https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article Lifestyle Factors and Symptoms of Gastroesophageal Reflux Disease: A Cross-sectional Study ABSTRACT Background and Objectives: Gastroesophageal Reflux Disease (GERD) is a condition characterized by heartburn and acid regurgitation without signs of oesophagal mucosal injury on one hand, and erosive oesophagitis and Barrett's oesophagus consequences like oesophagal cancer on the other. The aim of this study was to explore the involve- ment of different lifestyle-related factors in the aetiology of symptomatic GERD. Methods: In this cross-sectional study, 79 patients (28 men and 51 women) aged be- tween 20-68 years old were recruited randomly through a direct interview between Jan- uary to October 2021, and they were prescribed Proton Pump Inhibitors. Prior to starting this study, the approvals had been granted by the ethics committee and oral consent was gained from the participants. A questionnaire was designed and consisted of demographic and clinical characteristics regarding GERD. Statistical analysis was done using SPSS version 25 for describing frequencies and percentages, followed by Chi- square and Fisher’s Exact tests as inferential statistical analysis for finding associations between variables. Results: Among the total of 79 patients with gastroesophageal reflux disease, the find- ings indicated that more than half of the study sample (58.2%) were overweight and obese (26.6% and 31.6% respectively), and the heavy smokers made the highest per- centage among smokers (19%). There was a statistically significant association between gender and smoking and BMI among GERD patients (P-value = 0.001 and < 0.001 respec- tively). There was a very highly significant association between BMI and heartburn and nausea and vomiting (P-value = 0.001 for both), while there was a non-significant associ- ation between BMI and chest pain, cough, and sleep pattern disturbance (P-value = 0.324, 0.558, and 0.907 respectively). Conclusion: A higher BMI and smoking are associated with a higher likelihood of GERD symptoms. Keywords: Lifestyle Factors; Gastro-Esophagus Reflux Disease; Population-Based Study. Asmaa Awni Haydar; College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq. Muzhda Haydar Saber; Department of Medical Analysis, Faculty of Applied Sciences, Tishk International University, Erbil, Kurdistan Region, Iraq. Goran Noori Saleh; Department of Nursing, Faculty of Nursing, Tishk International University, Erbil, Kurdistan Region, Iraq. Dara Abdulla Al-Banna; Department of Nursing, Faculty of Nursing, Tishk International University and Hawler Medical University, Erbil, Kurdistan Region, Iraq. (Correspondence: dara.abdulla@tiu.edu.iq) 98 Received: 24/05/2022 Accepted: 27/09/2022 Published: 30/11/2022 Copyright ©2022 The Author(s). This is an Open Access article which licensed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It permits no additional restrictions on use, distribution, and reproduction in any medium provided the original work is properly cited. mailto:dara.abdulla@tiu.edu.iq https://creativecommons.org/licenses/by-nc-sa/4.0/ https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article Gastroesophageal reflux disease (GERD) or acid reflux occurs when the liquid content of the stomach regurgitates (backs up or refluxes) into the oesophagus. GERD is a long-term illness. It usually lasts a life- time once it starts. Heartburn, regurgita- tion, and nausea are symptoms of simple GERD [1]. A condition in which the reflux- damaged epithelium of the oesophagus is replaced by metaplastic columnar epitheli- um is known as Barrett's oesophagus (BE) and has been hypothesized as the end con- sequence of a stepwise disease process that transitions through GERD and oesoph- ageal adenocarcinoma [2]. Gastroesopha- geal reflux disease (GERD) is particularly frequent in Asians, with prevalence rates ranging from 50 to 70% [3]. Endoscopic evaluation of oesophagal mucosal changes in patients with reflux symptoms is essen- tial for diagnosing patients