptidase IV inhibitors: a disproportionality analysis from the WHO database Method: We performed a disproportionality analysis using data from the WHO pharmacovigilance database by a case-noncase study, until the 14/12/2017. We extracted all individual cases safety reports (ICSRs) included in the high level term "angioedemas", according to the Medical Dictionary for Regulatory Activities classification. Given the absence of term "BMA", we selected only the ICSRs of angioedema without associated symptoms evoking another underlying mechanism, such as histamine angioedema (e.g. pruritus, urticaria, rash, etc.). Drug class exposure was "ACEi" and "DPP4i", considered suspect or concomitant, using the ATC classification. We Results: There was no correlation between mother's disorders such as periodontitis, rhinitis, diabetes etc. and the onset of AR (P > 0.05). A multivariate analysis showed, neonatal jaundice (P < 0.001), respiratory system infection (P < 0.001), diarrhea (P < 0.001), eczema (P < 0.001) in the first 6 months of life and home environmental factors (house decoration (P < 0.001), mold environment (P < 0.001), keeping flowers (P < 0.001), passive smoking (P < 0.001)) increased the risk of AR. Besides, there was no significant difference in current height and birth weight of the participants between AR and control group. However, AR group had significantly lower current weight (P = 0.003) and age (P < 0.001) compared with the control group. Paternal age and maternal age in the AR group were significantly higher than the control group (P < 0.01).

Conclusion: Diseases in the first 6 months of life and home environmental factors increased the risk of sequential AR. the older parents increased the possibility of AR in the offspring. The data of general Characteristics of participants were statistic analysis by z text analysis. *Significance at P < 0.05. Results: Anosmia was more frequent in CRS than in rhinitis (28.1% vs 3.9%, P < 0.001) and in CRSwNP than in CRSsNP (40.6% vs 13.4%, P < 0.001). LMS was higher in CRS than in rhinitis (8 [4-15] vs 0 [0-0], P < 0.001) and in CRSwNP than in CRSsNP (10 [6-18] vs 5 [1] [2] [3] [4] [5] [6] [7] , P < 0.001). In addition, LMS was associated with loss of smell in patients with hyposmia (OR = 2.66 [1.27, 5.53 Clinics. Patients were submitted to confirmatory exams including Oral Provocation Test with Aspirin. Nasal polyps were removed by Functional Endoscopic Sinus Surgery and eosinophils in this tissue were quantitated. Eosinophil counts in peripheral blood was obtained. Serum Periostin was measured by ELISA and total IgE was determined using ImmunoCAP. As control groups, 12 (9F/3M) patients with PAR and 23 healthy subjects (14F/9M) were selected.

Samples of nasal tissue and blood were collected from these subjects during elective surgery for correction of anatomical variations, and compared with the patients with AERD. Results: AR symptoms were significantly improved in the treatment group compared with the control group (76.6% (36/47) vs 21.7%

(10/46); P < 0.05). Furthermore, the mean total VAS score for patients in the treatment group was reduced from 6.21 ± 1.83 before treatment to 1.36 ± 1.51 after treatment (P < 0.05). Moreover, the reduction in free IgE levels was greater in the treatment group than in the control group.

The results of this study suggest that the Chinese herbal medicine BER may be effective for improving the symptoms of AR. A multicenter clinical trial is needed to confirm this finding. Results: In patients with "eosinophilic" polypoid rhinosinusitis, mucociliary transport was 35.2 ± 0.80 minutes, pH 7.4 ± 0.01, suction-88.6 ± 6.5 minutes, excretory-57.9 ± 0.9 mlg and in patients with "neutrophilic" polypous rhinosinusitis, mucociliary transport was 34.5 ± 0.65 minutes, pH 7.3 ± 0.01, suction-76.2 ± 5.0 minutes, excretory-54.9 ± 0.8 mL. The study showed that disruption of the transport function, changing the concentration of hydrogen ions Method: This prospective controlled study was carried out on CRS patients underwent ESS. Patients participating in the study were divided into two groups-group 1: partial middle turbinectomy (n = 22) and group 2: partial middle turbinectomy and middle turbinate fenestration (n = 23). Objective assessment of olfactory function using the University of Pennsylvania Smell Identification Test (UPSIT) and subjective assessment of symptom using visual analogue score (VAS) were performed before and 3 months after surgery.

Results: There were significant improvement comparing postoperative and preoperative UPSIT in both group 1 (35.23 ± 2.96 vs 32.23 ± 2.54, P = 0.000) and group 2 (36.09 ± 2.35 vs 32.04 ± 2.64, P = 0.000). The VAS were also significantly improved postoperatively compared to preoperatively in both group 1 (5.77 ± 0.75 vs 6.73 ± 1.08, P = 0.000) and group 2 (5.13 ± 0.81 vs 6.78 ± 1.28, P = 0.000). Patients undergoing partial middle turbinectomy and middle turbinate fenestration were more likely to show improvements in UPSIT (4.00 ± 1.20 vs 3.00 ± 1.11, P = 0.014) and VAS (1.59 ± 0.21 vs 0.95 ± 0.15, P = 0.000) compared to those with only partial middle turbinectomy.

Conclusion: Partial middle turbinectomy and middle turbinate fenestration during ESS is an effective method for improving postoperative olfactory function.

1109 | Nasal irrigation for the alleviation of nasal symptoms in pregnant women with allergic rhinitis We sought to determine specific IgE responses to bacterial pathogens in sera from cystic fibrosis patients and analyze their kinetic during disease course. genes, respectively. In contrast, most of healthy donors had normal homozygous genotype with TT-60.0 ± 8.9%(N = 18) and CC-56.6 ± 9.0%(N = 17) with low frequency of mutations; GG-16.6 ± 6.8%(N = 5) and TT-23.3 ± 7.7%(N = 7) and heterozygous genotype TG-23.3 ± 7.7%(N = 7) and CT-20.0 ± 7.3%(N = 6) for IL-2 and IL-4 genes, respectively. Following a 2 month treatment, there was a significant reduction of cytokine levels in the IL2-29.5 ± 0.5 and increased in the IL4-16.6 ± 0.4, when compared to the beginning of therapy and after 2 months (P < 0.001) Results: At baseline the 1st group had serum levels of IL-2 (43.6 ± 0.8) pg/L; IL-10 (34.8 ± 0.8) pg/L and IFN-γ (108.2 ± 1.1) pg/ L; 2nd group had IL-2 (39.6 ± 1.5) pg/L; IL-10 (38.6 ± 1.2) pg/L and IFN-γ (103.3 ± 1.4) pg/L vs IL-2 (21.6 ± 0.8) pg/L; IL-10 (50.2 ± 1.2) pg/L; IFN-γ (63.8 ± 2.2) pg/L in the control group. After 2 months, there was a significant decrease in pro-inflammatory cytokine levels in the 1st (IL-2: 35 ± 0.9; IFN-γ: 75.6 ± 1.9) pg/L and 2nd group (IL-2: 28.6 ± 1.3; IFN-γ: 66.7 ± 3) pg/L, respectively. Conversely, IL-10 increased in 1st and 2nd groups to 41.9 ± 0.9 pg/L and 46.0 ± 1.7 pg/L (P < 0.05).

Conclusion: Prior to the study initiation patients with tuberculosis had higher IL-2, IFN-γ and lower IL-10 content than healthy controls. Two-month chemotherapy produced significant reduction in proinflammatory cytokines and increase in anti-inflammatory IL-10, with levels approaching those of healthy controls. Thus, tuberculosis drugs appear to have the anti-inflammatory effect in tuberculosis patients, which was predictive of positive clinical outcome.

1114 | Antibiotic resistance: ligands of innate immunity take the challenge In this work, we aimed to perform an ex vivo HRSV infection in precision-cut lung slices (PCLS) from human, rhesus, and cynomolgus macaques, comparing whenever possible the response with the viral surrogate poly I:C.

Method: PCLS containing airways were prepared from lung sections of human, rhesus, and cynomolgus macaques. The slices were inoculated with HRSV-A2 10 6 IU/mL, UV-inactivated HRSV, or vehicle control for 48 hours. Macaque slices were also incubated with

Poly I:C 100 μg/mL with and without the immunosuppressive dexamethasone 50 μg/mL. Viral replication, tissue viability, and immune response assays were assessed in supernatants, lysates, or slices.

The inoculum infectivity of 10 6 IU/mL as well the UV-inactivation were confirmed by plaque-assay on Hep-2 cells.

Immunofluorescence staining using a FITC-labeled anti-RSV showed the presence of infected macrophages in PCLS, but not in mock infected samples. HRSV stimulation slightly decreased tissue viability, as seen by Live/DEAD staining and LDH assay. The viral infection increased IP-10 production in PCLS of human, rhesus, and cynomolgus macaques, reaching respectively 13.3, 3.4, and 1.7 fold-increase in comparison to the vehicle controls. Poly I:C stimulation caused IP-10 response comparable to HRSV in rhesus and cynomolgus PCLS.

The IP-10 production ratio comparing HRSV/Poly I:C was 1.1 in rhesus and 0.9 in cynomolgus PCLS.

Conclusion: HRSV infects ex vivo PCLS of human and non-human primates, inducing the release of the pro-inflammatory chemokine IP-10. This response is comparable to the viral surrogate poly I:C. In the future, these systems can be used to further investigate host response to HRSV, especially in the context of asthma development. However, a relatively small number of reports are related to the association of EBV with allergic diseases, in particular atopic ones.

We found that among patients with activated EBV infection, polysensitization was found to be 2.2 times more frequent, chest syndrome was 1.32 times more common and hyper-IgE syndrome occurred 1.5 times more frequently. In most of these patients, atopy was not detected in medical history. Method: We evaluated the laboratory test results of five boys (45.4%) and six girls (54.6%), 11 children (6 with HboV and 5 with CoV). Their average age at the study time was 59.2 ± 45 months.

Nasal swab specimens were taken from these patients who admitted to our hospital with respiratory symptoms between 2015-2016.

Patients are recalled after an average of 21 ± 2.5 months. ISAAC questionnaire and skin prick test to common inhalated allergens were performed.

Results: Only one patient had family history of atopy. Forty percent of the patients with CoV and 50% of the patients with HboV developed rhinitis. One patient with CoV and one patient with HboV developed recurrent wheezing. One patient with CoV developed atopic dermatitis. All skin prick tests were negative. It was noteworthy that 72.7% of the patients were passive smokers.

Conclusion: HboV and CoV may be associated with rhinitis but there is a need for more patient groups for a clear result. RNA_lig (ccg-agg-aug-cga-ggc-uug-uu) . To study chemotaxis in vitro, a Boyden96 chamber was used -WellFiltrationPlateMultiscreenTM -MIC with a pore size of 8 μm (Millipore, USA). Chemotaxis was studied in dynamics after 10, 60 minutes and a day using the above ligands. As control, RPMI-1640 medium without glutamine was used (PanEco, Russia). The statistical analysis was carried out using the computer statistical program BioStat2009 Conclusion: With all the data provided, a drug induced hypersensitivity was diagnosed. We present a case of immediate allergic reaction with eosinophilia due to Carbapenems, with tolerance to other beta-lactams antibiotics. Written informed consent of patient has been obtained in the two cases.

Discussion: The first case shows cutaneous immediate hypersensitivity response to INFbeta1a. Literature reports a few cases of urticaria and anaphylaxis but this is the first for the pegylated formulation. Polyethylene glycol (PEG) confers to a drug modified pharmacokinetics, solubility and immunogenicity. Immediate reaction to PEG (macrogol) have been described when combinated in vaccines or drug pils.

DMF is a known cause of contact dermatitis related to footwear, wallets and furniture. Flushig is a reported side effect of DMS in MS managed with dose reduction. This case shows the possibility to immediate sensitization to DMF. As the armamentarium to treat MS now combines immunomodulatory and biologic drugs, the avaliability of diagnostic and desensitization protocols for hypersensitivity reactions must be keeped in mind. Case report: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon but serious hypersensitivity drug reaction, manifested with rash, fever, lymphadenopathy and visceral organ involvement. table) . Drug withdrawal and prednisolone treatment leaded to attenuating of mentioned skin symptoms within 2 days, associated by occurrence of a exfoliative dermatitis. One week after admission, the patient developed fever that lasted for 4 days with enlarged lymph nodes on submandibular, paracervical, axillar and inguinal regions. A preventive antibiotic therapy is started and 2 weeks later, the lymph nodes were not palpable and the skin got the normal appearance. Corticoid therapy is reduced gradually according to symptoms resolvement.

Case 2: A 56-year old woman presented to our department with a 6-day history of pruritic, macular rash, periorbital swelling, cheilitis and fever. She had started some weeks ago the allopurinol for asymptomatic hyperuricemia, had longer history for treatment of arterial hypertension and type-2 diabetes mellitus (olmersartan, nitrendipine, methyldopa, furosemide, regular and glargine insulin), and experienced nephrectomy and cholecystectomy. The patient was febrile, while blood tests revealed eosinophilia, increased seric creatinine/urea levels (due to nefrectomy), and severely-altered liver parameters (see table) . The allopurinol withdrawal, topical and systemic corticoid therapy, and the liver protectors attenuated serologic transaminases levels and patient's skin lesions within few days, followed by substantial improvement of laboratory findings one week after therapy start. The treatment dosage was gradually tapered and finally stopped within a period of 2 months in accordance with attenuating and complete resolvement of the clinical and laboratory abnormalities.

Our case demonstrated that DRESS syndrome is a severe drug reaction, but the immediate introduction of treatment and supportive measures can improve disease's outcome even after a temporary exacerbation or severe affection of internal organs. Case report: A 40-years-old woman, diagnosed of ischemic cardiopathy, developed an anaphylactic shock 5 minutes after the administration of 2 mL sulphur hexafluoride intravenous during an echocardiogram. She was treated in emergency room with a total recovery. 2 months earlier, she had developed an extensive erythematous-maculopapular rash converging in plaques in relation with adhesive dressings which had been placed during a hospitalization due to thoracic pain. An allergic contact dermatitis was suspected and recommendations thereon were given. Interestingly, an arteriogram with iodixanol (ICM) was carried out one week before skin reaction with good immediate tolerance.

Methods: Blood test: Blood count and serum chemistry were done during both reactions to contrast media. Serum tryptase level was not measured during the anaphylaxis, but its baseline level was quantified later. Conclusions: We present a patient with a double sensitization to parenteral contrast media: an anaphylactic shock due to sulphur hexafluoride and an atypical delayed exanthema related to iodixanol, and diagnose was obtained with ST in both cases. This is the first documented case with a positive immediate ST to sulphur hexafluoride. with the culprit drugs mixed with 10% and 30% petrolatum resulted negative. Patient was suspected to have Behcet's disease, and consulted to rheumatology department. Oral colchicum dispert twice a day was prescribed. Afterwards, patient achieved to take oral amoxicillin-clavulanate for a week without any hypersensitivity; and has been following by oral colchicum dispert maintenance therapy since then. 

The reported patient had one anaphylactic perioperative reaction to morphine and another anaphylactic reaction to tramadol during her diagnostic investigation. Remain the question if this patient had two allergic anaphylactic reactions with cross-reaction between morphine and tramadol, or two non-allergic anaphylaxis due to "hypersensitive" mast cells. Case presentation: A 61-year-old female was diagnosed with rectal adenocarcinoma. One year after radical surgery, progression with pulmonary metastasis was shown. In first line of systemic therapy she received premedication with pantoprazole, metoclopramide, clemastine and dexamethasone, followed by cetuximab infusion.

During first minutes of infusion, grade 4 anaphylactic reaction occurred. A reaction started with generalized pruritus, urticaria, rhinitis, followed by hypotension, bradycardia and loss of consciousness.

She was treated with fluids, clemastine and methylprednisolone.

Next day she received same premedication followed by panitumumab. During first 30 minutes she had grade 1 reaction with generalized urticaria. The third day she had generalized urticaria 10 minutes after metoclopramide application. Skin prick tests with cetuximab (5 mg/mL) were negative, but intradermal test were posi- BAT response was highly positive for both cetuximab and alpha-gal, with comparable values and dose response curves. Thus, we showed 70%, 63%, 58%, 35% and 4% of CD63 positive basophils for stimulation with cetuximab (500-0.1 μg/mL), and 67%, 40%, 17%, and 1%

for stimulation with alpha-gal (33.3-0.033 ng/mL). BAT response to panitumumab was negative (<5%; 500-0.1 μg/mL). Drug provocation with panitumumab was negative and patient received treatment with panitumumab. In the operating theatre, the skin is disinfected using povidoneiodine and pupil dilation is carried out with Tropicamide (showing no immediate reaction in the surgery).

Method: As we are dealing with a late cutaneous reaction, the study of the medicine involved is carried out by means of epicutaneous medicine testing.

In order to do the study of Aflibercept, we wore gowns, two sets of gloves, a mask, eye protection and in a containment hood in the outpatients hospital. 

The patient diagnosed himself with dermatitis when in contact with Povidone-iodine and despite the fact that the cutaneous provocation was negative, it is known that when there is surgery involved, there needs to be moistness and occlusion for it to show up clinically.

The application of this antiseptic seems to lose its irritation and allergic properties when it dries on the skin and therefore tends to give a negative result in these patients, but this does not mean that they are not allergic to this antiseptic. We report the case of a 60 year old man who experienced erythema and pruritus immediately after an intravenous injection of ranitidine and hyoscine butylbromide given for gastric pain treatment.

Results: SPT and IDT were performed for ranitidine (10 mg/mL and 0.01 mg/mL respectively) and hyoscine butylbromide (0.5 mg/mL and 0.005 mg/mL respectively) being exclusively positive for ranitidine at IDT dose with a 15 × 25 mm papule (histamine control 23 × 35 mm). Oral provocation test for hyoscine butylbromide was negative. BAT for ranitidine and famotidine were carried out, being negative for both drugs.

Conclusion: Skin tests for H2RA are the best option when studying a suspected reaction to H2RA and are also useful for assessing cross-reactivity between other H2RA. The sensitivity for BAT in diagnosis of drug allergy is about 50%, and the specificity up to 93%, although these percentages make reference to the common drugs studied (beta-lactams, quinolones, pyrazolones, etc). Specific studies for H2RA are still to be done. In our case we had a negative result for the BAT test, although we proved ranitidine was responsible for the reaction. Conclusion: Gentamicin is an aminoglycoside antibiotic used systemically for septicemia and as prophylaxis during surgery. Immediate type allergy (type I) to gentamicin is rarely reported. Since 2016, approximately only five cases have been reported in literature. In our case, initial theories were pointed towards cefazolin as beta-lactams report a higher rate of allergic reactions. After an exhaustive allergological study, results disproved our initial theory indicating gentamicin as the responsible drug.

Giangrande N 1 ; Bobadilla-González P 1 ; García-Menaya JM 1 ; Cámara-Hijón C 2 1 Allergy Department, Infanta Cristina University Hospital, Badajoz, Spain; 2 Clinical Immunology Department, San Pedro de Alcántara Hospital, Cáceres, Spain Background: Polyethylene Glycol (otherwise known as Macrogol or PEG) is a polymer with a wide application as an excipient, solvent and dispersing agent in food, cosmetic and pharmaceutical industry.

It presents distinct length polymer chains with a molecular weight from 200 to 10 000 000 g/mol conferring them specific properties.

Macroglol with a molecular mass between 3500 and 4000 g/mol is commonly used as osmotic laxative previously to colon endoscopy and radiologic examinations. After the introduction, anaphylactic reactions to Macroglol are rarely reported, considering it safe and well tolerated. We report on a 56-year-old man who, immediately after of the topical application of benzindamine in left inferior limb developed acute urticaria in this limb, which reverted in approximately 2 hours with systemic steroids.

She had previously tolerated this product without any problems.

Skin prick-tests with benzindamine (0.06 mg/mL) and latex were realized in the patient.

Skin prick-tests with benzindamine were realized in eleven healthy control subjects.

Results: Skin prick-test with latex was negative in the patient.

Skin prick-test with benzindamine was positive in the patient (6 × 5 mm).

The prick-tests with benzindamine were negative in eleven healthy control subjects.

We report on a case of contact urticaria due to benzindamine and triggered by an immediate, probably IgE-mediated, hypersensitivity mechanism.

Some of the drug used in daily clinical practice can cause allergic contact urticaria and should therefore be borne in mind. Background: The use of new oral anticoagulants which act as direct inhibitors of activated factor X is constantly increasing, due to lower rates of serious and fatal bleeding events than warfarin/acenocoumarol. Rivaroxaban, the first commercialized drug in this group, is the most used for prevention of thromboembolic events. However, <10 cases of hypersensitivity reactions have been described so far, most of them delayed and severe. To present a case of delayed hypersensitivity to rivaroxaban, diagnosed by a positive LTT (lymphoblastic transformation test).

A 79 year old woman with hypertension and chronic atrial fibrillation (AF) was referred to our clinic for suspected drug allergy. She reported that 2 months before, for AF she was started on oral amiodarone and rivaroxaban, presenting on the seventh day with both of them generalized erythema, pruritus, micropapular rash and facial angioedema. No oral or other mucosal were observed, neither pustules, vesicles or blisters. Blood eosinophilia, enlarged lymph nodes, renal and hepatic injury were discarded in Emergency, where the new drugs were discontinued and replaced by acenocoumarol.

The rash subsided one week later, with oral antihistamines. Before and after the episode the patient also has been taking losartan and hydrosalurethyl, with good tolerance. She denied other adverse reactions. In Allergy department we performed skin prick tests and intradermal tests with amiodarone (0.05 mg/mL and 0.5 mg/mL) and rivaroxaban (0.1 mg/mL and 1 mg/mL), and a LTT with both drugs, 3 months after the reaction. Background: Patients with history of beta lactam allergy, often self-reported, are commonly encountered in the hospital setting. This frequently leads to increase use of broad spectrum and more expensive antibiotics that may be unnecessary or even less efficacious at times due to fear and concerns about potential disastrous outcomes.

Nonetheless, with increasing awareness, many patients are now being referred to Allergy Service for formal evaluation. We aim to look at patients who underwent evaluation for beta-lactam hypersensitivity and determine the number of patients that were successfully de-labelled.

Method: A retrospective analysis was conducted with patients referred for evaluation of questionable beta-lactam allergy to the Allergy Service in our institution from the years 2016-2017. Initial evaluation process included a thorough history to determine the type of hypersensitivity reaction and suitability for further testing.

Patients underwent skin prick test (SPT) and intradermal (IDT) with either (a) both major and minor determinants of penicillin, benzyl penicillin, amoxicillin and ampicillin, and/or (b) the culprit drug itself.

If skin testing was negative, oral or intravenous (IV) drug challenge was then performed after informed consent. Clinical details and reactions were documented. Patients were also contacted post challenge to ensure no delayed reaction had occurred.

Results: A total of 130 patients were evaluated for beta-lactam allergy in the 2 year period, of these 80 were females and 50 were males. 107 of the referred patients had presumed penicillin group allergy and 29 had cephalosporin group allergy (3 patients had both penicillin group+cephalosporin allergy). 95 cases (73%) were successfully de-labelled. Beta-lactam allergy was confirmed in 26 patients (20%); identified by positive SPT in two patients, positive IDT in six patients and positive drug challenge in 18 patients (15 patients developed rash/urticaria, 1 had respiratory symptom and 2 patients developed anaphylaxis). 14 patients were referred before any drug allergy labelling was done, out of which 10 were confirmed not to have beta-lactam allergy.

Conclusion: In our study, 80% of patients were confirmed not to have true beta-lactam allergy. We were able to successfully remove beta-lactam allergy label from the electronic record for 73% of the patients. Results: A total of 66% referred amoxicillin-clavulanic acid (AX-CLV) as trigger for the hypersensitivity reactions (HRs), followed by AX (21%), penicillin (6%) and cephalosporins (5%). Almost 80% of HRs were immediate (<60 minutes). Positivity of skin tests was observed in 65% subjects, of BAT in 61% and of RAST in 68%. In Conclusion: The label of penicillin allergy is quite often erroneous.

This involves using of more expensive and less effective therapeutic alternatives, which also facilitate the emergence of multi-resistant micro-organisms. Hence the importance of confirming the diagnosis of allergy. Finally, we did not find differences in the study of penicillin allergy in patients older than 60 years compared with the general population. Background: Severe cutaneous delayed drug reactions (toxic epidermal necrolysis -TEN-, Stevens-Johnson syndrome -SJS-, acute generalized exanthematous pustulosis -AGEPand drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome -DRESS/DiHS-) among others, are a rare but potentially fatal complications of drug treatment. Although its epidemiology has been described in different latitudes, it is unknown in Latin America.

Our aim was to describe the epidemiological characteristics of severe cutaneous reactions to drugs in countries of Latin America.

Method: An online questionnaire was designed to report new and old cases (since 2013). It was a modified and adapted version of ENDA questionnaire for drug allergy interesting group. Sociodemographic data, type of reaction (TEN, SJS, DRESS-DiHS, AGEP), culprit drug (s), treatment, complications, mortality and sequelae, were described. Three centers from Colombia, one from Argentina, one from Brazil and one from Paraguay were included. An Excel database was created, in which cases were recorded and analyzed.

Results: Thirty seven cases were reported. 24 (65%) were women.

The median age was 47 years. 19 (51%) had DRESS/DIHS, 6 (16%) TEN, 3 (8%) SJS, 3 (8%) AGEP, 3 (8%) other not classified SCARs, and 1 (2.7%) overlapping TEN/SJS. The main culprit drugs were aromatic anticonvulsants in 17 cases (46%), beta lactam antibiotics in 6 (16%), non-beta lactam antibiotics in 3 (8%) and allopurinol in 2 (5.4%). In 100% of the patients the suspect drug was withdrawn.

Thirty one patients (83.7%) received systemic corticosteroids. Complications occurred in 17 cases (49%) and death in one patient (2.7%). Seven patients (19%) had some type of sequelae.

countries, DRESS/DIHS was the most frequently reported clinical entity, and the anticonvulsants were the main triggers. Complications were frequent, but mortality was low.

1155 | Drug-induced cough: analysis of nationwide spontaneous reports in Korea over ten years using WHO-Adverse Reaction Terminology (WHO-ART) indicative of cough.

Results: From 856 524 cases of spontaneously reported adverse drug event cases, a total of 9003 cases (4.5%) were identified as drug-induced cough. Most cases occurred in adults (93.4% of the subjects) and females were more common than males (54.9% vs 45.1%). Regarding severity, only 629 cases (7.0%) were classified as serious based on WHO criteria. The most common causative drug category was antineoplastic and immunomodulating agents (24.8%), followed by cardiovascular drugs (24.2%). The most common causative drugs were ACE inhibitors including perindopril and ramipril.

Conclusion: In the nationwide spontaneous reports of adverse drug events, many cases of drug-induced cough have been reported so far. Much attention is needed to find new causative drugs of cough in the future. Background: Allergological assessment to determine the mechanism of the perioperative reaction and to identify the agent responsible and recommendation of a range of drugs or agents likely for future surgery is essential, but it often poses a significant challenge.

In this study, we analyze our experience in the investigation of adverse reactions during anesthesia in the last 4 years.

Method: A total of 15 patients who attended our Allergy Unit with suspected perioperative reactions between January 2014 and December 2017 were reviewed retrospectively.

The severity of the perioperative allergic reactions was graded according to Ring and Messmer system. Results: Grade III, II and I reactions were observed in 9, 1 and 3 patients, respectively. In 2 patient we didn't know the reaction suffered.

Tryptase measurements were available for 11 patients. Of those, 3 and 4 patients had elevated and normal levels respectively and suffered grade 3 reaction.

IgE mediated reactions was diagnosed in 9 patients (60%): 3 for ßlactam antibiotics (33.3%), 2 for Patent Blue (22.2%), 1 for neuromuscular blocking agents-NMBAs (11.1%), 1 for latex (11.1%), 1 for colloids (11.1%) and 1 for ranitidine (11.1%) . Cefazolin was the ß-lactam antibiotics causing the largest number of reactions.

Non-IgE-mediated reactions was diagnosed in 6 patients (40%). The allergy tests were negative and tryptase levels were normal.

Conclusion: In our series, among the 9 patients who suffered allergy reactions during anaesthesia and the cause was subsequently identified, ß-lactam antibiotics were the most common causative agent (33.3%), followed by Patent Blue (22.2%), NMBAs, latex, colloids and ranitidine (11.1% each agent). In contrast, data from other authors indicated that NMBAs were the most common cause of anaphylaxis, followed by latex, hypnotics, antibiotics, plasma substitutes and opioids.

These differences might be due to the small size of our study, which was limited to our centre over the last 4 years and thus may not be representative. diagnostic evaluation. All patients signed an informed consent. We made a retrospective analysis of their clinical records and excluded 11 patients whose records were missing or incomplete. It was analyzed each patient's medical history (focusing allergic disease) and clinical reaction to the suspect drugs. Signals/symptoms at PCC were characterized. We also studied the variation of the DPT's results when it was performed after a PCC. Aim: To define and quantify the ongoing pharmacy needs in sustaining a large drug allergy assessment program.

Method: A retrospective review of pharmacy files was used to identify and quantify the drugs and dosages most frequently used and to determine prescription trends within the allergy testing program over the last 3 years. Results: Initially, this reaction was thought to be a result of a drug allergy, but upon further review and the onset of fever, we determined that it met the diagnostic criteria of JHR.

His twin brother was diagnosed with penicillin and betalactamic allergy. Neutrophilia 83% was to be underlined in the blood test.

After this, drug oral challenge with PENICILLIN was performed, ruling out penicillin allergy.

Conclusion: It is not uncommon to confuse drug allergy with JHR.

JHR should be an anticipated reaction to early doses of antibiotic treatment for treponemal diseases, such as syphilis.

Antibiotic treatment should be continued; it is not a warrant to stop treatment.

Clinicians should be aware and anticipate JHR as a potential complication to early doses of antibiotic for spirochetal diseases such as syphilis or Lyme, leptospirosis. The patient was unresponsive in oral drug provocation tests with amoxicillin-clavulanic acid, clarithromycin and trimethoprim sulfamethoxazole for 6 months. The patient could use these drugs. Results: Chronic abacterial inflammation of the prostate gland was accompanied by a significant increase in concentration of SLPI, IL-8, TNF-α, IL-17 in the seminal plasma and serum concentration, and a decrease in the concentration of IL-6 and TGF-β1 compared to healthy men (P < 0.05). There was no statistically significant difference between SLPI, IL-8, TNF-α, IL-23, IL-17, and TGF-β1 in the ejaculate of patients with inflammatory and non-inflammatory forms of CAP (P < 0.05). The concentration of IL-6 in ejaculate of patients with inflammatory forms of CAP was significantly greater than in patients with non-inflammatory form of CAP (P = 0.01).

The inflammatory and non-inflammatory forms of CAP are pathologically similar with changes in the concentration of the studied cytokines except for IL-6 in both forms with signs of inflammation. The terms "leukocytic" vs "non-leukocytic" chronic abacterial prostatitis are more correct than "inflammatory" and "non-inflammatory" when describing chronic abacterial prostatitis. Results: The status of all patients after DC immunotherapy was evaluated as satisfactory. Heart rate, blood pressure in patients remained within the age norm. Skin had normal color without rash or peripheral edema. There were no local or systemic allergic reactions. The body temperature after the injection did not exceed 37°C. Conclusion: These results show, for the first time, that among mastocytosis patients, besides the already known periodontal disease risk factors that include diabetes, age, osteoporosis and alcohol consumption, the bone marrow mast cell burden is also associated with increased periodontal disease severity. Results: Metformin at relatively low doses (1-10 μM) was shown to mildly suppress IgE-mediated responses, including degranulation (34% reduction, P = 0.0135), TNF-α (23% reduction, P = 0.0139) and IL-13 (38% reduction, P = 0.0015) secretions in BMMCs. Importantly, metformin at the same doses potently inhibited mast cell responses in all parameters (100% reduction, P < 0.0001 for degranulation; 87% reduction, P < 0.0001 for TNF-α; 90% reduction, P < 0.0001 for IL-13) in mast cells treated with an AhR ligand, 5,11-dihydroindolo[3,2-b]carbazole-6-carbaldehyde (FICZ). Mechanistically, its inhibitory effect was mediated through the suppression of FICZ-induced MAPK activation, intracellular calcium release and ROS generation.

Metformin also blocked AhR-mediated PCA in vivo (90% reduction, P < 0.0001).

Conclusion: Metformin, a common anti-diabetic agent, was shown to exert inhibitory effect on AhR-mediated mast cell activation in vitro and in vivo, suggesting its potential utility as a newer form of therapy for asthma and allergic diseases; this is particularly relevant when considering the adverse effect of the exposure to environmental polycyclic aromatic hydrocarbons.

Gasser P 1 ; Brigger D 1 ; Zbären N 1 ; Jardetzky T 2 ; Pennington L 2 ; Eggel A 1 Results: In one of affected family members, we were able to identify the c.9886A>G mutation in the plasminogen (PLG) gene that was recently described to be associated with hereditary angioedema.

This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the 3rd kringle domain of plasminogen.

There is no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in early adulthood, with swelling of the face, the tongue and the larynx. The frequency of attacks was variable, between once in a year to once in a month.

In one of the three family members, we found a slightly decreased level of coagulation factor XII and of plasminogen. Icatibant proved to be very effective for the treatment of acute attacks in the affected family.

The occurrence of the same c.9886A>G (p.Lys330Glu) mutation in the PLG gene in many families with no or only unknown distant relationship suggests that the disease might have been inherited through the generations without being purged from the population. The mutated amino acid exchange appears to be significant for the function of plasmin or plasminogen. We found a decrease in plasma levels of coagulation factor XII and plasminogen, which may be beneficial markers for diagnosis and monitoring of this disease. Several biomarkers are useful in the diagnosis (fibrin degradation products (FDPs), D dimer (DD), and fragments of prothrombin 1 + 2). Also, a correlation between the levels of biomarkers and activity phases of the disease has been detected.

Alterations in coagulation parameters have an etiopathogenic role in the AE attack, but have not been considered as biomarkers of activity phases.

TGT is a global coagulation test which quantifies in vitro the ability of plasma to generate thrombin and estimates alterations in coagulation parameters.

The objective is to assess the usefulness of the thrombin generation test (TGT) to characterize patients with hereditary angioedema (HAE).

Method: Seventeen HAE patients from Hospital La Fe were recruited to obtain blood samples in remission and during AE attacks. None of them experienced thromboembolic events.

Plasma was collected in citrate tubes to obtain platelet rich plasma.

Hemostatic parameters were analyzed:.

TGT was conducted using a Calibrated Automated Thrombogram (CAT) method and a Fluoroskan Ascent as a reader. Results were analyzed via Thrombinoscope v5.

Citrated plasma was incubated with calcium, tissue factor, phospholipids and a fluorogenic substrate.

A thrombin generation curve is generated, obtaining parameters: latency time (Lagtime), thrombin generation maximum speed (Vo), maximum peak of thrombin generated (Peak), time to generate the maximum peak of thrombin (ttPeak), total quantity of generated thrombin (ETP), and the end time of thrombin generation (StartTail).

TGT parameters from 322 healthy donors were used as controls.

Results: Thirty-eight samples were collected from seventeen HAE patients (58.8% female). Fifteen (39.5%) samples were collected during AE attacks.

TGT parameters and FDPs were significantly higher in HAE patients compared with controls (P < 0.0001), although no significant differences were found in TGT between acute attacks and remission.

A decrease trend in TGT is observed in AE attacks.

FDPs were increased during AE attacks, but normalized at remission periods.

These results support the involvement of coagulation in the pathophysiology of HAE, although no increase in prevalence of thrombosis is observed during acute attacks. Method: The repeated measures design study included 108 patients in two groups: the SLIT group, 63 patients-67 follow-ups per allergen (P), and the VIT group, 45 patients-54 P. The SLIT group had patients treated for HDM (41 P), and patients on pre-coseasonal pollen AIT (grass 11 P, ragweed 10 P, birch 5 P). The VIT group had 28 patients on rush protocol (18 for bee and 9 for wasp) and 18 patients on conventional protocol (9 bee, 2 wasp, and 7 for both). The IgE and IgG4 levels were measured by the ImmunoCAP method. The Friedman test was used to compare data. Results: When compared to placebo group, SLIT+vitamin D group therapy was more effective in the reduction of nasal symptoms (P = 0.04), asthma symptoms (P = 0.001) and combined symptommedication score (P = 0.001); there was no significant difference between groups in medication and ocular scores. We observed a significant improvement of FEV1 (vitamin D group P = 0.014, placebo group P = 0.015) and FEV1%VC levels (vitamin D group P = 0.004, placebo group P < 0.001), within both groups, between visits. FENO results did not differentiate statistically significantly the study participants in terms of receiving SLIT along with vitamin D or placebo.

Significant increase in the percentage of CD4 + CD25 + Foxp3 + and in TLR positive cells in children receiving SLIT+ vitamin D was observed compared to placebo group. Increase in CD4 + CD25 + Fox-p3 + induction, and in TLR positive cells recruitment were independently associated with better clinical effect of SLIT in children. Conclusion: Overall, AIT with a high-polymerized ash pollen extract was well tolerated. As ash pollen are supposed to be an important allergen during spring time, it is recommended to include SPT and NPT with ash pollen in the test panel for allergological diagnostic.

Additionally, determination of ash pollen specific IgE could be applied. Furthermore, appropriate AIT should be considered for ash pollen allergic patients.

1194A | Impact of sublingual immunotherapy with a five-grass pollen tablet on grass pollen allergic rhinitis and asthma: A real-life, long-term analysis in France Background: Data on the fulfilment of prescriptions of symptomatic medications in patients with grass pollen allergy were analysed to evaluate the long-term effectiveness of sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma.

Method: By using data in the Lifelink ™ Treatment Dynamics database (IQVIA, Paris, France), we compared two cohorts of patients with AR: a group treated with Oralair® (Stallergenes Greer, Antony, France) SLIT tablets (n = 617), and a matched control group having received symptomatic medications only (n = 10 990). Oralair®'s effectiveness was assessed as the change in symptomatic medication fulfilments between the pre-index period (before the initiation of SLIT) and the follow-up period (after SLIT), and as the onset of asthma or the progression of pre-existing asthma (based on fulfilments of prescriptions for asthma medication). The number of fulfilments per year was calculated for each patient and each period.

Results: In line with prescribing guidelines, the mean duration of treatment with Oralair® was 6.3 months per season for either 2 seasons or 3 seasons. The mean number of symptomatic medications for AR fulfilled per patient and per year in the pre-index period was 6.7 ± 5.9 in the SLIT tablet group and 9.6 ± 7.7 in the control group.

In the follow-up period, this value fell for the SLIT tablet group (to 2.6 ± 4.2) but did not change significantly in the control group (8.6 ± 8.1). When considering individuals not taking any asthma medications in the pre-index period, asthma onset during the treatment period was observed in 12.1% of those in the SLIT tablet group and in 15.8% of those in the control group. The corresponding values for the follow-up period were 1.2% in the SLIT tablet group and 5.8% in the control group. When considering individuals already taking asthma medications in the pre-index period, the mean ± SD number of asthma medication fulfilments in the pre-index period was lower in the SLIT tablet group (4.7 ± 4.6) than in the control group (8.1 ± 7.9). The corresponding values for the treatment period were 4.1 ± 5.4 and 10.2 ± 9.5, respectively. In the follow-up period, the number of asthma medication fulfilments fell more in the SLIT tablet group (to 2.3 ± 4.1) than in the control group (7.2 ± 9.0).

Oralair® tablets have long-term effectiveness by relieving allergic rhinitis and slowing a progression to asthma.

1194B | A real-life, retrospective analysis evidencing slower long-term progression of asthma in grass pollen allergy patients treated with sublingual immunotherapy tablets 1195 | An examination of the reasons for treatment discontinuation and non-compliance to allergen immunotherapy Background: Allergic rhinitis (AR) patients treated with subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) may be non-compliant or discontinue treatment too early, which can negatively impact efficacy. Therefore, understanding the reasons for non-compliance and treatment discontinuation is vital to help improve compliance, persistence and thus outcomes. This study reported reasons for treatment discontinuation to SCIT and SLIT and non-compliance to SLIT in patients with AR in published real-world studies.

Method: A literature review was conducted in Embase, MEDLINE, EBM reviews, PsycInfo and EconLit (1998-2017) using key search terms for allergic rhinitis, SCIT, SLIT, non-compliance and non-persistence. Across all studies,~20% of patients were non-compliant, and

1-year drop-out rates ranged from 23% to 74%. Reasons for noncompliance and treatment discontinuation in this subset of patients were stratified according to the WHO dimensions for adherence (patient-related, treatment-related, or socio-economic).

Results: From the 428 publications identified, six studies reported reasons for non-compliance to SLIT (n = 3) or treatment discontinuation (n = 3) to SCIT or SLIT, and the results were grouped for analysis. The majority of patients cited treatment-related factors as the primary reason for discontinuation (66% for SLIT, 50% for SCIT).

Common reasons were a length of treatment for SLIT and frequency of injections for SCIT. 45% of patients discontinued SCIT due to patient-related factors such as travel to doctors and waiting time for administration. Only 24% of SLIT patients discontinued due to patient-related factors. Socio-economic reasons for discontinuation were low for both therapies (10% SLIT and 5% SCIT). Conversely, for non-compliance to SLIT, socio-economic factors were the most frequently cited reasons (50%), and included taking time off work and financial concerns.

