MISCELLANEOUS Smoking and Lower Urinary Tract Symptoms Mustafa Suat Bolat,1* Ekrem Akdeniz,1 Sevket Ozkaya,2 Ali Furkan Batur,3 Kerem Gencer Kutman,3 Resit Goren,4 Fikret Erdemir,5 Ferah Ece2 Purpose: Pharmacologic effects of nicotine are multifaceted and complicated. Despite numerous studies, the ef- fect of smoking on lower urinary tract functions, have not been yet studied in detail. In this study, we aimed to investigate the effects of smoking addiction on lower urinary tract and sexual functions on the basis of respiratory functions. Materials and Methods: A total of 186 male patients who have been evaluated between May 2014 and January 2015 were recruited in this study. Smoking history, respiratory symptoms, respiratory function tests, uroflowmetry parameters relating to lower urinary tract symptoms (LUTS), prostate volume, post-voiding residual urine volume and sexual functions of patients have been retrospectively investigated. Results: We determined that as the mean number of cigarettes smoked daily increases, post-void residual urine volume and International Prostate Symptom Score (IPSS) also increase. Moreover in accordance with this finding, mean urinary flow rates and quality of life scores were statistically significantly decreased. In smoking addicts who have high mean package/year, post-void residual urine volume and IPSS levels were increased but proportionately maximum urinary flow rate and average urinary flow rate plus quality of life scores were found to be statistically significantly decreased. In patients with forced expiratory volume in first second:forced vital capacity (FEV1/ FVC) ratio less than 80%, mean urinary flow rates were found to be statistically significantly low. Also, we deter- mined that in smoking addicts who have high mean package/year, erectile functions were statistically significantly impaired. Conclusion: We showed negative impacts of smoking addiction on LUTS, patient’s quality of life, and sexual functions. Keywords: risk factors; smoking; adverse effects; lower urinary tract symptoms; etiology; urinary bladder. INTRODUCTION World Health Organization (WHO) defines the smoking addiction as ‘world’s fastest growing and longest epidemic.(1) Cigarette smoking is associated with increased peripheral vascular disease and erectile dysfunction (ED). Smokers have increased risk for both pulmonary and cardiac complications.(2) Pharmacologic effects of nicotine are multifactorial and complicated. Nicotine might induce a contraction through an inter- action with nicotinic receptors located on the terminal nerves of, possibly, (i) parasympathetic cholinergic, (ii) sympathetic non-adrenergic and (iii) non-sympathetic purinergic nerves in guinea-pig detrusor preparations. In addition a portion of the contraction is due to the pu- rine nucleotide released which may be potentiated by 1 Department of Urology, Samsun Training and Research Hospital, Samsun, Turkey. 2 Department of Pulmonology, Faculty of Medicine, Bahcesehir University, Istanbul, Turkey. 3 Department of Urology, Nafiz Körez State Hospital, Sincan, Ankara, Turkey. 4 Department of Urology, Faculty of Medicine, Baskent University, Adana, Turkey. 5 Department of Urology, Gazi Osman Pasa University, Tokat, Turkey. *Correspondence: Department of Urology, Samsun Training and Research Hospital, Samsun, Turkey. Tel: +90 362 3111500. E-mail: msbolat@gmail.com. Received March 2015 & Accepted October 2015 intramural prostaglandin(s). Parasympathetic choliner- gic output might be modulated by an unknown excita- tory substance released by nicotine from sympathetic nerve.(3) Despite numerous studies, those investigate effects of smoking on different organs and systems, the effect of smoking on lower urinary tract functions, have not been yet studied in detail. Some researchers suggested that the current cigarette smoking was not consistently associated with the lower urinary tract symptoms (LUTS) and the possible association in for- mer smokers warrants further investigation.