with varying degrees of severity [4]. Many studies have looked at the relationship between GERD and risk factors like age, gender [4-5,] BMI, and obesity, but there have been few large -scale studies focusing solely on GERD symptoms. Because GERD is such a com- mon disease that affects millions of individ- uals all over the world, it is critical to un- derstand the underlying lifestyle variable that causes varied GERD symptoms [6]. This gender differential in the spectrum of GERD has previously been linked to sex steroid hormones, albeit little is under- stood about the mechanism behind it, ac- cording to several epidemiologic studies, the prevalence of GERD in women is strongly associated with reproductive sta- tus, implying a probable link with estrogen levels [7]. The inactivation of mast cells by the anti-inflammatory activity of estrogen may account for the gender difference in the GERD spectrum. Other research has investigated the role of female steroid [2]. hormones in the gender gap in these disor- ders, while obesity is a major risk factor for GERD, and estrogen has been shown to influence fat metabolism. Furthermore, smoking is associated with an increased risk of GERD in the elderly [8]. Acidic foods, the amount and timing of meals as well as a lack of sleep can all contribute to GERD symptoms [9]. Lifestyle factors such as smoking, being overweight or obese, and eating late at night have been linked to an increased risk of developing gastroesopha- geal reflux disease (GERD) [10]. People who eat spicy foods and sleep on their left side are more likely to get GERD. Excessive painkiller usage, eating in between meals, drinking too much coffee, and taking un- needed drugs can all cause GERD [11]. al- so, GERD was found to be associated with meals before bedtime in past studies [12]. Endoscopic observation can detect reflux esophagitis (RE) and non-erosive reflux dis- ease (NERD), two pathological stages of gastroesophageal reflux disease (GERD) (NERD, mainly diagnosed based on upper gastrointestinal symptoms). According to most studies, NERD patients make up more than half of all GERD patients [13]. In a study that used a newly developed and validated GERD questionnaire with an in- terview-based observational study to standardize the symptom-based diagnosis and evaluate treatment response in pa- tients with GERD showed that a total of six symptoms, four positive and two negative predictors, were used to evaluate the fre- quency of GERD, the positive predictors included heartburn and regurgitation, as well as sleep disturbance, and the use of additional over-the-counter medication; while the negative predictors included pain or discomfort in the stomach and nausea [14]. When the normal symptoms of heart- burn and regurgitation were combined with endoscopic evidence of esophagitis, GERD was identified. 99 Copyright ©2022 The Author(s). This is an Open Access article which licensed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It permits no additional restrictions on use, distribution, and reproduction in any medium provided the original work is properly cited. INTRODUCTION https://creativecommons.org/licenses/by-nc-sa/4.0/ https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article process was not completed. A question- naire was designed as a tool for data col- lection and consisted of two main parts. Part One included some demographic characteristics like age, gender, body mass index based on weight and height, and cur- rent smoking status. Part Two included clinical characteristics regarding GERD such as heartburn, chest pain, cough, nausea, vomiting, and disrupted sleep patterns. Statistical analysis was conducted using SPSS version 25 computer software “Statistical Package for Social Sciences”. The quantitative data were described by frequency and percentage. The inferential statistical analysis was assessed by using Chi-square and Fisher’s Exact tests. The P- value was considered significant at ≤ 0.05. The study enlisted the participation of 79 patients with gastroesophageal reflux