Conclusion: Of patients who discontinued therapy, treatmentrelated factors were the most cited reasons for SCIT and SLIT, reflecting concerns with administration and treatment length. Noncompliant SLIT patients cited socio-economic factors as common reasons for non-compliance, suggesting financial concerns over a long treatment course. Differences in reasons for non-compliance and treatment discontinuation may be due to patients assigning differing importance for compliance (a day-to-day decision) compared to the long-term decision to discontinue treatment. Results: 53% of patients had monosensitization to rBet v1 component. The rest 47% had combinations IgE to rBet v1 and IgE to one, two or even three minor allergens (35%, 10%, 2% accordingly).

After 2 courses of SLIT by standardized pollen extracts symptoms of ARC and PFAS decreased in 90% and 63% patients accordingly.

In group 54 patients with monosensitization to rBet v1: 49 patients had a reduction of ARC (85% had 3-4 degree by ADO); 41 patients had reduction of PFAS. 3 patients hadn't finished treatment due to allergic reactions.

Among 26 patients with sensitization to rBet v1/v6: 24 patients had a reduction of ARC (75% -3 to 4 degree by ADO); 17 had reduction of PFAS. 1 patient hadn't finished treatment due to allergic reactions.

In 9 patients with sensitization to rBet v1/v2: 7 patients had a reduction of ARC (57% -3 to 4 degree by ADO); 3 had reduction of PFAS. 10 patients with sensitization to rBet v1/v2/v6 showed the similar results: 10 patients had a reduction of ARC (57% -3 to 4 degree by ADO); 3 had reduction of PFAS.

2 patients had sensitization to all CRA, and only 1 patient who also received SLIT with grass allergens had reduction of ARC only (2 degree by ADO).

As the result of the study it was identified that beneficial effect of SLIT is highest in patients with monosensitization to rBet v1. The increase of sIgE sensitization profiles to minor birch allergens caused less efficacy of SLIT treatment. Dermatophagoides pteronyssinus immunotherapy is independent of sensitization to Blomia tropicalis among children with allergic rhinitis and asthma Method: 95 children (5-17 years old) with allergic rhinitis and asthma sensitised to both DP and BT received 3 years DP-SCIT. Clinical symptom and medication scores, serum specific IgE and specific IgG 4 were evaluated during DP-SCIT. In order to investigate whether the treatment outcome was dependent on the sensitisation pattern between DP and BT, patients were further grouped into DP and BT co-sensitisation and cross-reaction, according to positive or negative IgE against BT major allergen (BTMA) Blo t 5 and Blo t 21. BTMA+ group, with specific IgE to either Blo t 5 or Blo t 21, was defined as the co-sensitized group; BTMA-group, with no detectable IgE to both Blo t 5 and Blo t 21, was defined as the cross-reactive group in this study.

Results: All the recruited 95 patients completed 1 year of DP-SCIT, 74 (78%) patients completed 3 years of treatment. After 3 years of DP-SCIT, compared to baseline, all patients had significant reduction in symptom and medication scores. Lung function (FEV 1 ) was significantly improved as well. 65% of the patients were free of medication use and asthma symptoms, 3% of them were free of rhinitis symptom, and the FEV 1 % in all patients were higher than 95% of predicted. DP-SCIT induced significant increases in DP and BT specific IgG 4 . In 50% of patients, DP specific IgG 4 increased more than 67 fold and BT specific IgG 4 increased more than 2.5 fold. Further investigation in BTMA groups showed moderate correlation (spearman r = 0.48, P = 0.004) between specific IgE against DP and BT in the BTMA-group (n = 34), indicating specific IgE cross-reactivity. No specific IgE correlation (spearman r = 0.03, P = 0.82) was found in the BTMA+ group (n = 61) indicating co-sensitisation to both DP and BT. The two groups showed almost identical change in clinical responses. DP and BT specific IgG4 significantly increased during DP-SCIT, no difference was found between the two BTMA groups.

Conclusion: DP-SCIT can induce specific IgG4 cross-reacting with BT allergens. Patients with specific IgE sensitisations to both DP and BT may have clinical benefit from DP-SCIT treatment. Moreover, the clinical benefit of SCIT was independent of IgE cross-reactivity or co-sensitisation to DP and BT. Method: We investigated 16 allergic rhinitis children who were basically sensitized to house dust mite and received house dust mite SLIT for 1 year and 6 months. Among 16 patients, 9 patients were mono-sensitized to house dust mite (Group 1) and 7 patients were poly-sensitized aside from house dust mite (Group 2). We also assigned another 7 allergic rhinitis children who were only treated by medication as control group. Nasal symptoms (rhinorrhea, sneezing, nasal obstruction, nasal itching, sleep disturbance) and anti-allergic medications use were assessed at every 6-month visit.

Results: The symptoms of allergic rhinitis started to improve after 6 months of SLIT and significantly improved after a year and a half in group 1 and group 2 compared with control group. There was no significant difference between group 1 and group 2. Anti-allergic medication use in group 1 and group 2 significantly decreased after a year and a half compared with control group and there was no significant difference between group 1 and group 2.

Conclusion: House dust mite SLIT was more effective than treatment only by medication. The effect of house dust mite SLIT was similar between mono-sensitized and poly-sensitized allergic rhinitis children. House dust mite SLIT could also be recommended to polysensitized allergic rhinitis children. Method: A prospective, randomized, double-blind, controlled, multicenter phase II study was conducted with four different concentrations of cluster allergoid CLUSTOID Wiesenlieschgras (group 1: 2000 TU/mL; group 2: 10 000 TU/mL; group 2: 30 000 TU/mL; group 4: 50 000 TU/mL). Out of 103 patients screened, 83 grass pollen allergic patients (18-59 years) were randomized. The cluster build-up phase was followed by four monthly maintenance injections of 0.5 mL. The efficacy was evaluated by the change of the threshold concentration step needed to induce a positive reaction in a titrated nasal provocation test (tNPT) before start and after end of the study (pre-post analysis). The safety profile was assessed for each treatment group by analyzing treatment-related adverse events. Background: Allergen immunotherapy relies on the consistent administration of allergen extract, therefore compliance to these treatments (subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) tablets and drops) is vital for efficacy. As SCIT is administered as an injection by a healthcare professional, and SLIT is self-administered, compliance to SCIT may be perceived as superior. Therefore, a review of real-world studies investigating compliance to SCIT, SLIT-tablets or SLIT-drops was conducted. Real-world studies, instead of clinical trials, were included in this review as they are more likely to reflect actual clinical practice and patient compliance.

Method: A literature review was conducted in Embase, MEDLINE, EBM reviews, PsycInfo and EconLit (1998-2017) using key search terms for AR, SCIT, SLIT-tablets and SLIT-drops, and real-world compliance. Compliance was reported according to ISPOR Medication Compliance and Persistence Work Group definitions.

Results: From the 428 publications identified, eight studies (seven SLIT [one SLIT-tablets, two SLIT-drops, four unspecified], one both SCIT+SLIT-tablets) reported compliance rates and were included in the analysis. Real-world compliance rates ranged from 80% to 81% for SLIT administration and 83% for SCIT administration. Only one study compared compliance of SLIT to SCIT, with similar rates reported over three years (81% and 83% respectively). Three studies reported "good" compliance (physician-reported or patients consuming >60% of allergen extract) to SLIT-drops or SLIT-tablets. The good compliance rates were higher for SLIT-drops (90%-99%) compared to SLIT-tablets (77%-80%). Observed compliance to SLIT-drops or SLITtablets did not vary by country or geographical region. The percentage of patients defined as having "good" compliance to SLIT-tablets or SLIT-drops did not vary by study length or patient population.

Conclusion: Whilst compliance to SCIT may be perceived as superior to SLIT-tablets and SLIT-drops, comparable compliance rates between SCIT, SLIT-tables and SLIT-drops were identified across real-world studies. Differences between perception and real-world results may be explained by a lack of direct comparisons between SCIT and SLIT administration. Limitations included discrepancies in definitions of compliance, as well as methodology between studies.

However, these are common to reviews analysing compliance, regardless of therapy area. Conclusion: In the allergic rhinitis patients, successful compliance for 3-year SLIT compared with control was approximately 52%. Method: IgG inhibition ELISA: Rabbit IgG antibodies specific for grass allergen allergoids are pre-incubated with different concentrations of alum-adsorbed grass pollen allergoid. The mix is added to an allergoid coated microtiter plate. Unbound IgG will bind to the allergoid coat and is subsequently incubated with anti-IgG HRP labeled conjugate and stained with TMB. Results are expressed as percentage inhibition relative to the uninhibited value. The concentration of alum-adsorbed allergoid that is required to inhibit 50% IgG is used as read-out. Circular Dichroism: Far-UV CD spectra (190-260 nm) were recorded on a J-815 Spectropolarimeter. A cuvette with a stirring compartment was used to keep the suspension homogeneous during measurement.

Results: The IgG inhibition ELISA assay is specific for grass pollen allergoids (not for other allergen allergoids), has a good inter-and intra-assay precision and is robust for assay variation. Thermally stressed alum-adsorbed grass pollen allergoids were used to show that the IgG inhibition assay can be used as a stability indicating method. Severe thermal stressing resulted in a higher 50% inhibition value, indicating a loss of IgG epitopes. Furthermore, far-UV CD analyses showed that there is a close relation between the decreasing IgG binding capacity (50% inhibition values) and the loss secondary protein structures by unfolding (CD-ratio 207/222 nm values).

The IgG inhibition assay was demonstrated to be a valuable method to determine the stability of alum-adsorbed grass pollen allergoid preparations. In addition, a relation was shown between the IgG binding capacity and the change in secondary protein structures.

1205 | Design of a pivotal phase III trial of allergen specific immunotherapy (AIT) using a high-dose house dust mite (HDM) allergoid in patients with allergic bronchial asthma Method: 1038 male and female outpatients (age 12-65 years) asthmatics allergic to HDM are enrolled. During the baseline phase, the patient's minimal dose of ICS required to achieve asthma control will be assessed. After the baseline period, approx. 446 patients will receive double-blind placebo-controlled treatment for approx. 8 months, followed by a 2nd period of 16 weeks to assess the minimal ICS dose and further 2 months of observation for the assessment of asthma exacerbation. Based on the results of the dose finding study regarding the efficacy endpoints and the safety profile, the optimal allergoid dose is considered to be 5400 PNU.

Results: Competent Authorities and Ethic Committees in all participating 12 EU countries, Serbia, Russia and Ukraine approved the study design. The primary endpoint of the trial is the change in predefined dose steps of the minimal daily ICS dose required to achieve asthma control after approximately 8 months of subcutaneous AIT.

All efficacy data will be determined using daily questionnaires and the ACQ6 by e-diary for 4 months from October to January.

The aim of this clinical trial is to demonstrate efficacy and to evaluate safety of AIT with an allergoid preparation of major allergens of Dermatophagoides pteronyssinus in patients suffering from allergic bronchial asthma caused by house dust mites. Asthma increases the burden of allergic disease and health care costs, especially when uncontrolled. With the development of a high-dose preparation we intend to treat asthmatic patients highly efficiently.

Romantowski J; Jassem E; lata J; Wasilewska E; Chelminska M; Specjalski K; Niedoszytko M

Background: Specific Immunotherapy (SIT) is the only causal treatment in patients allergic to airborne allergens. It has been proven to be widely effective in allergic populations, but individual patients vary in terms of response to the therapy. The aim of the study was to assess the factors that might affect the efficacy of SIT.

Method: Patients treated with SIT for grass pollen or house dust mites were included. The efficacy of SIT was assessed with the use of Allergy Control Score (ACS), performed before and at least after one year of SIT. The following variables were assessed as potential risk factors for a poorer response to SIT: age, gender, type of allergy, type of allergen, type of vaccine, type of SIT and smoking history. Background: Specific immunotherapy (SIT) is a suitable treatment option for asthma and allergic rhinitis (AR), but it is not commonly used in Korea. In the achievement of the treatment, it is important that immunotherapy is applied with ideal dose and regular intervals and it is essential for the patient compliance. The aim of this study is to investigate evaluate compliance with immunotherapy protocols of patients who were treated with SIT in clinic and their satisfaction of the treatment.

We performed a multicenter, cross-sectional survey using a specially designed questionnaire that was given to allergy specialists and patient in Korea. A member of the trained research group conducted face-to-face questionnaire interviews with each respondent. Conclusion: This study shows that most patients are AR with asthma. In our study SIT compliance and satisfy are found to be high in both groups. Aim: To identify the frequency of regress claims in a dermatological setting and to assess its impact on general prescription behaviour and immunotherapy.

Method: All physicians of the Psoriasis-Praxisnetz Süd-West e.V.

(n = 222) were invited to participate in a web based questionnaire study on the topics of dermatology and medical law. The survey was separated into two sub-polls which were carried out after a first poll deciding whether the topic of medical law is of any interest for the dermatological practice. The topic of interest was located in the second poll.

Results: Overall, 66 dermatologists participated in this study. Most participants were form Bavaria, Baden-Wuerttemberg or Rhineland-Palatinate and had more than 10 years of experience as a dermatologist. Out of the 66 participating physicians 28.8% (n = 19) already experienced a previous regress claim. Of these, 73.7% (n = 14) stated, that the experienced regress claim changed their prescription behaviour. Half of these participants (n = 8) further stated, that the fear of a possible recourse affects their prescription behaviour, whereas only 4 out of the 47 other participants declared a possible influence. Missing values excluded, this leads to a substantial hesitation in physicians who experienced a prior recourse (50.0% vs 16.7%). Nevertheless, this seems not to affect the usage of allergen immunotherapy, as all 19 physicians who already experienced a regress claim, stated to use allergen immunotherapy.

The fear of a possible regress can change physicians' prescription behaviour but does not seem to have an effect on the prescription of allergen immunotherapy. Therefore, the topic should be addressed from another perspective such as providing trainings on relevant regulations for physicians who experienced a prior recourse claim. This approach could also improve patient centred care related to modern treatments. Results: The SDS were significantly reduced in patients subjected to SLIT (P < 0.01) 1 year after the onset it. VAS also was significantly reduced (P < 0.05) with satisfied control of SAR and the same time with translation from moderate-severe to mild-moderate SAR, after SLIT. NBH was also significantly reduced (P < 0.05) 1 year after the onset SLIT. In patients receiving PhT only, SDS, VAS and severity of SAR did not change and significantly higher (P < 0.01) from the value obtained in the experimental group. NBH also remained unchanged and significantly higher (P < 0.05) then in experimental group.

Precoseasonal SLIT added to PhT shows short-term beneficial clinical effects in polysensitized patients with SAR and SCUAD phenotype. Results: Ten studies (248 children, 99 adults; median sample size, 28) met the inclusion criteria. The risk of bias was moderate to high in all but one studies. Low strength evidence supports the assumption that AIT is effective in reducing symptoms and medication use, with only 5 out of 10 studies reporting higher benefit in the AIT group vs comparator group. Subgroup analyses of studies sharing similar characteristics did not explain inconsistency. Safety does not appear was not major concern for Alternaria AIT.

Conclusion: This is not enough strength of evidence to suggest that mold AIT is efficacious for the treatment of respiratory allergies.

High-quality studies with an adequate sample size are needed. ABSTRACTS | 627 1213 | Tolerability of a two week rush updosing with modified trees, modified grasses or modified grasses/trees mixture in pollen allergic subjects in the day-to-day practice Table) Severe systemic reactions (grade III and IV) did not occur. Conclusion: Rush Immunotherapy is an effective therapeutic method for patients with allergic rhinitis. It seems that in cases requiring faster response to treatment, this immunotherapy can be considered as a substitute for conventional immunotherapy.

1217 | Design of a pivotal phase III allergen immunotherapy study to assess the efficacy and safety of subcutaneously administered tyrosine adsorbed modified birch allergen+MPL Results: The design of this study, including sample size and primary and secondary endpoints, will be discussed based on prior experience gained in two dose finding studies. In addition, the number of patients screened and randomized will be presented by country, gender and/or age and screen failures will be categorized. Results: The primary analysis showed an absolute difference in TCS between placebo and 12 DU of 3.02 (40%, P < 0.0001). The odds of experiencing a severe day during the BPS were approximately doubled in the placebo group compared to the 12 DU group (OR = 2.12, P < 0.0001) and the odds of experiencing a mild day were halved (OR = 0.52, P < 0.0001). Similar results were seen for the tree pollen season (TPS), covering both alder, hazel and birch pollen seasons. The total RQLQ score was improved for 12 DU compared to placebo during the BPS and TPS (P < 0.05, except for the last week of the TPS), with the most pronounced effects during week 2-5 of the BPS (absolute difference: 0.47-0.58, P < 0.0001).

Treatment was well tolerated. The most frequent adverse reactions were mild or moderate local reactions related to the sublingual administration. No deaths were reported and no serious adverse events were assessed as related to the SQ tree SLIT-tablet.

Conclusion: Treatment with the SQ tree SLIT-tablet improved ARC symptoms and need for symptomatic treatment. The 12 DU group had less "severe days" and more "mild days" during the pollen seasons. The quality of life was similarly improved. These findings substantiate the clinical relevance of the SQ tree SLIT-tablet for patients with ARC induced by pollen from the birch homologous group.

Nagaraju K 1 ; Nagaraju K 2 ; Katare S 3 ; Kapatkar V 3 ; Shah A 3 ; Rathod R 3 Results: Total n = 57 subjects (mean age 4.6 ± 2.09 years, 61.4% males) completed entire study. The mean incidence of ARTIs reduced from 7.7 ± 2.34 episodes at baseline to 1.4 ± 1.23 (P < 0.001), with 31.6% subjects not suffering from any episode. The mean duration of episodes reduced from 8.2 ± 3.58 to 2.5 ± 1.23 days (P < 0.001).

64% of episodes (vs 95% at baseline, P < 0.05) required antibiotics for mean duration of 2.3 ± 0.98 days (vs. 6.6 ± 1.76 days, P < 0.001). None of ARTI episodes in follow-up period required hospitalization as against 22.8% episodes, (mean duration 5 ± 2.06 days; P < 0.05) before pidotimod therapy. The number of school days lost & work days lost showed reduction of 3.6 ± 5.34 days(P < 0.001) & 0.1 ± 4.07 days(P = 0.871) respectively. The average expenses incurred in treatment of ARTIs shows significant reduction of Rs. 13 193 ± 1541 (P < 0.001). 11 adverse events were reported in 8 (14%) subjects, which were mild in nature. A statistically significant increase in absolute counts of T-& NK cells was seen in explorative assessment of immune markers.

The study shows Pidotimod to be well-tolerated effective therapy in reducing the incidence and severity of recurrent ARTIs, thereby providing additional benefit of reduction in discomfort & healthcare cost due to recurrent ARTIs. Thus, Pidotimod can be considered as potential therapeutic option for treatment of recurrent ARTIs in children.

Martignago I 1 ; Ridolo E 1 ; Incorvaia C 2 1 Department of Medicine and Surgery, University of Parma, Parma, Italy; 2 Cardiac/Pulmonary Rehabilitation, ASST Pini/CTO, Milan, Italy Background: Two registered sublingual immunotherapy (SLIT) products are available to treat grass-pollen induced rhinoconjunctivitis, consisting of the 1-grass (Phleum pratense) and the 5-grass pollen tablets. No study of direct comparison of the efficacy of the two products was performed. We report the case of a patient who was treated in different years with the 5-grass or the 1-grass tablets with contrasting efficacy.

The patient was a 18-year old woman suffering from 3 years of grass pollen induced rhinoconjunctivitis. In 2015 SLIT was started with the 5-grass pollen tablets, but in 2016, due to unavailability of the product, SLIT was performed by the 1-grass pollen tablets. In the third year of treatment SLIT with the 5-grass pollen tablets was resumed. For the 5-grass tablets SLIT was initiated before the pollen season and stopped after 7 months of treatment, while for the 1-grass tablets the treated was prescribed to be continuous. The efficacy of SLIT was evaluated by symptom-medication scores as reported in diary cards by the patient during the month of May, when the grass pollen usually reach the higher concentration in the atmosphere in Lombardy, where the patient lives.

Results: The mean symptom-medication score in the first year of treatment (5-grass tablets) was 4.35, compared with a mean score of 7.2 in the second year (1-grass tablets). The patient was unsatisfied of the symptoms control and asked to resume for the last year of SLIT the 5-grass tablets. The mean symptom-medication score in such year was 0.77. No clinically relevant adverse event was reported with any SLIT product.

Conclusion: Based on the momentary unavailability of the 5-grass pollen tablet, it was possible to assess in a same patient the clinical outcome associated to either of the two registered SLIT products. A significantly different efficacy of SLIT with the 5-grass tablets compared with the 1-grass tablets was observed.

1222 | Fusion proteins consisting of Bet v 1 and Phl p 5 form IgE-reactive aggregates with reduced allergenic activity Najafi N 1 ; Hofer G 2 ; Gattinger P 1 ; Smiljkovic D 3 ; Blatt K 3 ; Selb R 4 ; Stoecklinger A 5 ; Keller W 2 ; Valent P 3 ; Niederberger V 4 ; Thalhamer J 5 ; Valenta R 6 ; Flicker S 6 Background: Bet v 1 and Phl p 5 representing major allergens in birch and grass pollen, occur as monomeric proteins with high allergenic activity as assessed by clinical provocation testing in patients. She did not suffer more hymenoptera stings after the last reaction.

One bee sting several years before BST resulted in no reaction. She has no symptoms with honey, vegetable or other food ingestion.

Methods: Total IgE and specific IgE were determined using Inmu-noCAP system (Thermofisher, Scientific Inc).

Apis, Vespula and Polistes (Hørsholm, Denmark) were also performed. Prick tests showed negative results for all extracts tested. Intradermal skin tests were positive for Apis at 1 μg/mL, but negative for Vespula and Polistes.

Our patient was diagnosed of anaphylaxis due to Apis venom, thus BST was contraindicated and an epinephrine autoinjector was prescribed. She rejected hymenoptera venom immunotherapy.

Conclusion: To our knowledge, this is the first case of anaphylactic reaction after bee sting therapy.

Bee sting therapy should be considered a risk factor for anaphylaxis. Patient reported good control of their disease, improved their quality of life, tolerating contact and exposure to numerous horses as well as contact with clothes of people who had been exposed.

Although ITA is absolute contraindication on uncontrolled asthma with a degree of evidence Ia, our case had only "transitory" con- 

and ImmunoCAP among wasp allergen components-i3, i209, i211 were 88%; 0.5, 90%; 0.6 and 68%; 0.4 respectively and honey bee allergen components-i1, i208, i217 were 95%; 0.9, 93%; 0.7 and 97%; 0.9 respectively. Agreement between Polycheck and Immuno-CAP i1 and i3 allergen components were 85%; 0.7 and 66%; 0.3 respectively. Agreement between Polycheck and EUROLINE i1 and i3 allergen component were 86%; 0.7 and 61%; 0.2 respectively.

Based on wasp and bee components in all three systems, sensitization pattern was analyzed. Similar test results were found between EUROLINE and ImmunoCAP systems.

The comparative studies carried out showed a markedly higher compliance of results with the EUROLINE tests compared to Polycheck with the ImmunoCAP system. Percent agreement was extremely high and kappa value was substantial or almost perfect in the case of bee venom allergy between EUROLINE Results: A total of 113 patients were included; 80 (71%) males, with a mean age of 38 (±15) years; 23 (21%) beekeepers, 25 (23%) were atopic, 4 (4%) had asthma, 14 (13%) rhinitis and 18 (16%) cardiovascular disease, and 14 of these patients were on ACE/beta blockers. VIT with honeybee was proposed in 73 (64%), wasp 38 (34%) and Polistes 2 (2%).

The mean duration of VIT was 45 (±16) months. However, 23 completed less than 36 months. Of the total, 28 patients (25%) were not treated with VIT.

Eighty-eight patients (78%) participated in the telephone interview: 49 completed VIT (56%), 15 were still on VIT (17%) and 24 did not undergo VIT (27%). Of those who completed VIT, 14 (29%) were restung and 3 went to the emergency department (ER). Twenty-four patients (36%) were stung while still on VIT. Of those never on VIT, 12 (50%) were re-stung and 9 went to ER.

The severity of the reactions according to Mueller of the patients who completed VIT (mean follow-up time was 45 months (1-110 months)) and were stung again was: local reaction in 11 (79%), grade I in 1 (7%); grade III in 1 (7%). One had a toxic reaction after multiple stings. In those who were stung during VIT, 20 (87%) had local reactions, 1 (4%) grade I and 2 (9%) grade III. Of those who were not treated and were re-stung: 3 (25%) had grade I, 4 (33%) grade III and 5 (42%) grade IV. In this series, the patients who did not undergo VIT presented a greater number of systemic reactions when re-stung as well as more severe reactions (P < 0.01).

Conclusion: In this group with indication for VIT, the reactions of the re-stings were less severe in the patients who had completed or who were on venom immunotherapy, as expected. Three quarters of those who did not undergo treatment had severe anaphylactic reactions when they were stung again. This study reinforces the importance and the efficacy of immunotherapy in the treatment of hymenoptera venom allergy. Method: This is a retrospective, descriptive study of cases diag- Method: Data were issued from the reference centre in mastocytosis of Toulouse University Hospital. MS diagnosis was determined using World Health Organization diagnostic criteria. Hymenoptera venom immunotherapy was performed with an ultra-rush protocol (Table) .

Results: Seven patients were included (4 women, 3 men), median age 47 years old. During the anaphylactic reaction, cutaneous signs missed in all cases. The reaction was most often severe: grade 2 (n = 1), grade 3 (n = 5), grade 4 (n = 1). Three patients suffered from digestive symptoms and one from respiratory manifestations. Basal tryptase in serum reached 10.1-41.7 μg/L. Hymenoptera venom specific IgE were low (0.11-1.51 kUI/L) except for one patient (35.6 kUI/L). AIT was initiated with Vespula venom in 3 patients, Polistis in 1 patient, Apis mellifera and Vespula in 1 patient, Vespula and Polistis in 2 patients. No reaction was observed during AIT. Four restringing accidents led to increase the cumulative dose to 150 μg and 200 μg in 2 patients. In these patients, the diagnosis of mastocytosis was made due to the resting.

Conclusion: Hymenoptera venom AIT using ultra-rush protocol seems well tolerated in patients with systemic mastocytosis. Specific studies are necessary to determine the real tolerance profile of this protocol. Collaboration with reference centres for mastocytosis should be considered for all patients with mastocytosis associated to hymenoptera venom allergy.

Dose (μg/mL) Results: See Table. Conclusion: There is a shift or immunomodulation in terms of sIgE to vespids. even in patients double sensitised who were receiving venom of only one of the vespids.

Albanesi M Background: SLIT has been suggested as an alternative route for allergen-specific immunotherapy. Aim of this study was to investigate allergen-specific antibody responses in birch pollen allergic children who had received SLIT for two years using recombinant allergens.

Method: Children (n = 28; 5-12 y o) with respiratory symptoms of birch pollen and oral allergic syndromes (OAS) were studied. Ten children received SLIT with Staloral, 10 were treated by SLIT with Microgen, and 8 children received only symptomatic therapy (control group). sIgE and sIgG levels to rBet v 1, rBet v 2, rBet v 4 were measured twice (before therapy started and after two years) using quantitative ImmunoCAP and a panel of more than 170 microarrayed allergens using ImmunoCAP ISAC technology. Clinical efficacy of SLIT was evaluated by recording symptoms upon allergen contact and need of rescue medication.

Results: All 28 children were sensitized to the major birch pollen allergen, Bet v 1 and one patient from each of the groups showed to Bet v 2, no patient had sIgE to Bet v 4. After two years of SLIT clinical improvement was observed in the SLIT patients. In the Staloral group there were no respiratory symptoms in 3 patients and a decrease of symptom severity in the other 7 cases as well as a partial or complete tolerance to PR10 allergen-containing food in the 10 patients. Microgen treatment had no influence on OAS symptoms but decreased of pollinosis severity in 8 children. However, there were no statistically significant differences of Bet v 1-specific levels measured before and after treatment in the SLIT and control groups (Mann-Whitney, P > 0.05).

In this real-life study we found that birch allergic children who had been treated with SLIT showed a reduction of clinical symptoms but we did not find a significant induction of allergen-specific IgG levels in the SLIT-treated group when compared with children who had only symptomatic treatment. Conclusion: Our study confirms the scarcity of food additives allergy. It also suggests that even when the diagnostic of allergy was excluded with a negative oral food challenge, families remain suspicious about industrials feeding products containing food additives.

These results should reassure health professionals and parents who incriminate too frequently food dyes and conservators when a manifestation which mimics allergic reactions occurs. Background: Autumn/winter birth has been reported to be a risk factor of food allergy (FA) development. A putative mechanism is that dry/cold weather causes and exacerbates infant atopic dermatitis (AD), which is a major risk factor for food sensitization through inflamed/damaged skin. We investigated prevalence of FA among infants under well skin care in relation with seasons of birth (SoB).

We recruited full-term newborn infants without perinatal diseases at an obstetric/pediatric clinic. Participants were followed up for skin status and food allergy symptoms until 12 months of age. SoB were defined as spring (March-May), summer (June-August), autumn (September-November) and winter (December-February). AD was diagnosed based on the United Kingdom Working Party's criteria. Use of moisturizer (Mo) and topical corticosteroids (TCS) was recorded. Primary outcome was FA based on apparent immediate allergic reaction after ingestion of causative food. We classified infants who avoided any food because of sensitization or mother's anxiety as suspected FA.

Results: Six hundred and thirty-one infants were screened for 12 month-period and 531 infants were enrolled in this study. Of them, 277 infants were born in spring-summer (S-born) and 254 infants were born in autumn-winter (W-born). FA developed in 24 (4.5%) infants and 31 (5.8%) infants had suspected FA. There was no difference (P = 0.68) in prevalence of FA and suspected FA between S-born and W-born. Multivariate analysis revealed AD at 2 and 7 months of age was a significant risk factor for FA with OR=2.6 (95%: 1.1-6.0) and OR=3.5 (95% CI: 1.4-8.9), respectively. Prevalence of AD at 2 months of age was higher in W-born than S-born but prevalence promptly decreased thereafter and stayed low with early use of Mo and TCS. Prevalence of AD was rather higher at 7 months in S-born than W-born. Results: 160 cases and 126 controls were included. The median age was 44 years, (Q1-Q3 33-53). Men and women were almost equally represented (50.35% males). Alcohol consumption associated with the intake of mammalian meat or innards as the trigger factor.

The overall prevalence of a positive result of sIgE to α-Gal was ABSTRACTS | 645 15.7% IC95% (11.5, 20 .0); cases _26.3% IC95% (19.4, 33.1) controls _2.4% IC95% (0.0, 5.1)_. Among cases sIgE anti α-Gal positivity rate ranged from 55.8% (rural), to 35.7% (half-urban) and 12.6% (urban).

The rates of positivity were 69.5%, (Northern) 1.4% (Center) and 0% (Mediterranean). A positive result of sIgE to α-Gal was more frequently observed among men (24.31%) than women (7.04%) and associated with history of tick bites, practice of outdoor activities, pet's ownership and the antecedent of having eaten mammalian meats or innards previously to the development of symptoms Background: A special challenge in the 21st century for allergists is allergy to food, which is considered "the second wave" of epidemics of allergic diseases. Panallergens occur in unrelated organisms and perform a similar function in them. In their structure, they have highly conserved amino acid sequence regions and a similar three-dimensional structure, and thus meet the requirements for cross-recognition by IgE. Results: In 46 patients (92%) ISAC test has been shown to have specific IgE for panallergen components. Mostly, the presence of IgE for PR-10 proteins has been shown in 41 patients. In 12 patients IgE to LTP; 11 patients IgE to CCD; 6 patients to profilin; 5 patients to tropomyosin; 4 patients to serum albumin, 1 person to TLP. An important aspect is undoubtedly the occurrence of simultaneous sensitization to several panallergens. Analysis of data from the study group showed that isolated sensitization to one panallergen concerned only PR10 proteins (24 patients), tropomyosin (2 patients) and profilin (1 patient).

In the remaining 19 patients, the analysis of the ISAC test results showed that two or more panallergens were allergic. In the study group, asIgE for the component responsible for the occurrence of real food allergy was detected in 13 (26%) patients. Mostly, the presence of IgE for Jug r 2 has been shown in 9 patients.

In the study group, panallergens were more likely to be responsible for food intolerance than specific food allergens. Results: Of 43 children, 14 children had peanut allergy only, 14 children had tree nut allergy only, and 15 children had both. The mean age was 3.3 ± 1.9 years in peanut allergy, 5.0 ± 3.6 years in tree nut allergy, and 4.2 ± 3.0 years in both. Male to female ratio was significantly higher in tree nut allergy (78.6%) than peanut allergy (42.9%). Among tree nut allergens identified, walnut (75.9%) was most frequent, followed by almond (55.2%), hazelnut (34.5%), pine nut (20.7%), chestnut (13.8%), cashew (6.9%), pistachio (3.4%), and macadamia (3.4%).

Mean serum total IgE level was 888 kUA/L in tree nut allergy and 1440 kUA/L in peanut allergy. Mean serum specific IgE level to peanut, walnut, almond, hazelnut, and pine nut was 30.0, 21.9, 14.2, 22.4, 5.6, and 6 .3 kUA/L, respectively. Children with peanut allergy had higher rate of co-sensitization with soybean and higher soybean-specific IgE levels than children with tree nut allergy. However, there was no difference in co-sensitization rate with tree pollen between peanut and tree nut allergy. Children with peanut allergy showed significantly increased co-sensitization rate with egg white and wheat compared to children with tree nut allergy. A 42.8% of the children with peanut allergy and 28.6% of tree nut allergy showed co-sensitization with aeroallergens. A total of 75% of the children with peanut allergy showed decreased specific IgE levels within 1-5 years. Conclusion: Prevalence of peanut and tree nut allergy is similar.

Tree nut allergy develops later than peanut allergy and more common in male. Children with peanut allergy showed higher co-sensitization rate with soybean, egg white and wheat compared to children with tree nut allergy.

1257 | Natural history of egg allergy in a large cohort of infants with food allergy shows its high prevalence but also its transient nature in a 36 months of follow-up Background: The cohort of 80 infants (55 boys,25 girls,3-36 months) with the food allergy has been followed for 36 months.

As more than 70% of infants manifested atopic dermatitis (AD), a condition closely linked to egg sensitisation, we focused our attention on egg allergy, following its natural history as well as a development of atopic march.

Method: The diagnosis of food allergy was based on a personal history, clinical examination, skin prick tests and/or atopy patch tests with native foods. Laboratory tests were performed within 1 year of age the latest. The specific IgE levels against food allergens were measured using ImmunoCap or Immulite.

Patients with AD were scored according to SCORAD system. The oral food challenges (OFCs) with cooked/baked egg were done in children at the age of 12 months except for children at risk of anaphylaxis.

Results: Within the whole cohort the allergy to cow milk proteins was confirmed in 70 pts (87.5%), to egg in 35 pts (43.7%), to wheat in 8 pts(10%), to lentil in 3 pts (3.75%) to banana in 3 pts (3.75%), to soya in 2 pts (2.5%) and to potatoes in 1 pt (1.25%).

In a cohort of 35 egg allergy patients we found out that: 83% of pts presented the early onset of allergy-up to 3 months of age, 80% of pts presented severe AD (SCORAD >50), 46% of pts showed cosensitisation to peanuts, 34% of pts had early sensitisation to inhaled allergens, and majority 54% of pts presented with early onset allergic rhinitis and/or asthma.

We proved that egg allergy is closely linked with the early onset of allergy symptoms, with severe forms of AD, co-sensitization to peanuts, early sensitisation to inhaled allergens and an early onset of allergic rhinitis and/or asthma.

We also proved that the egg allergy in infancy is transient. The tolerance to baked/cooked egg was achieved in about 75% of pts at the age of 3 years, unlike previously published results claiming the reach of tolerance in 75% of pts at the age of 7 years. In these patients we studied: sex, personal history, type of reaction they presented, time of onset of symptoms and food involved.

Results: Out of a total of 1479 patients over 60 years of age (from 60 to 99 years old) who have been attended the consultation for the first time during these period, 70 patients (4.7%) ask about possible allergic food allergies. Of these patients who came for possible allergic pathology, 28 patients (40%) presented positive results.

These are the other item we have studied:

1. Sex of patients: 55% of the patients are women. these patients because of that, it is important to remember that food allergy can also appear in old people.

The food that is mainly involved in our population is fish and seafood. A much higher percentage than in other populations, probably due to the Mediterranean diet of Spain. The symptoms mainly involved are itching and skin lesion, which is the characteristic symptom of a mild allergic reaction.

In our population, there was 3 patients with a anaphylactic shock, a much higher percentage than in other studies.

The experience with this group of patients is still limited. More studies are needed to know better this patient profile. Background: Cow's milk allergy (CMA) is the first atopic disease in children. Diagnosis suspicion in the emergency room (ER) is increasingly frequent, however, further assessment by an allergist is often difficult to schedule. Therefore, screening for CMA through a blood test (specific IgE) while the infant is still in the ER has gained momentum in recent years. We set out to analyse (a) symptoms which had led the emergency physician to prescribe specific IgE, (b) the prevalence of confirmed CMA among infants screened in the ER, and (c) the long-term outcome of the screened infants.

Method: A retrospective study of medical records and laboratory results was performed. Patients were infants under 6 months, without a previous diagnosis of CMA, attending one of the two Pediatric ER of the University Hospitals of Marseille, France.

Allergy blood tests were specific IgE to cow's milk extract (Immuno-CAP, ThermoFisher, Sweden). In infants with specific IgE to cow's milk extract of 0.12 kUA/L or higher, IgE directed to the main three individual proteins (casein, alpha lactalbumin et beta lactoglobulin) were also measured.

Results: 482 infants were included from December 2011 to June 2016. The sex ratio was 1.45. 40% of infants were atopic et 48% were currently or had been breastfed. The most prevalent symptoms were vomiting and reflux. One third of infants were hospitalized after the ER visit.

Following the ER visit, 25% of infants attended a specialized consultation with an allergist. 15% of infants with a follow-up visit were diagnosed with an IgE mediated CMA.

18 infants with CMA developed further food allergies (egg, nuts, cashew…).

it is difficult to diagnose it. The emergency pediatrician are increasingly confronted to infant with symptoms evoking CMA. Thus they prescribe sIgE and extensively hydrolysed proteins because they know that IgE-positive infants can be IgE-negative during the interval between the ER visit and the follow-up one. After bad results interpretation of blood assay after ER visit, CMA was probably over diagnosed without prick test for IgE positive allergy and no eviction/ reintroduction test for non IgE.

The lack of allergist is probably leading to over prescription of blood assay in ER to diagnose CMA and prolonged eviction of milk. Results: A total of 96 patients were included (59% female) aged from 18 to 82YO with an average 33.9 ± 15 years. 77% of patients had history of atopic disease: 60% rhinitis, 30% asthma, 9% prior food allergy, 8% eczema, 6% drug allergy, 5% eosinophilic esophagitis (EE) and 3% chronic urticaria. Mean serum total IgE was 441.9 UI/mL. Sensitization to aeroallergens was present in 63% of patients, the most common were dust mites (22.9%), pollen (15.6%) or both (25%). In 69(72%) patients, first symptoms of FA appeared ≥18 YO, with an average age of 35 ± 15.4 YO. In this group, 4 were diagnosed with EE, 1 with eosinophilic colitis and 2 with eosinophilic gastritis. From the remaining 62 patients, 20 had history of reaction with more than 1 food group (FG). Cutaneous reactions were referred in 60% of patients followed by anaphylaxis (20%) and gastrointestinal symptoms (10%). The FG most commonly implied were:

Fresh fruits (N = 26), seafood (N = 19) and tree nuts (N = 6). FA diagnosis was confirmed in 66% of patients, the remaining had negative OFC.

In 27(28%) patients, their symptoms started under 18 YO, with an average age of 11.5 ± 5YO. From this group, 10(44%) were diagnosed EE. From the remaining 17 patients, cutaneous complaints were the most frequent (47%) followed by gastrointestinal (35%) and respiratory symptoms (17%). The most common FG implied were:

Fresh fruits(N = 9), seafood(N = 4) and tree nuts(N = 3). Only one anaphylaxis was referred. FA was confirmed in 82%, the remaining had negative OFC.

In patients with history of anaphylaxis 13 of 14 had positive ST and/ or sIgE; one had negative SP and sIgE, with OFC positive. 

The 401 blood donors were classified based on their clinical symptoms related to possible AS contact via fish intake: allergic to AS (1%), chronic urticaria (0.5%), unspecific dyspepsia (2.8%) and asymptomatic (95.5%). The prevalence of sensitization (anti-AS IgE >0.35 KUA/L) were 12.7% (IC: 9.6-16.4%; mean 0.69 KUA/L; median 0.03 KUA/L) with a maximum value of 40.70 KUA/L. Raw fish consumption was the only variable associated with statistical significance (P < 0.05) to AS sensitization (20.4% vs 9.5%, respectively).

Albacore and codfish were the most consumed species associated to seropositive results (15%), followed by hake (10%). Coastal population (13.6% vs 9.3%), non-previously frozen fish consumption (13.7% vs 9.2%) and >3 times per week fish consumption (51.2%) were other seropositive associated factors. 

Background: Oral allergy syndrome (OAS) is an IgE-mediated allergy caused by raw fruits and vegetables in patients with pollen allergy, which is known as the most common food allergy in adults.

However, there has been no nation-wide study on oral allergy syndrome in Korea. The aim of this study is to investigate the prevalence and clinical manifestations of OAS in Korea.