(4-6) In this study, we aimed to investigate the effects of smoking addiction on lower urinary tract and sexual functions on the basis of spirometry parameters. Miscellaneous 2447 Smoking and LUTS-Bolat et al. MATERIALS AND METHODS Study Population A total of 186 male patients who have been admitted to Samsun Training and Research Hospital and Sam- sun Gazi State Hospital between May 2014 and January 2015 were recruited in this study. Data regarding smok- ing history, respiratory symptoms, respiratory function tests, and uroflowmetry parameters relating to LUTS, prostate volume, post-void residual urine volume and sexual function of patients were gathered from the med- ical records. Urine analysis has also been performed for excluding bladder cancer. Smoking history of patients were evaluated as pack/year and stick per day. In pack / year group, patients were categorized into 2 subgroups as low smoking group (smoked less than 28.6 pack / year) and high smoking group (smoked more than 28.6 pack / year). Patients were also classified as light smoker (< 20.9 daily cigarettes) and heavy smoker (> 20.9 daily cigarettes). The study was performed in ac- cordance with the ethical principles in the Good Clin- ical Practice guidelines, in addition to applicable local regulatory requirements and the study protocol was ap- proved by local ethics review boards. All the patients read the patient information form about the study proce- dure and written informed consents were obtained. Evaluations Spirometry was performed for evaluation of respira- tory functions. International Prostate Symptom Score (IPSS) and International Index of Erectile Functions (IIEF) questionnaires were used for evaluation of LUTS and erectile function, respectively. Average urinary flow rate (Qave), maximum urinary flow rate (Qmax) and urination time were measured using uroflowmetry. Prostate volume and post-voiding residual urine vol- Table 1. Characteristics of study patients. Characteristics Values* Age (years) 61.1 ± 8.9 (30-82) Smoking, no. Daily 20.9 ± 9.6 (1-60) Pack/year 28.6 ± 20.4 (1-120) Pulmonary function test results, (%) FEV1 (mL) 2809 ± 870 (96.9 ± 30.9) FVC (mL) 3421 ± 986 (95.4 ± 30.5) FEV1/FVC 86.4 ± 47.3 Uroflowmetry results Qmax (mL/s) 20.5 ± 7.8 (7-54) Qave (mL/s) 10.4 ± 4.5 (3.3-32) QoL 2.2 ± 1.3 (0-6) IPSS 15.1 ± 4.9 (1-29) Serum PSA levels (ng/mL) 1.6 ± 1.4 (0.1-10.3) PVR, mL 30.2 ± 36.6 (0-212) Prostate volume (mL) 44.6 ± 19.2 (12-139) Erectile dysfunction, no. (%) Severe 44 (24.2) Moderate 48 (26.4) Mild to moderate 29 (15.9) Mild 23 (12.6) None 38 (20.9) Abbreviations: ED, erectile dysfunction; FEV1, forced expiratory vol- ume in 1 second; FVC, forced vital capacity; IIEF, International Index of Erectile Function; IPSS, International Prostate Symptom Score; PSA: prostate specific antigen; PVR, post voiding residual urine volume; QoL, quality of life. * Data are presented as mean ± SD (min-max). Characteristics Low Group (Daily Cigarette) High Group (Daily Cigarette) P Value* QoL 2.7 ± 1.6 2.1 ± 1.2 .01 IPSS 12.8 ± 4.8 15.7 ± 47 .00 Urine volume (mL) 294 ± 184 303 ± 178 .849 Qmax (mL/s) 19.6 ± 7.9 20.7 ± 7.8 .49 Qave (mL/s) 10.7 ± 5.9 10.4 ± 5.2 .04 Voiding time (s) 59.9 ± 12.2 37.3 ± 16 .03 Serum PSA level (ng/mL) 1.57 ± .9 1.7 ± 1.5 .59 PVR (mL) 14.4 ± 27.1 34.4 ± 27.7 .00 Prostate volume (mL) 41.1 ± 22.2 45.5 ± 22.3 .21 Abbreviations: IPSS, International Prostate Symptom Score; PSA, prostate specific antigen; PVR, post voiding residual urine volume; Qave, average urine flow per second; Qmax, maximum urine flow per second; QoL, Quality of life. * Data are presented as mean ± SD. Table 2. The relationship between daily cigarette consumption with QoL, uroflowmetry