dis- ease. Table 1 shows some demographic characteristics of the study sample. The majority of the study sample was between 30-39 and 40-49 years old (26.6% and 25.3% respectively). Males made up 35.44% of the overall sample, while fe- males made up 64.56% of the participants. Regarding the Body Mass Index, more than half of the study sample (58.2%) were overweight and obese (26.6% and 31.6% respectively). Furthermore, half of the par- ticipants were light smokers (7.6%), mod- erate smokers (11.4%), heavy smokers (19%) and shisha smokers (10.1%). Heavy smokers made the highest percentage among smokers (19%). Table 2 shows the association between patients in each BMI category with age, gender, and smoking. A non-significant difference was found be- tween age and BMI among GERD patients. There was a statistically significant associa- tion between gender and smoking with the BMI among GERD patients (P-value = 0.001 and < 0.001 respectively). Patients who exhibited symptoms of reflux esophagitis and had been treated with pro- ton pump inhibitors (omeprazole 20 mg twice daily) for 14 days were deemed to have GERD in the same external environment (e.g. similar time of sleep, daily activity, etc) so it has been sug- gested that the association with regular Protein Pump Inhibitor (PPI) use was the result of indication bias, i.e., the relation- ship was due to the fact that regular PPI use was more common in patients with more severe GERD [15]. The aim of this study was to explore the involvement of different lifestyle-related factors in the ae- tiology of symptomatic GERD in those treated with Proton Pump Inhibitors. This cross-sectional study was conducted between January to October 2021. The 79 patients (28 men and 51 women) aged be- tween 20-68 years old were recruited ran- domly in the Department of Gastroesopha- geal Reflux Disease at Rizgary Teaching Hospital in Erbil city, Kurdistan Region of Iraq between February and June 2021. The data were collected through a direct inter- view (face-to-face) method of approxi- mately 45 minutes duration with each par- ticipant. They were prescribed Proton Pump Inhibitors by their physicians. Formal approval was obtained by the ethical com- mittee of the College of Pharmacy, Hawler Medical University under the code HMUPE 461 on 24th January 2021 and carried out in compliance with the ethical standards. Before the explaining purpose of this study to each participant, informed oral consent was obtained from each of them. The re- searchers guaranteed to keep the patient's information confidential and use the data for this study only. In addition to the above, the researcher told each participant that participation was voluntary, and he or she could leave at any time even if the 100 RESULTS METHODS Copyright ©2022 The Author(s). This is an Open Access article which licensed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It permits no additional restrictions on use, distribution, and reproduction in any medium provided the original work is properly cited. https://creativecommons.org/licenses/by-nc-sa/4.0/ https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article 101 Table 1: Demographic characteristics of the study sample Demographic characteristics F. (%) Age group (years) 20-29 30-39 40-49 50-59 ≥60 14(17.7) 21(26.6) 20(25.3) 15(19) 9 (11.4) Gender Male Female 28(35.44) 51(64.56) BMI Underweight Normal Overweight Obesity 5 (6.4) 28(35.4) 21(26.6) 25(31.6) Smoking Non-smoker Light smoker Moderate smoker Heavy smoker Shisha 41(51.9) 6(7.6) 9(11.4) 15(19) 8 (10.1) Table 2: Association between Body Mass Index and Demographic characteristics Demographic characteristics BMI Category P-Value Underweight F.(%) Normal F.(%) Overweight F.(%) Obesity F.