Method: Twenty two investigators from 19 hospitals and 2 private clinics participated in this study. The patients with allergic rhinoconjunctivitis and/or bronchial asthma with pollen allergy were enrolled to the survey. The questionnaires include demographics, a list of fruits and vegetables, and clinical manifestations of food allergy. Pollen allergies were diagnosed by positive results of one or more pollen allergens including birch, alder, hazel, beech, oak, willow, poplar, bermuda, meadow, orchard, rye, timothy, mugwort, ragweed, Hop japanese on allergy skin prick tests (allergen/histamine ratio ≥3+) and/or serum specific IgE levels using Multiple Allergen Simultaneous tests (MAST ≥2+) or immunoCAP (≥0.35 kU/L). Conclusion: This is the first nation-wide study for OAS in Korea.

The prevalence of OAS in Korea was 41.7%, in which substantial proportion had anaphylaxis. These results will provide useful information for clinicians to apply in clinical practice. 

We conducted a self-administered, questionnaire-based survey in 2013-15 during the 18-month checkup. Children were considered to have food allergies if they were diagnosed by a physician or if they had been instructed to avoid a causative food after medical examination by interview.

We divided the year into three periods. The months of March-June were considered spring, July-October as summer/fall, and November-February as winter. While the season of onset for the 4095 boys occurred in 8.2%, 12.7%, and 15.3% in spring, summer/fall, and winter, respectively, it was 6.9%, 10.5%, and 12.2%, respectively, for the 3922 girls. Thus, the onset rate was the highest in winter for both genders.

In boys whose mothers did not consume folic acid (FOL − ), the food allergy onset rate was significantly higher for boys whose mothers ate no eggs and for boys whose mothers ate 2-5 eggs per week than for those whose mothers ate eggs daily according to the Dunnet multiple comparison test. However, no relationship was observed with egg intake if the mother had consumed folic acid (FOL + ).

On the basis of seasons, FOL − and egg intake by mothers affected only children born in winter, with a significant difference in the Dunnet multiple comparison. Among mothers who did not eat eggs, FOL + was 15.2% and FOL − was 28.2%; for mothers who ate 2-5 eggs per week, FOL + was 16.5% and FOL − was 12.9%; and for mothers who ate eggs every day, FOL + was 17.9% and FOLwas 4.9%. Thus, consumption of folic acid seemingly annulated the effects of eating eggs.

However, for girls, neither folic acid nor eating eggs had any effect on the onset rate.

Conclusion: Since this effect varied according to the birth season, consumption of folic acid, a methyl group donor, appeared to affect the allergy onset in children. Results: Skin prick test with commercial extracts of tuna (7 mm), cod (5 mm), rooster (8 mm), hake (6 mm), salmon (4 mm), trout (7 mm) and Anisakis (7 mm IgE to shrimp, lobster, crab and mixed seafood were all undetectable.

Dermatophagoides pteronyssinus 10, to assess for tropomyosins was negative.

Outcome: The patient continues to react to both HDM and shrimp, despite undetectable IgE levels to tropomyosin associated components. This is the only testing available in South Africa currently and hence we are unable to look at other proteins.

The relationship between tropomyosins in shellfish allergy and mite allergy has been well documented and investigated, but other allergens are now also being implicated in cross-reactions. We also established the level of IgE specific to allergen components using the ImmunoCap ISAC method. Allergen-specific IgE was not elevated to any shrimp allergens available in ImmunoCap ISAC: n Pen m1 (tropomyosin), n Pen m2 (arginine kinase) and n Pen m4 (calcium binding sarcoplasmic protein).

The patient was diagnosed with a shrimp allergy. The molecular diagnostics used did not explain which allergen component is the patient allergic to. It is possible that the patient is allergic to hemocyanin, which can also cross-react with house dust mite allergens, but confirmation of this diagnosis requires further investi- Results: The groups were identical in terms of the age and sex (Table 1) . Ara h 2 IgE correlated (Spearman test) with the cumulative protein dose (threshold dose) r = −0.439 (P = 0.023) but not with reaction severity r = 0.091 (P = 0.348), or the use of adrenaline r = 0.300 (P = 0.093). Patients with Ara h IgE < 10 kU/L had higher threshold doses (644 vs 71 mg) than children whose Ara h 2 IgE was ≥10 kU/L (P = 0.016). There were no significant differences in severity of the reaction or in use of adrenaline (Table 1) .

The level of Ara h 2 IgE is relevant in predicting the threshold dose at peanut exposure. A low reaction threshold dose increases the risk of reaction at an accidental exposure leading potentially to a severe reaction. Flaxseed allergy is uncommon and most of the cases reported involved anaphylaxis. Cross reactivity has been described with other seeds.

Case report: A 9-year-old atopic girl diagnosed with egg allergy and rhinoconjunctivitis and asthma due to pollens.

When she was eight, she presented two reactions consisting of conjunctival, periorbicular, malar erythema and abdominal pain after eating egg free French toasts cooked with flaxseed. She was treated with oral antihistamines.

The allergic workup included prick-by-prick test with flaxseed which was positive and skin prick tests with mites, molds, cockroach, cat, dog, profilin, LTP and pollens with positive results for olive and grass pollens. The serum total Immunoglobulin (Ig) E was 476 U/L, and specific IgE to flaxseed was 7.23 kUA/L.

The flaxseed extract was resolved with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and an IgE immunoblotting was performed under nonreducing conditions.

The patient's serum showed specific recognition of a 18-kDa band in the immunoblot.

Proteins were identified using mass spectrometry (MALDI-TOF) that

showed results highly consistent with conlinin, a 2S storage protein of flaxseed.

We described for the first time a patient with allergy to flaxseed due to conlinin, a 2S storage protein of flaxseed. Background: Cyperus esculentus is an herbaceous plant that has edible tubers called tiger nuts. In Spain, they are used mainly in the elaboration of the well-known "horchata" or tiger nut milk, which is obtained by macerating tiger nuts with water and sugar.

Tiger nut allergy has rarely been reported, despite of its widespread consumption.

Case report: We present the case of a 19-year-old male with a history of oral syndrome allergy with several fruits (peach, melon, banana, kiwi, apple, pear and plum) and seasonal allergic rhinoconjunctivitis due to grass pollen.

He reported oral pruritus, vomiting and cutaneous itching in both arms and hands immediately after drinking tiger nut milk. He became asymptomatic without treatment after 3-4 hours.

The allergic workup included skin prick tests with profilin, LTP, latex and fruits that were positive to melon and watermelon and negative to profilin, LTP, latex and the rest of the fruits. Prick-by-prick tests with melon, banana, kiwi, apple, pear, tiger nut and tiger nut milk were positive.

The serum total immunoglobulin (Ig) E was 68.7 μg/L, and specific

IgE was negative to profilin, LTP, bet v1 and all the tested fruits. Background: Specific blood IgE tests for food allergens are mainly used to confirm a suspect food allergy than to diagnose such an allergy. This is due to the low positive predictive value and the high negative predictive value they have. Nevertheless, they are very helpful when they are interpreted in the context of medical history by an experienced allergist. We analyzed the prevalence of sIgE in children with suspected food allergies.

We retrospectively analyzed the all the consecutive laboratory tests of sIgE for food allergens during the two-year period (2015) (2016) (2017) . Tests were of children diagnosed or suspected to have food allergies. A quantitative immunoblot assay was used to measure the circulated 30 different sIgE. T-test, Wilcoxon Signed Rank test, and chi-square were used to make comparisons.

Results: Fifty-six (55.4%) men and 45 (44.6%) females, 3.4 + 3.2 years old with a maximum of 16 years and a minimum of 2 months old were part of 101 children whose tests were analyzed.

One-third of the tests (30.7%) reveals more than one sIgE present and 55.4% of the tests resulted negative for the sIgE for the 30 allergens tested (Table) .

Only 3 (3.0%) children have very high concentrations (>100 IU/mL) of Egg Whites sIgE, and 2 (2.0%) have Egg yolk sIgE. Concentrations of 79.27% of sIgE positive cases were 0.35-3.5 IU/mL.

In our study more than half of the children suspected of food allergies resulted negative for sIgE for 30 most common food allergens. Seventy-nine percent of the positive cases had relatively low sIgE. Only a few positive cases have higher sIgE than 100 IU/mL. Our data support the recommendation that sIgE couldn't be decisive in food allergic diagnosis, but they may help if they are interpreted cautiously. Method: Seven patients with a mean age of 61.4 years and female to male ratio of: 3:4, with a background history of hypertension treated with an ACEi presented with oro-pharyngeal irritation (itch, tingling), face and tongue angioedema and laryngeal constriction, on ingesting fresh fruits (cherries, apples, plums, peaches, apricots, strawberries, grapes), vegetables (parsnips) and/or nuts (peanuts, hazelnuts). Two patients required admission to emergency department and three received adrenaline auto-injector. Six out of seven patients underwent skin prick testing to common aeroallergens and the index foods. In five cases, Immunocap/ISAC testing was undertaken. In one case the diagnosis was based on the history and in one other case it was based on history and skin prick tests.

Results: A diagnosis of PFAS was confirmed in all patients through the clinical history, SPT and/or specific IgE serology to the offending food confirming predominant sensitisation PR-10 allergens. Primary food allergy and spontaneous angioedema was excluded in all patients.

In the cohort studied, the PFAS symptoms were unusually severe. We therefore postulate that this was secondary to concurrent use of ACEi. The management of these patients to sensitization to a β-casein with high homology between only the first 3 milks. More precisely, the allergen candidate could be γcasein, which is derived from β-casein by proteolysis, whose abundance increases during cheese production from fresh milk, and which is absent in cow's milk. A lactoglobulin specific to buffalo's milk may also be responsible.

In case of ewe's and goat's milk allergy without cow's milk allergy, sensitization to buffalo's milk should systemically be seeked out.

We recommend inclusion of all mammalian milks in the list of the 14 mandatory allergens for declaration on food products. Method: Prick tests with fruit battery, LTP and profilin was made.

Analytical with blood count, immunoglobulins, triptasa, total IgE and specific IgE to banana, apple and orange. Finally, open oral provocation with fruits was performed.

The diagnostic key was given by the mother of the patient who attended consultations because the infant had erythema in the temporary zone after drinking sea water on the beach. Associated with salivation, the patient presented erythema in the malar area lasting a few seconds many times.

The prick tests with fruits, LTP and profilin were negative.

Hemogram: 100 eosinophils/μL, total Ig E: 4.9 IU/mL, specific IgE to fruits were negative. Triptase: 5.1 μg/L. Method: Here we describe a variety of cases of nsLTP allergy presenting to a tertiary allergy centre in the North West of England.

Results: nsLTPs have been found to be major allergens in various foods and they are likely to produce severe and systemic allergic reactions. This is reflected in the cases we present here. These proteins are highly cross-reactive due to extensive sequence homology and are panallergens. nsLTPs are remarkably heat stable and retains its allergenicity in processed foods. It is assumed that nsLTPs may sensitise both by inhalation and ingestion. An intriguing aspect in nsLTP hypersensitivity is the extreme variability of its clinical expression. Co-factors are often needed for the clinical expression of nsLTP hypersensitivity.

Conclusion: Patients regardless of where they are from, presenting with multiple severe/systemic food allergies need to be investigated for nsLTP allergy. These patients require specific dietary advice on foods to avoid and a tailored management plan on how to deal with their allergic reactions. Cow's milk as well as cow's milk products are tolerated.

Material and Methods: Skin prick tests with different sorts of milk, cheese and milk proteins were performed, specific IgE antibodies were measured, a basophil activation test with cow's and goat's milk was performed and an oral provocation test (OPT) with cow's milk, cow's milk cheese, raw milk and raw milk cheese was conducted.

Results: Skin prick tests were positive for sheep's milk, goat's milk, goat's milk casein, feta, pecorino and parmesan cheese. Elevated specific IgE against goat's milk (12.7 kU/L) and sheep's milk (11.7 kU/ L) were detected. Activation of basophil granulocytes after incubation of the patient's blood with cow's milk and goat's milk was measurable but also in the non-incubated control blood. All cow's milk products were tolerated in the OPT.

Conclusion: Despite consistent homologies between whey and casein proteins of mammals and high cross-reactivity between cow's, goat's and sheep's milk an isolated goat's and sheep's milk allergy with tolerance of cow's milk is possible. Skin testing and specific IgE help to distinguish from allergy against cow's milk proteins. Diet counseling is possible after OPT. Introduction: Salmon roe's allergy, without concomitant fish allergy, is rarely described in western countries. There are few studies on its allergenicity.

Objective: To report of a case of salmon roe allergy without concomitant fish allergy in a western country.

Case report: A 26-year-old male with house dust mite allergic rhinitis and asthma, describes for the 1st time, in 2015, an acute episode of dyspnoea, rhinorrhoea, ocular pruritus, epigastric pain and nausea, a few minutes after the ingestion of a sushi meal with rice, salmon, salmon roe, wasabi, soy and ginger. These complaints motivated observation in the emergency room, where it was still documented uvular oedema. He was prescribed intramuscular adrenaline, intravenous steroids and anti-histamines with complete symptoms resolution. The patient declares not had eaten other foods, taken any drugs including NSAID, been infected or practised exercise. Skin prick tests with food extracts (salmon and other fish, shellfish, soy, rice, egg total, egg white, egg yolk, ovalbumin and ovomucoid) were negative. Skin prick-prick tests were positive for salmon roe (17 × 10 mm) and negative for egg (white and yolk), ginger, salmon, flying fish roe (tobiko), sturgeon roe (caviar) and black scabbard fish roe. Specific-IgE (sIgE) to salmon roe extract was 0.28 kUA/L (Immu-noCAP-Phadia) and negative against extracts from salmon fish and other fish (<0.1 kUA/L). SDS-PAGE Immunoblotting with salmon roes extract showed a 20 kDa-IgE binding band, that may correspond to a lipovitelin. After the allergic reaction the patient have tolerated ABSTRACTS | 659 salmon fish and other fish roes (tobiko, caviar and black scabbard fish). No oral provocation test with salmon roes was performed given the severity of the reaction.

Conclusion: This report is an example of a severe allergic reaction to salmon roe without concomitant fish allergy, where the clinical history and the in vivo and in vitro tests were important to an accurate diagnosis. The authors believe this is the first report of a salmon roe anaphylaxis in our country and highlight the importance of this allergen in the western countries, given the increase of sushi consumption in these countries. Case report: The prevalence of food allergy is increasing worldwide and consumer habits are changing. Pomegranate (Punica granatum) was commonly consumed in the Mediterranean area but in the last few years became also popular in the different parts of Europe.

A 5-year-old boy was admitted to our emergency department suffering from allergic reaction within 10 minutes after consumption of pomegranate. He presented with skin pruritus, generalized urticaria and eyelid edema. Symptoms resolved within an hour after oral intake of cetirizine. Prick-to-prick test with pomegranate was positive (wheal diameter 13 × 7 mm). He had a history of anaphylaxis with egg (urticaria and wheezing) at the age of 9 month, meanwhile consumption of egg is well tolerated. An episode of anaphylaxis with unknown origin appeared at the age of 4 years (urticaria, wheezing and abdominal pain). Skin prick tests with aeroallergens revealed birch pollen allergy and he was diagnosed with allergic rhinoconjunctivitis. Dietary elimination of pomegranate was suggested and adrenaline auto-injector was provided. 

We have analyzed omalizumab effectiveness and safety in patients with CSU from our database. Clinical response was categorized as: no response, partial or complete response by using the Urticaria Activity Score 7 (UAS 7). Furthermore, the dosage, administration frequency and any side effects were recorded.

Results: Effectiveness: 23 out of 25 patients (92%) achieved complete response. 15 (65.2%) after a single dose of 300 mg (8 patients) or 150 mg (7); 5 patients (21.7%) after two doses of 300 mg (4 patients) or 150 mg (1) Results: Multi-ethnic adolescents accounted for approximately 1.2% of the total sample of adolescents. Prevalence of asthma was significantly higher in multi-ethnic group than non multi-ethnic group. We examined if maternal or paternal foreign born status had a differential effect: in multi-ethnic family with foreign-born father, prevalence of asthma was significantly higher. Parental region of country at birth had a significant influence on the prevalence of asthma. Adjusted logistic regression analysis was used to determine risk factors for occurrence of allergic disease. Residential area, perceived household economic status, parental region of country at birth, and body mass index (BMI) had a significant effect on prevalence of asthma.

Conclusion: Population admixing appears to have significant effect on the prevalence of asthma. Further study will be needed to clarify the effect of population admixing on prevalence of allergic disease. Several studies have aimed to explore the possibility of miRs as biomarkers for various diseases. In our study we examined six different miRs, previously shown to be involved in eosinophil development and other immune responses, in serum from non-allergic and allergic asthmatics and healthy control subjects in order to determine their potential ability to be used as biomarkers for varying forms of asthma.

Method: Serum from healthy individuals as well as age matched non-allergic asthmatics (NAA) and allergic asthmatics (AA) were utilized. Additionally, the NAAs and AAs subjects had high eosinophila (≥0.4 × 10 9 cells/L) compared to healthy controls (≤0.1 × 10 9 cells/L) and eosinophil cationic protein (ECP) in serum was measured. Asthmatic subjects were included irrespective of inhaled corticosteroid usage. RNA was extracted from serum, reverse transcribed and subjected to qPCR analysis. Expression changes in six candidate miRs, miR-126, -145, -146a, -155, -223, and -374, were investigated. Results: Two miRNAs, miR-155 and miR-146a, were significantly upregulated in AAs as compared to NAA or healthy subjects. Additionally, miR-223 was upregulated in NAA, but not AA or healthy subjects. Furthermore, the expression change observed in the AA miRs appeared to correlate with the use of inhaled corticosteroids, but not in the NAA miRs. Finally, miR-223 and miR-374 expression levels were altered based on the number of eosinophils, which correlated to ECP levels, in NAA subjects.

Conclusion: Using six miRs found in the literature to be involved in eosinophila or immune responses, we were able to detect expression changes in the serum of healthy and asthmatic individuals.

Moreover, were able to distinguish between healthy individuals, AAs, and NAAs on inhaled corticosteroids or with differing eosinophil levels, leading to the possibility that these miRs may be valuable future biomarkers for asthma. Background: Some studies report that certain sensitization profiles may increase the risk of a more serious allergic respiratory disease.

The aim of this study was to describe the sensitization patterns to major allergens of dust mites in our area and investigate the association of these patterns with a specific clinical picture.

Method: Multicenter study performed in 3 hospitals for 4 months.

We recruited 133 patients older than 5 years with rhinitis and/or bronchial asthma, with a history of allergy to dust mites and both skin test and specific IgE to D. pteronyssinus, D. farinae or L. destructor positive.

Der p1 and Der p2 were determined to all of them.

We analyzed 133 patients with an average age of 28.25 years, 60.9% women, 9.7% smokers, 69.9% rhinitis and asthma, 17.3% only rhinitis and 12.8% only asthma. 94% of patients presented sensitization to D. pteronyssinus, 83.5% to D. farinae and 63.2% to L. destructor. The detected sensitization patterns were:

both Der p1/Der p2 positive 73.9%; Der p1 positive 8.4%, Der p2 positive 11.8% and both Der p1/Der p2 negative 5.9%. It was observed that patients with higher specific IgE levels had more severe forms of respiratory disease, with isolated asthma or associated with rhinitis. For D. pteronyssinus, D. farinae, Der p1 and Der p2 > 50kU/L there is a greater number of cases of asthma associated with rhinitis, while for L. Destructor >3.5kU/L greater number of cases of asthma. No relationship was observed between a specific sensitization pattern and an increased risk of asthma.

Conclusion: 1. Specific IgE values greater than 50 kU/L for D. pteronyssinus, D. farinae, Der p 1 and Der p 2, were significantly associated with a higher probability of asthma and this association was significant for L. Destructor>3.5 kU/L (class 3).

2. There are four well-defined sensitization patterns in our population that are influenced by geographic location, being the double sensitization to Der p 1 and Der p 2 the most prevalent and allowing the correct characterization of 94% of the cases. None of them increased the risk of asthma.

Kobori T 1 ; Nagao M 1 ; Ekenkrantz T 2 ; Borres M 2 ; Sjölander A 2 ; Fujisawa T 1 1 National Mie Hospital, Tsu-City, Japan; 2 Thermo Fisher Scientific, Uppsala, Sweden Background: Reliable biomarkers for diagnosis and management of asthma in young children are needed since pulmonary function test and exhaled NO measurement, good biomarkers for asthma in older children and adults, are difficult to perform in young age. We have developed a sensitive and stable assay system to measure eosinophil-derived neurotoxin (EDN), an eosinophil granule protein, that is released upon activation, and that may serve as a marker for eosinophilic inflammation also in young children.

Method: Volunteer children from 0-6 years old were recruited and an ISAAC-based questionnaire was filled out by their caregivers.

Venous blood was obtained to measure serum and plasma EDN and eosinophil count. EDN was measured with a research assay developed on the ImmunoCAP ® platform. Conclusion: Blood EDN may be a reliable biomarker for diagnosis of asthma in preschool children. Conclusion: FeNO measurement as an add-on option in asthma management to identify asthma patients with Th2 driven airway inflammation is less costly than the use of standard diagnostic methods. New biologics may have an additional impact on overall asthma treatment costs. Our model demonstrates that incorporating FeNO measurement may help to optimize asthma medication and reduction in physician visits as well hospitalizations due to severe exacerbations.

1294 | Peripheral airway inflammation assessed by fractional measurement of the exhaled breath temperature is a leading feature of asthma Background: Airway inflammation is considered to be a hallmark of asthma. The potential clinical benefits of assessing it non-invasively has led us to develop a method and device for measuring the temperature of the exhaled breath (EBT=exhaled breath temperature) reflecting the thermal state of the airway mucosa. Studies have demonstrated that EBT is increased in asthma, proportionately to the level of control of the disease. In an attempt to further increase the usefulness of this approach, we have further developed a device to allow the assessment of the relative contribution of the central and peripheral airways (Caw and Paw). Now we present the FrEBT data gathered from patients with suboptimal control of their asthma and from healthy subjects.

Method: In this cross-sectional study we included 120 volunteers: 71 patients with suboptimally controlled asthma of mild to moderate severity (median age 44, range 18-68 years, 31 men) and 49 nonsmoking subjects without respiratory disease (median age 49, range 18-70 years, 17 men). We measured the fractions corresponding to Caw and Paw sampled with a fast reacting inflatable balloon valve system operated by a computer during a single breathing cycle. It allows steering of the expired airflow through channels with sensitive temperature sensors. During an initial deep inhalation, the inspired volume is measured and the sequence of valve openings is adjusted so as to yield volumes of air characteristic of Caw or Paw during expiration. The ratios between [PawEBT-CawEBT] over the total EBT [%] measured during the same manoeuvre (fractional EBT, frEBT) were calculated and compared between asthmatics and controls.

Results: There was high statistically significant difference between the frEBT ratios of asthmatics and controls: 16.25 ± 0.51 (mean ± SEM) vs 12.66 ± 0.28, P < 0.001. As the magnitude of the ratio depends on the difference between PawEBT and CawEBT, higher values of the frEBT ratio point to bigger contribution of the peripheral lung tissues, presumably indicative of peripheral inflammation.

Multiple regression analysis with frEBT ratio as dependent variable identified only asthma diagnosis as significant predictor (P < 0.001) and excluded all other anthropometric indices.

Conclusion: Peripheral airway inflammation assessed by frEBT measurement appears to be a leading characteristic in asthmatics compared to healthy subjects. Method: We examined 142 outpatients (30% male, aged 18-82 year, mean age 54.7 years) with severe asthma according to ERS/ ATS (2014) definition treated with high dose of ICS/LABA± tiotropium, antileukotrienes and omalizumab. Some patients (n = 21) had orally steroid-dependent asthma. They referred to our secondary care center by GPs. Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Skin prick tests or serum specific IgE to common inhalant allergens (house dust mite, animal dander, pollen) were used to assess atopic status.

Results: Seventy five percent (n = 107) of patients with severe asthma had FAO in 50% of those was diagnosed concomitant COPD. Duration of asthma was 14.6 years in patient with reversible airway obstruction (RAO) and 14.5 years in those with IAO (P > 0.05). Early (before age 12 years) onset of asthma was established in 13% of patients with RAO and in 9% of patients with FAO (P > 0.05). Prevalence of atopy did not differ between both groups (81% vs 81%, P > 0.05) but total IgE level in serum was higher in severe asthmatics with RAO than FAO (924 ME/mL vs 330 ME/mL respectively, P < 0.01). Most of atopic patients with severe asthma both with FAO (91%) and ROA (83%, P > 0.05) were sensitized to house dust mites (D. pteronyssinus and D. farinae). Hypersensitivity to pollen was diagnosed in 36% patients with FOA and in 17% with RAO (P > 0.05), to cat and dog dander in 49% and 25% respectively (P < 0.05).

The majority (75%) of patients with severe asthma had FAO. Hypersensitivity to house dust mites was most common in severe atopic asthmatics with FOA and ROA where as sensitization to animal danger was associated with presence of FOA.

1296 | Loss of smell as a clinical marker of severe asthma and its association with upper airway inflammatory diseases Background: Asthma is frequently associated with rhinitis and chronic rhinosinusitis (CRS) while severe asthma is more associated with CRS with (CRSwNP) than without (CRSsNP) nasal polyps. Loss of smell (LoS) is associated with CRS, mainly with CRSwNP.

We aimed to assess loss of smell as a clinical marker to discriminate CRS from rhinitis and severe from non-severe asthma.

Method: In a cross-sectional multicentric study, asthmatic patients (N = 383) were evaluated by pulmonologists and ENT specialists using GINA, ARIA, and EPOS definitions. LoS was evaluated by severity [VAS scale, 0-100 mm, median (IQR,Inter-Quartil Range)] and by prevalence of anosmia (hyposmia VAS >0-70 mm, anosmia VAS>70 mm).

Results: LoS was present in 55.4% of asthmatics (hyposmia 41.5%, anosmia 14.9%). LoS was more severe [22 mm (0-75), P < 0.001] and anosmia more frequent (26.4%, P < 0.001) in severe persistent asthma than in moderate [10 mm (0-50); 11.4%] mild [0 mm (0-28); 10.7%], or intermittent [0 mm (0-45); 8.6%] asthma. In addition, LoS was more severe [38 mm (2-76) vs 0 mm (0-20), P < 0.001] and anosmia more frequent [28.1% vs 3.9%, P < 0.001] in CRS than in rhinitis patients. In those asthmatic patients with CRS, LoS was even more severe [50 mm vs 20 mm (0-56) P < 0.001] and anosmia more frequent (40.6% vs 13.4%, P < 0.001) in CRSwNP than in CRSsNP.

Conclusion: Loss of smell and specially anosmia may clearly discriminate severe from non-severe asthma and CRS (specially with NP) from rhinitis alone in asthma patients. Thus, LoS may be considered a significant clinical marker of severe asthma and its association with upper airway inflammatory diseases.

1297 | Last station in the eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis march: Eosinophilic asthma with radiological findings associated with blood eosinophilia Yilmaz I 1 ; Nazik Bahçecioglu S 2 ; Türk M 3 ; Tutar N 1 ; Oymak FS 2 ; Gülmez I 3 1 Erciyes University School of Medicine, Kayseri, Turkey; 2 Department of Chest Diseases, Kayseri, Turkey; 3 Division of Immunology and Allergy, Kayseri, Turkey Background: Eosinophilic asthma with chronic rhinosinusitis and/or nasal polyposis (EACRS/NP) is a subphenotype of adult-onset eosinophilic asthma. Blood eosinophil levels are shown to be highly elevated in patients with EA-CRS/NP and have potential for tissue infiltration. We aimed to demonstrate the clinical features of the patients who have a blood eosinophil level above 10% and have thorax computed tomography findings due to blood eosinophilia. Results: We identified 36 patients who met the above criteria. We defined this group as "Eosinophilic Asthma with chronic Rhinosinusitis and/or nasal polyposis with Radiological findings related to blood eosinophilia" (EARR). The mean age was 44.9 ± 11 years and 64% was female. Nasal polyps, aspirin exacerbated respiratory disease and atopy was present in 81%, 47% and 25% of the patients, ABSTRACTS | 665 respectively. The mean blood eosinophil count was 1828.6 cells/mm 3 (19%). The majority of EARR patients had upper lobe dominant ground-glass opacities. The mean follow-up period was 3.2 ± 2.5 years. EARR patients did not evolve into eosinophilic granulomatous polyangiitis in the follow-up. Method: We aimed to identify features more probably associated with asthma in a unselected group of patients with diagnostic criteria for ACO. We consecutively selected the first 10 consecutive patients with diagnostic criteria for ACO. All patients were evaluated by accurate clinical history interview, assessment of Asthma Control Test (ACT) and COPD Activity Test (CAT), lung function and exhaled nitric oxide (FE NO ) measurements, sputum cytology, blood eosinophil count, serum total IgE and periostin levels, methacholine and adenosine-mono-phosphate (AMP) bronchial challenges. All these measures were repeated after an oral corticosteroid (OCS) trial of methylprednisolone 32 mg/day for 14 days. We defined 9 parameters that we expected improved after the OCS trial, and therefore considerable as markers of asthma: FEV 1 , FEF 25-75 , FEV 1 /FVC, FE NO , ACT, sputum and blood eosinophilia, methacholine and AMP challenges. Patients with improvement of at least 4 of these parameters after OCS trials were defined as "responders" to the treatment, and therefore more likely to be asthmatic than COPD or ACO.

Results: Five (50%) patients were classified as responders and they were characterized by having basal higher FE NO values (102.8 ± 34.2 vs 13.6 ± 3.5 ppb, P = 0.032), greater bronchial reversibility Basal values of serum periostin and total IgE, and blood eosinophils were higher in responders but without reaching the statistical significance.

Conclusion: FE NO and the degree of bronchial reversibility (and possibly also the degree of response to an AMP challenge) are reliable biomarkers to distinguish asthmatics among those with suspect ACO. Method: The preliminary case-control study included 52 obese persons with asthma who were matched for age and sex and 48 nonobese asthma subjects. Non fasting serum levels of adiponectin, and leptin were measured by commercially available immune assay kits, and routine biochemical parameters were analyzed in both the study groups.

The results show statistically significant lower levels of serum adiponectin and higher serum leptin levels in obese asthma subjects with respect to non-obese asthma patients (P < 0.001).

Moreover, an inverse correlation was also observed between serum adiponectin and serum leptin in obese asthma subjects (P < 0.05).

Our results indicate the association of these hormones might act as a significant predictor in the progression of asthma.

Moreover, the role of serum adipokines is promising and might potentially act as a meaningful drug target in the pathogenesis of asthma. Background: Overweight/Obesity is known to be a possible factor for poor asthma control. The aim of the study is to determine the serum concentrations of leptin in atopic asthmatic patients and its relationship with body mass index (BMI), asthma severity defined by medical treatment and asthma control defined by the Asthma Control Test (ACT).

Method: We randomly selected 33 adult patients previously diagnosed with allergic asthma based on GINA (global initiative for asthma) guidelines, returning for follow-up to an outpatient allergy/ immunology clinic during November 2017. Following an informed consent, the patients were asked to fill ACT, their BMI was recorded, and ELISA blood assays for leptin were drawn. Exploratory data analysis, Spearman's correlation (95% CI by bootstrapping), and partial correlations were performed.

Results: Female/male ratio was 24/9, mean BMI was 27.2 ± 4. Conclusion: Leptin was significantly associated with overweight/ obesity in asthmatic subjects, and showed higher values for women.

Leptin inverse correlation with ACT did not reach statistical significance, likely owing to underpowered estimates, in a small sample characterized by an elevated mean BMI and severe allergic asthma. Background: Immunoglobulin lowering may be associated with recurrent wheezing symptoms and clinic by increasing the tendency to viral respiratory tract infections. In this study, it was aimed to investigate the frequency of immunoglobulinemia in preschoolers with wheezing.

The study was conducted between 01.01.2013 and 01.01.2016 between. University of Health Sciences, Ankara Child

Hospital, The Children Allergy and Immunology Clinic included patients who had been followed up and treated for at least one year with recurrent wheezing attacks within younger than 48 months.

The immunoglobulin (G, A, M) values of the patients were retrospectively analyzed. Immunoglobulin levels were determined to be normal and low according to age limits.

The study included 585 patients (65.6% male, 34.4% female) under the age of 6 years with a mean age of 26.9 months. The mean follow-up period of the patients is 2.2 years. In 33.7% of these patients, at least one immunoglobulin was found to be low. None of these patients had any signs or symptoms of immunodeficiency.

Immunoglobulin A was low in 21% of the patients, immunoglobulin G in 18%, and immunoglobulin M in 7.5% of all patients.

Conclusion: Immunoglobulin was found to be low in these patients when there was no immunodeficiency and preschool wheeze was diagnosed. This should be etiologically investigated as to whether if this is a special group in preschoolers with recurrent wheezing and hypogammaglobulinemia combination. Method: Asthma Severe Unit is formed by allergists, pneumologists, pediatricians and otorhinolaryngologists. Hematologists and immunologists make specific collaborations. We present the partial results of our data collection, which include 75 patients with severe asthma according to ERS/ATS task force, selected by peripheral eosinophils >220 according to Wagener et al. We followed them up to assess control for 1 year. We obtained cellularity in sputum using induced sputum technique. Values of IL of TH2, TH1, TH17 pathway, periostin and ILC were not yet available.

Results: Median age was 36 ± 24, FeNO 45 ± 34, exacerbations previous year 1.8 ± 2.4, ACT 17.7 ± 5, FEV1 75% ± 21 and dose of inhaled corticoids (budesonide equivalent) 1235ug ± 618. Most of the patients were sensitized (78%) and 15.9% were polysensitized.

The most frequent sensitization was dust mites (81%). 27% had received immunotherapy of whom 35.3% with lack of response. Not sensitized patients were older. Sputum cell analysis of 54 patients was performed, 37% had sputum eosinophils>3%, mean sputum eosinophil value was 4.1 ± 4.7 and peripherally 518 ± 384. Correlation among sputum and peripheral eosinophilia was 0.097 (P = 0.485). The peripherally eosinophil value >220 had a sensitivity of 80% and a specificity of 54% for the detection of sputum eosinophils >3%. No differences were observed in sputum cell count depending on allergic sensitization. 64% had an uncontrolled asthma. Presence of polysensitization, rhinitis or polyposis were not statistically related with the control.

Different patterns were observed in function of cause of poor control:

Patients with obstructive pattern (FEV1 < 80%) were older and received more inhaled treatment. Patients with high rate of exacerbations had more sputum eosinophilia and neutrophilia. Both groups had worse ACT and received more oral steroids.

Patients who received oral steroids were more often sensitized to fungi in some follow-up visits. Not significant differences were observed in control according to the ACT.

Asthma had more sputum neutrophilia, were older, received higher inhaled steroids dose and had adult onset asthma. The only control variable related with sputum eosinophilia was exacerbation. Fungi sensitization was more frequent among patients with oral steroids. Method: A randomized, double blind, placebo controlled study with 80 patients from the De La Salle University Medical Center with a mean age of 44 with partly or uncontrolled asthma. They were assigned to either cm glucan or placebo group for two months. ACT score and %FEV1 postbronchodilator were assessed at the 1st visit, 4th week follow up, and 8th week follow up visits. An independent and paired t-test were used to determine mean changes in ACT Scores and %FEV1 between the groups.

Results: In the two treatment groups, those in the CM glucan group had a greater % FEV1 mean change of −6.95 compared to placebo which had only −14.1, a mean difference of −7.15, and a trend toward significance with a t-test P value of 0.061. In terms of changes in ACT score, those in the CM glucan group had a mean change of 10.12 and 9.75 for placebo, a mean difference of 0.37 and was not significant at t test P value of 0.718.

The result of the EMANUEL trial showed a trend of improvement among patients on both groups in terms of ACT score and %FEV1 postbronchodilator. However, it was not statistically significant.

1306 | Lung function improvements with tiotropium in patients across all ages: Impact of episodes of asthma worsening during phase 3 trials Vogelberg C 1 ; Casale TB 2 ; Bleecker ER 3 ; Goldstein S 4 ; Szefler S 5 ; Engel M 6 ; El Azzi G 6 ; Dewberry H 7 ; Hamelmann E 8 Method: Post hoc analyses involved 6 Phase III, randomized, double-blind, placebo-controlled trials: 4 in patients aged 6-17 years (RubaTinA-/CanoTinA-/VivaTinA-/PensieTinA-asthma) who received tiotropium (5 or 2.5 μg) or placebo, as two puffs once-daily via the Respimat, as add-on to ICS ± other controllers; and 2 in adults (Pri-moTinA-asthma replicate trials) who received once-daily tiotropium 5 μg or placebo, as add-on to ICS/LABA ± other controllers. We analyzed change from baseline for peak FEV 1(0-3h) and trough FEV 1 at

Week 12 in VivaTinA-and PensieTinA-asthma, and Week 24 in Pri-moTinA-/RubaTinA-/CanoTinA-asthma, comparing patients with and without episodes of asthma worsening during the trials. Asthma worsening was defined as an episode of progressive increase in dayto-day asthma symptoms (recorded by patients and confirmed by the investigator) or a decrease of patient's best morning PEF ≥30% from mean for ≥2 consecutive days. As a post hoc analysis, P values are nominal.

Results: There were no differences in baseline disease characteristics between those who experienced episodes of asthma worsening and those who did not, within specified age and asthma severity groups. Placebo-adjusted lung function improvements were observed with tiotropium 5 μg in patients who experienced episodes of asthma worsening and those who did not during the trials (Table 1) .

There was some variability in subgroups with low numbers of patients.

Conclusion: Once-daily tiotropium add-on had a similar efficacy in adult and pediatric patients with symptomatic asthma, irrespective of whether they experienced episodes of asthma worsening or not during the trials. These data support the broad efficacy of tiotropium and show largely consistent improvements in lung function even in patients who experience episodes of disease worsening.

1307 | Cochrane review of the use of antibiotics for acute exacerbations of asthma Method: We searched the Cochrane Airways Trials Register, trial registries and reference lists of primary studies. We extracted outcome data and assessed risk of bias in duplicate and used current Cochrane methodology throughout. Our primary outcomes were intensive care unit (ITU) admission, duration of symptoms/exacerbation and adverse events.

We included six studies, including a total of 681 adults and children. Trials were of varied methodological quality and we were able to perform only limited meta-analysis. One study reported a single ITU admission but no other studies reported admissions to ITU. Two studies investigating macrolides reported diary card symptom score and showed antibiotics improved symptoms (MD −0.34, 95% CI −0.60 to −0.08). One study including 40 participants reported more symptom-free days in the macrolide group than usual care. One study of a penicillin including 69 participants reported asthma symptoms at hospital discharge; the between group difference was reported as non-significant. Serious adverse events were rare; 10 events were reported across the three trials (n = 502). The pooled effect estimate for all adverse events from three studies was imprecise (OR 0.99, 95% CI 0.69-1.43). No deaths were reported. Conclusion: Our results confirmed that omalizumab significantly improves disease control and is a safe add-on therapy. Also in appropriate patients with controlled disease over time, efforts to stepdown other asthma medications will be appropriate. (45) AERD: aspirin exacerbated respiratory disease; SD: standard deviation. Data are n (%), mean ± SD or n/N (%). C-ACT: Asthma Control Test for children, FEV1: forced expiratory volume in one second; FEV1/FVC: the ratio of forced expiratory volume in one second to forced vital capacity, PEF: peak expiratory flow; FeNO: fractional exhaled nitric oxide, VAS: visual analogue scale *These included allergic rhinitis, asthma, eczema, atopic dermatitis, food allergy, etc. **There were 11, 13 and 18 missing data in treatment A, B, and C, respectively. This study examines the potential treatment effects of SQ ® HDM SLIT-tablet on QoL measured by SF-36v2 in people with AA and AR.

The analyses are based on data from the MT-04 trial (EudraCT no. 2010-018621-19) and utilize data from the 12 SQ-HDM treatment group (282 subjects) and the placebo group (277 subjects).

Throughout the trial, QoL was measured at each of visit 3-13 via SF-36v2. This yielded psychometrically-based physical and mental health summary measures, as well as a SF-36v2 total score. According to trial design, the use of inhaled corticosteroid (ICS) was reduced by 50% for a three months period (visit 10 and 11) and completely withdrawn for the last three months of the trial (visit 12 and 13).

Results: By estimating a simple regression on differences in SF-36v2 total score from baseline measurements (visit 3), a positive and statistically significant treatment effect on the overall QoL of the 12 SQ-HDM treatment compared to the placebo group in visit 9 and 10 was found.

Further analyses show that the QoL improvements are mainly driven by increases in the general mental health score, which are carried through to visit 12. In particular, the mental health and role emotional domains show statistically significant improvements.

The results show that the SQ ® HDM SLIT-tablet improves QoL measured by SF-36v2 in patients with HDM induced AA and that this effect is driven by improvements in the mental health domains.

1315 | Impact of treatment prescription, adherence to treatment and use of inhalers in asthma control-Results of the EFIMERA study Method: Cross-sectional multicenter observational study conducted with patients who use any type of medication with inhaler devices.

Patients referred from primary care and seen by a pneumologist or allergist for the first time were evaluated. The following data was collected in a single visit: adequate prescription according to GINA2015 guidelines (GINA); specific and general treatment adherence using Morisky-Green questionnaire (MG) and Inhaler Adherence Test (TAI); disease control with Asthma Control Test (ACT) and assessment of inhaler use technique were measured with the extended TAI.

Results: Patients included in this study (n = 1682) had a mean age of 45 ± 17 years, an average disease evolution of 14.9 ± 14.1 years, 64% of which were women. According to GINA recommendations, 35.9% of patients have insufficient or inadequate prescription. When measured by the MG test the 68.5% of patients showed bad adherence, meanwhile measured by the TAI test adherence was 76.8%

Measurements of inhaler use technique resulted in 17% of patients having one or more mistakes regardless of whether the device was a MDI or DPI. Several factors showed to be related with bad asthma control: inadequate prescription (OR: 8.05 [5.74-11.27 Background: It is well known that the constant and prolonged tobacco smoking affects the natural history of asthma.