and urological parameters. Vol 12 No 06 November-December 2015 2448 ume (PVR) were calculated tridimentionally by using suprapubic ultrasound. Statistical Analysis Results were analyzed using the Statistical Package for the Social Science (SPSS Inc, Chicago, Illinois, USA) version 17.0. Results are presented as mean ± standard deviation and P < .05 was considered as statistically significant. Descriptive data were compared using the unpaired Student t-test and Pearson chi-square test. RESULTS One hundred and eighty-six male patients were enroll- edin to the study. The characteristics of patients are presented in Table 1. Mean age of patients was 61.1 ± 8.9 years. Mean duration of smoking addiction was 28.6 ± 20.4 years; mean number of cigarettes smoked were 20.9 ± 9.6 daily. Results of respiratory test functions for forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) (FEV1/FVC) ratio were 2809 ± 870 mL (96.9% ± 30.9%), 3421 ± 986 mL (95.4% ± 30.5%), and 86.4% ± 47.3%, respectively. Mean IPSS was 15.1 ± 4.9; Quality of Life (QoL) score was 2.28 ± 1.3. Number of patients according to their IIEF score for severe, moderate, mild to moderate, and mild ED and without ED were 44 (24.2%), 48 (26.4%), 29 (15.9%) and 38 (20.9%), respectively. Mean PVR was 30.2 ± 36.6 mL, and mean serum prostate specific an- tigen (PSA) level was 1.6 ± 1.4 ng/mL. Regarding to uroflowmetry parameters, mean Qmax was 20.5 ± 7.8 mL/s and mean Qave was 10.4 ± 4.5 mL/s. Evaluation of relationship between smoking addiction level with QoL and uroflowmetry parameters demonstrated that PVR and IPSS were statistically significantly high (P = .00) but Qave (P = .04) and QoL (P = .01) were statis- Table 3. The relationship between pack/year smoking status with QoL, uroflowmetry and urological parameters. Characteristics Low Group (pack/year) High Group (pack/year) P Value* QoL 1.9 ± 1.2 2.6 ± 1.3 .00 IPSS 13.9 ± 4.9 16.7 ± 4.5 .00 Flowvolume (mL) 329 ± 206 274 ± 149 .24 Qmax (mL/s) 22.3 ± 8.1 18.2 ± 6.7 .00 Qave (mL/s) 11.3 ± 4.7 9.3 ± 4 .00 Voiding time (s) 44.5 ± 71.4 37.6 ± 16.8 .42 Serum PSA level (ng/mL) 1.4 ± 1.2. 1.9 ± 1.6 .04 PVR (mL) 22.3 ± 29.5 40.7 ± 42.3 .00 Prostate volume (mL) 42.6 ± 16.4 47.2 ± 22.3 .11 Abbreviations: IPSS, International Prostate Symptom Score; PSA, prostate specific antigen; PVR, post voiding residual urine volume; Qave, average urine flow per second; Qmax, maximum urine flow per second; QoL, Quality of life. * Data are presented as mean ± SD. Characteristics FEV1/FVC < 80% FEV1/FVC ≥ 80% P Value* QoL 2.3 ± 1.2 2 ± 1.2 .28 IPSS 15.5 ± 4.4 15 ± 4.7 .49 Flowvolume (mL) 277.9 ± 222.1 306.8 ± 175.3 .64 Qmax (mL/s) 19.3 ± 7.7 21.8 ± 7.8 .08 Qave (mL/s) 9.6 ± 4.3 11.3 ± 4.7 .03 Voiding time (s) 39.5 ± 19.5 35.9 ± 15.2 .20 Serum PSA level (ng/mL) 1.9 ± 1.6 1.5 ± 1.4 .16 PVR (mL) 28.4 ± 34.4 31 ± 36.6 .69 Prostate volume (mL) 48.9 ± 22.9 41.9 ± 16.1 .03 Abbreviations: IPSS, International Prostate Symptom Score; PSA, prostate specific antigen; PVR, post voiding residual urine volume; Qave, average urine flow per second; Qmax, maximum urine flow per second; QoL, Quality of life; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity. * Data are presented as mean ± SD. Table 4. The relationship between pulmonary function test results with QoL, uroflowmetry and urological parameters. Smoking and LUTS-Bolat et al. Miscellaneous 2449 tically significantly low in heavy smoker group (Table 2). When correlation between smoking addiction level (mean smoked package/year) and QoL with uroflow- metry parameters were evaluated, QoL and Qmax val- ues were found to be statistically significantly low (P = .00), in contrast PVR and IPSS values were statistically significantly high (P = .00) in heavy smoker group (Ta- ble 3). Qave values of patients with FEV1/FVC ratio less than 80%, were statistically significantly low (P = .04) (Table 4). When correlation between erectile func- tions and mean number of cigarettes smoked daily were compared with those who have FEV1/FVC ratio less than 80%, erectile function was statistically significant- ly lower (P = .001) in heavy smoker group (Table 5). DISCUSSION Because studies comparing the correlation between smoking addiction level, respiratory function test pa- rameters and LUTS are lacking, the discussion part of this article is limited. When we investigated the cor- relations between smoking addiction levels and QoL with uroflowmetry parameters, we determined that as the mean number of cigarettes smoked daily increases, PVR and IPSS values increase. Also in accordance with this finding, mean urinary flow rates and QoL scores were statistically significantly decreased. In smoking addicts who have high mean package/year ratio, PVR and IPSS levels and proportionately Qmax and Qave plus QoL scores were found to be statistically signifi- cantly decreased. In a study with similar setting to ours, it has been reported that in 40-75 years age group, inpa- tients with ≥ 35 cigarettes smoked daily, development of benign prostate hyperplasia is statistically signifi- cantly higher.(7) The main reason attributed to this in- crease was elevated serum testosterone levels in heavy smokers. In patients with FEV1/FVC ratio less than 80%, mean urinary flow rates were found to be statistically sig- nificantly low. We reported a parallel reduction in air flow rate and mean urinary flow rate. We hypothesize that stimulating and inhibitory effects of nicotine might be the cause of this reduction. In a study that analyz- ed the effects of nicotine on detrusor muscles in rats, the authors have shown stimulating effects of nicotine onmuscarinic (M 1 ) receptors and inhibitory effects on M 2 receptors at synaptic junctions.(7) In addition, we de- termined that in smoking addicts who have high mean package/year, erectile function was statistically signif- icantly impaired. Numerous studies have investigated the association between cigarette smoking and ED, and it has been reported that smoking nearly double the risk of moderate or severe ED at a ten years follow up.(8) At another study in men aged 30-79 years old, it has been shown that, risk of ED has increased 2.3-fold in men with history of 20 package/year of smoking.(9) In concordance with our study, it has been reported that there is a statistically significant correlation between cigarette smoking and ED development, and this cor- relation becomes stronger as the mean number of ciga- rettes smoked daily increases.(10) CONCLUSIONS In conclusion, as with other studies in which the effects of cigarette smoking on LUTS have been investigated, we also showed negative impacts of smoking addiction on LUTS, patient’s QoL and sexual functions. In this study, interestingly we would like to express that we de- termined a statistically significant relationship between spirometry and uroflowmetry parameters in smoking addicts. CONFLICT OF INTEREST Table 5. The relationship between erectile function with daily cigarette consumption, pack/year smoking status and pulmonary function test results. Characteristics Severe ED Moderate ED Mild to Moderate ED Mild ED No ED P Value Daily Smoke, no. (%) Low group 6 (15.8) 9 (23.7) 5 (13.1) 4 (10.5) 14 (36.8) .11 High group 37 (26.2) 38 (26.9) 23 (16.3) 19 (13.4) 248 (17.0) Pack/year,no. (%) Low group 15 (14.7) 29 (28.4) 16 (15.6) 17 (16.6) 25 (24.5) .01 High group 28 (36.3) 18 (23.3) 12 (15.5) 6 (7.7) 13 (16.8) FEV1/FVC, no. (%) < 80% 15 (33.3) 11 (24.4) 7 (15.5) 7 (15.5) 5 (11.1) .38 ≥ 80% 21 (20.1) 26 (25) 19 (18.2) 16 (15.3) 22 (21.1) Abbreviations: ED, erectile dysfunction; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity. Smoking and LUTS-Bolat et al. 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