(%) Age group (years) 20-29 30-39 40-49 50-59 ≥60 1(1.32) 0(0) 2(2.63) 1(1.32) 1(1.32) 4(5.26) 6(7.89) 8(10.53) 6(7.89) 0(0) 3(3.95) 9(11.84) 5(6.58) 3(3.95) 1(1.32) 6(7.89) 6(7.89) 5(6.58) 4(5.26) 5(6.58) 0.848 Gender Female Male 4(4.12) 1(1.03) 18(18.56) 10(10.31) 9(9.28) 12(12.37) 20(20.62) 5(4.15) 0.001 Smoking Non-smoker Light Moderate Heavy Shisha 1(1.03) 0(0) 0(0) 2(2.06) 2(2.06) 12(12.37) 3(3.09) 5(5.15) 4(4.12) 4(4.12) 9(9.28) 2(2.06) 1(1.03) 7(7.22) 2(2.06) 19(19.59) 1(1.03) 3(3.09) 2(2.06) 0(0) < 0.001 Copyright ©2022 The Author(s). This is an Open Access article which licensed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It permits no additional restrictions on use, distribution, and reproduction in any medium provided the original work is properly cited. Table 3 demonstrates the association be- tween patients in each BMI category with clinical characteristics regarding GERD. There was a very high statistically signifi- cant association between BMI and heart- burn and nausea and vomiting (P-value = 0.001 for both), while there was a non- significant association between BMI and chest pain, cough, and sleep pattern dis- turbance (P-value = 0.324, 0.558, and 0.907 respectively). https://creativecommons.org/licenses/by-nc-sa/4.0/ https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article 102 According to the current study, exoge- nous exposures in the form of lifestyle- related factors such as being overweight, and smoking have a crucial role in the aetiology of GERD. It found that there was a significant association between obesity and frequent GERD symptoms, but non-significant with smoking. A study done by Yamamichi et al showed a sig- nificant association between BMI and obesity in GERD adult subjects. However, in contrast to previous studies [16-18] that showed a positive correlation be- tween obesity or overweight and both erosive reflux disease, it only looked at the symptoms of GERD. Several epidemi- ological studies have found a link be- tween smoking and GERD or reflux symp- toms [19-20]. Cigarette smoking is thought to aggravate reflux disease by causing acid reflux and perhaps causing a long-term reduction in lower oesophagal sphincter pressure. The age of the partic- ipant has an effect and an increased risk of serious consequences in an elderly patient may require a more aggressive treatment approach [21]. Although the examination and management of GERD in elderly individuals are largely the same as for all adults, there are some unique issues of cause, evaluation, and treat- ment that must be considered whe work- ing with the elderly [22]. A study done by Wang et al (2016) ob- served a positive relationship between GERD and increasing age [14]. This study showed a significant association between gender and GERD, and females' propor- tions grew with age, but males' propor- tions were lowest. Increased body mass may or may not be a cause of cough. GERD symptoms can be avoided by maintaining a healthy weight, getting adequate sleep, and adhering to a healthy diet. An associa- tion between BMI and the frequency of chest pain was found to be insignificant. Retrosternal burning, regurgitation, cough, sleep disturbances, and reflux esophagitis are all recognized as symptoms of GERD [23]. The latter is the most common mani- festation of oesophagal injury as in a study of 3153 people with severe heartburn or regurgitation symptoms by Nilsson et al. in a case-control study among GERD patients [24]. The findings of this study imply that an increased BMI is associated with a higher incidence of GERD symptoms. The effects of smoking on gastroesophageal reflux disease appear to be significant. The author reports no conflict of interests. The authors (s) report no funding support. Table 3: Association between Body Mass Index and Gastro-intestinal symptoms Demographic characteristics BMI Category P-Value Underweight F.(%) Normal F.(%) Overweight F.(%) Obesity F.