Vaping is the act of inhaling and exhaling the vapor produced by an electronic device called e-cigarette (e-cig), whose basic structure includes a power source and an atomizer. two types of vaping are the most popular ("MTL" and "cloud chasing").

We have created a web-survey with questions concerning epidemiological data, quality of life and symptoms worsening in asthmatic vapers. The survey has been advertised through various social networks and local press. 2403 people responded, including 437 asthmatics (18%).

The asthmatics were: Males 88%, under 18 3%, 18-25 years 36%, 26-30 years 19%, 31-65 years 42% and over 65 0%. 70% used ecig-only, 30% smoked and vaped together, 0%. Those who preferred MTL-type of vape were 43% and "cloud chasing" were 57%.

Results: To the question: "Has vaping ever worsened asthma symptoms?" 90% answered no, 10% yes.

To the question: "As asthmatic, would you suggest to an asthmatic smoker to start vaping instead of smoking?" 1.3% answered no, 98.7% yes.

To the question: "How much nicotine do your vaping liquids have?"

15% answered 0 mg/mL, 4% 1.5 mg/mL, 62% 3 mg/mL, 11% 6 mg/ mL, 6% 9 mg/mL, 1% 12 mg/mL and 0% 18 mg/mL.

To the question: "Do you take medications for your Asthma?" 57% declared to use a drug as needed, 0% used a single drug daily, 16% used more than one drug daily and 27% declared "I don't take any asthma medication".

We related (χ2 test) the worsening of asthma symptoms with the nicotine content (P = 0.313), the type of vaping (P = 0.305), the current therapy (P = 0.123) and we did not find a statistically significant correlation.

Vaping has undoubtedly shown an advantage in terms of improvement of symptoms compared to cigarette smoking (P = 0.016), in particular 82.5% subjects who smoke and vape did not have a worsening of symptoms, while 17.6% of them had a worsening. The vaper-only users who never worsened were 271 (90.6%) and 28 (9.4%) had a worsening.

Conclusion: Despite the limits related to the online survey as a data source, e-cigs seem to be a useful tool in the pathway to quit smoking. In fact, 98% of the asthmatics who smoked traditional cigarettes would recommend switching to e-cig and 90% did not worse their asthma symptoms. Background: Despite the success of pharmacotherapy, more than half of patients with persistent bronchial asthma (BA) do not achieve disease control. In recent years, the issue of approaches to treatment based on the identification of phenotypes of the disease has been increasingly discussed. This approach becomes the key to optimizing therapy for asthma, allowing the personification of treatment. Anti-IgE-therapy using omalizumab is one of the most researched variants of phenotype-specific treatment.

Method: Aim of our study was to investigate of the causes of uncontrolled predominantly atopic asthma, the frequency and effectiveness of the personalized therapy in real clinical practice. 54 patients with uncontrolled severe atopic asthma were examined in outpatient department of the city hospital during 2017. All patients underwent physical examination, pulmonary function testing, and total serum IgE evaluation.

Results: 35% of patients had uncontrolled asthma due to inadequate basic therapy of the disease. The change in therapy allowed them to achieve control of the disease. Obstructive sleep apnea syndrome (OSAS) was revealed in 11.1% of patients. These patients underwent CPAP (Continuous Positive Airway Pressure) therapy. 13% of patients had gastroesophageal reflux disease (GERD). 25% of patients had an elevated level of serum IgE level and needed anti-IgE therapy. In 7.4% of cases, the initial serum IgE level was more than 1500 IU/mL which was a contraindication to therapy of omalizumab. 8 patients received omalizumab therapy. This therapy led to relief of symptoms and decreased frequency of asthma exacerbations. Results: It was found that the prevalence of obesity among the 367 patients with asthma and being treated in inpatient conditions in 2013-2015 was 44.9% of patients, which is comparable to the prevalence of obesity among the population in general.

The data of the patients suffering from asthma and obesity treated both in inpatient and outpatient conditions, was analyzed and it is set that obesity does not affect the severity of the clinical course of asthma. It is shown that obesity does not affect the control of symptoms of asthma. Thus, the control of asthma symptoms depends on timeliness of diagnosis, the adequacy and terms of appointment of basic asthma therapy, the presence, severity and adequate treatment of concomitant diseases, psychoemotional background of patients, their compliance and adherence to therapy. Results: The causes of smoking in asthmatics were not significantly different from the control (P > 0.05). Patients most often used smoking as "support for emotional stability". The motivation to smoking cessation was higher in the asthmatics group (58%) than in the control group. The main reason for smoking cessation was a deterioration in health -60%. The majority of smokers -85%, performed attempts for smoking cessation. Low level of BR was revealed in 90% asthmatics (27% non-smoking asthma patients and 18.5% of cases in the control group, P < 0.001), CF had low values and was lower in asthmatics group in compare to the control group (P < 0.05). The PAC values correlated with the level of BR: a low level was determined in 100% in smoking asthmatics, in 50% in nonsmokers with asthma and 7.4% in smokers of the control group 

Obstructive sleep apnea (OSA). All of the patients were on regular treatment with low dose inhaled corticosteroids for at 12 months and start treatment with continuous positive airway pressure (CPAP) .To assess quality of life, we used asthma symptom control tools (Asthma control test) .Patients performed daily peak flow meter and Spirometry (once a week) during period of 4 weeks after start using CPAP.

Results: During the study, 47 of the followed patients had no exacerbation of asthma. Four of patients during this period had exacerbation, due to upper airway infection so they were excluded from study.

Results of following showed that there was improvement in quality of life in all 47 patients included in study but there no statistically significant improvement in pulmonary function tests FPT. 

Huang Y 1 ; Yao T 1 ; Huang Y 1 ; Chiu C 1 ; Tsai Z 1 ; Kao P 1 ; Lu K 1 ; Fang H 1 ; Lin C 1 ; Gau C 1 ; Lee W 1 ; Tsai H 2 Results: The rate of preterm birth among the study subjects was 18.2%. The prevalence of physician-diagnosed rhinitis was 50.6%.

There was no significant association between preterm birth and physician-diagnosed rhinitis (P = 0.43). When stratifying by atopy status, we found that preterm birth was associated with physiciandiagnosed rhinitis among children without atopy (adjusted OR

[AOR] = 0.33, 95% CI = 0.12-0.93, P = 0.04), but not among children with atopy (P = 0.77). When further classifying by gender, greater protective effect of preterm birth on rhinitis was only found in boys without atopy (AOR = 0.12, 95% CI = 0.03-0.56, P = 0.007).

The results suggest that preterm birth may have a protective effect against the development of childhood rhinitis in our study population. The protective effect is only observed in boys without atopy. Further investigations will be merited to confirm these findings and to investigate underlying mechanisms.

Background: Folic acid supplementation (FAS) during pregnancy has been suggested due to its protective effect against neural tube defects. At present the effect of FAS during pregnancy on childhood rhinitis has remained unclear. We aimed to investigate the relationship between FAS during pregnancy and childhood rhinitis. Logistic regression analysis with covariate adjustment was performed. Adjusted covariates included sex, age, number of older siblings, breast feeding duration, maternal smoking during pregnancy, maternal allergy, maternal education level, maternal age and socioeconomic status Results: The prevalence of physician-diagnosed rhinitis was 55.3%.

There is a significant association between FAS and physician-diagnosed rhinitis (adjusted odds ratio [AOR] = 2.07; 95% confidence interval [CI] = 1.25-3.43 for FAS ≥3 months) compared to the group of never use. In the stratified analysis by atopy status, maternal FAS during pregnancy was significantly associated with physician-diagnosed rhinitis in the atopic group (AOR = 1.91, 95% CI = 1.07-3.40 for FAS <3 months; and AOR = 2.34, 95% CI = 1.19-4.58 for FAS ≥3 months), but not in the non-atopic group. When further stratified by gender, significant association between maternal FAS during pregnancy and physician-diagnosed rhinitis was only found in boys with atopy (AOR = 3.23, 95% CI = 1.39-7.50 for FAS <3 months;

and AOR = 4.02, 95% CI = 1.51-10.72 for FAS ≥3 months).

The results demonstrate that maternal folic acid supplementation during pregnancy might increase the risk of childhood rhinitis, especially among boys with atopy. Further investigation will be needed to validate our findings and to understand potential underlying mechanisms. According to sequence data 13 from 16 detected AdV (in all groups of patients) belongs to species F 41 type and 3 samples to species C 1 type (REI group). BV type 1 was identified in 3 strongly positive (Ct ≤ 25) swab samples in ARI group.

Conclusion: Simultaneous testing of respiratory and stool samples together shown that at least 6.6%/7.9% of 151 study subjects had dual/mixed infections, respectively, including 11%/9.5% of 63 respiratory disease patients, 3.6%/7% of 56 gastroenteritis patients and 3.1%/6.2% of 32 patients with combined respiratory/enteric infections. We found no virus combination specific for different groups of patients. 1327 | Neonatal respiratory supports and future asthma-like presentation in prematurity with bronchopulmonary dysplasia Results: Of all the tests analyzed 54.4% were males and 45.6% females with a mean age 5.7 ± 4.8 years old. Half of the tests (49.2%) reveals positive specific-IgE to more than one allergen and 38.6% (66) have no serum specific-IgE for the tested allergens (Table 1) .

Sixteen patients (9.4%) have very high concentrations (>100 IU/mL) of Derm. Pteronyssinus specific IgE, 13 (7.6%) of Derm. Farina, 7 (4.1%) of Rey pollen and 6 (3.5%) of Oak and Timothy grass pollen. Further studies are needed in order to elucidate the effect of these cytokines on allergy development and protection.

Shinohara M 1 ; Matsumoto K 2 1 Department of Pediatrics, Ehime University Hospital, Toon, Japan; 2 Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan Background: Probiotics consumption during perinatal and postnatal periods reportedly reduces the risk of atopic dermatitis in the offspring, whereas such probiotics consumption did not affect IgE levels or the risks of other allergic diseases; the precise mechanism how probiotics consumption reduces the risk of atopic dermatitis remains unknown. We hypothesized that probiotics consumption may reduce skin hypersensitivity to histamine. To test this hypothesis, we investigated whether perinatal/postnatal consumption of yogurt associates with skin hypersensitivity to histamine or not.

Method: This was a cross-sectional study enrolled 256 motherinfant (≥6-months-old) pairs. Physician-diagnosed allergic diseases and food consumption, such as milk, fermented drinks, and yogurt, by mothers during the third trimester of pregnancy and by infants during the first 6 months of life were assessed using self-questionnaires. Skin prick tests (SPTs) to saline and 1 mg/mL histamine were performed using bifurcated needles, and wheal sizes were measured 15 minutes after the puncture.

The SPT wheal sizes in infants with eczema/atopic dermatitis (n = 44) were significantly larger than those in infants without eczema/atopic dermatitis (n = 156; 4.6 ± 1.9 mm vs 3.8 ± 1.8 mm, respectively, P = 0.015), and thus these infants were excluded from the further analyses. The SPT wheal sizes to histamine in infants with daily yogurt consumption during the first The aim of this study was to evaluate the prevalence and clinical relevance of sensitization to profilins in atopic patients with food allergy.

The study was performed on a group of 43 children age 2-14 years with sensitization to at least one plant-derived food allergen (IgE > 0.7 KU/L). The included patients had never been treated with allergen immunotherapy before the study. The presence of IgE to recombinant (r) rBet v 2, rArt v 4 and rAmb a 8 in serum was evaluated using ELISA method as previously described (JBC 2016; 291:15447) . In addition serum level of IgG4 to rBet v 2, rArt v 4 and rAmb a 8 was also evaluated.

Results: Sensitization to profilins was found in 8 out of 43 (18.6%) patients (P+). Sensitization to all 3 studied profilins was demonstrated in each P+ patient. The remaining 35 children, with pollenfood sensitization, were not sensitized to any of the studied profilins and they served as a comparator group (P−). Analysis of the clinical status revealed that asymptomatic patients in regard to plant-derived food hypersensitivity were found more frequently among P+ (75%) than P− (37.1; P < 0.01) patients. Sensitization to profilin was associated with positive IgE to the same food allergens as in the control group. Clinical manifestation of pollen-food sensitization expressed as allergic rhinitis, bronchial asthma and atopic dermatitis was comparable between groups, except of oral allergy syndrome, which was not seen among P+ children. Similarly, history of anaphylaxis to plant-derived foods was registered only among P− (11.4%) patients.

Interestingly, all patients with sensitization to profilins had also elevated level of serum IgG4 against rBet v 2, rArt v 4 and rAmb a 8. Results: No significant difference of physician-diagnosed eczema (P = 0.88) or current eczema (P = 0.82) was observed between children born full-term and preterm. After stratifying by atopy status, we found that children born preterm had a more than three-fold higher risk of having physician-diagnosed eczema (adjusted OR (AOR) = 3.92; 95% CI = 1.25-12.29; P = 0.02) and current eczema (AOR = 3.16; 95% CI = 1.06-9.41, P = 0.04) than their counterpart in the non-atopic group. No statistical significance was observed for the association between preterm birth and eczema in the atopic group. No association between preterm birth and eczema was found when stratifying by gender.

Our results reveal that non-atopic children born preterm have a higher risk of developing eczema. The results suggest potential modifiable effect of atopy on the association between preterm birth and eczema. Further studies with a larger sample size are needed to validate the findings in this study. Background: There is a need for more knowledge about factors of importance for a successful transition from childhood to adulthood among adolescents with allergic disease and especially those with severe allergy. Therefore the aim of this study was to describe experiences of living with severe allergy from the adolescents and their parent's perspective and thereby identify factors of importance for transition from pediatric to adult care.

Method: A qualitative study was performed based on six focus groups interviews, two with adolescents and four with their parents.

In total 11 adolescents (age 10-16 years old) and 21 parents participated. The interview guide contained questions about experiences of living with severe allergy. The transcribed data was analysed using systematic text condensation.

Results: In total four themes were presented, two themes occurred in both the adolescent and the parent's focus groups, to be special and to be prepared. For two themes there was a difference between the adolescents and their parents. The theme, the importance of the parents, only occurred in data from the adolescents and the theme the meetings with health care only occurred in the parent's data.

The adolescents felt that they had low priority in the class and several stated they were teased at school and their parents felt that focus on their child often was in a negative way. The adolescents described that they took responsibility for their diseases while their parents expressed a need to protect. The adolescents stated that one of the parents were always present or had been during the years, the reason being safety and security. Only the parents mentioned experiences from healthcare. Parents who described that they had continuity in healthcare meetings and where met by high competence and with a professional approach were more satisfied with the support from the health care. One factor that was felt to be important was whether the doctor involved the youth in the conversation or not.

The teenagers in this study relied on their parents while also taking responsibility for their illness at the same time. Parents, on the other hand, showed a tendency to overprotect their adolescents. For healthcare professionals it is important to involve the adolescents in the care to facilitate the transition. Results: 50.9% of the children used antibiotics currently and 21.0% out of them used antibiotics ≥3 times yearly. Current wheeze (W) was established in 6.5%, sleep-disturbing W in 3.6%, exerciseinduced W in 1.7%, dry night cough apart from a cold in 12.2%, and asthma in 2.3%. Current antibiotics use ≥3 times yearly was positively associated with current W (aOR: 13.37; 6.14-29.11; P < 0.001), sleep-disturbing W (aOR: 7.87; 3.34-18.57; P < 0.001), exercise-induced W (aOR: 5.44; 1.89-15.61; P = 0.002), dry night cough (aOR: 3.80; 2.29-6.29; P < 0.001), and diagnosed asthma (aOR: 5.68; 1.96-16.50; P = 0.001) while antibiotics use <3 times yearly was positively associated only with current W (P = 0.003) and dry night cough (P = 0.011).

The results suggest an aggravating role of antibiotics use on asthma in school age thus further supporting the recommended restriction of antibiotics exposure. Results: After questioning 31.6% 95% CI, 23.2-40.9 were suffering from respiratory diseases, having symptoms of chronic disease: cough-86.1%, wheezing-41.66%, tightness in the chest-27.7%.

The risk factors (passive smoking, open fire house warming and no air conditioning) were commonly met in major cases at ill children rather than healthy ones (68.4% 95% CI, 59.1-76.8). As a result of studies made of the equal to 17.5 ± 0.3, comparative the end of lessons equal 19.2 ± 0.2 (P ≤ 0.05); Air relative humidity varies during lessons equal with 62.9 ± 1.4 (Norma toilet 30%-60%); CO2 concentration exceeds allowable limits −0.3 ± 0.02 (MAC −0.1%).

Conclusion: Respiratory morbidity in high school examined has a tendency to increase. We noticed deviations from the hygienic norms: the indoor temperature and relative humidity was lower and the CO 2 level was twice higher than the normal one.

The "Asthma ever" outcome was reported in 32 cohorts. 28 cohorts defined this as parental reported asthma (with or without specifying that it was doctor-diagnosed), 2 cohorts used GP records as the only source of diagnosis, and 2 used parental report or GP records.

The "Current asthma" outcome was reported in 40 cohorts. There was little consistency with how current asthma was defined or worded, with 23 different definitions used. The most common definition of current asthma, reported 16 times, was "asthma ever AND EITHER asthma symptoms in the last 12 months OR asthma medication in the last 12 months". Other criteria included in asthma definitions were bronchial hyper-responsiveness, reversible airway obstruction, positive exercise test, and asthma symptoms reported at a previous questionnaire. Only one "current asthma" definition was based exclusively on prescription data: "dispensed two asthma medication during the past year".

Nine cohorts reported asthma outcomes without specifying how it was defined, and were categorized as "Asthma unspecified".

Conclusion: "Asthma Ever" and "Current asthma" are two main asthma outcomes used to define asthma in child cohort studies. Definitions of asthma vary substantially across cohorts. Case report: Thereby we present two case reports of two children with impairment verbal communication as part of ASD and allergic diseases.

The first patient was a 3 year old boy with sneezing, rhinorrhea night cough and eye redness. He had been suffering for almost 2 years from the above mentioned symptoms. He had family history for atopic diseases and was for 7 month breastfed. Specific IgE revealed sensitization to birch, alder, hazel, oak, mugwort pollen and dog epithelia and Dermatophagoides farinae. Specific IgE resulted positive for nuts and rye flour.

The second patient was almost 3 year of age in the tame that he presented in our hospital. He cried and screamed all the time because of severe atopic dermatitis and typical symptoms such as itching all over the body and his impairment of verbal communication. Specific sensitization showed sensibilization to egg white and egg yolk, to nuts, rye and wheat flour. The food specific IgE leaded to positive results to alder, birch, hazel and oak pollen, but also to grasses, ragweed and mugwort. Prick by prick test showed positivity to egg white and egg yolk. Atopy patch test to pollens resulted negative.

Results: The first patient symptoms were well controlled after treatment with antileukotrienes. His verbal communication was also improved after a year or more.

The second three year old patient after required a combination of specific treatment with antihistamines, corticosteroids, immunosuppressive drugs and diet recommendation. Afterwards he had a reduced level of itching and anxiety but compared to other children he had a severe eczema. Erythema multiforme (EM) is an acute, immune-mediated, mucocutaneous condition that is most commonly caused by infection and drugs. It is characterized by targetoid lesions, sometimes accompanied by oral, genital or ocular mucosal erosions. There was no pediatric patient that had previously been reported in the literature with development of type 4 reaction after omalizumab treatment. We presented a case who developed EM to omalizumab therapy.

An 16 year-old female patient was admitted to pediatric allergy clinic with complaints of fever and rash. She had been diagnosed with chronic spontaneous urticaria (CSU) 8 years ago and she was planned to treat with omalizumab (75 mg, subcutaneously every 2 week) because of the inadequate response of antihistamines at a medical center. Her complete blood counts, liver, renal, thyroid function tests and serum C3,C4,C1 esterase inhibitor protein levels Introduction: Celiac disease is an autoimmune disease triggered by exposure to gluten in genetically predisposed individuals and characterized by chronic inflammation of the small intestine. Chronic urticaria is a skin disease, characterized by the appearance of pruritic wheals with or without angioedema, whose underlying mechanism cannot be identified.

Objective: To report a sporadic case of an 11-year-old boy with chronic urticaria associated with celiac disease.

Methods: An 11-year-old boy(weight 31 kg, 3rd-10th percentiles) was admitted to our clinic with a 6-year history of chronic urticaria. During the first three years, he was under antihistamine treatment(of incremental doses)and occasionally received preparations of cortisone according to the EAACI guidelines. He was asymptomatic for 2 years until treatment was discontinued. Eight months earlier, after a viral infection, a recurrence of urticaria, involving the trunk and extremities without angioedema was noted. Subsequently, he was under antihistamine treatment with cetirizine but had an UAS-7 score of 11. Total laboratory investigations were performed.

Results: Laboratory control was negative except for positive antibodies to celiac disease(Anti-transglutaminase >200 U/mL, anti-endomysial, gliadin antibodies).Further control with colonoscopy and biopsies (from duodenum and stomach) were obtained. The histopathological findings along with the clinical findings indicate celiac disease, type 3b Marsch-Oberhuber and grade B1 Corazza-villanacci. In the past, similar cases have been reported. Efforts have been made to associate chronic urticaria with celiac disease, although the mechanism remains unclarified. Evidence suggests that the duration of gluten exposure, among otherwise asymptomatic patients with celiac disease, is related to the development of other autoimmune mechanisms. This can be explained by resolution of urticaria manifestations after the onset of gluten-free diet. In our case, three months after gluten-free diet, an improvement of urticaria with decreased UAS-7 score of 5 was observed.

Conclusion: he specific case of subclinical diagnosis of celiac disease in a child with chronic resistant urticaria further reinforces the suggestion that screening for celiac disease should be included in the diagnostic approach of chronic urticaria.

1350 | Allergy to gingival balm in an infant with cow's milk protein allergy 

We report a case of an infant with a diagnosis of CMPA with an allergic reaction to a gingival balm caused by the presence of CMP in its constitution. Furthermore, it is important to reinforce that milk proteins were labeled in an unusual form which might increase the risk of misunderstanding. These findings illustrate the difficulty in implementing total avoidance of common food allergens as well as the need to improve their labeling, particularly in non-food products.

Bakiri AH Results: After specific treatment with corticosteroids, antihistamines, emollient creams, disinfectants and antileukotriens he was feeling better, he was smiling again and wished to have the chance to play with his classmates again.

Conclusion: this case report shows an association between level of stress and risk for atopic dermatitis. As previously showed children with low educational level parents and boys with higher stress have increased risk of having severe atopic dermatitis as compared to "no stress" boys. So early treatment and diagnoses are key important factors improving the children`s social life. Results: The data cover 69 immigrants (mean age 39.0, range 8-62) and 232 locals (mean age 40.8, range 9-80). A slight difference in male prevalence (30.4% vs 47%, P = 0.01), and pet possession (20.2% vs 41.8%, P = 0.01) were found between immigrants and locals, respectively. No differences were find in term of age and symptoms at presentation. The pattern of sensitization to the different allergens showed no statistically significant differences between migrants and controls. The rate of monosensitization resulted slightly higher in migrants (27.5%) than controls (21.1%). Pollen-only sensitization was statistically higher among migrants than control (39.1% vs 22.4%, P < 0.01). Monosensitization was more frequent among patients who have been living in Italy for less than 4 years (52.6% vs 20%, P = 0.05). The opposite phenomena can be seen among polysensitized patients.

Conclusion: Migrants are more frequently monosensitized than locals and tends to cluster towards either a pollen or dust mite sensitization. Sensitization to house dust mite tends to appear early (< 4 years of stay). Pollen or mixed sensitization is more frequent the longer the residence time.

1353 | AllergenOnline.org: Update of comprehensive allergen and celiac protein searchable databases for risk assessment of novel food proteins Goodman RE 1 ; Baumert JL 1 ; Taylor SL 1 ; Ebisawa M 2 ; Ferreira F 3 ; Bohle B 4 ; Van Ree R 5 ; Kleine-Tebbe J 6 ; Abdelmoteleb M 1 ; Koning F 7 ; Amnuaycheewa P 8 Conclusion: Allergen and CD databases have been updated following a described review process. They can be used to identify proteins that might represent risks of food allergy or CD for affected consumers.

Han DH 1 ; Lee JW 1 ; Yim HJ 1 ; Ko YK 1 ; Kim D 1 ; Rhee C 2 1 Seoul National University Hospital, Seoul, South Korea; 2 Seoul National University Bundang Hospital, Seoul, South Korea Background: Stress can change the immune response and aggravate various allergic diseases. We already demonstrated in previous allergic rhinitis cohort (ARCO) kids study that stress might be a risk factor for pediatric allergic rhinitis (AR). The aim of this ARCO study is to investigate relationship between stress intensity, symptoms severity and quality of life as well as allergic markers in adult AR patients. Results: As stress intensity increased, the proportion of moderatesevere AR patients was significantly increased. AR patients in high stress group was likely to belong to moderate-severe group (OR, 1.60; 95% CI, 1.01-2.50). Global VAS of AR symptom was 7.0 ± 1.9 in high stress group and 6.7 ± 2.0 in low stress group, respectively. The each 7 RQLQ domain score was significantly higher in high stress group than in low stress group. Total RQLQ scores were 75.3 ± 35.5 in high stress group and 57.4 ± 36.0 in low stress group, respectively. However, as the level of stress increased, there were no significant changes in serum levels of allergic markers.

Our results suggest that stress may affect AR symptom severity and quality of life in AR patients.

1355 | Skincare and synbiotics for the prevention of atopic dermatitis or food allergy in newborn infants: A 2 × 2 factorial randomized non-treatment controlled trial Dissanayake E 1 ; Tani Y 2 ; Sahara M 2 ; Mitsuishi C 2 ; Nagai K 3 ; Sato Y 4 ; Suzuki Y 5 ; Nakano T 1 ; Yamaide F 1 ; Shimojo N 1 (n = 118). The skin care group was advised to apply an emollient 2-3 times/day especially on cheeks and peri-oral area. The synbiotics group consumed a mixture of FOS (1 g) and Bifidobacterium bifidu-mOL6378 (7 × 10 9 )/day. The last group received both. Emollient application was not prohibited in the no-intervention group. Interventions were carried out from birth to 6 months of age. The development of AD was assessed at 1 month, 6 months and 9 months by a pediatrician and at 1 year by a questionnaire. AD was diagnosed using guidelines of the Japanese Society of Dermatology. Sensitization to food allergens was assessed by allergen-specific IgE levels at 9 months of age.

Results: Skin care and synbiotics, alone or in combination, did not prevent the development of AD at 1 year of age or the sensitization to food allergens at 9 months of age.

Conclusion: Our data suggest that skin barrier protection using emollients may be insufficient to prevent the development of AD as other factors affecting skin barrier integrity and trans-epidermal water loss such as the method of skin washing may have an additional effect. The probiotic bacterial species used may also affect the outcome as Lactobacilli have been shown to be more beneficial.

More studies are required to confirm the effects of skin care and synbiotics on AD. Results: In the population number of girls exceeded the one of boys (P < 0.001), especially within the age group from 4 to 15 years.

Questioning, for 12 months, symptoms of allergic rhinitis (rhinorrhea, sneezing, nose itch, nasal obstruction and eyes' itch) were identified in 19.5 (P < 0.05); symptoms of bronchial asthma (wheezing (14%), episodes of cough at night (8.3%), intolerance to physical load (2.5%), indoor and outdoor (13.6%), coughing and rales in response to stimulus (7.2%)) in 9.8% of the population; atopic dermatitis (dermatitis, itch, revelation in early age, involvement of large areas in early age, damage of extremities bending and stretching surfaces in adults)-5.7% (P < 0.01); food allergy-3.7% (P < 0.001) etc. At the second stage of clinical studies, on the basis of prick-testing, average IgE, in our case, was 3-5 times greater than normal level. Results of study of allergens showed sensibilization to domestic dust (D.F. and D.P.) (64, 43%) (P < 0.05). In 25.46% of cases there was stated sensibilization conditioned by cat and dog epidermal allergens Results: Among the 2624 women with available serum, 39.3% were sensitized of whom 12.5% were monosensitised, and 25.3% polysensitised (to two or more allergens). Sensitisation to inhalant allergens dominated (38.9%), with grass being most common (25.5%).

Only 4.0% were sensitized to food allergens, most often to peanuts (2.6%), while among the 11.4% who reported DDFA, IgE reactivity to foods were identified in 17.5%. Compared to women with no asthma, women with DDA (14.9%) were in a significantly higher Background: Regular exercise has been known as beneficial that it reduces the risk of chronic diseases including allergic diseases. However, little has known regarding the relationship between exercise and allergic diseases in Korean adolescents. We analyzed the national data whether exercise is related to the prevalence of allergic diseases in the population of Korean adolescents Method: Data from sixth Korean National Health and Nutrition Examination Survey (2013-2014) that included 1272 adolescents from 12 to 18 years old was analyzed. We defined regular exercise according to physical activity guidelines for Americans. Multivariate regression analysis was performed to find whether lack of exercise could be a risk factor for allergic diseases.

Results: The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were 1.3%, 9.3% and 5.2% in Korean adolescents, respectively. After adjusting for factors, lack of exercise was not associated with asthma and AR, but was significantly related to AD in Korean adolescents (adjusted odd ratio 3.254, 1.202-8.810 , Results: It was found that over 43% of Ch up to 14 y.o. having the AD within allergic disease (ADs). The most significant symptom was a long-lasting itchy rash lasting for 6 month in 12.42 ± 0.56% of 1G and 9.23 ± 0.49% of 2G. The first morbidity of AD was noticed at the age of up to 2 y.o. among 56.29 ± 1.27%. At the age of Ch 2-4 y.o. and older than 5 y.o. the skin ADs onset was noticed for 31.12 ± 1.11% and 12.58 ± 0.57% accordingly. The AD SL was determined as follows: 52%moderate (Mo), 12%severity (S), 36% were 13 ± 10 kuA/L, 344 ± 132 IU/L respectively. Skin prick tests were positive in 43.4% of the patients (61.7% multiple allergens).

Grass pollens (53%) and dermatophagoides (45.2%) were the most common allergens.

Average vitamin A and D levels were 469.8 ± 108 μg/L (257-832), 54.8 ± 21.3 (13-187) respectively. Thirty percent of the patients vitamin D levels were mildly low, 8.6 percent was low. In control group 20% was mildly low, Vitamin A levels was low in 6.7% of the patients. None of the children in control group had low vitamin A levels. We didn't find any statistical significant difference for both vitamin levels between patient and control groups. Vitamin A deficiency was mostly found in asthma patients whereas Vitamin D deficiency was mostly in allergic rhinitis and asthma groups. Passive smoking and vitamin D deficiency was significantly related (P = 0.09). There wasn't any relation between asthma attacks and vitamin levels.

Conclusion: In conclusion vitamin A and D levels weren't found significantly related with allergic diseases but was found lower than control group. Patients having chronic diseases are one of the population groups that are chronically exposed to drugs. This study aims at evaluate the impact of this factors in developing drug allergies in the medical staff.

Method: This was a cross-sectional study that included 639 nurses from the UHC "Mother Theresa" of Tirana. They were asked to fill up a questionnaire where questions about chronic diseases and drug allergies were included. 92.18% were females and the mean age was 43.28 (+10.71) years old. Relative Risks with 95% CI were calculated for different groups.

Results: 40.69% (260) nurses reported to have at least a chronic disease. The most common non-atopic disease was HTA followed by the groups of autoimmune and thyroid diseases. Nurses who had one chronic disease have a RR of 1.82 (95% CI = 1.03-3.21, P < 0.05) to develop a drug disease higher than those who didn't had any chronic disease, and those who have more than one chronic disease have a RR of , P < 0.05) to develop a drug disease.

The presence of chronic diseases can be a risk factor to develop a drug allergy probably through the increased risk to drug exposure. These patients may be exposed to drugs not only through therapy but also through hospitalizations and other forms of health care.

Lapeere H 1 ; Oosterlinck P 2 ; Vermeir P 3 ; Vermeire I 2 ; Coppens M 3 ; Gevaert P 3 1 Ghent University Hospital/Ghent University, Ghent, Belgium; 2 Ghent University Hospital, Ghent, Belgium; 3 Ghent University Hospital/Ghent University, Ghent, Belgium Background: The key to managing latex allergies in healthcare professionals and patients lies in correct recognition and appropriate action. 7.7 million people are employed in the health care sector. While there are no overall statistics on the prevalence of latex allergy in that work force, studies do indicate that 8%-12% of health care workers regularly exposed are sensitized, compared with 1%-6% of the general population.

Latex allergy is defined as an immune mediated reaction to latex products (e.g. balloons, contact dermatitis for gloves, condoms, surgical catheters); these encompass immediate and delayed hypersensitivity reactions.

Method: Based on the experience of the Belgian Dutch Pathway Network, a 7-phase method to develop, implement, evaluate and continuously follow up a care pathway for latex allergy was designed and implemented.

The purpose of the study was to develop and implementation of latex allergy clinical care pathways to provide all staff at Ghent university Hospital with appropriate knowledge and skills to identify and manage patients who have a known latex allergy or those at risk of developing latex allergy.

Results: Care pathways, also known as clinical pathways, are used all over the world to implement and monitor patient-centered care processes in a transparent way. Care pathways are defined as a complex intervention. 7 -phase method consists of: 1) screening phase; 2) project management phase; 3) diagnostic-and objectification phase; 4) development phase; 5) implementation phase; 6) evaluation phase and 7) continuous follow-up phase. This phased approach is based on the Deming cycle, better known as the "plando-study-act" (PDSA)-cycle.

Conclusion: This method can offer support to multidisciplinary teams (re)designing and implementing safe, efficient, effective, person-centered, timely, equitable, continuous and integrated care processes. However, the method is no guarantee to success. The key to success is the collaboration and critical attitude of the entire multidisciplinary team when implementing pathways. Background: Cord blood IgE (CB-IgE) were considered to be a useful predictive tool for allergic symptoms especially in early childhood.

There is only sparse knowledge about their importance for health in later life. The aim of our work was to determine the importance of CB-IgE for allergic symptoms in young adults. We also studied the possible modifying factors for CB-IgE concentration. Results: Resutls shown as daily mean, pollen grains/m³: Table 1 .

The daily means of pollen concentrations of Cupressus arizonica, Platanus acerifolia and Plantago lanceolata in our area differs from other sites in Madrid city.

Although Cupressus arizonica and Platanus acerifolia counting were lower, Plantago lanceolata counts were higher, representing a relevant pollen in our area.

The clinical relevance of these findings is under evaluation by our group. Method: Grass pollen counts were performed since 1979-2016 using a Burkard 7 days spore trap located in our allergy center in

Madrid.

The beginning of the algid period of pollination was considered the first of three consecutive days with more than 10 grains/m 3 and the end, the last day of three consecutive days with more than 10 grains/m 3 .

Madrid, Barajas meteorological station data, was used.

Skin prick tests (PT) to grass pollen was also studied in comparison Conclusion: Total grass pollen concentration did not suffer any increase or decrease in its counts despite the dramatic increase of the temperature.

An advance at the beginning and the end of the season was seen.

These changes significantly correlate with the temperature increase during may and july.

Discrete decrease in the sensitization prevalence. Since several years, the reference method to monitor the biological particles concentrations has been the Hirst method: a volumetric pollen trap, located on the roof of building for background measurements, sucks continuously 10 L of air per minute, particles depositing by impaction on a coated tape. The tape is then analyzed by optical microscopy.

The Hirst method produces accurate but past data. Nowadays, many researches are focused on the development on new devices to get real time information.

Method: Rapid-E from Plair SA is a device using red laser beam to determine the size and the shape of sucked particles and an ultraviolet ray to measure the fluorescence of these particles.

The Results: The correlation coefficients got between Rapid-E and Hirst trap are higher than 70% for most of calibrated pollens, this correlation reaching 86% for all pollen taxa:

• Plane 99%

• Pine 99%

• Birch 96%

• Oak 82%

• Plantain 75%

• Dactylus 73%

• Urticaceae 55%

Conclusion: New calibrations are planned for 2018 and a real time information will be set up. Results: The quinquennial media concentrations since 1979-2016 were 3.866; 4.903; 6.610; 13.454; 9.501; 7.248;11.027 and 19.406 grains/m 3 .

The quinquennial media temperatures were 14.2; 13.8; 14.3; 14.9; 14.2; 14.7; 14.9 and 15.8°C. Increase of 1.4°C (r s = 0.9 P < 0.05).

The beginning and the end of the actual season advanced 5 days respectively in regard to the period from 1979 to 1983.

The annual prevalence of positive PT to Platanus in 1979 was 2% an 52% in 1994. The quinquennial media from 1999 to 2016 was 50, 38, 26 and 29%. Conclusion: Platanus pollen counts had a dramatic increase that meaningfully correlates with the dramatic increase of the temperature.

A discreet advance at the beginning and the end of the season was seen. These changes did not influence in a longer duration of the season.

We observed a significant increase in Platanus pollen sensitization prevalence whiting Madrid pollinosis patients. Results: The quinquennial media concentrations since 1979-2016 were 1963, 4813, 5455, 6948, 6985, 5976, 6727 and 9298 grains/m 3 .

The quinquennial media temperatures were 14.2; 13.8; 14.3; 14.9; 14.2; 14.7; 14.9 and 15.8°C. Increase of 1.4°C (r s = 0.9 P < 0.05).

The actual season beginning advanced in 51 days and the end has Results: Over 60% of house dust samples collected between April and May from Central European countries were found to contain

Bet v 1 allergen at levels well above the Limit Of Detection of 0.0039 μg/g for ELISA 2.0 EP kit and 0.001 μg/g on MARIA. Samples were found to have much higher levels of Bet v 1 allergen from midto-late April, particularly those that were collected in Germany, Belgium and Hungary. Samples taken from outside of the pollination season were tested and found to be negative for Bet v 1.

In conclusion, we found that Bet v 1 allergen can be detected and quantified in house dust samples. These data suggest that household dust is a source of pollen allergen and could therefore be contributing to asthma and allergic rhinitis symptoms in individuals affected by pollen allergy. Household dust may also be considered as a source of Bet v 1 allergen which could contribute to allergic sensitization.

1383 | Cupressaceae pollen in the atmosphere of alentejo: Disruption of pollen grain during air transport spring, depending on the temperature. Despite being considered moderately allergenic, it might be responsible for winter allergic outbreaks. As ornamental trees, they are found scattered throughout the territory but are more abundant in pockets of wild forest, outside Alentejo. Despite being more common in mountain, this pollen type is captured in considerable amounts in Alentejo, Portugal, where its aerobiological features and allergenic impacts are poorly characterized.

The aim of this work is to characterize the aerobiology of Cupressaceae pollen, to evaluate the effect the meteorological conditions and the source of this allergenic pollen type in the atmosphere of Evora, Alentejo.

Method: Pollen were collected using a Hirst type 7-day pollen trap and pollen was identified following standard methodology. Background: Allergic rhinitis caused by pollen is one of the most common allergic diseases. The presence of pollen in the air is currently centrally monitored at roof top levels, and not in the direct living environment of sensitized subjects. In the current project we aimed to develop a handheld pollen sampler, called pollensniffer, that can collect pollen in the living environment of the allergic subjects.

As a first step this device was validated against the standard Burkard pollen sampler and used to monitor local pollen concentrations at street level in the city of Leiden.

Method: Rooftop level pollen were monitored routinely by a Hirst type pollen sampler (Burkard, UK). The pollensniffer ( 1385 | Does the allergy risk due to pollen exposure information is useful for the allergy sufferers?

Sindt C; Oliver G; Thibaudon M

Background: In France the information for the allergy sufferers is not made with pollen counts, which have not a real signification, but with the allergy risk due to pollen exposure.

Method: Since more than 20 years, RNSA (Réseau National de Surveillance Aérobiologique), the French aerobiology network, has measured the pollen exposure in the main cities of France, using Background: The effect of environmental factors on allergic sensitizations is still unclear. Rural areas vs cities have different exposure levels to pollutants and aeroallergens. These differences could give clues on the causes of higher allergic sensitization rates in children exposed to city air.

Method: Two studies with children aged 5 years old were initialized to analyse the airborne drives of allergic sensitization: SEAL (Günzburg, 350 children) and Ae2R Kids (Munich, 200 children). Capillary blood was collected and the parents filled in a questionary.

Sensitization rates were quantified using the ImmunoCAP ® ISAC sIgE array. Pollen data were measured at both locations.

Results: In Günzburg more children were sensitized to aeroallergens, however Munich children showed significant higher sensitization to Phl p 1 (P < 0.05), despite the lower concentration of pollen.

In Günzburg 66% children had no sensitization at all compared to 58% in Munich. 80% of the children in Munich spend at least 1 hour per day outside and 91% of the total have no animals at home. 23%

felt symptoms of hay fever in the last 12 months, the majority between March and June, which correlated with the pollen flight. Results: The total rate of atopy in CRD patients was 36.1%, and asthma patients was the highest (45.9%). The positive rate of Phadiatop in urban asthma patients (56.0%) was significantly higher than that in rural areas (25.0%, P < 0.05) and the Phadiatop positive rate of office staff (62.5%) was significantly higher than that of outdoor workers (37.5%, P < 0.05). The total rate of atopy in COPD patients was 32.7%, and in patients with acute exacerbation was 42.9%.

Beside, atopy is a risk factor for dyspnea (OR = 1.22, P < 0.05), and the FVC levels in COPD patients with atopy were significantly lower than those without (2.06 L vs 2.63 L, P < 0.05). Optimal scaling analysis show that, there were a correlation between the tIgE and smoking coefficient (Cronbach's Alpha = 91.1%). In addition, the correlation between the level of tIgE and Phadiatop sIgE was so strong in the patients with mild to moderate asthma (r s = 0.709, P < 0.001), but it was weak in severe asthma patients (r s = 0.486, P < 0.001), and up to 35.0% of the GOLD III IV patients with low Phadiatop level (≤10 kU/L) had a high level of tIgE (≥1000 kU/L) compared GOLD I II (5.5%).

Conclusion: The rate of atopy in patients with CRD is high, and atopy is an important factor affecting the process of CRD. The patients with severe COPD or asthma is likely to has high serum tIgE level but the level of common allergen sIgE is low, so the allergy screening strategy should be adjusted and we should pay attention to those patients, Therefore, it is necessary to screen the sensitization situation of CRD patients at first, and the results can guide the treatment, management and prevention of CRD. Background: Due to a limited amount of epidemiological data [1] it has been thought that many severe allergic asthmatics in Germany remain unidentified and are therefore not adequately treated. A pilot project demonstrated that more than 50% of patients, having been Mean total IgE (SD) was 366.4 (692.2) kU/L. 26.5% of the patients had no sensitization towards any of the specific IgEs tested, whereas 24% were positively tested on 5-10 allergens and further 23.5% showed sensitizations towards >10 allergens.

Conclusion: Approximately 75% of 392 online recruited (severe) asthmatics had a total IgE level of >30 kU/L and ≥1 sensitization (allergen-specific IgE) towards atopic allergens. This further supports the high prevalence of atopy in asthma. Results: 875 patients (mean age: 26 ± 11.9 years, range 2-64 years, M/F ratio: 0.89) who suffered from allergic rhinitis or allergic rhinoconjunctivitis enrolled in this study. Highest rate of skin sensitivity was for weeds/grasses pollen including Salsola Kali, Amaranthus Retroflexus, Chenopodium Album and Compositae family (74.3%, 62.5%, 50.9% and 39.3% respectively). Among tree's pollen;

Ash (49%), Walnut (46.9%) and Mesquite (29.3%) were the most common. Less than 20% of patients showed skin reactivity to indoor allergens and Storage mites, mix of Cockroaches and house dust were the most common (17.6%, 17.3% and 9.8% respectively).

The results of current study confirmed the importance of weed/grass and trees pollen as the major source of allergic sensitization in our area. Interestingly the rate of sensitization to indoor allergens was low which can be explained by geo-climatic situation. Background: There are few studies of cutaneous sensitivity to gramineae in our region. Mostly of them use allergens of foreign species. The study aims to estimate the prevalence of skin sensitivity to widespread grasses in our region.

Method: This is a retrospective observational study of 894 patients with seasonal allergic rhinitis. Patients were studied using skin tests with pollens extracts from Pooideae, Chloridoideae and Panicoideae grass species.

Results: The prevalence of positive reaction to pollen from Pooideae subfamily was 86.8% (IC: 84.4%-88.9%). In turn, prevalence of allergy to Panicoideae subfamily pollens was 69.6% (IC: 66.5%-72.5%) and positive reaction to Chloridoideae subfamily reach 48.1% (IC: 44.8%-54.1%). Cochran test suggests that prevalence in those three groups is different (χ2 = 319.11, P < 0.01). When comparing just the groups of allergens from Pooideae and Panicoideae differences are also significant (χ2 = 71.43, P < 0.01). In particular, 52.5% (IC: 49.2%-55.7%) of patients were allergic to Paspalum notatum.

Regarding cross-reactivity between subfamilies, we find a no crosscorrelation between Pooideae and Panicoideae (χ2 = 2.197, P = 0.138).

Conclusion: In Bahia Blanca, patients with seasonal rhinitis are sensitive to Pooideae, Chloridoideae and Panicoideae. Paspalum notatum, belonging to Panicoideae, has a significant prevalence, high reactivity and low cross-reactivity within the group of species studied.

This last species is relevant because it is a native grass from the Northwest region of our country, Paraguay and the South of Brazil.

Prevalence of grass positive skin tests in patients with seasonal rhinitis by species.

Allergen Frequency Percentage 95% CI Results: Correlation analyzes were performed between sIgE and SPT and area results. The concentration with the highest correlation by diameter and area for Blo t was 30 μg/mL and for Der f of 400 μg/mL.

In the case of Der p the concentration with the highest correlation for the diameter was 30 μg/mL and for the area of 3 μg/mL. When evaluating the reproducibility of the results according to the area and the greater diameter of the SPT, a strong agreement was observed for Blo t in the concentrations of 3 μg/mL and 0.3 μg/mL. Results: Among the 94 patients, the majority of allergens-positive was t20, accounting for 60.6%, followed by f14 (59.6%), f13 (58.5%), ds1(57.4%) and CCD (56.4%). The prevalence of plant-related allergens (t20, w1, f14, f13, w6 and u80) in CCD-positive patients were significantly higher than those in CCD-negative patients (all Results: With our new point-of-care methods using a selected recombinant protein e other markers, we were able to detect the disease early as 10 days post-infection and more than 95% of positive cases from chronic and low endemicity areas (which are characterized by hard to detect patients with extremely low parasite load, <10 eggs per gram of feces) were obtained. Plus, chromatography POC-CCA ® test was improved by our group with a urine concentration step that turned its sensibility from 6% to 56%.

Conclusion: Monoclonal antibody and recombinant protein technologies allowed superior detection methods when comparing it to the conventional ones. In conclusion, data showed 100% of sensitivity of chronic patients and 98% of acute patients.

Marton C County Hospital, Oradea, Romania Background: Allergic rhinitis is a disease that affects about a quarter of the population, a disease with an important negative impact on daily activities, both on learning and working ability, as well as spending leisure time or sleeping. In the Western part of Romania, the most popular and blamed allergen is Ambrosia, in the late summer months. It is a plant of the Compositae/Asteraceae family, along with goldenrod, sunflower, dandelion, cocklebur, chamomile, wormwood, daisy, etc.

Allergen identification is important for applying prophylactic measures, but especially for determining the allergen to be desensitized.

Considering the possible cross-reactivity within the Compositae plant family, as well as the possibility of co-sensitization, as well as the number of patients sensitized to these pollens, which is steadily increasing, I considered is necessary a broad screening for a more precise identification of the allergen and increase chances for a successful desensitization.

Method: The observational study includes 37 patients who presented on October for testing with standardized allergen extracts, as recommended.

Criteria for inclusion: Patients with specific symptoms of rhinoconjunctivitis in August and September, with or without asthma symptoms, who returned for allergic prick test after the end of treatment.

Criteria for exclusion: Patients who disagreed with cutaneous testing, who did not discontinue antihistamine treatment or who had been treated for other diseases with drugs that influence skin testing. Background: In recent years, cationic liposomes are thought to be the most effective and non-toxical nucleic acids`transport system, so most of gene therapy drugs are developed on their base. However, lipoplexes are quickly captured by reticuloendothelial system cells after the injection and taken out of a blood stream. There are many modification methods of liposomal surface for liposomes with prolonged pharmacokinetic properties production. Addition of hydrophilic polymers (PEG) is seemed to be the most promising approach, that is able not only to create steric barrier on the particle`s surface and prevent the interaction with blood plasma lipoproteins, but also inhibits the protein adsorption, opsonisation and subsequent degradation in human body. The aim of this study is the evaluation of liposomal surface modification by hydrophilic polymers influence on nucleic acids`lipoplexes conjugation and on their physico-chemical and biological properties.

Method: Liposomes preparation (including PEG-modified liposomes), size determination by photon-correlation spectroscopy, examination of transfection efficacy by luciferase assay. (C16H33)2) were obtained. Also the modified liposomes were produced by addition of 5% of PEG (by mass) during thin lipid layer preparation step.

The size distribution was analysed by photon-correlation spectroscopy. It was shown that PEG addition does not increase the par- Conclusion: It can be noted that addition of PEG can change the lipoplex formation but the cationic liposomes still remain an effective RNA delivery system. And PEG modification will be able to impart prolonged properties for the vehicle in bloodstream.

Foundation (grant № 17-74-10111). Ory c4 may cause a cross reaction with Fel d4 (cat), Can f6 (dog), Equ c1 (horse), Mus m1 (mouse) and Rat n1 (rat).

February 2017 eight patients that were treated at our institution were diagnosed with rabbit allergy.

Results: All eight patients with the diagnosis of rabbit allergy presented with signs of upper respiratory involvement.

Two patients had itching teary eyes, watery nasal discharge and sneezing while feeding farm rabbits. One of those also presented with dyspnea.

Four patients developed problems whenever in contact with domestic rabbits. One patient developed allergic rhinoconjunctivitis whenever she was home-her parents own a rabbit, but while away in her college room she had no problems. Another patient had dyspnea whenever visiting his girlfriend's house. She owned a rabbit. Two patients developed asthma-like symptoms, one also presented with angioedema. The other two had developed allergic rhinoconjunctivitis.

Two patients have problems in contact with cats, one of them also with cows, however skin prick tests were also positive to rabbit.

Three out of eight patients developed allergic asthma with a positive methacholine test. Six patients had a positive house dust mite prick test.

All patients were diagnosed with a positive prick tests to rabbit allergens. All were treated with a nasal steroid and antihistaminesic. They were also advised to avoid contact with the animal.

Conclusion: Domestic rabbit-induced asthma and/or allergic rhinoconjunctivitis is possible, however it is still rare in our environment.

It is very important to always ask the patient about their pets in general, not just focusing on cats or dogs. Only with a thorough examination and history we can find the true cause of the patient's allergy where pets play an important role. Korea. Changes of protein and major allergen concentration were measured over one year by Bradford assay, two-site ELSIA, and SDS-PAGE after reconstitution of the lyophilized allergen extracts in various buffer (normal saline, 0.3% phenol saline, and 10 or 50% glycerol with saline) and stored at room temperature (RT, (18) (19) (20) (21) (22) (23) (24) (25) (26) or refrigerated (4°C).

Results: More than 90% of the initial protein concentration in all four extracts examined was detected over one year when 50% glycerol was added and refrigerated, whereas 57.9%-94.5% remained in the extracts at RT. The addition of 50% glycerol to the storage buffer was found to prevent protein degradation at RT. All four extracts were found to be stable when reconstituted in 50% glycerol. Amb a 1, a major allergen of ragweed, was almost completely degraded in 9 weeks at RT when reconstituted in a buffer without 50% glycerol.

However, 55.6%-92.8% of Amb a 1 content was detected after one

year of incubation at 4°C in all buffer conditions except 0.3% phenol.

Conclusion: Addition of 50% glycerol as well as refrigeration was found to be the important to increase the shelf-life of allergen extracts from pollens of allergenic importance. Results: This is the first genetic study of the Bulgarian HAE patients. Genetic defects were identified in 10 HAE families are: 3 nonsense, 2 splice-site defects, 2 frameshift mutations, 1 indel non frameshift, 1 missense, and 1 large deletion of exon 4. Novel mutations, not previously reported in human gene mutation databases were discovered, and were predicted to be deleterious due to the expected effect on DNA transcript and protein. Descriptive statistics were used to summarize the EQ-5D-Y descriptive system responses and VAS scores by treatment and visit.

Results: Twelve patients with HAE type I and a median (range) age of 10.0 (7) (8) (9) (10) (11) years were enrolled, 7 (58.3%) of whom were female.

During BOP, treatment with 500U C1 INH, and 1000U C1-INH, ≤33.3%, ≤22.2%, and none of the patients, respectively, reported having problems with mobility, self-care, doing usual activities, pain or discomfort, and feeling worried, sad or unhappy. The mean [SD] EQ-5D VAS scores increased from 78.3 (13. Results: Overall, the model-derived median exposure and peak concentration across all weight ranges in paediatric patients is predicted to be higher with 5 WB vs weight-based dosing (Table) . The effect was most pronounced in patients aged 2-5 years, where the 5WB dosing achieved approximately 30% higher values than weight-based dosing for median AUC 0-6 (1251 ng hour/mL vs 853 ng hour/mL, respectively) and C max values (777 ng/mL vs 529 ng/mL, respectively). The 5WB levels are closer to those in adults receiving 30 mg icatibant (median AUC 0-6 2975 ng hour/mL; median C max 1254 ng/ mL) but never exceed them. Results: Samples from 124 patients were analysed. Lanadelumab concentrations in plasma increased with higher doses and dosing frequencies. Steady state was reached around week 10 (range week 8 to week 14 as evaluated by predose concentrations). At baseline, mean (SD) cHMWK levels were 49. 9% (28.8), 47.7% (27.1), 53.7% (24.5) and 48.4% (30.0) for patients in the placebo and lanadelumab 150 mg q4 wks, 300 mg q4 wks and 300 mg q2 wks treatment arms, respectively. By Week 14, mean (SD) cHMWK levels decreased to 24.0% (13. 3), 28.7% (17.2), and 22.4% (11.5) following treatment with lanadelumab 150 mg q4 wks, 300 mg q4 wks, and 300 mg q2 wks, respectively, and remained reduced throughout the treatment period. Conversely, cHMWK levels remained elevated at 52.3% (28.1) at Week 14 in patients who received placebo. Patients in the placebo group had the highest attack rates over the 26-week treatment period (mean 2.46 attacks/month), whereas the rates were markedly lower in patients treated with lanadelumab 150 mg q4 wks (0.48 attacks/month), 300 mg q4 wks (0.60 attacks/month) and 300 mg q2 wks (0.31 attacks/month).

dose-and frequency-dependent manner. Exposure to lanadelumab was associated with decreased cHMWK levels (indicating inhibition of plasma kallikrein activity) and lower HAE attack rates, corroborating the efficacy findings and utility of cHMWK as a bioactivity marker in the HELP Study. with cyklokapron (tranexamic acid) since she was 9 years old and took the medication very irregularly due to lack of efficacy. One year before presentation at our clinic, she married and moved to Vienna.

We started a treatment with the bradykinin-2 receptorantagonist icatibant SC at the beginning of the menses and if needed a second time at the time of ovulation. She responded well until she got pregnant. During pregnancy, she developed weekly attacks with increasing severity. Therefore, a weekly treatment with humanplasma-derived, pasteurized, nanofiltered C1-inhibitor (INH)-concentrate, 1000 Units IV once a week was started and had to be increased to twice per week after one month of therapy due to increasing number and severity of attacks.

Results: With this treatment attack frequency and severity attenuated. In January 2016 she had a normal delivery at term and gave birth to an otherwise healthy son. Treatment had to be continued during 1 year of lactation period and also thereafter due to persistent attack severity.

Conclusion: There are only limited data for the use of humanplasma-derived, pasteurized, nanofiltered C1-INH concentrate during pregnancy and lactation period. This case confirms the safety and efficacy of the named drug during these periods. wheals are yet classified. The best characterized stem from hereditary or acquired C1 inhibitor deficiency (C1-INH-HAE and C1-INH-AAE) .

Last year, the French angioedema network (CREAK) joined the registry of angioedema without wheals (Cloud-R HAE). Here we present the contribution of the Grenoble Alpes University Hospital (CHUGA) to this disease registry.

The study population is composed of patients with a proved diagnosis of C1-INH-HAE/AAE.

The following items are collected: patients' personal-demographic data, clinical/laboratory/genetic characteristics, major comorbidities, treatments (prophylaxis/acute attacks). Data from existing registries at CHUGA are merged into Cloud-R HAE and missing data obtained at follow-up visits. As from Cloud-R HAE structure, patients can directly provide information on angioedema attacks and their treatment through a dedicated electronic app, web connection or paper support, which is then transferred into the registry at CHUGA. Method: In a retrospective study, we included a total number of 48 patients, suffering from a chronic skin disease, whose lesions did not improve or even worsened under immunosuppressive treatment (18 chronic ulcers/pyoderma gangrenosum, 21 bullous autoimmune diseases, 9 skin lymphomas). FFPE tissue was examined for the presence of CMV DNA by PCR. Next, within the framework of a small prospective study (n = 29) we analyzed the seroprevalence of CMV as well as the presence of CMV DNA in lesional skin in patients that had been diagnosed with a chronic skin disease and in whom longterm immunosuppressive therapy had been initiated.

Results: In the retrospective study CMV DNA could only be detected in 1/18 chronic ulcers/pyoderma gangrenosum (5.6%), but not in bullous autoimmune diseases and skin lymphomas. 21/29 patients (72.4%) of the prospective study group were seropositive for anti-CMV-IgG, as compared to 55/87 patients (63.2%) in an ageand sex-matched control group. Anti-CMV-IgM could be detected in Method: In this study, we aimed at testing the diagnostic potential of skin function measurements in SS. Sixteen patients with conformed diagnosis SS were enrolled in the study. Skin fibrosis was assessed by conventional RSS and involvement of inner organs and serum inflammation parameters were determined. Four objective criteria, namely transepidermal water loss (TEWL), corneometry, pH and elasticity, were assessed at nine predefined sites of the body.

Results were compared to patients with atopic dermatitis (n = 19) and acne vulgaris (n = 22). Method: A multicenter prospective observational study was conducted to investigate the clinical significance of serum SCCA2 in children as a biomarker for AD. Patients with AD younger than 16 years old and age-matched healthy children without any allergic disease were enrolled in this study. The severity of AD was evaluated using the objective SCORAD (O-SCORAD). The serum levels of SCCA2, TARC and total IgE were also measured.

Results: In total, 176 patients with AD and 159 non-allergic healthy children were recruited. The serum levels of SCCA2 had the strongest significant correlation with O-SCORAD, compared with TARC and IgE (r = 0.622, 0491 and 0.407, respectively). After standard treatment with topical steroids and emollients resulting in an improvement of symptoms, the serum levels of SCCA2 and TARC decreased significantly. The area under the curve (AUC) for the ROC curve was higher for SCCA2 (0.929) than for TARC (0.871) or IgE (0.820). The difference in AUCs between a single cut-off value and age-dependent cut-off values was not significant for SCCA2, compared with that for TARC (0.042 and 0.064, respectively).

Conclusion: SCCA2 is a more reliable biomarker than TARC for the diagnosis of AD and for determining the clinical severity of AD in children. challenges in predicting severity of atopic eczema patients Results: Before modeling, we checked for significant differences between patients and controls. These were detected for the levels of CCL17, CCL22, CXCL10, IgE and LDH. Next, we assessed whether single serum proteins already explain disease severity by calculating correlations. Twelve of the proteins, namely GCSF, IL-5, IL-13, IL-22, CCL22, IL-1Ra, CXCL8, IFNg, CCL3, IL-1ß, CCL17, and IL-6, significantly correlate with severity (r 2 range: 0.3-0.45). Finally, we built a model for the severity of AE based on all measured serum proteins. Ten of the proteins are included in the best-fit model (adjusted r 2 =0.47). The overall correlation between original and predicted severity scores is high (r 2 =0.759) nevertheless the cross validation prediction error is substantial with 19%.

Conclusion: Applied in daily practice, a prediction error of 19% translates to a possible miscalculation of 19 SCORAD points in both directions and therefore the model is of no practical use. Aside from using model-based quality measures like cross validation prediction errors to infer the usefulness of predictive models, testing them in independent cohorts could validate these models. Collaborations among scientists working on similar approaches would lead to an increase in statistical power and ideally to more robust models. Only robust and validated models are going to have the chance to take the step forward from being a result of computational modeling to being applied in the clinical practice of assessing disease severity in patients.

Jargosch M 1 ; Lauffer F 1 ; Pätzold K 1 ; Krause L 2 ; Garzorz-Stark N 1 ; Schmidt-Weber C 3 ; Eyerich S 3 ; Eyerich K 1 Preclinical studies in cell cultures, mice, guinea pigs and rabbits, comprising sterility, cytotoxicity, systemic toxicity, skin irritation, delay contact sensitization and phototoxicity tests, demonstrated safety of this therapeutic agent.

We next conducted a single-blinded, intra-individually controlled, 2phased clinical trial on patients with keloids. The aim was to determine the effects of 1-month therapy on keloid volume and symptoms of pain and itch. Two similar keloids on each subject were selectedone was treated with once-daily, self-administered application of triamcinolone-loaded (0.015 mg/patch) microneedles for 4 weeks, while the other served as control with no intervention.

Outcome measures were (a) keloid volume using a 3-dimensional high-resolution (0.1 mm) scanner and (b) pain and itch scores on 0-10 numerical rating scales. Evaluations were performed at baseline, 4 and 8 weeks. In Phase 2 of the trial, the whole process was repeated using microneedles loaded with a higher dose of triamcinolone (0.1 mg/patch). Case report: A 15-year-old girl was admitted to our department with a single round-shaped lesion in the popliteal fossa which spread to extremities, trunk and face and persisted for several weeks and then faded slowly to residual hyperpigmented patches. Courses of antihistamines, antibiotics, cyclosporine A, fluconazole, hydroxychloroquine, prednisolone and topical steroids were ineffective. Also patient has had history of itchy urticarial rash and angioedema since 5-year-old, suffered from the flares triggered by physical exertion, stress, cold air and water, spicy food, which resolved within 3-4 hours. The patient's father and 7-year-old brother also had chronic urticaria induced by the same stimuli. The physical examination revealed multiple pink-to-red non-scaly, non-pruritic papules coalescing into annular, arcuate, polycyclic plaques (4-5 cm) with central clearing, centrifugal spread, indu- 1448 | The role of humoral immunity in the pathogenesis of psoriasis Results: We found significantly increased levels of IgA in the serum of treatment-naïve psoriasis patients correlating with disease score.

However, IgA was only observed in dermal vessels of skin sections.

We next performed in-depth analysis of peripheral B cell subsets using flow cytometry. Among all investigated subsets, we only found a moderate positive correlation of CD138 + plasma cells with IgA levels and disease score in untreated psoriasis patients. However, in the group of treated psoriasis patients, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score, rather hinting at an epiphenomenal finding. Confirming our hypothesis that psoriasis can develop in the absence of proper humoral immunity, we present a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID).

Conclusion: Here, we provide new insights in the immunology of psoriasis, demonstrating the clear dominance of T cells over shifts in B cell subsets. Conclusion: Allergic diseases show an increasing incidence in geriatric age. This is partly due to the growing emphasis on a more accurate and careful diagnosis of the aging population. We must also take into consideration the influence of other factors, besides comorbidities and therapeutic regimens in elderly that might affects the immune response, such as environmental pollution as well as food contamination and changing dietary habits of elderly such as easy access to exotic food.

One of the challenges in the decades to come is recognizing and fulfilling the need for accurate and timely diagnostics of allergic manifestations in elderly patients, as important part of achieving the best possible quality of life for this growing age group. Method: Sixty-eight patients with various forms of psoriasis and 30 healthy subjects (healthy control group) were assessed after informed consent was obtained. All subjects were asked to complete a questionnaire including age, gender, duration of psoriasis, concomitant diseases and medications. In the group of patients psoriasis was with only skin involvement with skin plus joints involvement ranging from moderate to severe. Psoriaticplaques were evaluated by a specialized medical team using the Psoriasis Area and Severity Index (PASI). All patients were seen by a dermatologist and clinical immunologist, who collected data considering the demographic, health status and any other relevant details. Blood samples included serum levels of 25-hydroxycholecalciferol and TNF-α using an ELISA kit (Germany). Method: 30% ethanolic extract of SP (SP EtOH ) and its five major chemical constituents are prepared. To elucidate whether human ORAI1 modulated by SP EtOH and its chemical constituents, conventional whole-cell patch clamp performed in hORAI1-overexpressing HEK293T cell. We also assessed whether SP EtOH and its constituents could inhibit mast cell degranulation and T cell activation.

Results: In Jurkat T lymphocytes, we found that 3 mg/mL SP EtOH inhibited ORAI1 current (I ORAI1 ) by 81.0 ± 11.1%, while one of its constituents (Compound V (Com v ); 100 μM) inhibited I ORIA1 by 48.9 ± 8.71%. Investigation of human primary T cell proliferation induced by co-stimulation with antibodies to cluster of differentiation 3 and 28, and of RBL-2H3 mast cell degranulation following IgE-antigen complex stimulation, revealed that 100 μM Com v inhibited both T cell proliferation (by 34.8 ± 6.08%) and mast cell degranulation (by 36.7 ± 0.07%); these effects were concentrationdependent, and no cytotoxicity was observed.

Conclusion: Considering that most regional plants have not been investigated chemically or pharmaceutically, they remain as untapped potential sources of topical agents for drugs and other application.

Our findings suggest that Com v , which derived from SP EtOH , represents a promising candidate compound for the development of therapeutic agents for the prevention and treatment of allergic diseases. Results: The cohort consists of 14 caucasian patients. Eight of them (57%) are women. The mean age (and range) at the clinical presentation of disease was 33 years (4-51 years). The mean age at diagnosis for men was 23 years and 48 years for women. All patients have a positive history of recurrent and/or persistent lip swelling, 3 of them (21%) report oral ulceration, 5 cases (36%) have history of previous or current facial palsy and 4 patients (28%) present tongue fissuring. Concurrent CD has been diagnosed in one patient. Biopsy reports were available for 10 patients (71%); in 6 cases (60%) non-caseating granulomas were seen. Various therapeutic approaches have been described: intralesional corticosteroids had a good response in 6 patients, infliximab was partially effective in 3 cases; oral corticosteroids and/or methotrexate seem to cause a partial symptoms improvement.

Conclusion: This is the first attempt, in our knowledge, to (a) centralize all data of patients with OFG in a National Registry with the aim of carrying out epidemiological data and (b) develop Italian guidelines including a diagnostic-therapeutic flow chart, shared by the participating centers. The registry will guide the clinicians in the identification and management of the OFG patients, reducing the diagnostic delay and hopefully improving quality of life. Case report: A 10-year-old girl without personal history of atopy, got a temporary tattoo with henna. After three days, she developed a local exudative, erythematous eruption with painful blisters lesions that followed the contours of the tattoo. She had neither fever nor other lesions. She was treated with topic methylprednisolone-gentamicin showing an important improvement 10 days after. As a liquenoid scar remained in tattoo area, Trofolastin ® (Centella asiatica, αtocopherol, hydrolysed collagen, elastin) patch was prescribed to be placed on the scar. Forty-eight hours later, the patch was removed and was newly observed an exudative, erythematous and painful wound that required oral treatment with amoxicillin-clavulanic. After three days, the girl developed on a maculopapular, generalized and itching rash. She was treated with dexchlorpheniramine and methylprednisolone with a complete resolution in 4 days and she was referred to our allergy unit to be studied because of a suspicion of drug allergy to amoxicillin-clavulanic acid.

An allergy workup was performed after obtaining an informed consent. Case report: It may be sometimes difficult to find the causing allergen in allergic contact dermatitis. Face is a region on which various materials contact. In this manuscript a woman case is presented who shows patch test positivity to her husband's shaving product.

A 35 years old woman applied because of allergic contact dermatitis on her face. It is learnt that lesions have been continuing for a long time, occasionally getting well with corticosteroid creams; but continuing again. Patch test was performed with European standard series and cosmetic products she was using. Negative result was observed. Following, patch test was performed for the products her husband was using. 2 positive results were obtained for the shaving cream of her husband was using. In detailed anamnesis, it is learnt that the lesions developed approximately 1 month after her husband started to use this cream. It is advised not to use this product to her husband. The disease did not repeat again.

It should not be forgotten that cases with allergic contact dermatitis could get in touch with allergenic materials via individuals in close contact.

Gül Ü Akdeniz University Faculty of Medicine, Department of Dermatology, Antalya, Turkey Case report: TNF-alpha plays role in etiopathogenesis of allergic contact dermatitis (ACD). In mice which lack TNF-alpha, the response of late type hypersensitivity is spoiled. In addition, TNFalpha blocker are also used in some cases with ACD. In this poster the results of European standard patch test is given in which ACD is observed and TNF-alpha blocker are used without dermatological indication.

3 cases who use TNF-alpha blocker applied because of ACD: There was lesion in one case on face, in other case on face and hand, and in the last case only on hand. European standard patch test was performed to patients who were continuing to use TNF-alpha blocker.

In one case no positive response was observed, while in two cases positive response to more than one allergen were obtained.

In conclusion, TNF-alpha blockages cannot suppress the response of delayed type hypersensitivity.

1459 | Case of allergy to nickel on the background of its intake in food Peredelskaya M

Case report: Nickel is one of the most commonly used metals; it is used for the manufacture of jewelry, plates and dishes, and medical products.

A patient N, 32 years old, female, complains of pruritic rash on the body skin with the itch intensity up to 8-9 points and the number of lesions more than 50.

Allergic background: for quite some time now the patient noted occasional eruptions on her skin after a contact with jewelry made of non-precious metals. Previously patch skin tests with nickel showed a positive reaction.

The patient sought emergency medical care with complaints of a number of itchy lesions erupted on her whole body during the last 24 hours.

On admittance: state of moderate severity, the patient was emotionally labile, focused on her body sensations, tearful. On the skin of face, upper and lower extremities and torso a punctuate purpura with lesions up to 0.5 cm diameter, prone to confluent. A physical status was within normal limits.

In order to control the itching, as well as to sedate the patient, antihistamines of the first generation were administrated parenterally; but the eruptions kept to progress and to intensify; lesions were spread throughout the whole body, merged in gigantic areas. System glucocorticosteroids therapy was administrated, with 120 mg of prednisolone, but then new lesions kept appearing in a large number, including after-meal rash. Water, tea, bakery products, thin yoghurts did not impact the skin condition, whereas the intake of pasta, cereals, and similar products provoked intensifying of eruptions. The patient observation revealed a sharp increase in the rash after such manipulations as intravenous injections or blood sampling from the vein, the process spreading from the injection site to the entire arm.

A detailed anamnesis of the disease: on the eve of the start of hives, the patient purchased a coffee machine (with metal nickel-plated parts) and started to use it. diagnosis: A systemic contact dermatitis. An allergy to nickel.

The injection treatment was discontinued and a therapy with per oral GCS and antihistamines of the second generation was administrated. A recommendation was given to cook and to eat food using ceramic or wooden utensils. Three days later marked positive dynamics of the skin process has been noted. the episode of systemic contact dermatitis has developed due to exposure to nickel from ingestion in food, as well as during the parenteral treatment. Background: Anaphylaxis reactions during anesthesia can have a mortality of 3%-6%.

2/3 of the anaphylaxis in the operating room are due to the use of neuromuscular blockers. Rocuronium is frequently involved because is oftenly used.

We present a case of a 41 years old man with an anaphylaxis shock due to the administration of Rocuronium.

Method: 41 years old man with no personal history of interest that is going to undergo vertebral surgery. Minutes after anesthetic induction with Fentanyl, Propofol and Rocuronium he started with lowering of oxygen saturation. Orotracheal intubation is performed and, with the suspicion of anaphylaxis shock, adrenaline, antihistamines and corticoids were administered. After 20 minutes without improvement, 500 mg of Sugammadex was administered, given the possibility that the condition was secondary to the use of Rocuronium.

Tryptasa level was 63.

Results: Skin test to Fentanyl, Propofol, látex and Rocuronium were done 6 weeks after and only Rocuronium test was positive.

Conclusion: In summary, the occurrence of anaphylactic shock after neuromuscular blockers is widely described in medical literature.

There are conflicting data about the use of Sugammadex as coadjutant treatment in case of anaphylaxis due to the use of Rocuronium.

We believe is a good option when conventional treatment is not useful. Case report: A 31-year-old woman with past history of allergic rhinitis and hypertension was admitted to the obstetrics service in labor of first child in April 2016. Epidural anesthesia with ropivacain and sufentanil was administered. As there was no labor progression, eighteen hours later she was admitted to undergo cesarean section and epidural anesthesia was re-administered. Metoclopramide, ampicilin and ranitidine were given intravenously. During ranitidine perfusion, the patient presented general cutaneous erythema and pruritus, tongue, lips and eyelids angioedema and dyspnea. Perfusion was suspended and hydrocortisone and supplementary oxygen administered.

She denied any type of previous adverse reaction to drugs and any symptoms with use of latex-containing material. Allergic evaluation revealed negative latex skin prick test (SPT) and negative penicillin, amoxicillin and ampicillin specific IgE assay. Skin prick and intradermal tests with sufentanil, PPL, MDM, amoxicillin and ampicilin were negative. Oral amoxicilin and metoclopramide provocation challenge were negative. SPT and subcutaneous provocation challenge with ropivacain were negative. SPT with ranitidine was negative but skin intradermal test proved to be positive. The patient was taught to avoid histamine H2 receptor antagonists and use as a safe alternative proton pump inhibitors.

Conclusion: Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. The identification of responsible drugs is a complex task. We report a case in which a commonly used and generally safe drug caused a severe reaction, which demonstrated that even the least obvious culprit should not be disregarded. Epidemiologic data suggest that the number of cases of CHX allergy appears to be increasing. Background: Chlorhexidine is a synthetic chemical with excellent antiseptic and disinfectant quality frequently used in everyday products and medical devices. The prevalence of allergic reactions towards chlorhexidine is rare, though there is increasing evidence for its allergenic potential. In this case we report about a patient with serious perioperative anaphylaxis. Next to multiple potential allergens that he was exposed to, a chlorhexidine containing lubrication gel has been used for urinary catheterisation. Within minutes post-exposure, the patient developed generalized urticaria, bronchospasm, tachycardia and hypotension.

Material and Methods: We performed skin prick tests and intradermal tests with all substances documented in the anaesthesia chart, further we analysed specific immunoglobulin E (sIgE) antibodies and performed oral provocation challenges for exclusion.

Results: In the skin tests all substances except for chlorhexidine (SPT: 7 mm wheal diameter/31 mm erythema) were negative. A sensitization for chlorhexidine was further corroborated by chlorhexidine-specific IgE antibody (4.08 kU/L) in the patient's serum. In addition, the challenges for the drugs without sensitization (cefuroxime, lidocaine) were tolerated. Considering all potentially relevant allergens that the patient was exposed to and the proof of specific sensitization, we diagnosed an immediate-type allergy towards chlorhexidine.

Conclusion: With the ubiquitous use of chlorhexidine an increase in hypersensitivity reactions including immediate-type allergic reactions is observed. Anaphylactic reactions are rare, but potentially life-threatening, the diagnosis is crucial. As a warning declaration in medical devices is missing, the diagnosis of chlorhexidine allergy might be easily under-recognized or misdiagnosed. Unfortunately, until now validated provocation tests are not existent, but the evaluation of combined skin tests and sIgE is sensitive and specific.

1464 | An approach to incidence of death due to anaphylaxis in Spain (1998 Spain ( -2011 Background: Reports about death due to anaphylaxis are still scarce because of its rarity and limited information to few countries.

Also, data source analysis is usually not included. We report incidence of death due to anaphylaxis in Spain using two databases.

Method: We used a Hospital series of anaphylaxis deaths from the Spanish Hospital System and a series from the National Institute of Toxicology and Forensic Sciences (INTCF) predominantly formed by extra-hospital deaths. Deaths from the Spanish Hospital System were extracted using codes from ICD-9-CM, related to anaphylaxis among all deaths occured in the 1998-2011 period. For extracting deaths due to anaphylaxis at the INTCF in the same period, two allergist researchers identified these deaths among cases with suspicion of anaphylaxis cause. A regression logistic was run to discriminate the probability of anaphylaxis death belonging to each database. Incidence rates were calculated for the different groups (age, sex) using the Spanish population as the denominator. Temporal trends were calculated from the Hospital database using Poisson regression models with the number of cases of anaphylaxis detected each year as the dependent variable, and age and sex as covariates.

Results: There were four positive predictors of fatal anaphylaxis after the logistic model (usual allergen, positive specific IgE, suggestive symptoms and previous reaction to the same allergen Case report: We were informed that a girl was admitted to the pediatric endocrinology department due to early breast development.

She had been diagnosed as central precocious puberty (PP). Later, triptorelin acetate (TA) therapy had been started monthly.

Within 20 minutes after first SC injection of TA at home, she had developed shortness of breath, decreased air entry, and coughing for ten minutes and lastly she had developed vomiting for 15 minutes.

Her symptoms were accompanied by a pruritic blanchable maculopapular rash on her ears, cheeks, lips, and eyelids approximately for two hours. Although they had applied emergency department of the local hospital.

Based on the diagnosis of anaphylaxis she was immediately treated with adrenalin. She was subsequently hospitalized for possible recurrence and discharged next day without any further events.

Treatment with another preparation, Leuprolide Aseptate(LA-LUCRIN), as an alternative treatment was started with premedication against anaphylaxis risk only at first time and the patient did not develop any reactions. The patient is still on this treatment with no complications.

Anaphylaxis is diagnosed in the presence of a detectable allergen accompanied by symptoms of two systems. Our patient had symptoms of the three systems as described above, that is, dyspnea with coughing, hives, nausea, and vomiting.

Main treatment of anaphylaxis is the epinephrine use. Early usage maximizes the likelihood of survival.

Diagnostic tests with culprit drug were not performed in our hospital if the patient had the anaphylactic drug reaction and grouped as "physician diagnosed anaphylaxis".

There has been only one report regarding anaphylaxis to TA treatment in CPP in Turkey. In the literature, anaphylactic reactions against TA have been reported only in few pediatric cases.

GnRH analogues are important to ensure the physiological growth in precocious puberty. Because anaphylaxis can be lethal, and GnRH analogues are similar structure; the present case suggests that one should bear in mind the possibility of anaphylaxis in all patients who receive gonadotropin-releasing hormone and anologs and monitor such patients carefully as needed. Furthermore, we must provide sufficient information of adverse reactions, including anaphylaxis, to patients. Hence, managements against anaphylactic shocks should be recognized and treatment should be given immediately.

1467 | An anaphylactic shock induced by the rocuronium anesthesia: A case report Cabrera V; Barrios J; Callero A; González CE; Pérez E; Martínez JA Hospital Universitario Nuestra Sra de la Candelaria, Santa Cruz, Spain Background: The anesthetic act is a unique pharmacological situation, where the patient is exposed to a multitude of substances.Among them, neuromuscular blocking agents are the leading cause of preanesthetic anaphylaxis, with a frequency of between 50%-70%.Followed by latex in second place and antibiotics in third place. Among the neuromuscular relaxants, most reactions are due to suxamethonium or succinyl-choline in 60.6%, followed by atracurium, rocuronium and verocuronium.The one that produces the least reactions is cisatracurium.

Method: A 61-year-old woman presented a type III anaphylaxis of the Brown classification during the anesthetic induction in a surgery scheduled for laparoscopic cholecystectomy. For which adrenaline, dexchlorpheniramine, hydrocortisone, ranitidine and sugammadex was administered and was transferred with orotracheal intubation to the anesthetic resuscitation room. Due to good evolution of the patient, she was extubated within three hours. The drugs involved in the reaction were: rocuronium, amoxicillin-clavulanic, fentanyl, propofol, midazolam, lidocaine and atropine. There was a high suspicion by the anesthesiology and resuscitation service that the ABSTRACTS reaction could have been due to the neuromuscular relaxant used, in this case rocuronium, since the reaction was reversed with sugammadex. The patient had undergone surgeries under general anesthesia previously without incidents. A specific allergy study was performed with laboratory tests with tryptase, skin tests with drugs and basophil activation test for rocuronium, sugammadex-rocuronium mixture and cisatracurium.

• Serial measurement of serum tryptase: 12.9 U/L, 10.9 U/L y 3.42 U/L There is no activation of basophils for sugammadex-rocuronium mixture and cisatracurium.

The patient is diagnosed with rocuronium allergy.

Sugammadex not only acts as an antidote to reverse the neuromuscular block against rocuronium, but also has antiallergic properties by inhibiting mast cells.

As an alternative for future interventions, the patient can use cisatracurium, as the skin tests and the basophil activation test are negative.

Unal D yedikule chest disease, istanbul, Turkey

Case report: Tetracycline hydrochloride may rarely cause hypersensitivity reactions.

(HRs). Immediate type reactions are at the level of case presentations and anaphylaxis is reported.

We report a patient with late onset anaphylaxis caused by tetracycline.

A 47-year-old woman referred to our Allergy Outpatient Clinic because of urticaria due to an antibiotic that she does not remember the name of. The patient reported that many years before she had presented urticaria on her arms and legs one hour after taking the drug.

To confirm drug allergy invivo and invitro testing have to performed. For many drugs there was no validated skin test. For all that invitro tests are often less sensitive and more expensive. Therefore single blind placebo controlled drug provocation tests (SBPCDPT) is the gold standard in the diagnosis of drug hypersensitivity reactions.

We did not know which group of antibiotics were allergy to the patient. Because the patient had history of asthma and atypical pneumonia we were performed the allergy tests with clarithromycin and she had tolerated.

It was necessary to use tetracycline because of patient had vaginal infection. Skin tests have not yet been validated for tetracyclines.

For skin prick tests of tetracycline that is only available as tablet, not in a soluble form.

Therefore, the tablet was smashed and diluted with 0.9% NaCl. It was also tested.

10 healthy controls to exclude irritation. Because of skin prick tests with tetracycline negative.

SBPCDPT was planned. SBPCDPT was performed by progressively increasing four divided doses at 30 minute intervals.

Two hours after last dose the patient experienced dyspnea, palpitations, and hypotension.

As the reaction was considered to be anaphylaxis, she was given 0.5 mg of intramuscular epinephrine, intravenous 45 mg of pheniramine, and 40 mg of methylprednisolone. The reaction resolved within 3 hours.

Blood tryptase level was 14.9 ug/L taken at the 2nd hour of the reaction approximately 2 months after the anaphylaxis, serum tryptase level was 1.59 ug/L the serum tryptase level and the patient's clinic confirmed anaphylaxis due to tetracycline.