(%) Heartburn Chest pain Cough Nausea and Vomiting Disrupted sleep 4(4.12) 1(1.03) 0(0) 4(4.12) 0(0) 23(23.71) 5(5.15) 2(2.06) 15(15.46) 1(1.03) 16(16.49) 2(2.06) 3(3.09) 10(10.31) 1(1.03) 17(17.53) 5(5.15) 2(2.06) 17(17.53) 1(1.03) 0.001 0.324 0.558 0.001 0.907 DISCUSSION Copyright ©2022 The Author(s). This is an Open Access article which licensed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It permits no additional restrictions on use, distribution, and reproduction in any medium provided the original work is properly cited. CONCLUSION CONFLICT OF INTEREST FUNDING https://creativecommons.org/licenses/by-nc-sa/4.0/ https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article Jan 1;132(1):87-95. Available from: https:// www.sciencedirect.com/science/article/abs/ pii/S0016508506024747. [Accessed 21st March 2021]. [9] Emerenziani S, Zhang X, Blondeau K, Silny J, Tack J, Janssens J, et al. Gastric fullness, physical activity, and proximal extent of gas- troesophageal reflux. Official journal of the American College of Gastroenterology| ACG. 2005 Jun 1;100(6):1251-6. Available from: https://journals.lww.com/ajg/ Abstract/2005/06000/ Gatric_Fullness,_Physical_Activity,_and_Pro ximal.8.aspx. [Accessed 21st March 2021]. [10] Ness-Jensen E, Hveem K, El-Serag H, Lager- gren J. Lifestyle intervention in gastroesoph- ageal reflux disease. Clinical gastroenterolo- gy and hepatology. 2016 Feb 1;14(2):175-82. Available from: https:// www.sciencedirect.com/science/article/abs/ pii/S1542356515006357. [Accessed 24th March 2021]. [11] Khawaja MN, Khan MA, Khawaja ZN. Psycho- social Determinants of Gastroesophageal Reflux Disease. Pakistan Journal of Medical and Health Sciences. 2009;3(2):117-120. Available from: https:// www.pjmhsonline.com/2009/apr_june/pdf/ ii%20%20%20Psychosocial% 20Determinants%20of% 20Gastroesophageal%20Reflux% 20Disease.pdf. [Accessed 24th March 2021]. [12] Cho YK, Kim GH, Kim JH, Jung HY, Lee JS, Kim N. Diagnosis of gastroesophageal reflux dis- ease: a systematic review. The Korean Jour- nal of Gastroenterology. 2010 May 1;55 (5):279-95. Available from: https:// synapse.koreamed.org/articles/1006662. [Accessed 24th March 2021]. [13] Steevens J, Botterweck AA, Dirx MJ, van den Brandt PA, Schouten LJ. Trends in incidence of oesophageal and stomach cancer sub- types in Europe. European journal of gastroenterology & hepatology. 2010 Jun 1;22(6):669-78. Available from: https://journals.lww.com/eurojgh/ Abstract/2010/06000/ Trends_in_incidence_of_oesophageal_and_ stomach.4.aspx. [Accessed 10th April 2021]. [14] Wang HY, Leena KB, Plymoth A, Hergens MP, Yin L, Shenoy KT, et al. Prevalence of gastro- esophageal reflux disease and its risk factors in a community-based population in south- ern India. BMC Gastroenterology. 2016 Dec;16(1):1-6. Available from: 103 [1] Antunes C, Aleem A, Curtis S. Gastroesoph- ageal Reflux Disease. National Center for Biotechnology Information advances sci- ence and health. Available from: https:// www.ncbi.nlm.nih.gov/books/NBK441938/. [Accessed 19th June 2021]. [2] Asanuma K, Iijima K, Shimosegawa T. Gen- der difference in gastro-oesophagal reflux diseases. World Journal of Gastroenterolo- gy. 2016;22(5): 1800-10. Available from: https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC4724611/. [Accessed 24th July 2021]. [3] Goh K. Changing epidemiology of gas- troesophageal reflux disease in the Asian- Pacific region: An overview. Journal of Gas- troenterology and Hepatology. 2004;19: S22-5. Available from: https:// pubmed.ncbi.nlm.nih.gov/15324378/. [Accessed 20th March 2022]. [4] Moayyedi P, Talley NJ: Gastro-oesophageal reflux disease. Lancet. 2006;367(9528). 2086-2100. Available from: https:// www.sciencedirect.com/science/article/ abs/pii/S0140673606689320. [Accessed 1st May 2021]. [5] Dent J, El-Serag HB, Wallander M, Johans- son S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. British Medical Journal-Gut. 2005 May 1;54(5):710 -7. Available from: https://gut.bmj.com/ content/54/5/710.short. [Accessed 21st March 2021]. [6] Lagergren J. Influence of obesity on the risk of oesophagal disorders. Nature reviews Gastroenterology & hepatology. 2011 Jun;8 (6):340-7. Available from: https:// www.nature.com/articles/ nrgastro.2011.73. [Accessed 21st March 2021]. [7] Zagari RM, Fuccio L, Wallander MA, Johans- son S, Fiocca R, Casanova S, et al. Gastro- oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano–Monghidoro study. British Medical Journal-Gut. 2008 Oct 1;57 (10):1354-9. Available from: https:// gut.bmj.com/content/57/10/1354.short. [Accessed 21st March 2021]. [8] Zheng Z, Nordenstedt H, Pedersen NL, Lagergren J, Ye W. Lifestyle factors and risk for symptomatic gastroesophageal reflux in monozygotic twins. Gastroenterology. 