We had proved late onset anaphylaxis due to tetracycline with the patient's clinic and serum tryptase level. Anaphylaxis due to tetracycline is limited to case reports and small series but to our knowledge, there is no previous report of late onset tetracycline anaphylaxis.

1469 | Case series of IgE mediated anaphylactic shock due to polysorbate Case 2: An 86-year-old male patient with hypertension, hypothyroidism and episodes of sustained monomorphic ventricular tachycardia (SMVT), developed an anaphylactic shock after the administration of injectable amiodarone due to SMVT. Serum tryptase levels reached 34.8 μg/L during the reaction (baseline 6.59 μg/ L). Skin tests were positive to injectable amiodarone (prick 50 mg/ mL, Intradermal 0.5 mg/mL) and polysorbate 80 and 20 (prick-prick).

Skin prick-prick to amiodarone and dronedarone tablets were negative. The patient tolerated oral amiodarone. 

We report an anaphylactic reaction during the first intravenous administration of amiodarone in a female patient being treated for supraventricular tachycardia.

BAT was positive, suggesting a direct effect on basophil activation, as the patient was not previously exposed to the drug.

1472 | Anaphylaxis during labor: Don't forget to think of an amniotic fluid embolism Case report: A 32-year old primigravida (40 weeks of gestational age) was admitted with signs of pre-eclampsia and labor was induced. Benzylpenicillin and ropivacaine (epidural anesthesia) was administered >3 hours before the event. Eighteen minutes after starting an infusion with oxytocin (15 mL/h) and a vaginal toucher, the patient developed a decreased level of consciousness, generalized edema/erythema and thoracic pain, followed within 3 minutes by fetal bradycardia and maternal collapse. After resuscitation, an urgent sectio was performed, and a baby girl was born. Patient was extubated the same day. Serum tryptase, 1 hours after the event, was 11.2 μg/L (basal tryptase level 3.4 μg/L). Allergy workup demonstrated negative specific IgE and skin tests for latex and chlorhexidine, negative skin and provocation testing for ropivacain. However, skin testing was hampered by dermographism: intradermal (IDR) testing of benzylpenicillin (10 000 IU/mL, 1/1000-1/1) and oxytocin (10 IE/mL, 1/10 000-1/100) showed extensive erythema. IDR testing of oxytocin in healthy volunteers showed pallor around the injection site (n = 3). Intravenous provocation with benzylpenicillin was uneventful. A basophil activation test with oxytocin (patient and control) was negative. An additional bone marrow evaluation showed no evidence for mastocytosis. Although clinical criteria for anaphylaxis were fulfilled, a diagnosis of an amniotic fluid embolism (AFE) was concluded. No drugs were prohibited. Patient gave consent for publication.

Conclusions: AFE is one of the most devastating conditions in obstetrics, occurring typically during labor and delivery or immediately postpartum. The pathogenesis remains incompletely understood, however, it has been suggested that AFE involves an anaphylactic reaction to fetal tissue exposure associated with breaches of the maternal-fetal physiological barrier, supported by transiently increased serum tryptase levels. The diagnosis is primarily clinical, and generally one of exclusion. No specific antemortem diagnostic tests are available to confirm AFE. Postmortem identification of fetal squames in the maternal pulmonary circulation gives final diagnosis. Differential diagnosis includes drug-induced anaphylaxis or mastocytosis, which were ruled out in our case. Method: The patient presented after Hymenoptera stings dyspnoea, generalized erythema with pruritus, edema of the face that required emergency therapy in 3 episodes.

Results: An angio-CT was performed at the inferior limbs with Optiray and 5 minutes after the end of the investigation, the patient presented an anaphylactic shock requiring admission to the ICU for 4 days.

Conclusion: The patient's progression was slowly favorable. Results: Thirty seven cases were reported. 24 (65%) were women.

The median age was 47 years. 19 (51%) had DRESS/DiHS, 6 (16%) TEN, 3 (8%) SJS, 3 (8%) AGEP, 3 (8%) other not classified SCARs, and 1 (2.7%) overlapping TEN/SJS. In 100% of the patients the suspect drug was withdrawn. Thirty one patients (83%) received systemic anti-inflammatory treatment. Twenty six patients (70%) received intravenous (IV) corticosteroids alone, 3 (8%) IV corticosteroids plus IVIG, 1 (2.7%) IV corticosteroids plus IVIG, infliximab and colchicine, and 1 (2.7%) IV corticosteroids plus infliximab and cyclosporin. There were complications in 17 cases (49%), and death occurred in the patient with overlapping TEN/SJS who had received corticosteroids plus immunoglobulin. In this study, our aim was to evaluate severe IHR to ICM.

Method: We retrospectively analysed patient who consulted to our Allergy Unit between July 2011 and July 2016 reporting symptoms within 1 hour after ICM administration. From a total of 109 patients, we selected eight that had suffered an anaphylactic reaction. A written informed consent had been obtained for diagnostic procedures. Introduction: Immediate type hypersensitivity reactions to pemetrexed have been reported as very rare case reports. As limited availability of alternative therapies in chemotherapeutic allergy, desensitization plays an important role in ensuring reuse of the culprit drug. We report a case of pemetrexed anaphylaxis and successful desensitization.

Case: 43 years old female patient with lung adenocarcinoma had been treated with cisplatin-pemetrexed as second-line therapy. During the 5th cycle within 5 minutes after the end of pemetrexed infusion she had chest pain, shortness of breath, cough, swallowing difficulty, erythema on face and body, nausea and vomiting. She was diagnosed as anaphylaxis and adrenaline was administered besides antihistamine and methylprednisolone. Symptoms and findings of the patient were improved within 15 minutes.

Oncologists decelerated no suitable alternative therapy for the patient. Although skin tests (prick test with 1/1 concentration, intradermal test with 1/10 000-1/10 concentration) were negative with pemetrexed, taking into account the severity of the reaction, pemetrexed desensitization was applied with the consent of the patient.

No reaction was observed during the procedure Result: Desensitization is a successful and safe method of reusing the culprit drug. Successful desensitization of pemetrexed with immediate type hypersensitivity reaction is described. The 28 years old man was admitted emergency department with fever, rash (maculo-papular) and pain in joints. It was the 9th day of taking of amoxicillin. The hematological abnormalities were revealed -eosinophilia, increased erythrocytes sedimentation rate. The level of serum ECP was 183 μg/L. The liver functional tests were increased too. Hepatomegaly and cervical lymphadenopathy were observed. The patient was treated as a DRESS syndrome (infusion therapy, systemic steroids) and discharged after 2 weeks with improvement. All hematologic parameters were in normal limits. Lymphadenopathies were resolved. The level of ECP was retaken -84 μg/L. Patient was prescribed oral steroids till normalization of limits of ECP. It lasted 2 weeks after discharging.

The serum level of ECP can play key role in the management of DRESS syndrome and in the making of diagnostic processes. Until now, allergic or anaphylactic reactions to PEG have been rarely reported. Although patient with hypersensitivity to PEG should avoid PEG-containing drugs or products, patient who needs colonoscopy has few alternative bowel cleansing methods. No successful desensitization to PEG has been reported to date. We report a case of successful desensitization and subsequent safe colonoscopic examination in patient with allergic reaction to PEG.

Method: A 50-year-old woman developed generalized urticaria, pruritus, throat swelling, and shortness of breath immediately after taking a bowel preparation solution for colonoscopy. She had the first symptoms 3 years ago, and has had 2 more experiences so far.

The symptoms appeared within 20-30 minutes of taking cleansing solution, and the endoscopy was no longer possible. Seven years ago, she underwent endoscopy with no specific symptom. When the last symptom occurred a year ago, she was treated at emergency room because of severe dyspnea and dizziness. The patient came to our clinic for the proper diagnosis of allergy reaction and possible colonoscopic evaluation. Objectives: To describe a successful desensitization to vedolizumab in one patient diagnosed with ulcerative colitis, refractory to infliximab and intolerant to azathioprine and sulfasalazine.

Methods: Our patient was a 38 year old woman receiving treatment with intravenous vedolizumab (300 mg/cycle). Cycles 1 and 2 were well tolerated, but in cycles 3, 4 and 6 she experienced hypotension and dyspnea, in spite of premedication with oral dexamethasone and metoclopramide. During cycle 6, she also showed facial angioedema, systemic urticarial reaction and oropharyngeal pruritus treated with methylprednisolone and ebastine.

The results of prick (vedolizumab concentration 60 mg/mL) and intradermal skin tests (1:10 and 1:100) with vedolizumab were negative in our patient and in ten healthy controls. Total IgE level was 26.4 UI/mL and specific IgE against Dermatophagoides were positive, being negative for hamster epithelium and latex.

Since vedolizumab was the only therapeutic alternative, the patient was planned to undergo vedolizumab desensitization according to an 8-step protocol. Patient informed consent was obtained previously.

Premedication consisting of ebastine, acetylsalicylic acid, montelukast and methylprednisolone one hour before desensitization was administered. Desensitization protocol was performed with a total duration of 4 hours and 35 minutes and a total dose of 293 745 mg. Dose steps were 0.015, 0.03, 0.3, 0.6, 1.2, 9, 18 and 264.6 mg.

Conclusions: Our 8-step protocol desensitization to vedolizumab resulted safe and effective in our patient and it has allowed the continuation of treatment with vedolizumab for her ulcerative colitis. Montelukast, anti H1 and H2 blockers were used for the pretreatment of desensitization. All procedures (skin and blood tests, desensitization) were carried out with the informed consent of the patient. We present an exceptional, non-immediate case of fever after cisplatin and etoposide infusion with positive skin test.

Case report: A 63-year-old man, recently diagnostic of lung cancer stadium IV, in first line of treatment with cisplatin and etoposide, started 2 hours after finishing the 2nd infusion: facial erythema that becomes generalized after 4-5 hours from infusion. Twelve hours later, developed warmth sensation, shivering and fever (39°C) that persisted despite the use of several oral antipyretics treatment.

Infectious disease was discarded, so he was referred to our department in order to assess further administration of cisplatin and etoposide.

Methodology: Skin testing was performed 30 days after the last reaction to minimize false-negative results, as follows (a) cisplatin prick test (1 mg/mL) and intradermal tests (0.1 mg/mL); (b) etoposide prick test (20 mg/mL) and intradermal tests (2 mg/mL); with histamine as the positive control and NaCl-diluent as the negative control.

The results of skin test were negative for immediate reading. But two hours later, intradermal test for cisplatin turned into red and itchy and 12 hours later, still associated a wheal.

The patient was classified as high-risk (lung diseases, forced expiratory volume in 1 second <1 L) and underwent programmed inpatient desensitization according to the standardized Birmingham Women's Hospital protocol.

Desensitization was performed in the medical intensive care unit.

The patient received only standard oncology premedication. He tolerated the final dose of cisplatin with no breakthrough reactions followed by etoposide standard infusion.

Two additional desensitization procedures were performed, with no breakthrough reactions. Therapy ended when the disease worsened.

The importance of this case, lies in the fact that fever has not been described as a clinical hypersensitivity reaction for cisplatin but for oxaliplatin. Although a non-immediate reaction at the 2nd infusion of cisplatin could scarcely suggest a hypersensitivity reaction, the positive skin test and successful desensitization with this drug, could suggest it. Introduction: Propylthiouracil is commonly used as the first treatment option in patients with hyperthyroidism. Although it is generally a well-tolerated drug, it may lead to some side effects including liver damage, leucopenia and skin rash. Among skin rash findings, urticaria is considerably common. Nevertheless, in cases that developed urticaria, a rapid desensitization protocol specific to propylthiouracil has not been encountered. We represented a case in which we applied successful oral desensitization via a scheme in accordance with general desensitization principles in a case that developed propylthiouracil-induced urticaria.

Case report: Propylthiouracil at a dose of 50 mg/day was initiated for a 36 year-old female patient with diagnosis of hyperthyroidism in internal diseases clinic. The patient developed widespread itching and swelling in the body 5-6 hours after she took the first dose of the drug.

She had experienced a similar reaction with use of propylthiouracil in 2012. The patient who was breastfeeding a baby and did not have any treatment option other than propylthiouracil was referred to us with pre-diagnosis of drug allergy. The patient was thought to have propylthiouracil-induced hypersensitivity reaction and desensitization was planned. We prepared a desensitization scheme in accordance with general desensitization principles (Table 1 ). In accordance with this prepared scheme, we successfully applied the desensitization protocol with propylthiouracil for the patient. The patient gave informed consent before testing and desensitization.

Results: SPT was negative, but IDT reaction was positive at 1:1000 Method: We present a desensitization protocol to intravenous etoposide used in a 35-year-old male for non-Hodgkin's lymphoma who was referred to the Department of Allergy at Sotiria General Hospital of Athens. Within 5 minutes after receiving the first dose of the drug, the patient complained for flushing, retrosternal pain, difficulty in breathing and weakness. The infusion was ceased immediately and the patient received proper treatment with gradual recovery of the symptoms. The next day, skin prick test (SPT) and intradermal test (ID) were performed with etoposide at dilution 1:10 (2 mg/mL).

Both of the tests, SPT and ID, were negative. Histamine and NaCl 0.9% were also used as positive and negative controls, respectively.

A desensitization protocol of three-day cycle with intravenous etoposide was conducted. Premedication for 3 days was administered including methylprednisolone, cetirizine, ranitidine, paracetamol and montelukast.

Results: The desensitization protocol of the first day consisted of 11 steps of rapid pulses administered at increasing infusion rates every 15 minutes, and 1 step of drip infusion at a final rate of 60 mL/hour (372 mg/232.5 mL) until completion of the infusion. The following 2 days, the patient received a modified rapid protocol consisting of the administration of the calculated dose of 400 mg in only one step of infusion rate of 60 mL/hour completing in only 4 hours and 15 minutes. The same protocol was applied in another three-day cycle with no adverse reactions.

Conclusions: HSRs to etoposide are rarely described in the literature. We propose a three-day modified rapid desensitization protocol to intravenous etoposide that could be particularly useful compared to other time-consuming desensitization protocols. Case report: Imatinib, a tyrosine kinase inhibitor, sometimes causes cutaneous reactions that can be of various severity. We present a case of a patient who was started on imatinib 400 mg daily and after 3 months developed diffuse mildly pruritic rash with some desquamation of palms of the hands. The dose of imatinib was reduced to 300 mg daily and therapy with prednisone 30 mg was started. After resolution of rash, the dose of prednisone was tapered to 10 mg daily, but the rash reappeared, although milder in intensity.

The dose of prednisone was increased and levocetirizine added and rash resolved. Prednisone was slowly discontinued and rash did not appear. In the case of reactions to imatinib the dose of drug can be reduced and short course of oral corticosteroid given. Milder reactions can be treated with antihistamine or topical corticosteroid.

Therefore, when adverse skin reaction to imatinib occurs, induction of tolerance to this important drug should be attempted. Method: The exosomes were collected from in vitro primary human sinonasal epithelia cell, which derived from three different groups (normal control, chronic rhinosinusitis and chronic rhinosinusitis with asthma). Generation of exosomes in epithelia was confirmed by nanosight, TEM and western blot. The proteins of exosomes were identified by proteomics analysis. The cellular proliferation and ciliogenesis were analyzed by CCK8 and QPCR.The ciliary beat frequency was detected by SAVA system.

We found that epithelial cellular exosomes from chronic rhinosinusitis and chronic rhinosinusitis with asthma could reduce the multiplication rate of normal epithelial cell at a certain concentration (≥10 μg/mL).We found that exosomes from chronic rhinosinusitis with or without asthma could interrupt the cellular ciliogenesis and ciliary beat frequency. Using mass spectrometric analysis we demonstrated that the epithelial exosomes contained different proteins in different disease states.

Conclusion: Our findings first identified that exosomes could be secreted by nasal epithelial cells. We also demonstrated exosomes from chronic rhinosinusitis with or without asthma could be a pathogenic factor in the remodeling of sinonasal mucosa. It could be considered as a significant biomarker for detecting the progress of chronic rhinosinusitis and a alternative therapy target. Background: Mucociliary transport (MCT) is a major respiratory tract host defense mechanism and chronic exposure to allergen can deteriorate the these defense mechanism. The aim of this study was to investigate the effects common allergen (DP/DF) on human nasal mucociliary transport in allergic rhinitis patients, and to determine the pathophysiology of ciliary beat frequency (CBF) during allergeninduced change Method: Allergic nasal mucosa cells of allergic rhinitis patients were exposed to common allergen (DP/DF), and CBF was analyzed using an optical flow technique with the peak detection method Results: The allergen(DP/DF) exposed group showed a decreased CBF when compared to the control group. In the cytotoxicity assay, difference in survival rates was not found between the two groups.

In the allergen(DF/DF)-exposed group, protein kinase C (PKC) activity was increased during a PKC activity assay. The broad PKC inhibitor, Calphostin C abolished the allergen(DP/DF)-induced decrease of CBF. The allergen-induced decrease of CBF was abolished by GF 109203X, a novel PKC (nPKC) isoform inhibitor, whereas the decrease was not attenuated by G€o-6976, a specific inhibitor of conventional PKC (cPKC) isoform.

Conclusion: Allergen may inhibit CBF via an nPKC-dependent mechanism. Therefore, we have confirmed that chronic exposure to allergen could decrease CBF by increasing PKC activity. Method: OVA-Alum allergic rhinitis mouse model (AR model) and poly(I:C) induced IL-17 dominant mouse model (neutrophil dominant model) were used. Both mouse models were exposed to TiO2 particles for 2 hours twice daily for 7 days, while the controls (n = 5)

were not. Sirius red staining for eosinophil infiltration, immunohistochemistry for neutrophil and IL-17A, serum immunoglobulin (Ig) G and E were assayed by using enzyme-linked immunosorbent assay.

In addition, the expression of interleukin (IL)-4, IL-17, and interferon (IFN)-γ in the nasal mucosa and cervical lymph nodes was measured by immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR), IL-17 monoclonal antibody (Secukinumab) was administered in vivo to evaluate IL-17A dependency.

Results: TiO2 exposure did not influence eosinophil infiltration in both AR and neutrophil dominant model. However, TiO2 exposure increased neutrophil infiltration in both models and neutrophil infiltration was correlated with IL-17 expression in the nasal mucosa.

Serum IgG and IgE levels were changed significantly in the TiO2exposed group. Th2 cytokines (IL-4, IL-5) and Th1 cytokine, IFN-γ were not changed significantly in both models after TiO2 exposure, however, Il-17 were increased in TiO2 exposure group. And these increased type 17 pathway and neutrophil infiltration were reversed after IL-17 monoclonal antibody administration.

Conclusion: Exposure to airborne TiO2 induced neutrophil infiltration in the nasal mucosa. The Type 17 response seems to play a dominant role in the nasal immune response following airborne TiO2 exposure.

1501 | Toll-like receptor 9 ligands increase type i interferon induced b-cell activating factor expression in chronic rhinosinusitis with nasal polyposis Results: First: PAF-r mRNA expression was very low in fibroblasts from NM and NP (data not shown). PAF-r mRNA expression was detected in whole sinonasal tissue, submerged and ALI epithelial cell cultures from both controls NM and NP. PAF-r mRNA was also detected in peripheral blood eosinophils. Although no differences were found between NM and NP tissues and cultures, PAF-r mRNA expression was significantly higher (P < 0.001) in eosinophils than in upper airway tissues and cells.

Second: Protein PAF-r was found expressed in whole tissue (predominantly in the epithelium and submucosal glands), submerged and ALI epithelial cell cultures from both NM and NP. Peripheral blood eosinophils also showed PAF-r protein expression.

Conclusion: Both PAF-r mRNA and protein expression was found in sinonasal NM and NP tissues (epithelium and submucosal glands) and in peripheral blood eosinophils. These findings suggest the PAF/ PAF-r system could play a pathophysiological role in CRSwNP through the modulation of structural and inflammatory cell functions.

"This study was funded with a research grant from Uriach Group". Background: Allergic rhinitis (AR) is an increasingly more common nasal inflammatory disease in which an antigen such as pollen or dust mites triggers symptoms such as itching, sneezing, and rhinorrhea, which can lead to nasal obstruction. AR is mediated by Thelper type 2 cells together with mast cells, eosinophils, and several inflammatory cytokines and chemokines. For example, recent ABSTRACTS | 757 research indicates that hypoxia-inducible factor 1α (HIF-1α) is involved in the mechanism of AR development. The anti-heart failure drug digoxin has a specific inhibitory effect on HIF-1α, and thus, the aim of the present research was to explore the anti-hypertensive effect and mechanism of digoxin in AR.

Method: An animal model of ovalbumin-induced AR was established in guinea pigs. The experimental group was treated with digoxin through the tail vein. For the comparison of symptoms between the experimental and control groups, the incidence of sneezing was recorded, and the eosinophilic interleukin IL-4 and IL-5 levels in nasal secretions were measured by enzyme-linked immunosorbent assays. Western blotting and reverse transcription polymerase chain reaction analyses were conducted to evaluated HIF-1α expression in guinea pig nasal mucosa.

Results: The AR symptoms of guinea pigs in the experimental group were significantly improved after administration of digoxin. Specifically, the experimental group exhibited a significantly lower numbers of sneezing times(average 36.0 ± 1.10 vs 7.4 ± 0.78, P < 0.05) and lower IL-4 and IL-5 secretion levels (P < 0.01) compared with the control group. Moreover, guinea pigs of the experimental group showed less severe nasal mucosa edema, lower HIF-1α production, and reduced eosinophil infiltration in nasal mucosa compared with the control group.

Conclusion: The anti-heart failure drug digoxin may ameliorate the symptoms of AR by inhibiting HIF-1α production.

Campo P 1 ; Eguiluz I 1 ; Bogas G 1 ; Gomez F 1 ; Ariza A 2 ; Espino T 1 ; Torres MJ 1 ; Rondon C 1 1 Allergy Unit-Regional Hospital of Malaga-IBIMA, Malaga, Spain; 2 Allergy Laboratory_Regional Hospital of Malaga-IBIMA, Malaga, Spain Background: Similarly to what has been described in allergic rhinitis, there is an important association of local allergic rhinitis (LAR) with lower airway symptoms suggestive of asthma, being selfreported in 24.4% of LAR patients after five years of follow-up, and increasing to 30.7% after 10 years. However, clinical suspicion alone it is not enough for asthma diagnosis and could overstate its real prevalence. The aim was to evaluate the real prevalence of asthma in LAR patients based on validated objective methods.

Method: Seventy-five patients (29 with LAR, 20 with non-allergic rhinitis (NAR), 18 with allergic rhinitis (AR)), and 8 healthy controls (HC) were included. All patients had perennial history of rhinitis and bronchial symptoms suggestive of mild-moderate asthma for at least two years. Non-specific airways hyperresponsiveness (methacholine challenge test, using tidal breath method following ATS guidelines) was performed in all subjects.

Results: Subjects were mostly young females, non-smokers. Median μg/day of inhaled corticosteroids (budesonide/equivalent dose) was similar in all groups. Median FEV1% in AR group (75.5%) was significantly lower compared to LAR (90%, P = 0.002), NAR (85%, P = 0.007) and HC (88%, P = 0.005). In the LAR group, 15/29 (51.7%) had a positive methacholine, 12/20 (60%) in the NAR, 15/18 (83.3%) in AR group and 0/8 (0%) in HC. Patients with LAR had a significant lower percentage of confirmed asthma than AR (P = 0.031) and similar to NAR (P = 0.771).

No differences were detected between AR vs NAR (P = 0.155).

Conclusion: Presence of objectively demonstrated asthma was lower in LAR compared to AR, and with better lung function. Conclusion: Ambient air pollution influenced the hospital visit of patients with rhinitis, even, the level of pollutants, below the national standard. SO2, O3, NO2, and PM10 could increase an incidence of rhinitis and/or induce an aggravation of rhinitis symptoms. Health care provider might expect upraising patients with rhinitis in the clinic with increase of air pollutants, even under the standard levels. Results: During relapse of erosive oral lichen planus mononuclear cells obtained from peripheral blood of patients showed increased number of NK-cells CD3 + CD56 + in acute (15.5 ± 4.5%) and chronic (14.9 ± 6.3%) disease periods, and CD16 + GrB cells in acute (18.1 ± 1.5%) and chronic (14.5 ± 2.5%) disease periods, P < 0.05. In patients with the non-erosive forms of OLP there were CD3 + CD56 + and CD16 + GrB cells in acute (8.9 ± 2.5%) and (7.3 ± 1.3%) and chronic disease (9.5 ± 2.2%) and (8.2 ± 3.1%), P < 0.05. The number of CD3 + CD56 + and CD16 + GrB cells in the controls were (9.8 ± 2.1%) and (6.2 ± 5.4%), P < 0.05.

Conclusion: Acute relapse of erosive oral lichen planus, unlike nonerosive forms, is characterized by increases in the number of CD3 + CD56 + and CD16 + GrB cells. Chronic disease in patients with erosive oral lichen planus showed a steady increase in the number of CD3 + CD56 + killer cells and CD16GrB lymphocytes. bite", were observed in 6 patients (85%). Typical hyper-and hypopigmentation were observed in six patients mainly on the fingers and the cheekbones. Fibrosis of the skin of the fingers often leads to flexion contractions, which we observed in 6 patients. We were watching two-sided swelling of the fingers, but it was very pronounced in 5 patients (71%). 86% of our patients have impaired motility of the esophagus. Accelerated ESR and C-reactive protein were found in 5 patients as follows-2 intensively accelerated and 3 moderate. In our patients with positive ANA, we observed 4 patients -at low titer 1:40 at 2 and titration 1:80 in 2 patients. The spectrum of ANA found by us in Raynaud's syndrome patients is closer to scleroderma than to lupus. We underline the importance of ANA (57%) and anti-CC antibodies (27%) for the early diagnosis of Raynaud's syndrome and scleroderma, which is also seen in our patients.

Anti-SCL-70 antibodies were observed in 3 patients coinciding with other publications describing about 40% of the patients. Low levels of complement were observed in 2 patients. Low hemoglobin levels were observed in 1 patient, with no iron deficiency.

Conclusion: 1. We observed a typical fibrinoid necrosis and polymorphonuclear infiltration, and collagen accumulation in the walls of small and medium-sized blood vessels. Results: Statistically significant increase of IL4 level (3.23 pg/mL [2.18; 5.02]; 3.42 pg/mL [2.8; 4.18] respectively) was determined in patients with UC both in acute stage and remission compared to controls (1.87 pg/mL [1.4; 3.2] , (P = 0.002; 0.009 respectively). Statistically significant increase of IL17A level (15 pg/mL [12.11; 23.38] ); 14.68 pg/mL [11.29; 17.19 ] respectively) was also observed in patients both in acute stage and remission compared to controls (7.36 pg/mL [5.18; 8 .06], P = 0.00007, P = 0.00029 respectively).

Besides statistically significant increase of IFNγ both in acute stage (176.15 pg/mL [65.15; 359.84] ) and remission (42. 6 pg/mL [29.4; 64.45 ]) compared to controls (16.5 pg/mL [12.3; 23 .2], P = 0.00107; 0.0118 respectively) was revealed. Background: The presence of antinuclear antibodies (ANA) is commonly associated with a broad spectrum of connective tissue diseases. Low titres might be detected rarely also in healthy individuals, especially in higher age. An indirect immunofluorescence (IIF) detection of ANA antibodies on Hep-2 cells is the most frequently used laboratory method in this respect. The method is quite reliable regarding sensitivity, however the specificity of this test is lower.

We would appreciate a biomarker for clinical discrimination of ANA- Other autoantibodies were tested in relation to basic diagnosis.

Results: A cohort of patients was divided into 6 groups according to main diagnosis: immunodeficiency, connective tissue diseases, bronchial asthma and allergic rhinitis, recurrent infectious diseases, gastrointestinal diseases, endocrinopathy and others and the last group was generated from healthy subjects. The presence of anti DFS70 antibodies was highest in the group of recurrent infections, mostly in females. In these subjects homogenous pattern of ANA antibodies by IIF was also detected quite often, probably induced by non-specific activation of immune system. On the other hand, in a group of connective tissue diseases, we have not found any anti DFS70 positive patient.

The clinical impact of anti-DFS70 antibodies is not yet finally confirmed, but their low frequency in connective tissue diseases and presence in 5%-10% of healthy subject suggests their potential role as a new biomarker to be used as a negative predictive factor in non AARD. Confirmation of presence or absence of anti-DFS70 antibodies seems to be helpful to exclude potential diagnostic errors in IIF ANA positive patients. Background: Multiple sclerosis is a debilitating autoimmune and degenerative condition of the central nervous system, that predominantly affects young adults. Both genetic and environmental factors are associated with increased risk for this disease. We propose that the effect of environmental factors, particularly latitude of childhood, is mediated through epigenetic mechanisms. Specifically, we propose that unfavourable gene methylation predisposes individuals to multiple sclerosis, that this is set in childhood and adolescence, and transmitted from haematopoietic stem cells to progeny.

Method: CD34 + , CD14 + and CD56 + cell subsets were isolated from peripheral blood of healthy controls. Libraries enriched for CpG islands and promoter regions were generated using modified reduced representation bisulfite sequencing and subjected to next generation sequencing. Site specific methylation profiling of genome wide CpG islands, including MS susceptibility genes was conducted using Methpipe software.

Results: Genomic coverage was consistent with other published methylomes using modified reduced representation bisulfite sequencing. The methylation signature of peripheral blood derived subsets showed greater differences in methylation compared to buccal cells than with each other. Individuals displayed differences in CD34 + methylomes, and these were recapitulated in the progeny CD56 + and CD14 + cells for those individuals. Methylation of specific genes regions (e.g. PRF1), were consistent with the known biological function of these genes and their potential contribution to MS risk.

The vast majority of CpG islands interrogated show recapitulation of their methylation signature from CD34 + to progeny. However, individual differences and cell subset differences identified, likely reflect the known biological function of these genes in progeny cells. Our preliminary results are consistent with the hypothesis that the epigenetic signature (that predisposes to MS risk) is set in childhood and adolescence. The physiological basis underlying the setting of this epigenetic signature is still to be elucidated, but may involve UV light and/or vitamin D, and may provide novel therapeutic targets, especially at a personalised level, for treatment of MS. Background: Auto-inflammatory diseases are rare disorders characterized by recurrent episodes of fever/inflammation affecting serosal surfaces, joints, eyes and skin without autoantibody production or an underlying infection. Innate immunity is implicated in their pathogenesis and the underlying genetic defect has been identified in a fraction of the syndromes. During last years, the increased knowledge about auto-inflammatory diseases and the difficulty in their characterization aroused great interest to better understand these pathologies.

The acidic soluble fraction of salivary proteome of patients and controls (HC) were analyzed by RP-HPLC-ESI-MS. 60 known salivary proteins (salivary acidic proline-rich phosphoproteins (aPRPs), histatins (Hst), salivary cystatins S, SN and SA, statherin, P-B peptide, α-defensins 1-4, cystatins B, C, thymosin β-4, S100A7, S100A8, S100A9, and S100A12 proteins) and several derivatives (acetylated, glutathionylated, phosphorylated, and oxidized forms) were searched in the chromatographic profiles by XIC (eXtracted Ion Current) procedure. 21 adult patients (mean age ± SD: 34.4 ± 10.1; 15 F, 6M) were enrolled and compared with 27 sex/age matched healthy controls (mean age ± SD: 33.4 ± 9.6; 18 F, 9M). Patients are classified on the base of clinical manifestations as follows: 6 patients with FMF (mean age ± SD: 33 ± 7.9; 5 F, 1M), and 15 with Unclassified fever syndrome (Uc) (mean age ± SD: 34.9 ± 11.1; 10 F, 5M).

Results: FMF patients showed low levels of α-Defensins 2, 3 and 4, this last was absent, with respect HC, and high levels of the glutathionylated proteoforms of cystatin B, and S100A9, and of antileukoproteinase (SLPI). Similar results were obtained on saliva of unclassified patients, which showed also levels of cystatin C higher than controls.

Interestingly, proteins and peptides typically secreted by salivary glands (cystatin C, histatins, statherin, aPRPs) were found more abundant in Uc patients than in controls, and in some cases also than FMF patients (see Table) . An evaluation of relative abundance of phosphorylation of phosphorylated proteins/peptides highlighted a significant hypophosphorylation of Hst-1, PRP-1 and PRP-3 in Uc patients with respect to controls, probably due to a less active Fam20C kinase responsible for their phosphorylation Conclusion: We show by a top-down proteomics approach a wide salivary modification, highlighting dysregulation in neutrophil-derived proteins and significant differences between FMM and Uc patients. The control group consisted of 10 healthy donors aged 40-50 years.

Immunological methods of investigation included determination of membrane antigens b cells: CD3 − CD19 + CD45 + , CD19 + CD5 + CD45 + , CD19 + CD23 + CD45, CD19 + CD25 + CD45 + , CD19 + CD40 + CD45 + , CD19 + CD86 + CD45 + , CD3 + CD4 + CD40L + CD45 + , CD19 + CD45RA + CD27 + CD45 + , by flow cytometry.

Results: In the study subpopulation composition of lymphocytes in seropositive variant form of RA visceral a statistically significant increase in relative amount as B1-cells with immunophenotype CD19 + CD5 + CD45 + (0.6 ± 0.01% 0.12 ± 0.03%) and B2 lymphocytes with the phenotype CD19 + CD5 − CD3 − CD45 + (16.4 ± 1.2% and 7.9 ± 0.5%). In the analysis of the processes of maturation and differentiation of B2 cells detected statistically reliable increase of the relative number of Mature CD19 + CD3 − CD45 + naïve B2 cells CD19 + CD45RA + CD27 number of Mature CD19 + CD3 − CD45 + naïve B2 cells CD19 + CD45RA + CD27 − CD45 + (11.8 ± 0.9% and 5.7 ± 0.5%) compared to the control group. In the study of surface markers B2 lymphocytes revealed an increase of expression of costimulatory CD19 + CD40 + (19 ± 1.3% and 7.0 ± 0.42%) molecules and increasing the relative amount of CD40L 0.9 ± 0.2% (0.3 ± 0.05%) ligand on CD3 + CD4 + CD45 + subpopulation of T-lymphocytes.

Analysis of surface antigenic receptor B2 cells in the visceral form of RA showed an increased expression of early markers of CD19 + CD23 + CD45 + (2.9 ± 0.08% and 0.91 ± 0.1%), CD19 + CD25 + CD45 + (1.6 ± 0.4% 0.05 ± 0.01%) activation in comparison with the control group. Case: A 44 year-old male patient who works as a dental technician with a history of lung silicosis and recurrent sinusitis applied to an orthopedics clinic for left hip pain and difficulty in walking.

He has a history of keeping a dog during childhood. Hip MRI revealed a 5 × 3 cm sized mass on left iliac wing extended to gluteus muscle and subcutaneous tissue. Incisional biopsy was reported as chronic granulomatous osteomyelitis. The lesion was considered as tuberculous abscess. Despite anti-tuberculous (fourdrug regimen) treatment for one year, the lesion showed no regression. Excisional biopsy was carried out by the same orthopedics clinic. Chronic inflammatory reaction and fibrosis was considered to be due to cyst hydatid in the detailed evaluation. Antiechinococcus IgG and IgM was performed with ELISA and found positive. No other lesion was detected in lungs and liver. albendazole 400 mg twice a day was initiated and substantial regression observed after three months. Atypical and sustained infections made us think of primary immunodeficiency disorders.

Immunoglobulin subgroups were as follows: IgA: <1 mg/dL (70- Case description: 31 year-old male was firstly admitted to gastroenterologist due to intermittent diarrhea, abdominal pain and reactive lymphadenopathy. Celiac disease was suspected as genetic test showed HLA DQ8 (HLA-DQA1*03 and HLA-DQB1*0302), histological evaluation of duodenum biopsy provided picture of lymphoid hyperplasia and Marsh IIIA variant. However, laboratory testing for celiac disease showed very low amount of antibodies against transglutaminase. Gluten free diet for almost one year was ineffective as patient had a continuous problem of gaining weight due to chronic diarrhea. Additional questioning revealed recurrent respiratory tract infections with a need of antibiotics more than two times/year during last decade. Lymphocyte phenotyping by flow cytometry showed that CD3, CD4, CD8, CD19 are in normal ranges, but amounts of all immunoglobulins are low: IgM <0.22 g/L, IgG 2.53 g/L and IgA 0.09 g/L. Based on clinical symptoms and immunological evaluation diagnosis of CVID was confirmed, and replacement therapy with subcutaneous immunoglobulin (400 mg/kg/month) was initiated. After six months of treatment patient affirmed reduction of gastrointestinal symptoms; he gained 12 kg of weight, has no more infections and stable sufficient level of IgG (7.9 g/L).

Conclusions: This clinical case shows the importance of immune testing for primary immunodeficiency in all subjects (despite age) with unusual symptoms of autoimmune and/or infectious disorders.

CVID may have manifestation of various symptoms, which can lead to misdiagnosis, as well as inadequate treatment. Results: In our sample, all patients who progressed to hypogammaglobulinemia were receiving lymphomas. There is no immunoglobulin dosage record prior to treatment. Of the 9 cases, mean age was 52 years (4 men and 5 women), 2 lost follow-up, and 1 of them also presented neutropenia. Seventeen patients who continued in followup required IVIG replacement, due to infectious exacerbations, mainly pneumonia and sinusitis. The mean serum IgG dosage at the time of onset of IVIG replacement was 491 g/dL. The mean time between the first dose of RTM and the need for IVIg replacement ranged from 2 to 8 years, with an average of 5 years. The IgA dosage was used as a parameter for the recovery of hypogammaglobulinemia, and it was observed that only 1 of the 7 patients presented recovery of the condition up to the moment.

Conclusion: Given the data, we considered the immunoglobulin dosage to be important before initiating RTM treatment and periodically, in order to indicate the replacement of IVIg or IgSC in a timely manner avoiding complications such as potentially serious infections. Background: Steinert's disease, also known as type 1 myotonic dystrophy (MD1), is the most common dystrophy of the adult. It is inherited with an autosomal dominant mechanism. It causes myotonia, progressive muscles atrophy, muscular weakness, and problems at the heart's conduction tissue and at the respiratory muscles. In patients with myotonic dystrophy, hypogammaglobulinemia is frequently described. The associations and the pathogenesis between those affections are not totally clear, but it is recognized an increased catabolism of the immunoglobulin in these patients. In most of the cases, hypogammaglobulinemia affects only the IgG class and does not become clinically manifest. However, replacement treatment is not always successful in these patients. We report the case of a patient with myotonic dystrophy and hypogammaglobulinemia.

Case report: A 44-years-old man with MD 1 came to our attention for a history of recurrent infections of the upper respiratory tract and persistent infection by Helicobacter pylori. At the laboratory tests, we documented low serum IgG levels (449 mg/dL), normal IgM and IgA levels and protective antibodies against tetanus consisting with the diagnosis of hypogammaglobulinemia. Due to the recurrent infections, he started replacement therapy with IVIg (0.4 g/kg/ months), switched one year ago to facilitated subcutaneous Ig (fSCIg) with achievement of protective serum IgG levels (>600 mg/dL) and significantly reduction of infectious episodes.

Conclusion: Hypogammaglobulinemia is frequently reported in patients with MD1. In literature most of the cases described does not become clinically manifest, but in our case, the patient was symptomatic with recurrent infections. The replacement therapy with fSCIg showed both clinical effectiveness and safety.

1532 | Real-world experience of a novel, highly purified 10% liquid iv human immunoglobulin for the treatment of antibody deficiencies Guidelines for Immunoglobulin Use (July 2011). A highly purified 10% liquid iv human immunoglobulin (Ig), with low levels of IgA, anti-A and anti-B haemagglutinins, factors XIa, XIIa, kallikrein and aggregates (I10E) was recently approved for use in the UK. Here I report our centre's experience in using this novel 10% I10E in three patients with antibody deficiencies.

Case presentations: A patient who presented in clinic with a first diagnosis of PID, was initiated on 10% I10E at 30 g infused every four weeks. After starting I10E, they experienced a decrease in the rate and frequency of infections, in line with expectations for IgRT.

A young patient on home therapy with a 20% subcutaneous Ig for PID presented in clinic with low trough IgG levels. Non-compliance was identified as the cause of these low trough levels and therapy was switched to 10% I10E at 40 g infused every four weeks in a clinical setting. Both the rate and severity of infections reduced and trough IgG levels normalised.

An older patient on IgRT for SAD was reviewed in clinic due to discontinuation of their current IgRT product. They were switched to 10% I10E at 20 g infused every four weeks. The efficacy and tolerability of I10E was comparable to their previous therapy.

A detailed analysis of patient, clinical and safety parameters associated with the initiation of 10% I10E will be presented, including infection rates, white cell counts, C-reactive protein levels, tolerability and infusion-related adverse events.

Conclusion: These cases highlight the real-world use of 10% I10E in two patients with PID and one patient with SAD. They show that I10E was well-tolerated and efficacious in one treatment-naïve, and two previously-treated patients. Method: Prospective study of families with one or more members with C1-INH-HAE followed in 7 hospitals in the northern area of Spain. A cohort of 105 patients from 28 families with C1-INH-HAE was evaluated for familiar diagnosis of C1-INH-HAE One or several patients from the same family were chosen and were given a questionnaire to identify the total family members from the family branch affected by C1-INH-HAE that had been already studied (members with diagnosis of C1-INH-HAE and healthy members) and those that had not been previously studied. We also register the difficulties for obtaining these data.

Family members not previously studied and that consent to be contacted were asked for study of C1-INH-HAE. For C1-INH-HAE screening we use C4 blood levels Results: We have studied 28 families with C1-INH-HAE, 24 (87%) type 1 and 2 (7%) type II; 13 families had all their known members already studied for C1-INH-HAE (50%): 12 families have all their members studied (42.8%), 18 families have 90% or their known members studied (64.2%) and 10 families had less than 50% of their total known members studied.

We have identified 85 members from 11 unrelated families that had not been previously studied for HAE, 10 healthy, 4 had low C4 levels and had presented symptoms of HAE; 1 had not presented symptoms of angioedema, had normal C4 levels, and low antigenic and functional C1-INH levels.

Difficulties for a complete family testing study have been: Family dispersion, scarce or no family relationship, do not wish to know their possible pathology Conclusion: It is crucial to insist on the study of the relatives of patients with HAE. We propose to include a questionnaire to identify all patient's relatives at medical reviews of HAE patients. Case: A-4 year old boy was admitted to our clinic with the history of recurrent respiratory tract infections. His all immunoglobulins were low (IgG <154 mg/dL, IgA <25.4 mg/dL, IgM <17.8 mg/dL) associated with the absence of B cells. His aunt cousin also had XLAA missense point mutation, c562C>T in exon 17 of the Btk gene was identified in both affected cousins. The patient was commenced on regular IVIG treatment every 3 weeks. At the age of 8, he suffered from intermittent fever attacks, abdominal pain and weight loss. Tests for giardia lamblia, clostridium difficile and cryptosporidium, noro virus or parasites were negative. MR-enterography revealed intra-abdominal fluid and thickened walls of his jejunum and cecum. Histopathological examination of the biopsy material obtained from terminal ileum, colon and cecum showed crohn disease. Initially, he was treated with prednisolone and infliximab.

Because of the lack of response, infliximab treatment was switched to adalimumab. Terminal ileum was resected to relieve obstruction complication. Although he had been treated with adalimumab for 1 year, a significant improvement was not observed. Vedolizumab (Entyvio ™ ), is a humanized monoclonal antibody α4β7 integrin-receptor antagonist, was commenced. Induction dosing was 300 mg infusions at 0, 2, and 6 weeks followed by a maintenance phase at 8week intervals. At the 6 month of the treatment, fever and abdominal pain attacks reduced, while his weight and oral intake increased. No side effects were observed.

Discussion: Vedolizumab is effective for inducing and maintaining remission in adults with inflammatory bowel disease (IBD); however, there is limited pediatric data. This is the first immunocompromised child treated with vedolizumab. The symptoms of the patient receded and no side effect observed during 6 months of the treatment. Results: Louis-Bar syndrome is a multisystem progressive disease with polymorphic manifestations which varies by age. The locomotor disability of these children is determined by neurological disorders, the exitus being caused by respiratory infectious and malignancies.

The children involved in the study, had frequent episodes of respiratory infectious (bronchitis, pneumonia, atelectasis, empyema, lung abscess), ENT infections (otitis, mastoiditis, sinusitis), chronic pulmonary disease (pulmonary fibrosis, bronchiectasis). Index of death in this group is high (66.7%). In one of the boy, the pulmonary CT showed lymphadenopathy, later was confirmed Non-Hodgkin lymphoma, with subsequent death. Another child died from pulmonary and systemic infectious complications. Results: In this paper we present the clinical and morphological analysis of children with Nezelof syndrome diagnosed post-mortem.

Clinically were predominantly the generalized intrauterine infections or their development in the postnatal period.

At macroscopic examination all patients had thymic hypoplasia. Later on the microscopic study of the thymus specimens determined dysplastic changes, defined by the presence of concentrically arranged epithelial cells. In all patients, was determined the total lack of Hassall corpuscles and its predecessors. Besides the above-mentioned modifications in all specimens, there was no cortico-medullary segregation. Thymic parenchyma outside pseudorrhagia was made up of a reticular stroma with total lymphocyte depletion.

Conclusion: Nezelof syndrome is a severe primary immunodeficiency associated with thymic dysplasia and alymphocytosis, which is manifested early with generalized infections and major risk of death in neonatal and infant. Background: The study was aimed to evaluate the cytokine profile in nasal secretion and blood serum in patients with seasonal (SAR) and perennial allergic rhinitis (PAR) with a potential for additional sensitization with microbial allergens.

Method: The inclusion criteria for AR were as follows: a diagnosis of AR for more than 2 years, the absence of nonallergic disorders of the nasopharynx, age of patients from 4 years to 60 years.Control Group: healthy volunteers at the age of 3-43 years without any allergic disorders at examination.In order to evaluate the innate and adaptive immunity, the cytokine profile of blood serum (IL-4, IL-10, and TGF-β) and nasal secretion (TSLP, IL-1β, TNF-α, and GM-CSF) was determined. To determine TSLP, TGF-β, IL-10, and GM-CSF concentrations, enzyme-linked immunosorbent assay kits were used (eBioscience, Bender MedSystems, R&D Systems, MN, USA).

We have noticed a significant correlation (r = 0 46, P = 0 014) between the TSLP concentration in nasal secretion and as-IgE level to Staphilococcus aureus enterotoxin (allergen component m80) in patients with PAR. There was a significant correlation Conclusion: Staphylococcal superantigens might be one of the stimuli of local TSLP hyperproduction by the epithelium. There was a significant correlation between GM-CSF concentrations in nasal secretion and the intensity of sensitization to a staphylococcal enterotoxin (SEB) in the patients with AR. SEB is one of the polyclonal T cells activators, which may account for increased concentrations of cytokines such as GM-CSF locally within the system of mucosal immunity. The patients with AR and additional high sensitization to SEs demonstrated a higher TNF-α production profile due to macrophage and Tcell activation by these toxins.

1547 | Evaluation of circulating osteopontin level as potential biomarker of allergic asthma in patients with Caucasian and South-East Asian ethnicity Background: Osteopontin (OPN) is a pleomorphic cytokine known to influence a wide range of immune cells; allergic asthma was previously associated with high circulating OPN levels. In the present study, we aimed to verify if OPN may qualify as biomarker of activated immune response in allergic patients belonging to two different ethnic groups: Caucasians and South-East Asians.

Method: Serum OPN levels were measured by ELISA test (Human Osteopontin Duoset, R&D Systems) in a series of 121 Italian adult patients affected by extrinsic asthma, allergic rhinitis, Hymenoptera venom allergy, food allergy, allergic contact dermatitis and IgE mediated hypersensitivity to beta lactams. 116 healthy subjects served as controls. 576 ethnic Chinese subjects were recruited at the National University of Singapore (NUS) as cross-sectional cohort of an ongoing epidemiological study on the national prevalence of allergic diseases, and OPN levels were detected by Luminex (Milliplex Map, Merck) and ELISA assays (R&D Systems).

Results: In the Italian cohort, OPN levels were significantly higher in cases compared to controls (P = 0.0010 by the Mann-Whitney test). Statistically higher OPN levels were found in asthma (P = 0.0269) and food allergy (P = 0.046) groups in comparison to controls. No significant differences were found (P = 0.597) between Singaporeans with lifetime asthma and healthy controls, only the highest OPN levels were heterogeneously found to correlate with asthma. However, a strong gender effect was shown, in both cases (P < 0.0001) and controls (P < 0.0001), with males presenting higher OPN levels in comparison to females. Consequently, we checked the mRNA expression levels of OPN gene (SPP1) with Illumina chips in whole blood of males and females, and no difference was found (P < 0.05). Several experiments with Western Blots and different gel types were performed to verify if possible post-transcriptional/posttranslational modifications of OPN could explain these findings.

Conclusion: OPN seems to be a promising biomarker for current, active allergic asthma in Caucasians even though technical difficulties, due to OPN intrinsically disordered structure, the complex enzymatic metabolism, and the low circulating levels, significantly affect the experiments. Further studies are needed to confirm these data.

1548 | Mortality, intubation, and healthcare cost in patients with allergic bronchopulmonary aspergillosis in a hospital setting: A nationwide study Fan X; Luo Y; Yue B

Background: ABPA is a complex hypersensitivity reaction to Aspergillus fumigatus that colonize in airways, it is almost exclusively seen in patients with asthma or cystic fibrosis(CF). This study is to estimate hospitalization outcomes and healthcare cost of hospitalized patients with ABPA.

Method: We conducted the study using data from National Inpatient Sample(NIS) from 2010 to 2014. Diagnosis were identified using ICD-9-CM codes. Hospitalization with a primary diagnosis of ABPA and hospitalization with a primary diagnosis of acute respiratory failure/acute and chronic respiratory failure/respiratory distress/ asthma/CF and a secondary diagnosis of ABPA were included. The study population was divided into groups including ABPA with asthma, and ABPA with CF. Mortality and intubation rate were the primary outcomes; length of stay and total hospitalization cost(adjusted to cost in 2014 based on medical care CPI) were secondary outcomes. Student t-test and Chi-square were used for univariable analysis, linear and logistic regression were used for multivariable analysis.

Results: A total of 6308 hospitalizations with ABPA were included, with 2896 hospitalizations with ABPA and asthma, and 2793 hospitalizations with ABPA and CF. The overall mortality rate was 0.82% (95% CI: 0.44%-1.50%), the mortality for ABPA with asthma was 0.69% (95% CI: 0.26%-1.83%) and for ABPA with CF was 0.56% (95% CI: 0.19%-1.63%). The overall intubation rate was 4.83% (95% CI: 3.77%-6.18%); the intubation rate for ABPA with asthma was 5.51% (95% CI: 3.91%-7.72%) and 84.0% were early intubation (<3 days); the intubation rate for ABPA with CF was 1.95% (95% CI:

1.13%-3.35%) and 36.6% were early intubation. The overall mean length of stay(LOS) was 8.7 (95% CI: 8.0-9.3) days, while the LOS for ABPA with asthma was 5.6(95% CI: 5.2-6.1) days and the LOS for ABPA with CF was 12.1 (95% CI: 11.1-13.0) days. The overall total cost was 147 million USD, the total cost for ABPA with asthma was 33.4 million USD with a mean of 12 069, while the total cost for ABPA with CF was 101 million USD with a mean of 38 005.

Conclusion: Mortality among hospitalized patients with ABPA is low<1%. Intubation rate is relatively low, intubation, especially early intubation (<3 days), is more common in patients with asthma.

Although ABPA is not a common disease in inpatient population, it does have a high health care cost and despite lower intubation rate, patients with ABPA and CF generally have a longer hospital stay with a higher hospitalization cost.

1549 | Frequent exacerbations of bronchitis with wheezing in adults: Is it possible to predict and prevent asthma? Case report: Frequent episodes of bronchitis, accompanied by wheezing and dry with a prolonged duration in adults, the clinical course may be similar to bronchial asthma.

The aim is to assess the risk of asthma in adult patients with 2 or more episodes of acute bronchitis per year, had a prolonged duration and accompanied by a dry wheezing.

For 5 years in two regional clinical pulmonology centers were observed in 46 patients (19 men and 27 women) with average age 34 ± 6.8 years. Each had at least 2 episodes of acute bronchitis per year, which was accompanied by prolonged cough and presence of wheezes. Average number of acute episodes per year was 3.2 ± 0.8.

In the course of the observation the patients were divided into 2 equal groups. The first group consisted of 23 persons treated in acute episodes of the disease symptomatic therapy, including inhaled β2-agonists short-acting short course. In the second group to the corresponding treatment added montelukast 10 mg per day lasting for 1 month. In all cases of exacerbation had a viral nature. Held in the period of remission of allergic sensitization, the survey revealed.

Starting from the first year of follow-up all patients were vaccinated against influenza annually.

By the end of the fifth year of observation in the first group in 5 cases was diagnosed of bronchial asthma-4 cases easy persistent asthma and 1 case moderate. The diagnosis was exhibited in accordance with the GINA criteria. In the second group, the diagnosis of bronchial asthma were exposed to 1 patient (hazard ratio of 0.18).

Prospective observation suggests that the use of anti-inflammatory potential antileukotriene medicines in complex therapy of recurrent acute episodes of bronchitis accompanied by a dry wheezing in adults may be a factor preventing the development of asthma. For more conclusive results require more extensive research. Background: Chemokine receptors play an important role in regulating the migration of T lymphocytes, monocytes and neutrophils from the peripheral blood into inflamed tissue, such as lung. However, little is known about their expression on natural killer (NK) and natural killer T (NKT) cells in patients with chronic obstructive pulmonary disease (COPD). Therefore the aim of the study was to determine the chemokine receptor profile of peripheral blood NK and NKT cells of COPD patients.

Method: For analysis of lymphocytes subtypes the flow cytometry method was used. The study population consisted of 57 smokers with COPD, 12 healthy smokers and 12 healthy non-smokers.

Results: We observed an increase in blood NK cells expressing CXCR3 receptors in smokers with COPD compared to healthy smokers (P = 0.003) and healthy non-smokers (P < 0.001). The percentage of NKT cells containing CXCR3 receptors was also significantly higher in blood of smokers with COPD compared to healthy smokers (P = 0.021) and healthy non-smokers (P < 0.001). COPD smokers had significantly higher proportion of CCR5 + NK cells than smokers without COPD (P = 0.002) and healthy non-smokers (P < 0.001). Increased proportion of blood NKT cells expressing CCR5 on their surface was observed in smoking COPD patients compared to healthy smokers (P = 0.002) and healthy non-smokers (P < 0.001). There were no significant changes in the percentage of CXCR3 + and CCR5 + NK and NKT cells between healthy smokers and non-smokers. In addition, no differences were seen in the proportion of NK and NKT cells expressing CXCR4, CXCR6, CCR6 and CCR7 among all studied groups. Method: 58 patients with COPD in stable condition (GOLD stage 2) aged 40-70 years old, smoking history of ≥10 pack-years, were studied. BMI of patients were divided into 2 groups: obese (n = 31) (BMI-30.0-39.9 kg/m 2 ) and non-obese (n = 17) (BMI-18.5-24.9 kg/ m 2 ). Ten subjects with normal lung function and BMI were the control group. The level of IL-26 assessed in induced sputum (pg/mL) was measured using an ELISA (RayBiotech ® ). Serum levels of CRP were measured using the "Vector-Best" (Russia Federation). Spirometry was performed according to American Thoracic Society and the European Respiratory Society (ATS/ERS) guidelines.

Results: Obese COPD patients had significantly increased concentrations of IL-26 compared with healthy subjects and non-obese COPD patients by 2.6 fold (139.0 ± 85.4 pg/mL vs 53.15 ± 18.5 pg/ mL) (P < 0.008) and 1.15 fold, (139.0 ± 85.4 pg/mL vs 120.6 ± 60.15 pg/mL)(P < 0.04), respectively. Non-obese COPD patients had higher levels of IL-26 by 2.3 fold compared with healthy subjects (120.6 ± 60.15 pg/mL vs 53.15 ± 18.5 pg/mL) (P < 0.008). Results: Among these three groups, the level of CER in lung cancer patients (0.35 ± 0.10 g/L) was significantly higher than that in ILD patients (0.31 ± 0.25 g/L) and healthy individuals (0.25 ± 0.04 g/L) (P < 0.05). Meanwhile, the levels of C3 and C4 in healthy individuals, which are 1.70 ± 0.29 g/L and 0.27 ± 0.34 g/L respectively, were both significantly higher than that in lung cancer patients (C3:

1.04 ± 0.26 g/L, C4: 0.24 ± 0.09 g/L) and ILD patients (C3: 0.97 ± 0.25 g/L, C4: 0.21 ± 0.09 g/L), (C3: P < 0.05, C4: P < 0.05).

Results from optimal scaling demonstrated that lung cancer was closely associated with immune factors including CRP, CER, C3 and C4 (Cronbach's Alpha = 84.7%).

Conclusion: For ILD patients, when the level of CRP and CER is increased and the level of C3 and C4 is decreased simultaneously, the risk of the development of lung cancer should be considered for these patients. Results: Among PBMC subpopulations, endurance exercises impacted the number of NKT and activated T cells with NKT cell numbers greater in male bobsledders vs bullet shooting and biathlon (42.4% and 44.3%, respectively). The number of activated T cells (CD25 + ) was greater in bullet shooting and bobsleigh athletes vs the biathlon group (34.9% and 22.7%, respectively). In female athletes the number of CD25 + cells in the shooting and bobsled groups was greater by 46.1% and 25.5%, respectively vs the biathlon group (P < 0.05). Increased IL-10 occurred in bobsleds in comparison to bullet shooting and biathlon: 32% and 80% in male and 70.5% and 83% in female, respectively (P < 0.05). The concentration of IL-18 in male bobsledders and biathlon was 30% and 34% greater, respectively, compared with bullet shooting (P < 0.05). Serum concentrations of IFNγ in male as well as female athletes showed an increase of 41.6% and 39.5%, respectively vs biathletes (P < 0.05). Increased IL-4 occurred in the male biathlon group by 39.7% and 13%, respectively, vs the bullet shooting and bobsleigh athletes (P < 0.05). IL-6 was increased in the male biathlon group, compared to bullet shooting and bobsledders by 76.7% and 70.3%, respectively (P < 0.05).

Conclusion: Prolonged endurance exercises impacts secretion of pro-and anti-inflammatory cytokines in athletes of different sport specializations. Concentrations of studied cytokines did not exceed reference values perhaps due to specialized sport nutrition, which may restore immune function during endurance exercises. Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. Recently, we have shown that the use of a mixture of short-chain-and long-chain fructo-oligosaccharides (scFOS/lcFOS) improves the efficacy of OIT in cow's milk and peanut allergic mice. However, concerns with regard to safety and long-term efficacy of OIT remain and there is a need to identify novel biomarkers (panels) that predict, monitor and/or evaluate the effects of OIT. Here we present a method for the selection of candidate biomarkers by using the computational approaches Bayesian networks (BN) and Topological Data Analysis (TDA).

Method: Data were used from scFOS/lcFOS diet-supported OIT studies performed in 2 independent cow's milk allergy (CMA) and 2 independent peanut allergy (PNA) experiments in mice. First, a subset of the data was used for learning the data structure and their interactions in terms of a BN. This BN was used to compare the key parameters in both experimental food allergy models. Finally, the relations within the dataset in combination with the BN were explored to identify and rank candidate biomarkers for the effect of OIT by applying TDA.

The BN was able to predict the efficacy of OIT in the CMA and in the PNA model with 82% and 80% accuracy respectively, thereby identifying a set of 5 parameters (allergen-specific IgE and IgG1, body temperature, mMCP-1, earswelling) being key in the mechanisms involved in both scFOS/lcFOS-aided OIT food allergy models. The TDA zoomed in on the full set of 67 previously analyzed parameters and identified clusters of biomarkers closely linked to biologically relevant clinical symptoms but also unrelated and redundant parameters within the network. Taken together, this enables the prioritization of candidate biomarkers. Moreover, the TDA indicated differences between PNA and CMA models in how the data are related to each other.

Here we provide promising bioinformatics methods to compare mechanistic features between two different food allergies and to determine the biological relevance of biomarker (panels) of OIT for food allergy. We have shown that the key drivers that influence PNA and CMA are similar, but that these phenotypically similar diseases show mechanistic differences in their subnetworks. These new insights provide excellent starting points to generate new hypotheses to explain why CMA has a different disease pattern than PNA and to select biomarkers that are useful in future clinical studies.

1562 | Functional and immunoreactive levels of igg4 correlate with clinical responses during the maintenance phase of house dust mite immunotherapy Basophils were identified as SSC low CD193 high , and CD63 was used as an activation marker. Reactivity was confirmed by anti-IgE as a positive control.

Results: In 4 patients, basophil reactivity and sensitivity was comparable for grass pollen extract and recombinant Phl p5, while Phl p1 only caused a lower basophil activation. In one patient, recombinant Phl p5 did not cause any basophil activation, while Phl p1 elicited an even higher sensitivity and reactivity than grass pollen extract.

Conclusion: In 4 patients, basophil reactivity was comparable for grass pollen extract and recombinant Phl p5, while Phl p1 only caused a minor basophil activation. In one patient, recombinant Phl p5 did not cause any basophil activation, while Phl p1 elicited an even higher sensitivity and reactivity than grass pollen extract. Reactivity of extract and the main sensitizing components correlated, while sensitivity did not.

1564 | In vitro assessment of hypersensitivity to allergen before and after allergen immunotherapy with whole blood basophil histamine release assay WBBHR assay in these patients was performed 7-10 days before and 7-10 days after AIT. Heparinized whole blood samples (8 mL) of each patient after substitution of plasma with PIPES buffer were incubated one hour at 37°C with different concentrations of birch pollen extract (T3) in U-shape 96-well micro-titer plates. After incubation plates were centrifuged and supernatants from each well of the plate were directly analyzed for histamine content by reversedphase high performance liquid chromatography with electro-spray ionization mass-spectrometry (RP-HPLC-ESI-MS). Results were expressed as ng/mL released histamine. Sensitivity (limit of quantification) was 5-7 ng/mL. To compare results of histamine release in patients before and after AIT data were calculated as area under the curve (AUC) values.

Results: In contrast to pre-immunotherapy activity of blood basophils there were significant decreases in HR induced by T3 extract after AIT. According to AUC values all patients demonstrated decrease in HR after AIT in compare to HR before AIT in a range of 25%-65% demonstrating a decrease of hypersensitivity to birch allergens. Analysis of basophil HR in patients received s.c. or s.l. The asthma and rhinoconjunctivitis symptom scores during and after pollination season decreased significantly and showed correlation with histamine release by T3. 1565 | Immunotherapy with the recombinant B cell epitope-based grass pollen allergy vaccine BM32 induces a biphasic allergen-specific IgG1 and IgG4 response Background: Immunotherapy with the recombinant B cell epitopebased grass pollen allergy vaccine has been shown to reduce symptoms of grass pollen allergy in a multicenter, double-blind, placebocontrolled study. Aim of this study was to investigate the levels and kinetics allergen-specific IgG responses in a double-blind, placebocontrolled phase IIb combined field and exposure chamber trial studying the effects of three, four and five pre-seasonal injections of BM32 as compared to placebo.

Method: A quantitative ELISA assay based on purified human monoclonal allergen-specific IgG 1 as well as IgG 4 antibodies as standards was developed to measure allergen-specific IgG 1 and IgG 4 concentrations induced by AIT with BM32.

Results: We found rises in levels of both tested allergen-specific IgG subclasses in the actively but not placebo-treated patients. Phl p 1-and Phl p 5-specific IgG 1 levels up to 83 μg/mL and 784 μg/mL, respectively and Phl p 1-and Phl p 5-specific IgG 4 levels of up to 468 μg/mL and 1423 μg/mL, respectively were measured in BM32treated patients. Five pre-seasonal injections induced the highest allergen-specific IgG levels. Interestingly, allergen-specific IgG 1 and IgG 4 antibodies showed a biphasic response with early rises of allergen-specific IgG1 which declined quickly after the pollen season and a delayed but very sustained allergen-specific IgG4 response.

Conclusion: Treatment with BM32 induces a biphasic allergen-specific IgG response consisting of an early IgG1 and a sustained allergen-specific IgG4 response which may be responsible for early and sustained protection against allergic symptoms.

1566 | T reg CD4 + CD25 high in peripheral blood in patient with grass pollen allergy during sublingual specific immunotherapy SLIT The aim of this study was to evaluate T reg CD4 + CD25 high in peripheral blood in patients with grass pollen allergy during sublingual immunotherapy SLIT.

Method: We examined 27 adult patients, aged 20-41, 13 female and 14 male. Patients were qualified to SLIT after confirmation of allergy-by skin prick tests, specific IgE and nasal provocation tests.

We determined T reg CD4 + CD25 high from blood sampling of those patients (by flow cytometry method), before the SLIT, after reaching the maintenance dose, before the grass pollen season, during the grass pollen season, and after one year of SLIT.

Results: During SLIT the percentage of T reg CD4 + CD25 high increase after reaching the maintenance dose, then it decreased before and during the grass pollen season, and again increase after one year os SLIT. We observed, that in the group with significant improvement of symptoms, T regCD4 + CD25 high decreased during grass pollen season, comparing to group without clinical improvement.

Conclusion: SLIT as a method of immunotherapy influence on levels of T reg CD4 + CD25 high cells. The observed decreased levels of these cells during the grass pollen season might be consider as a prognosing marker of clinical improvement.

1567 | T reg CD4 + CD25 high from peripheral blood during subcutaneous specific immunotherapy (SCIT) for grass pollen Hofman A; Hofman J; Hofman T Centrum Alergologii, Poznan, Poland Background: Specific immunotherapy is the only causal method for grass pollen allergic rhinitis. However, we don't observe in every patients satisfying clinical effects. Because the treatment of allergic rhinitis takes 3-5 years, and is quite expensive, everyone is constantly looking for a perfect parameter, which may prognose the effectiveness of specific immunotherapy (SIT).

The aim of this study was to evaluate T reg CD4 + CD25 high lymphocytes from peripheral blood in patients during subcutaneous specific immunotherapy (SCIT) for grass pollen .

Method: We examined 99 adult patients (36 female, 63 male), age 18-60, who undergo SCIT for grass pollen allergy. We have done skin prick tests and specific IgE in those patients. Additionally, we confirmed the allergy by nasal provocation tests. We have determined lymphocytes T reg CD4 + CD25 high from blood sampling from those patients, with flow cytometry method: before immunotherapy, after reaching the maintenance dose of SCIT, before and during the grass pollen season, and after one year of SCIT.

Our control group was represented by 12 adult healthy volunteers.

After one year of SCIT we divided patients into two groups-with and without clinical improvement.

Results: In allergic patients we have observed decreased levels of T reg CD4 + CD25 high compared to control group before the start for SCIT. During immunotherapy, the percentage of T reg CD4 + CD25 high increased after reaching the maintenance dose, however it did not reached the level of healthy volunteers. Again, levels of T reg CD4 + CD25 high decreased before and during the grass pollen season, and increased after one year of SCIT. We compared also patient with significant improvement of clinical symptoms, and without. And we observed that the level of T regs CD4 + Cd25 high decreased during pollen season in improved group, and increased in the group without clinical improvement.

Conclusion: In patients with grass pollen allergy, during the grass pollen season, decrease of T reg CD4 + CD25 high cells might be con- Results: In the group of patients treated with SIT gene expression analysis revealed significant change in IFNG expression (P = 0.03) (comparison between sample A and B). Comparison between samples A and C showed significantly different expression in genes: AFAP1L1 (P = 0.006), COMMD8 (P = 0.001), PIK3CD (P = 0.027), and TWIST2 (P = 0.0003). Duncan's multiple range test confirmed difference between sample A and C for COMMD8 (P = 0.004) and also revealed new significant difference in TBX21 in samples A and B (P = 0.035; in Wilcoxon's test P = 0.08). K nearest neighbors algorithm was built based on IFNG, PIK3CD, COMMD8 expression.

The results of the study indicate, that there is a significant change in the expression of a few genes during the build-up phase of SIT. It may be suspected, that this change contribute to the mechanisms involved in the building tolerance to allergen. K nearest neighbors algorithm may be useful for SIT efficacy prediction.

1569 | Regulation of cytokine thymic stromal lymphopoietin (TSLP) in modulating TGF-ß1induced interstitial inflammation and cellular fibrosis Background: Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, tissue fibrosis and organ dysfunction. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that underlying mechanism.

Method: An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-β1 (TGF-β1), after which the levels of various fibrogenic markers (e.g., fibronectin) and downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also, TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted to evaluate the fibronectin secretions.

Results: The level of fibronectin in the NRK-49F cells was doseand time-dependently increased by the administration of exogenous TSLP (P < 0.05). TSLP also significantly increased the level of fibrosis signaling, in addition to inducing a marked decrease in the down-regulation of Smad7. Interestingly, the application of TSLP shRNA caused a dramatic reversal of the TGF-β1-induced cellular fibrosis while simultaneously leading to the suppression of fibronectin and fibrogenic signal proteins.

Conclusion: Taken together, these observations provide insights into how extracellular matrices develop and could lead to potential therapeutic interventions for the suppression of renal inflammation and fibrosis. ABSTRACTS | 779 1571 | Effects of two years treatment with the recombinant B cell epitope-based grass pollen allergy vaccine BM32 on allergen-specific B and T cell responses Background: BM32 contains recombinant fusion proteins of nonallergenic peptides from IgE-binding sites of the four major timothy grass pollen allergens Phl p 1, 2, 5 and 6 and PreS protein from the Hepatitis B virus as a carrier. In a multicentre, double-blind, placebocontrolled trial, 181 grass pollen allergic subjects were treated for two years either with BM32 or placebo. Here we investigated in detail the effect of immunization with BM32 on allergen-specific T and B cell responses.

during the study from 35 subjects treated in the Vienna centre (BM32: n = 25, placebo: n = 10) were investigated regarding proliferation using 3 H thymidine incorporation and cytokine production in response to various recombinant allergens at 9 different time points.

Grass pollen allergen-specific IgE, IgG 1 and IgG 4 levels were determined by ImmunoCAP and ELISA.

Results: A significant increase of allergen-specific IgG 1 and IgG 4 levels was found in the BM32-but not in the placebo group in both years (year1 > year2) after treatment. There was no difference regarding T cell proliferation in response to Phl p 1 and Phl p 5 after first grass pollen season between actively and placebo-treated patients whereas proliferation in particular of Phl p 1-specific responses seemed to be blunted in the active group in the second year. No significant differences regarding allergen-specific Th1, Th2 and tolerogenic (i.e., IL-10) cytokines were observed between BM32and placebo-treated patients.

The findings indicate that the BM32 induces high levels of allergen-specific blocking antibodies which may reduce allergen-specific T cell proliferation but does not induce significant increases of regulatory cytokines in T cells.

This study was supported by grants F4605, F4613 and DK 1248-B13 of the Austrian Science Fund (FWF). 1 Hospital Universitario Ramón y Cajal, Madrid, Spain; 2 Department of Immunology IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain Background: Shiitake mushroom (SM) (Lentula edodes) is an edible fungi native to East Asia. It is traditionally cultivated and used in many Asian countries and its consumption is increasing worldwide.

Direct skin exposure to SM can cause cutaneous reactions, including allergic contact dermatitis and urticaria, while its oral intake may prompt "shiitake flagellate dermatitis" (SFD), which is a distinctive itching linear erythematous eruption. SFD is usually considered a toxic reaction to lentinan, a thermolabile polysaccharide that increases interleukin-1. We report 3 cases (P1, P2, P3) of shiitake flagellate dermatitis studied in our Centre.

Method: Skin prick tests (SPT) to environmental allergens-including moulds -, prick-by-prick and patch test with raw and cooked SM were carried out. Total IgE and specific IgE to mushroom, white mushroom and environmental moulds were also determined. A raw and cooked shittake mushroom extracts were prepared. Both extracts were analyzed in all the patients by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Results: Skin prick tests, prick-by-prick, patch tests and specific IgE were all negative except for P1, who had positive prick-by-prick to raw Shiitake mushroom. SDS-PAGE IgE immunoblotting assays with the patient's sera revealed IgE-reactivity with proteins ranging from 16 kDa to 32 kDa for P1, P2 and P3.

We report 3 cases of shiitake flagellate dermatitis with demonstrated IgE-sensitization. Physicians should take into account that some cutaneous reactions considered as toxic might be allergic reactions.

Vorozhko I 1 ; Sokolnikov A 1 ; Sentsova T 2 ; Donnikov A 3 ; Ilyenko L 2 ; Denisova S 2 Background: Allergic diseases such as asthma, rhinitis and food allergy have increased in recent decades in tropical countries. The tropics has climatic, environmental and ecological peculiarities that allow us to emit several hypotheses that could explain this phenomenon. In one of them, it is postulated that the increase of the sensitization to food, is due to the presence of lower serum levels of vitamin D, product of the adoption of a western lifestyle, with lower sun exposure, which in its turn diminishes the immunomodulatory action of this vitamin at intestinal level, favoring the sensitization against food antigens. We evaluate differences between the titers of serum antibodies against food antigens between two populations with African ancestry but different environment (rural vs urban) and investigate the influence of vitamin D levels.

Method: An observational, cross-sectional and descriptive study was carried out on 200 Afro-descendant children living in San Basilio de Palenque (Rural) or in the city of Cartagena, Bolivar (Urban). The sensitization was determined by a positive skin prick test to allergen extracts, including foods, and, specific IgE, IgA and IgG4 to egg, milk and peanut extract, as well vitamin D, were measured by ELISA.

Antibody and vitamin D titers were correlated by Spearman's test and comparisons between groups were done using the Wilcoxon rank sum test. A P < 0.05 was considered significant.

Results: Atopy was more prevalent in the urban population (24% vs 7%, P < 0.001). However, none participant tested was positive for food allergens. Regarding vitamin D levels, these were found to be higher in the rural population compared to the urban group (P < 0.001). Among the antibodies analyzed, only IgE against peanut showed differences, which were higher in rural population (P < 0.001) as well as those of IgA to peanut, which were higher in the urban population (P < 0.001). We observed only a significant correlation between peanut specific IgE (Rho 0.2127259, P < 0.005) and IgA (Rho -0.342434, P < 0.001) response and vitamin D.

Conclusion: In our study, we found differences between the peanut specific IgE and IgA response in urban and rural populations. The correlation between the levels of specific IgE and IgA to peanut and vitamin D, suggest that this vitamin may influence peanut sensitization in this population, besides other components like diet and genetic and environmental factors.

1580 | Evaluation of inhaled allergen sensitivity in patients with food allergies younger than two years of age Kulhas Celik I 1 ; Aldemir ES 2 ; Buyuktiryaki B 1 ; Ginis T 1 ; Toyran M 1 ; Dibek Misirlioglu E 1 ; Kocabas CN 3 ; Civelek E 1 carbohydrates and pyruvate was observed in the severe group compared to the rest of allergic groups. In addition, an increment in lactate was noticed. These metabolites were closely associated with the energy metabolism. Other metabolic changes included increased levels of fatty acids such as myristate, palmitate and laureate. These fatty acids might be precursors of arachidonic acid, a key molecule in inflammation. Finally, alterations in some amino acids and adenosine were found Method: To evaluate these critical processes, 22 five-week old germ-free C3H/HeN mice were split into two groups; 12 were intraperitoneally sensitized to the peanut allergen Ara h 2 and 10 remained NS. Upon reaching 8 weeks of age, mice were intragastrically challenged with purified Ara h 2. Mice were harvested in two groups: 30-minutes and 60-minutes post-gavage. Upon harvest, the left lobe of the liver was collected and sera were removed. Sera and livers were evaluated for DRP-Ara h 2 using an in-house quantitative sandwich enzyme-linked immunosorbent assay (ELISA). A sample of the proximal small intestine was monitored for DRP-Ara h 2 using immunohistochemistry (IHC) and for mast cell degranulation using Toluidine blue stain.

Results: Sensitization does not have a large effect on the concentration of allergen present in the sera or liver. However, S mice allowed to digest Ara h 2 for 60-minutes were more likely to display tissues positive for detection of DRP-Ara h 2 than NS mice at the same time point.

Conclusion: There is drastic biological variation among mice in their capacity to absorb and transport allergens. The ELISA used in these analyses proved effective in the quantitative detection of DRP-Ara h 2 in both liver and sera samples, while IHC provided inconsistent results for the detection of DRP-Ara h 2 in tissues.

However, in positive IHC samples, staining was indicative of paracellular transport across the epithelial barrier.

1583 | Eczema induces a high ovalbuminspecific IgE/IgG1 ratio and affinity maturation during the lactation period Irahara M; Kido H; Shinahara W Inst. for Enz. Res., Tokushima University, Tokyo, Japan Background: Recent articles have revealed that ingestion of foods induces oral tolerance and cutaneous sensitization induces food allergy. Relationships with levels of immunoglobulin subclasses, affinity of allergen-specific IgE, and development of food allergy have also been indicated. However, relationships with levels and affinity of specific immunoglobulins and eczema during early infancy remain poorly understood. Therefore, the present study aimed to elucidate these relationships.

Method: This study enrolled women who visited Naruto Hospital (Tokushima prefecture, Japan) in late pregnancy and their children.

Blood samples and information on skin condition were taken every 2 months from neonate to 6 months old. Egg white and milk allergen-specific immunoglobulin subclasses and affinity of ovalbumin (OVA)-specific IgE levels were measured using the densely carboxylated protein (DCP) microarray with 20 μL of serum.

Results: This study included 84 infants whose parents agreed to join this study. Of these, 42 infants (50%) were diagnosed with eczema by 6 months old. Egg white (EW) and milk-specific IgG4 were detected in a few subjects at 6 months old. However, these specific IgE and IgG1 were detected in some subjects at that time EW-and OVA-specific IgE levels and IgE/IgG1 ratios were significantly higher in participants with eczema than in those without eczema at 6 months old. Moreover, subjects with high OVA-specific IgE/IgG1 ratios showed higher affinity OVA-specific IgE antibodies than subjects with low OVA-specific IgE/IgG1 ratios. These results were not reflected in milk-specific IgE levels. The milk-specific IgE level differed between breast feeding and formula-fed infants, with no difference in the IgE/IgG1 ratio.

Conclusion: Eczema contributed to high EW-and OVA-specific IgE levels and IgE/IgG1 ratios. High OVA-specific IgE/IgG1 ratios involved high affinity OVA-specific IgE antibodies. However, the milk source during early infancy had no effect on the specific IgE/IgG1 ratio with eczema. These results suggest different sensitization routes provoke different results in levels and affinity of immunoglobulins.

1584 | Purification and characterization of naturally occurring post-translationally cleaved Ara h 6, an allergen that contributes substantially to the peanut allergome Background: The 2S albumin Ara h 6 is one of the most important peanut allergens. A post-translationally cleaved Ara h 6 isoform has been described in the past but had not been characterized in detail, nor had its relevance for peanut allergy been investigated.

Method: Post-translationally cleaved Ara h 6 (pAra h 6) and intact Ara h 6 (intact Ara h 6) were purified from Virginia type peanuts and the cleavage site was mapped using high-resolution mass spectrometry. Biochemical characteristics were determined by SDS-PAGE, UV absorbance spectroscopy, far UV CD spectroscopy, and immunochemical reactivity of both forms of Ara h 6 was compared by IgG immunoblotting and IgE-ELISA using sera from individuals sensitized to peanut. Reversed-phase liquid chromatography was applied to study the occurrence and abundance of pAra h 6 in various peanut types.

Results: Compared to intact Ara h 6, pAra h 6 lacks a 5-amino acid stretch, resembling amino acids 43-47 (UniProt accession number Q647G9) in the non-structured loop. Consequently, pAra h 6 consists of 2 chains; a N-terminal chain of approximately 5 kDa, and a C-terminal chain of approximately 9 kDa, held together by disulfide bonds. Intermediate post-translationally cleaved products, in which this stretch is cleaved but not removed, are also present. The secondary structure and IgE-binding of pAra h 6 resembles that of intact Ara h 6, indicating that the loss of the non-structured loop is not critical for maintaining conformational IgE-epitopes. Both forms of Ara h 6 were reactive with several commercially available IgG antibodies. The peanut cultivars Runner, Virginia, Valencia, and Spanish contained pAra h 6 at equivalent levels, suggesting pAra h 6 is a consistent and important constituent of the peanut proteome.

Conclusion: A post-translationally cleaved form of Ara h 6 is abundant in the main peanut market types, and has IgE-binding comparable to intact Ara h 6. This should be taken into account when Ara h 6 is investigated in peanut-containing products. 1585 | Release of major peanut allergens from their matrix at various pH and at saliva conditions; Ara h 2 and Ara h 6 are quickly bioaccessible Background: The oral mucosa is the first immune organ that encounters allergens upon ingestion of food. Peanut is often consumed in solid form, and it is not known if peanut allergens are released from the food already in the mouth. We set out to investigate the solubility of individual peanut allergens at conditions that mimic the first exposure site, i.e. the mouth.

Method: Light roast peanut flour was suspended in buffers of various pH mimicking saliva. Protein concentration was measured in supernatant, and release of major allergens Ara h 1, Ara h 2, Ara h 3, and Ara h 6 was assessed by SDS-PAGE. Also, the allergen profile of un-dissolved material was assessed.

Results: Peanut protein solubility is poor in the pH range 3-6, while at low pH (1.5) and at moderately high pH (>8), the solubility is higher. At all conditions tested, there was a substantial amount of un-dissolved protein. This indicates that the pH range of saliva, between 6.5 and 8.5 in healthy individuals, may be critical for the release of peanut protein from its matrix. In this pH range from 6.5 to 8.5, Ara h 2 and Ara h 6 are readily released, while Ara h 1 and Ara h 3 are poorly released. Increasing the pH from 6.5 to 8.5 slightly increased the release of Ara h 1 and Ara h 3, but still the recovery was low (approximately 20% for both Ara h 1 and Ara h 3) compared to that of Ara h 2 and Ara h 6 (approximately 100% and 65%, respectively). This remarkable difference in extraction kinetics suggests that Ara h 2 and Ara h 6 are the first allergens an individual is exposed to upon ingestion of peanut-containing food.

Conclusion: Based on our observations, we conclude that the peanut allergens Ara h 2 and Ara h 6 are quickly bio-accessible in the mouth upon ingestion of peanut. This new insight may contribute to the understanding of the extraordinary allergenicity of Ara h 2 and Ara h 6 compared to other peanut allergens. Background: In proven cases of non-IgE mediated cow's milk allergy clinical response can be partial even when treated with amino acid formulae e.g pain in infants. Residual intestinal symptoms can be related to ongoing nerve hypersensitivity, changes in microbiome or motility disturbance. Mast cells are thought to play crucial role in non-IgE mediated food allergy. Ketotifen is a first generation H1 antihistamine which has mast cell stabilising properties with pain blocking and anti TNF-a effect. Hence ketotifen could have important role in symptom resolution where diet elimination has not been successful. We aim to find out effectiveness of ketotifen to unresponsive/partially responsive symptoms such as pain in non-IgE mediated cow's milk allergy infants.