2007 REFERENCES Copyright ©2022 The Author(s). This is an Open Access article which licensed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. It permits no additional restrictions on use, distribution, and reproduction in any medium provided the original work is properly cited. https://creativecommons.org/licenses/by-nc-sa/4.0/ https://doi.org/10.15218/ejnm.2022.11 Erbil j. nurs. midwifery, Vol. 5, No. (2), Nov 2022 Original Article [21] Davidson S. Davidson's principles and practice of medicine. Elsevier Health Sciences; 2006. [22] Chait MM. Gastroesophageal reflux disease: Important considerations for the older pa- tients. World journal of gastrointestinal en- doscopy. 2010 Dec 16;2(12):388. Available from: https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3010469/. [Accessed 24th March 2021]. [23] Cicala M, Emerenziani S, Caviglia R, Guarino MP, Vavassori P, Ribolsi M, et al. Intra‐ oesophageal distribution and perception of acid reflux in patients with non‐erosive gastro ‐oesophageal reflux disease. Alimentary phar- macology & therapeutics. 2003 Sep;18(6):605- 13. Available from: https:// onlinelibrary.wiley.com/doi/full/10.1046/ j.1365-2036.2003.01702.x. [Accessed 24th March 2021]. [24] Van Soest EM, Dieleman JP, Siersema PD, Stur- kenboom MC, Kuipers EJ. Increasing incidence of Barrett’s oesophagus in the general popula- tion. British Medical Journal-Gut. 2005 Aug 1;54(8):1062-6. Available from: https:// gut.bmj.com/content/54/8/1062.short. [Accessed 24th March 2021]. https://bmcgastroenterol.biomedcentral. com/articles/10.1186/s12876-016-0452-1. [Accessed 10th April 2021]. [15] Mermelstein J., Mermelstein A. C., and Chait M. M. Proton pump inhibitors for the treat- ment of patients with erosive esophagitis and gastroesophageal reflux disease: cur- rent evidence and safety of dexlansopra- zole. Clinical and Experimental Gastroenter- ology. 2016; 9: 163–172. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4948703/. [Accessed 18th April 2021]. [16] Yamamichi N, Mochizuki S, Asada-Hirayama I, Mikami-Matsuda R, Shimamoto T, Konno- Shimizu M, et al. Lifestyle factors affecting gastroesophageal reflux disease symptoms: a cross-sectional study of healthy 19864 adults using FSSG scores. BMC medicine. 2012 Dec;10(1):1-1. Available from: https:// link.springer.com/article/10.1186/1741- 7015-10-45. [Accessed 10th April 2021]. [17] Hampel H, Abraham NS, El-Serag HB. Meta- analysis: obesity and the risk for gas- troesophageal reflux disease and its compli- cations. Annals of internal medicine. 2005 Aug 2;143(3):199-211. Available from: https://www.acpjournals.org/doi/ full/10.7326/0003-4819-143-3-200508020- 00006. [Accessed 2nd May 2021]. [18] Corley DA, Kubo A. Body mass index and gastroesophageal reflux disease: a system- atic review and meta-analysis. Official jour- nal of the American College of Gastroenter- ology| ACG. 2006 Nov 1;101(11):2619-28. Available from: https://journals.lww.com/ ajg/Abstract/2006/11000/ Body_Mass_Index_and_Gastroesophageal_ Reflux.28.aspx. [Accessed 2nd May 2021]. [19] Fujiwara Y, Kubo M, Kohata Y, Machida H, Okazaki H, Yamagami H, et al. Cigarette smoking and its association with overlap- ping gastroesophageal reflux disease, func- tional dyspepsia, or irritable bowel syn- drome. Internal Medicine.2011;50(21):2443- 7.Availablefrom:https://www.jstage.jst.go.J particleintenalmedcine/50/21/50_21_2443/ _article/-char/ja/[Accessed 2nd May 2021] [20] Matsuki N, Fujita T, Watanabe N, Sugahara A, Watanabe A, Ishida T, et al. Lifestyle fac- tors associated with gastroesophageal reflux disease in the Japanese population. Journal of Gastroenterology. 2013 Mar;48(3):340-9. Available from: https://link.springer.com/ article/10.1007/s00535-012-0649-1 [Accessed 2nd May 2021]. 104 Copyright ©2022 The Author(s). 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