Method: Children who presented to single specialist centre over 11 years had their case notes reviewed retrospectively. Inclusion criteria were those children with confirmed non-IgE mediated cow's milk allergy by elimination of cow's milk with improvement of symptoms and worsening of symptoms on reintroduction of dairy. Where symptoms partially responded e.g pain, ketotifen was used at 0.5-1 mg once at night for 4 weeks and symptoms were reassessed. Statistical analysis was performed using R v3.3.3 with significance was set at P = 0.05.

Results: 1031 patients were identified with 675 patients excluded due to unconfirmed non-IgE mediated allergy. Of the 358 case (206 males, age 3-50 months), atopic co-morbidities were found in 62% children. Common symptoms were abdominal pain (51%), vomiting (47%), back arching (37%), constipation (35%), bloating (33%), food aversion (29%) and diarrhoea (26%). We compared the children who had symptom improvement on ketotifen and cow's milk elimination against children who improved on cow's milk elimination alone. Significant difference of symptom improvement was found with abdominal pain; 69% using Ketotifen compared to 53% who did not use Results: A total of 3548 analysis for tTGIgA have been performed for a total of 2965 patients during the study period (2010, 2012, 2014, 2016) . 128 patients showed at least once a positive tTGIgA. Among these, 11 had a negative result at first testing, and were positive at the second (n = 10) or third testing (n = 1). Despite an increasing number of tTGIgA requests, the number of positive results decreased. WIgE were rarely requested but were positive in about 45% of tested sera (Table 1a and 1b).

The amount of laboratory requests for tTGIgA has increased, while those for WIgE remains stable and is rare. Wheat allergy seems to be rarely investigated in our center and may deserve more attention. Case report: Eosinophil-associated gastrointestinal disorders (EGIDs), including eosinophilic gastroenteritis (EoG), are a inflammatory diseases, characterized by gastrointestinal symptoms and eosinophilic infiltration. Patients with EoE have an increased incidence of allergy, with increased IgE mediated food and inhalant sensitivities. Use of either a targeted food allergen avoidance approach (based on allergy testing) or untargeted approach (based on food allergen avoidance) results in the resolution of eosinophilia in the gastrointestinal tract of 50%-70% of adult. We describe a case of a 27-year-old patient diagnosed with eosinophilic enteritis, associated to protein-losing enteropathy. The patient experienced severe diarrhea, nausea, vomiting and weight loss, that caused a severe dysproteinaemia and electrolytes abnormalities. An upper and lower endoscopy was performed, showing an ulcerative ileitis. The histological pattern was characterized by eosinophilic infiltration of ileum and duodenum>40 HPF. She presented also high levels of total IgE (800 K/UI), high serum tryptase (20 μg/L, n.v. ≤9.0) and sensitization to the lipid transfer protein (LTP) of peach. The patient was prescribed to a six-food elimination diet (SFED) and underwent high doses of oral and intravenously corticosteroids, but a satisfactory therapeutic response was not achieved. We hypothesized that IgE has a role in the mechanism of AEG and that blocking IgE would have improved disease symptoms and reduced allergic inflammation, as measured by a decrease in intestinal tissue eosinophilia. We started off-label administration of omalizumab 300 mg/month subcutaneously, the same dosage schedule used in allergic asthma and, by other authors, in eosinophilic gastrointestinal disease after achieving informed consent by patient. Except for an exacerbation of symptoms occurred 9 months after starting the therapy, when a further endoscopy, showing a gastrointestinal eosinophilic infiltration>50 HPF, was performed, a significant improvement of both gastrointestinal and cutaneous symptoms was observed during therapy, together with a normalization of laboratory parameters. After 30 months a clinical remission of disease was obtained and administration was stopped. Although a histological remission during the first few months of treatment was not obtained, in a subset of AEG patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission.

1590 | Fullerene C60 reduces the allergic inflammation in food allergy mouse model Background: A food allergy (FA) is an abnormal immune response to food. The signs and symptoms may range from mild to severe.

They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressure. Food allergy is becoming increasingly common. Fullerene C60 has the unique electronic properties making it an attractive candidate for allergic diseases therapy. The main purpose of our research was to assess therapeutic effect of fullerene C60 in a mouse model of FA.

Method: New efficient method for producing a water-soluble fullerene C60 has been developed. FA experimental model was induced in Balb/c mice by the intragastrical (IG) OVA administration after subcutaneous (SC) sensitization. Fullerene C60 was administrated IG once a week, or twice a week, or daily. OVA-specific antibodies were assessed by ELISA. Splenocytes cytokine production upon OVA in vitro stimulation was detected by ELISA. Samples of jejunum of the small intestine were removed for histological examination immediately after the last IG allergen administration.

Results: It was shown that OVA-specific IgE and IL-5 level were significant decreased in groups treated with water-soluble fullerene C60. The greatest effect was observed in mice receiving fullerene C60 daily. The IFN-gamma level was significantly higher in IG C60treated groups. The histologic analysis of jejunum of the small intestine samples showed that C60-therapy improved the histologic picture. The greatest effect was observed in mice receiving fullerene C60 daily too.

Conclusion: Taken together, these results demonstrate that the water-soluble fullerene C60 exhibits a significant anti-inflammatory effect in a mouse model of FA, and possesses a high therapeutic potential. Background: A 47-year-old male reported eight episodes of anaphylaxis after exercise. All the ingested food eight hours before each episode was analyzed. Before each episode, he had always eaten chicken or turkey meat, and he tolerated these foods without exercising. In one of the episodes the patient had taken a tablet of dexketoprofen a few hours before. Since several years, he referred chest tightness after eating some fish (emperor, salmon and whiff), however he tolerated others. The patient denied having eaten fish before any of the episodes of anaphylaxis.

Method: Commercial skin prick tests (SPTs) and prick by prick tests (PP) with all food ingested and fishes were performed. Tryptase, total serum IgE (IgE) and specific IgE (sIgE) (ImmunoCAP. Thermo-Fisher Scientific, Uppsala, Sweden) to the foods involved were determined. A controlled oral provocation test (OPT) with dexketoprofen was performed.

Results: SPT was positive to tuna extract (3 mm) and negative (0 mm) for the rest of fish extracts. It was also negative for chicken meat extract and other foods tested. PPs were positive for raw and cooked turkey meat (3 mm), raw and cooked tuna (6 and 8 mm), raw emperor (11 mm), raw and cooked whiff (9 and 8 mm) and raw hake (18 mm). PPs were negative to raw and cooked chicken meat. IgE was 700UI/mL and tryptase 2.95 ng/L. sIgE was slightly positive to hake, cod and chicken meat. Dexketoprofen OPT was negative. At that moment, we recommended the patient to avoid chicken and turkey, as well as the fishes which he had symptoms with. Since then, he has not suffered any new episode of anaphylaxis despite exercising daily. Protein extracts from turkey meat, tuna, emperor, salmon, hake and whiff were prepared and analyzed by SDS-PAGE. Conclusion: Recently, triosephosphate-isomerase (28 kDa) has been identified as a new chicken meat allergen. This allergen could be responsible for the cross-reactivity between bird and fish meat and the episodes of anaphylaxis after exercise in our patient. The triosephosphate-isomerase has not been implicated previously as a cross-reactive allergen involved in the fish-chicken syndrome. Results: Twenty-three patients were included, 61% male, median age 30 years (IQR 12.5), 48% atopic, 30% asthmatic. Non-specific lipid transfer proteins (nsLTP) were implicated in 70% (n = 16) and ω-5-gliadin in 30% (n = 7). Eighteen (78%) patients referred anaphylaxis in the reaction with co-factor, 7(22%) urticaria/angioedema, 2 had both depending on the co-factor.

All patients in which ω-5-gliadin was the allergen involved had anaphylaxis in the presence of co-factor, with tolerance to wheat without it.

In patients in which nsLTP was the allergen involved, 12 (75%) had anaphylaxis in the presence of co-factor. Reaction with co-factor was more severe than without in 13 (81%) patients; 4 patients had no previous history of reaction and subsequently tolerated the culprit food. Only 1 patient had anaphylaxis in the absence of co-factor; the remaining presented oral allergy syndrome and/or urticaria.

Exercise was the main co-factor, present in 22 patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the only co-factor in 6 patients; all of them had anaphylaxis, 4 with allergy to ω-5-gliadin, 2 to nsLTPs. All subsequently tolerated the NSAIDs involved.

Conclusion: nsLTPs and ω-5-gliadin were the most frequently involved allergens in CEFA, with exercise being the most frequent co-factor. NSAIDs were relevant co-factors, even when ω-5-gliadin was the allergen involved. Several patients subsequently tolerated culprit foods and NSAIDs, difficulting the diagnosis and further emphasizing the importance of a correct cofactor evaluation. Molecular allergens had an important role in the diagnosis, avoiding unnecessary OFC. Information about co-factors must be included in all patients with allergy to nsLTPs and ω- 5-gliadin. 1594 | Allergy to wheat-dependent exerciseinduced anaphylaxis (WDEIA) proteins, without? 5-gliadins as responsible Ferreira A 1 ; Castillo M 2 ; Martins S 1 ; Pineda F 2 1 Unidade de Imunoalergologia Hospital das Forças Armadas., Lisbon, Portugal; 2 Departamento de Aplicaciones. DIATER Laboratorios, Madrid, Spain Background: The second well-characterized form of allergy to wheat proteins is wheat-dependent exercise-induced anaphylaxis (WDEIA), with the ω5-gliadins (part of the gluten protein fraction) being the major group of proteins which are responsible, but other forms of food allergy have also been reported, with the proteins responsible including gluten proteins, CM proteins and non-specific lipid transfer proteins.

The patient was a 38-year-old man who visited the hospital with acute urticaria just eat bread before run (30 minutes).

According the components of bread. it was formed by a mixture of wheat, rye and barley. With a history (for several years) of episodes of severe urticaria after intake a mixture of cereals and/or different kinds of beer.

Results: Prick test and specific IgE with wheat, rye and barley were negative and the proteins from allergenic extract from these cereals, and also the gliadins and glutenins fractions were transferred onto a PVDF membrane to carried out a Western blot technique with the patient's serum. The patient's serum recognized several proteins from wheat and millet gliadins not compatible in molecular mass with a ω5-gliadins.

The association of w5 gliadin as responsible for the symptoms produced after the intake of products containing wheat and exercise is well referenced but in the case of this patient could have other proteins involved as triggers of their symptoms.

Suksawat Y Phramongkutklao Hospital, Bangkok, Thailand Background: Food-dependent, exercise induced anaphylaxis (FDEIA) is an anaphylactic condition that develops in patients who ingest specific food followed by exercise. A variety of foods have been described to be the cause including shellfish, wheat and vegetables. The mechanisms of FDEIA is believed that exercise increases allergen absorption or decreases threshold of mast cell. The investigations such as skin prick test or specific IgE for food are useful because food sensitization is demonstrated. However, a challenge test including ingestion of suspected food followed by exercise is the only method to diagnose this disease.

We report a case of FDEIA in a 17-year-old adolescent male.

Result: He presented with generalized urticaria and hypotension after eating a barbecue buffet which was one hour followed by playing taekwondo. After treatment with intramuscular adrenaline, antihistamine and systemic steroid, his condition was improved. The barbecue buffet consists of many kinds of food including shrimp, squid, salmon and pork meat which were previously tolerated. He had no past history of anaphylaxis or drug allergy. He was referred to our allergy unit for investigation. We performed skin prick test with food allergens and many kinds of fresh foods that he ate on that day and the result was positive to shrimp (6 mm. in diameter).

Three-day challenge protocol was set up a month after recovery and we used aspirin as a cofactor. On the first day, Open challenge for 500 gram of shrimp was administered and the result was negative.

On the second day, exercise challenge test based on the American thoracic society guideline was also negative. However, on the last day, he developed generalized urticaria five minutes after the same exercise challenge test which was 1 hour preceded by aspirin intake and 500 gram of shrimp ingestion. But his vital signs appeared to be stable. The patient was administered intramuscular adrenaline and antihistamine with full recovery. He was strongly advised to avoid shrimp for 4-6 hours before exercise and carry an adrenaline autoinjector.

The-three day challenge protocol is a definite tool to confirm the diagnosis of FDEIA. A correct diagnosis is important to avoid unnecessary restricted diet.

1596 | Food dependent exercise induced anaphylaxis in peach allergic patient-Case report consumption of different types of food (pancakes with cream cheese and fruit, peach, Chinese dish, sandwiches-all eaten on other occasions without symptoms) and co-occurring physical exercise (dancing, shopping, walking).

During diagnosis we performed SPT with inhaled and food allergens (Allergopharma), prick by prick tests with peach, banana, apple, pear and bread. We established the concentration of allergen specific IgE (peach, wheat flour, peanuts, hazelnuts) and the level of IgE specific to allergen components (ImmunoCap ISAC).

We performed exercise provocation test and open food challenge with peach.

Results: SPT were negative with all tested food and inhaled allergens (inc.egg; milk; cocoa; tomato; carp; apple; banana; strawberry; rye flour; wheat flour; peanuts; hazelnut; citrus, D. farinae; D.

pteronyssinus; grass; weeds; clad. herbarium; alt. tenuis; dog; cat; poplar; hazel; alder; birch; mugwort).

Prick by prick tests were positive with fresh peach. Concentration of peach specific IgE was 0.55 kU/L. In ImmunoCap ISAC we found elevated levels of IgE specific to LTPs from different allergen sources (Jug r 3 -1.3; Pru p 3 -0.8; Pla a 3 -0.6; Tri a 14 -0.5 [ISU-E]).

Open food challenge with a medium size peach was negative. Exercise provocation test without allergen exposition was negative. Exercise provocation test after eating a medium size peach concluded with severe lip and eyelids edema, followed by whizzing, dyspnea and urticarial. Patient received adrenaline 0.5 mg im, steroids and antihistamines with good clinical effect.

Conclusion: Patient was diagnosed with food dependent exercise induced anaphylaxis (FDEIA) due to LTP allergy. She was advised to eat peeled fruit and vegetables, avoid cofactors of allergic diseases and carry rescue set (adrenaline, steroids and antihistamines). Cases reports: We report 1case of FDEIA and 3 cases of WDEIA.

Case 1:24-year-old woman with intermittent severe allergic rhinitis and food allergies since childhood. In the last 7 years she registered weekly episodes of FDEIA (urticaria, angioedema, wheeze, drop of BP) especially when during effort and after alcohol intake.

Prick tests were positive for grass pollen, mugworth, ragweed, dust mites, celery, soy, sesame, pistachio, mango, honey and shellfish. She followed 3 years of subcutaneous immunotherapy for grasses pollen. The FDEIA episodes frequency and severity diminished during it. Provocation test for celery and mango were positive, for alcohol, soy, sesame, pistachio, honey and shellfish were negative.

Case 2:23-year old man with a 7-year history of acute gluten induced urticaria, recently developed 2 episodes of WDEIA (flushing, severe urticaria and angioedema, wheeze) when he went for gym.

Skin test was highly positive for wheat flour and dust mites, in vitro tests for 5 omega gliadin and wheat-specific IgE were positive. Food challenge for wheat was positive. He followed oral immunotherapy for wheat. The WDEIA episodes were rare and mild.

Case 3:30-years old female with mild allergic rhinitis and controlled asthma, with WDEIA (urticaria, angioedema, wheeze, drop of BP) in the last 3 years. Skin tests showed positive results for wheat flour, dust mites and dog hair. Omega-5 gliadin and wheat specific IgE were high, but the provocation test for wheat was negative meanwhile combined wheat and effort provocation test was positive. 25-year-old female athlete, otherwise healthy, experienced three episodes of FDEIA following running sessions. Two reactions were preceded by intake of salad containing lettuce, tomato and sunflower seeds and the third one occurred after eating celery salad. The patient denied occurrence of any symptoms with physical exertion or food ingestion alone. Physical examination and blood testing did not reveal any abnormalities. The differential diagnosis was performed. In skin prick test and specific serum IgE antibodies sensitization to house dust mite, grass and mugwort were found. The SPT and specific IgE assay to culprit and most common food allergens were negative. The molecular diagnostic has been applied (Faber, CAAM, Rome, Italy). The test scored positive for Art v, Blo t, Der f, Der p, Eur m, Lol p, Phl p. No positive results for available food molecules including celery, tomato, sunflower seeds and lettuce were found.

The detection of culprit food in FDEIA is of crucial meaning as the syndrome can be life-threatening. The molecular diagnostic has been applied already in diagnosis of wheat-dependent exercise-induced anaphylaxis (WDEIA) proving ω-5-gliadin sensitization in the majority of the cases. As the presented case did not reveal sensitization to culprit food in traditional allergy tests the molecular diagnostic was performed. This test did not show sensitization to culprit food either.

However, not all of the molecules are available in molecular assays yet. Cross-reactivity reaction to mugwort and grass has to be considered. The pathophysiological components of physical exertion has to be taken into consideration as well.

This could contribute to the assessment of reasonability of molecular approach in diagnostic work-up for FDEIA and to the establishment of standardized protocols for diagnosis and management of that syndrome. Case report: Food allergy to wheat is rare in adults, often reported in exercise-induced anaphylaxis. Food-Dependent Exercise-Induced Anaphylaxis (FDEIA) is a form of food allergy induced by exercise.

FDEIA symptoms can include urticaria/angioedema, respiratory and gastrointestinal manifestations and hypotension/shock. A 61-year-old male patient presented to the emergency department, was admitted after an episode of hives, hypotension and loss of consciousness. His consciousness was restored after treatment with epinephrine, glucocorticoids as well as fluids, and thereafter, the patient reported that the anaphylactic episode occurred when he started rapidly walking 1 hour after eating a slice of pizza. He mentioned that the offended food was tolerated always when it was not followed by a physical exercise. Review of his past medical history and family one were non-contributory with respect to this episode. The allergy skin prick testing for common foods revealed a positive response only to wheat, while and other laboratory test values were within normal ranges. The patient is discharged after instructions on the use of epinephrine auto-injector. He was also advised to avoid wheat containing products up to 6 hours prior to physical exercise.

Our case demonstrated that FDEIA can be characterized by the onset of anaphylaxis soon after physical exercise, when preceded by the ingestion of the responsible food. Avoidance of the combination of the exposure to respective allergen and exercise is the most efficient precautive measure toward subsequent FDEIA episodes. 1600 | Residual exercise-induced allergic reactions after successful rush oral immunotherapies for milk and wheat Method: We conducted ROIT for 55 children (median 8.7 years old) with milk allergy and 46 children (median 6.8 years old) with wheat allergy during 2010-2015. After 5-12 days of the rush phase in the hospital and a slow-increasing phase at home, patients consumed the maintenance dose (6.5 g milk protein or 5 g wheat protein). After at least three months of the maintenance phase without allergic symptoms, we conducted an exercise provocation test (EPT) after eating the target food. If the EPT was positive, we repeated it after a couple of years to check for remission. The presence or absence of EIARs was based primarily on the results of EPTs but also on the clinical history in some cases.

Results: As of December 2017, 44 milk-and 41 wheat-allergic patients were able to continue ingesting the maintenance dose (desensitization). In these patients, 38 milk-and 38 wheat-allergic patients underwent the first EPT at a median of 635 (228-2538) days after ROIT, and the result was positive in 19 (50.0%) and 19 (50.0%) patients, respectively. Among these EPT-positive patients, 10 milk-and 9 wheat-allergic patients conducted a second EPT at a median of 504 (119-1120) days after the first EPT. The result of the second EPT was positive in 7 milk-and 7 wheat-allergic patients. In addition, clinical histories of EIARs were subsequently observed in 4 milk-and 4 wheat-allergic patients after negative results on an EPT.

Altogether, 19 (43.2%) milk-and 21 (51.2%) wheat-allergic patients still had EIARs even after getting desensitization as of December

Conclusion: Patients with persistent milk and wheat allergy often have residual EAIRs even after three to five years of desensitization due to the administration of successful ROIT. ABSTRACTS | 791 1601 | Anaphylaxis caused by omega-5-gliadin initially diagnosed as idiopathic anaphylaxis: A case report Tziotou M 1 ; Syrigos K 2 ; Syrigou E 1 ; Sinaniotis A 1 1 Department of Allergy,, Athens, Greece; 2 GPP,, Athens, Greece Case report: We report the case of a 59-year-old man who experienced two episodes of wheat dependent exercise induced anaphylaxis, initially diagnosed as idiopathic anaphylaxis.

First episode: The patient woke up in the morning and drove to his resort. While driving, he ate a piece of cheese and ham pie. When he arrived, he walked some meters to the garden and started feeling pruritus and dizziness. He lost consciousness and recovered by himself. He was carried to hospital where his vital signs were normal.

The patient has a history of atrial fibrillation and has been on flecainide BID and aspirin at noon for the last four years.

A month after the first episode he visited an allergist. Skin prick tests to aeroallergens and prick to prick tests to the ingredients of the pie were negative. Tryptase levels were within normal limits and skin biopsy was negative for mastocytosis. An endocrinology workup was also negative. The patient was prescribed an epinephrine autoinjector and was asymptomatic for eight months.

Second episode: That morning he had a cup of milk and two slices of toast for breakfast and started working in the garden. Two hours later he experienced pruritus and urticaria and fell unconscious. His wife had to administer two epinephrine autoinjectors before he regained consciousness. After the second episode it was decided to start treatment with omalizumab.

Two months later he experienced an episode of urticaria while working in the garden. He could not recall what he had eaten before.

Based on history, we thought that a cofactor might contribute to the occurrence of anaphylaxis. We performed skin prick tests with peach (LTP) and gliadin, allergens associated with food dependent exercise induced anaphylaxis in our region. The test to gliadin was positive. Specific IgE in serum to omega-5-gliadin was also positive, while specific IgEs to all LTPs tested were negative. The patient was advised to avoid wheat and has been asymptomatic ever since.

Cases diagnosed with idiopathic anaphylaxis may actually be cases in which the culprit allergen has not been identified. Detailed history and extensive workup may contribute to the successful management of these patients.

Written informed consent has been obtained from the patient.

1602 | Wheat-dependent exercise-induced anaphylaxis (WDEIA) and NSAIDs: Clinical history is crucial Conclusions :We present a case clinically compatible with WDEIA with NSAIDs intake as augmenting factor. This case emphasizes that a carefully and thoroughly taken medical history is of crucial importance, otherwise WDEIA can easily be unrecognized. As a result, non-allergic hyperreactivity to NSAIDs could be excluded and the diagnose of selective allergy to arylpropionic acids was made. Exercise challenge test could not be performed in our case. Case report: Kounis syndrome (KS) has been defined as an acute coronary syndrome that manifests as unstable vasospastic or non-vasospastic angina, and even as acute myocardial infarction. It is triggered by the release of inflammatory mediators following an allergic insult.

A 77-year-old woman with type II diabetes and hypertension, and unstable angina pectoris as cardiovascular risk factors, has consumed chamomile tea. Thirty minutes later, she developed generalized itching, skin rash, swelling of the face and the throat, chest tightness, dyspnea and syncope. The patient was transferred immediately to the emergency department, and sodium chloride, 50 mg prednisolone, 8 mg dexamethasone, 80 mg methylprednisolone, 5000UI heparin, 75 mg voltaren were intravenously administered along the subsequent 60 minutes under simultaneous treatment with oxygen therapy. An EKG examination is performed based on the patient disease's history, showing a 2.5-3 mm ST-depression on D1-D3 leads, 1 mm on V3, and 3.5 mm on the V4-V6 ones. In addition, 2.5 mm ST-elevation on the aVR and 1 mm on the V1 derivation was observed, associated by a negative T-wave on the V1, V2, and aVR leads. Blood tests revealed a normal troponin I level (of 0.07 ng/mL).

Five hours later in the EKG was noticed: isolined ST-segments, and negative T waves on the D3, aVR, and V1 leads. Ultrasound examination revealed normal heart kinetics and function. Following the heart changes, the patient was administered sol. heparin 5000UI twice i.v., nebivolol 5 mg, plavix 75 mg, atorvastatin 80 mg, ABSTRACTS | 793 monocinque 20 mg, ordinary insulin 10UI s.c., glargine insulin 20UI s.c., and sol. furosemide 20 mg i.v. The patient progressed favorably, and four days after the anaphylactic episode the EKG revealed a 0.5 mm ST-depression on leads V4, and V5, negative T-wave on aVL lead, and normalized one on the V3 one.

This case emphasizes the role of serious allergic reactions as cause of acute coronary syndrome in patients with altered coronary arteries and food intake as cause of Kounis syndrome.

1605 | Recall urticaria in two young patients with alpha-gal-syndrome after tick bites Case report: Patient A (m, age 25) had suffered from 7-8 anaphylactic reactions (hives, nausea, dyspnea and dizziness) within the past 15 months. All episodes occurred 3-5 hours after ingestion of red meat, once with alcohol as a co-factor.

All episodes started with a wheal measuring about 0.5 cm in exact the same spot where he had been bitten by a tick one year before.

Specific IgE to galactose-alpha-1,3-galactose (alpha-gal) was positive (2.55 kU/L). Skin prick testing using raw pork kidney suspension and intradermal testing with Gelafundin ® 4% diluted 1:10 also showed positive reactions.

We performed an oral challenge with cooked pork kidney under careful monitoring being able to reproduce the recall urticaria as described above with a cumulative dose of 8 g pork kidney. We stopped the challenge and treated the patient with antihistamines and corticosteroids. Patient B (m, age 22) reported on several anaphylactic reactions within the past 4 years with symptoms including abdominal pain, diarrhea, as well as dyspnea and loss of consciousness in one of the episodes. All episodes occurred several hours after ingesting food.

Furthermore the patient remembered a tick bite about 2 years before the first anaphylactic reaction, which repeatedly became inflamed and only healed completely over months.

Every episode started with pruritus and a wheal in the area of the former tick bite (in loco).

Specific IgE to galactose-alpha-1,3-galactose was positive (4.37 kU/L) as well as the skin prick testing with cooked pork kidney and intradermal testing with Gelafundin ® 4% diluted 1:10.

This patient refused performance of oral challenge tests. An elimination diet of red meat for 12 months resulted in the absence of the symptoms as described.

The diagnosis of alpha-gal-syndrome with recall urticaria in loco was made in both cases. This symptom may also be useful in evaluating results of oral challenge tests as well as an important clinical sign in medical history.

Pali-Schöll I 1 ; Meinlschmidt P 2 ; Purschke B 2 ; Hofstetter G 1 ; Einhorn L 3 ; Mothes-Luksch N 3 ; Jensen-Jarolim E 3 ; Jäger H 2 Background: Insects have gained interest as alternative nutrient source for humans and animals. However, being a "novel food" in the industrialized part of the world, several safety aspects, like allergenicity, need to be thoroughly addressed. In the present work we evaluated the cross-recognition of IgE from patients allergic to crustaceans, house dust mite or stable flies, using house cricket Acheta domesticus (AD), desert locust Schistocerca gregaria (SG) and mealworm Tenebrio molitor (TM). We further investigated changes of immune-recognition in terms of IgE-binding in differently processed insect extracts.

Method: Migratory locust Locusta migratoria (LM) was subjected to different extraction methods, enzymatic hydrolysis or thermal processing, whereas TM larvae (TML) were evaluated after different centrifugation modes and pH levels.

Results: We revealed that IgE from patients with crustacean allergy shows cross-recognition of Acheta domesticus, Schistocerca gregaria and stable flies. IgE from house dust mite allergic individuals binds to Acheta domesticus and Schistocerca gregaria. Importantly, the cross-reactivity to LM can be deleted by enzymatic hydrolysis with different enzymes or heat treatment (cooking, autoclaving), but not by different extraction methods. Changes of pH and varying centrifugation steps are not sufficient to reduce IgE-binding to TML.

Our results show that patients allergic to crustaceans, house dust mite or stable flies-allergic patients cross-recognize desert locust and house cricket proteins, and crustacean-allergic patients also flies proteins. Furthermore, we confirm that the appropriate food processing method of insect proteins can reduce the risk of cross-reactivity for crustaceans-and house dust mite-allergic patients.

The study was supported by the Austrian Science Fund FWF (grant SFB F4606-B28 to EJJ). Results: The mean age at diagnosis was 10 years in children and 34 years in adults, more frequent in males (3:1). In the pediatric group, three had first-degree relatives with EoE and three had celiac disease. Two children had performed milk oral immunotherapy and five adults aeroallergens subcutaneous immunotherapy.

Most of them were atopics with sensitization to aeroallergens (77.5% of children and 82.5% of adults) and food allergens (75% of children and 82.5% of adults), without statistically significant differences. The most frequent foods were fruits and nuts in both groups.

We found significant statistical differences in fruits (35% of children ABSTRACTS | 795 and 57.5% of adults; P = 0.007) and cereals sensitization (5% of children and 47.5% of adults; P < 0.001).

In the clinical presentation we observed significant statistical differences in impaction (22.5% of children and 82.5% of adults; P < 0.001), dysphagia (42.5% of children and 77.5% of adults; P < 0.001) and abdominal pain (25% of children and 7.5% of adults; P = 0.034).

In the endoscopic findings children had more frequently exudates (92.5%; P < 0.001) and adults had esophageal trachealization (50%; P < 0.001). Significant statistical differences were found in the treatment with topical corticosteroids (30% of children and 77.5% of adults; P < 0.001) obtaining a variable positive response. 77.5% of patients in both groups received food elimination diet, 45% with four or more foods.

Conclusion: EoE presents differences in the sensitization profile, clinical manifestations and endoscopic findings according to the age of presentation. The response to pharmacological treatment is variable and a high percentage of patients receive food elimination diets.

It is a pathology difficult to control, therefore new non-invasive techniques would be useful in order to facilitate its management.

1610 | Modulation of gut microbiota in patients with nickel allergy and IBS after diet and probiotics supplementation

MB 1 ; García-Figueroa BE 2

Department of Allergy1

Department of Allergy

Fang L 12

United States 1431 | BCX7353 improves health-related quality of life in hereditary angioedema with C1-inhibitor deficiency

Bygum A 4

Fang L 16

Former Yugoslav Republic of; 6 Division of Clinical Immunology

Huissoon A 2

Bygum A 3 ; Panovska VG 4

United States

Callejas FDB 1

Alobid I 1 ; Muñoz-Cano R 1

Izquierdo I 2

Icahn School of Medicine at Mount Sinai

Method: The case report form was developed by experienced allergists, and the web-based registry was established in cooperation with a professional medical software team. Twenty-two departments from 16 hospitals took part during the first year

8%), whereas in adults, drugs (54.5%) were more common than foods (31.4%). The most common food triggers were eggs (27.1%), milk (15.8%), and walnut (7.9%) in children, and shrimps (21.1%), wheat (15.8%), and crab (7.9%) in adults. Among drug triggers in adults, antibiotics (50.0%) were the most common cause followed by NSAIDs (16.7%), and H2-blockers (13.6%). The onset time was≤10 minutes in 48.6%. In children, home was the place of occurrence in more than half of the cases, whereas adults experienced anaphylaxis in out-of-home settings more often than children. Cofactors were present in 19%. Among the 289 cases registered via the emergency department of participating hospitals, epinephrine was administered in 66.8% (62.5% in adults, 69.8% in children) and the route of administration was IM in 90.8%, IV in 6.3%, both IM and IV in 2.1%, and subcutaneous in 0.7%. The number of epinephrine administration was single in 83%

Conclusion: This multicenter prospective registry would provide a better understanding of anaphylaxis, and provide visionary modalities to improve the management and prevention of anaphylaxis in future

A case of Kounis syndrome after chamomile tea consumption characterized by symptoms related to esophageal dysfunction and esophageal mucosal infiltration by eosinophils

Objective: Characterize patients (Pts) with EoE diagnosis and analyze the differences between pts with diagnosis at pediatric (Ch, <18 years old) and adult age

Epicutaneous tests(EpicT)], serum total IgE and Eos, findings in upper digestive endoscopy (UDE) and biopsies. The correlation between food sensitization, clinical severity (visits to ER services or hospitalization due to complications of EoE, SClin) or severe histology

Results: 74 pts (81% male, average age 27 ± 17 years)

Ad 31 and 34, respectively. 96% Ch and 67% Ad were atopics. The most frequent symptoms of EoE were dysphagia (73%) and gastroesophageal reflux(46%) in Ch; impaction(85%) and dysphagia(46%) in Ad. 92% Ch and 71% Ad had aeroallergens sensitization. 77% Ch and 69% Ad had food sensitization. The most frequent positive tests were for Ch: SPT to milk(25%) and shellfish(19%), EpicT to shellfish(50%) and meat(19%); for Ad: SPT to milk(21%), fresh fruits and nuts both 18%), EpicT to shellfish(35%) and meat(13%). UDE showed: 65% striation and white plaques in 50% Ch

SHist (46%) was associated with SClin (35%), P = 0.001 in Ch; but this was not observed in Ad group

There was no correlation between food sensitization and SClin or SHist in both groups(P > 0.01). The average values of serum total IgE (KUA/L) were 653 in Ch and 458 in Ad; Eos were 679 and 413, respectively in Ch and Ad

Allergy Unit-Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore

Conclusion: LTP with a fixed dose (2000 IU in 4 mL) of ready-touse SHP616 led to fewer severe attacks, a higher proportion of attack-free patients, and a clinically meaningful and statistically significant reduction in cumulative attack severity and daily severity in HAE patients relative to placebo. Background: C1-INH-HAE is a rare, potentially life-threatening disease characterized by episodes of subcutaneous and/or submucosal swelling. APeX-1 was a Phase 2, double-blind, placebo-controlled study to evaluate the prevention of attacks with BCX7353, a once daily oral kallikrein inhibitor, in patients with C1-INH-HAE.Method: Patients with C1-INH-HAE with a history of at least 2 HAE attacks per month were randomized to receive four different doses of BCX7353 (350 mg, 250 mg, 125 mg, 62.5 mg) or placebo for 28 days. Blood samples for BCX7353 concentrations and kallikrein inhibition were obtained from patients before dosing and for 24 hours post-dose on Day 14. PK analyses and PK-PD modeling were done in Phoenix WinNonlin v 8.0 and SAS v 9.3.

The PK population included 16, 14, 14, and 7 subjects in the 350 mg, 250 mg, 125 mg, and 62.5 mg groups respectively.After daily dosing achieved steady state, C max was reached at a median of 3-4 hours after dosing. There was a greater than dose proportional increase in exposure (AUC tau and C max ) over the 62.5-mg to 350-mg dose range, with an approximate 14-fold increase in exposure with a 5.6-fold increase in dose. At doses ≥125 mg, which showed statistically significant and clinically meaningful reductions in HAE attack rates, geometric mean plasma trough concentrations (C tau ) were maintained at or above the minimum target concentration (4-fold EC 50 ) estimated to be required for adequate plasma kallikrein inhibition. Percentages of study subjects at steady-state with BCX7353 plasma concentrations>4-fold EC 50 were 0%, 57%, 100% and 100% in the 62.5, 125, 250, and 350 mg dose groups, respectively. A 125-mg dose provided a mean C tau of slightly above 4.0fold EC 50 , with a corresponding reduction in HAE attack rate of 69% (P < 0.001) compared with placebo. Consistent with the exposure data, a dose dependent inhibition of kallikrein was observed with BCX7353 treatment over the dose range. The drug effect on kallikrein inhibition was highly correlated with exposure (r = 0.867).

In patients with C1-INH-HAE, BCX7353 treatment at doses ≥125 mg resulted in clinically meaningful reductions in the mean weekly HAE attack rate. Concentrations of BCX7353 at doses ≥125 mg were maintained at or above a C tau of 4-fold the kallikrein inhibition EC 50 in most patients, and kallikrein inhibition was highly correlated with BCX7353 plasma concentrations.Background: C1-INH-HAE is a rare, life-threatening disease characterized by recurrent episodes of subcutaneous and/or submucosal swelling that lead to considerable morbidity and a poor quality of life (QoL). APeX-1 was a Phase 2, double-blind, placebo-controlled study to evaluate the prevention of attacks with BCX7353, a once daily oral kallikrein inhibitor, in patients with C1-INH-HAE.Method: Patients with C1-INH-HAE with at least 2 HAE attacks per month were randomized to four different BCX7353 doses (350 mg, 250 mg, 125 mg, 62.5 mg) or placebo. Subject-reported QoL assessments were conducted at the start and end of treatment using the disease specific angioedema quality of life (AE-QoL) questionnaire that measures 4 domains (function, fatigue, nutrition, fear/ shame) and has minimal clinically important difference (MCID) of 6 points. The changes from baseline in total and domain scores was compared between the treatment and placebo groups. Modified angioedema activity score (AAS) values across 4 domains (daily activities, appearance, physical discomfort, overall severity) were calculated for each attack and a total score was derived for each subject by summing scores from each attack. Total scores were compared to placebo using an ANCOVA model with adjustment for qualifying attack rate. Reduction of attacks was statistically significant for all 3 top doses and there was a dose related increase in adverse events.Results: In the 125 mg dose group, QoL assessed by AE-QoL was significantly improved after 4 weeks of treatment compared to placebo for AE-QoL total score (-26.0, P < 0.001) as well as across all 4 domains (function: -28.2, P = 0.002; fatigue: -12.7, P = 0.05; fears/shame: -36.5, P < 0.001; nutrition: -23.4, P = 0.012). All other treatment groups showed a trend towards improvement. QoL improved the most in the125 mg group, and 92% of subjects in the 125 mg group showed AE-QoL reduction of more than 6 points. Disease activity as assessed by the AAS was significantly reduced in the 350 mg, 250 mg and 125 mg dose groups as compared to placebo, whereas there was no significant reduction in the 62.5 mg dose group. Results: There were no marked differences in the age, sex, total IgE titer, comorbidity of bronchial asthma and atopic dermatitis or the starting dose of rush OIT among the groups. All patients in the low-BMFI group achieved ≥100% of the target dose, whereas 28.6% of the middle-BMFI group and 50% of the high-BMFI group failed to achieve the target dose (P < 0.05). Results: A total of 473 infants were diagnosed with food allergy (IgE-mediated and mixed type) at our center during the study period, 305 of these patients underwent prick test for inhalant sensitivity, and 220 (64.9% male) of these were younger than 2 years of age. Conclusion: Sensitivity to inhaled allergen were found in 14 of 292 (4.9%) patients with food allergy. Therefore, we believe that inhalant sensitivity should be evaluated in these patients. There is also a requirement for further studies to identify the influence of inhaled antigens on the disease activity of patients with allergic conditions. Method: In this study, we aimed to perform the metabolic profiling of severe profilin mediated food allergic patients looking for biomarkers that might both, predict the prognosis of the disease and understand the molecular mechanisms of inflammation underneath.

Other allergic patients (mild and moderate) and non-allergic were recruited in the study as comparative groups. The allergic patients class was predicted using a mathematical algorithm from non-allergic vs severe model Results: Plasma samples from non-allergic subjects, mild, moderate and severe allergic patients were measured using gas chromatography coupled to mass spectrometry (GC-MS). The samples were from 4 different hospitals in Spain covering the areas with the highest pollen exposure. The metabolic profile was composed of 95 metabolites for each sample. Results after the statistical analysis showed differences between the groups. Firstly, a clear reduction of several ABSTRACTS Conclusion: We found, as expected, a predominance of males with EoE diagnosis. Ch were more frequently atopic and had aeroallergen and food sensitization. Impaction and esophageal stenosis were more frequent in Ad than Ch. SHist was associated with SClin only in Ch. Method: Three children with EE, boys aged 1.5-11 years, were assessed over 6 months to 3 years.

Results: 2 cases developed in infancy. One had dyspepsia and low weight gain in infancy soon after feeding began. Another had symptoms in infancy but not diagnosed until age 6 with dysphagia and esophageal stricture.. The third case was diagnosed at 11 years old after 2 episodes of food impaction in the esophagus beginning at age 9. All cases had allergic comorbid diseases including atopic dermatitis in all 3 and allergic rhinitis in 2. Skin prick tests were positive to several food allergens (cow's milk, egg protein) in 2, to dust mite in 2 and to pollens in 1. Serum total IgE levels ranged from 490 to 1039 IU/mL. Eosinophils in peripheral blood were elevated in all 3, reaching 10%-13%. Treatment included restricted diet and topical budesonide 1-2 mg daily depending with periodic endoscopic biopsy.In all cases clinical improvement occurred by one month of treatment, with endoscopic confirmation. Morphological improvement fol- The study aimed to evaluate the effects of probiotic supplementation, in addition to diet, in IBS and SNAS patients, in terms of modulation of faecal microbiota population, reduction of GI and cutaneous symptoms, increase of patient's quality of life and modification of gut dysbiosis.Method: Forty patients aged between 18 and 65 years, affected by IBS, Ni sensitization and LTP sensitization were enrolled to evaluate gut dysbiosis. DNA extraction method (Next Generation Sequencing) with commercial kit (Microbiopassport ® ) was performed on stool samples. IBS patients were divided in two groups, according a gluten free diet prescription or a low FODMAPs diet prescription for three months. Similarly, (suspected) SNAS patients (confirmed by 5% Ni sulfate in petrolatum patch test) were prescribed a low Ni diet (100 μg/kg nickel content during the first four weeks and then up to 200 μg/kg up to three months). Two LTP (Lipid Transfer Protein) sensitized patients underwent a LTP free diet.Gut dysbiosis was re-assessed after a fixed probiotic supplementation. A sex-age matched group of individuals without history of IBS, SNAS or any gastrointestinal disease was considered as control.Gastrointestinal symptoms were evaluated using the visual analogue scale before and after treatment. Conclusion: Our preliminary findings suggest that probiotic implementation could be useful in patients with SNAS on a low-Ni diet to increase population diversity, which could contribute to restore the intestinal homoeostatic conditions.

