Gastroenterology Report, 8(4), 2020, 286–292 doi: 10.1093/gastro/goaa002 Advance Access Publication Date: 19 February 2020 Original article ORIGINAL ARTICLE Prevalence of gastroesophageal reflux disease: a population-based cross-sectional study in southern Chile 1,2, Carlos Manterola *, Luis Grande3, Luis Bustos4 and Tamara Otzen1 1 Center of Morphological and Surgical Studies, Universidad de La Frontera, Temuco, Chile; 2Department of Surgery, Universidad de La Frontera, Temuco, Chile; 3Department of Surgery, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain; 4Department of Public Health, Universidad de La Frontera, Temuco, Chile *Corresponding author. Center of Morphological and Surgical Studies, Universidad de La Frontera, Temuco 4811230, Chile. Tel: þ56-45-2325760; Fax: þ56-45-2325761; Email: carlos.manterola@ufrontera.cl Abstract Background This study assessed the prevalence of gastroesophageal reflux disease (GERD) in a general adult population from Temuco in southern Chile. The association of GERD with demographic variables was also examined. Methods A cross-sectional study among the general population of Temuco in southern Chile was conducted in 2017, using a validated and reliable questionnaire for detecting GERD. The urban area of Temuco, with a population of 245,317 inhabitants (2002 census), was divided into four zones, which were representative of the socioeconomic sectors of the city. The sample size was estimated assuming a prevalence of 52.8%, an accuracy of 3.0%, a confidence level of 95.0%, and a design effect of 1.15. Area sampling was used to build clusters. The prevalence of GERD was determined and associated factors were studied by means of bivariate and multivariate analyses. Results A total of 1,069 subjects (47.9% women, median age 40 years) from the selected subareas were interviewed. The prev- alence of GERD was 44.8%. The most frequently reported symptom was regurgitation (54.8%). One-third of subjects took medication to control symptoms and was considered ‘sick’ by the instrument, although >68% of them had never sought medical consultation. There was a significant association between GERD and age (P < 0.001) and female gender (P ¼ 0.001). Conclusions In this population-based study, the prevalence of GERD was high (44.8%). GERD was associated with age and fe- male gender. Key words: gastroesophageal reflux disease; prevalence; cross-sectional studies; evidence-based medicine; clinical epidemiology Introduction symptomatic subjects have esophagitis and that 70% require Gastroesophageal reflux disease (GERD) is a frequent cause of regular treatment for the control of symptoms, which can consultation. Typical symptoms, such as heartburn and regurgi- strongly affect their quality of life [1]. There are a few reports on tation are common in the community, occurring in up to 33% of the prevalence of GERD in the general population and most the adult population. It has been estimated that 30% of studies have been conducted in specific [2–6] or mixed Submitted: 28 May 2019; Revised: 26 August 2019; Accepted: 4 October 2019 C The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University V This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 286 Gastroesophageal reflux disease prevalence | 287 populations [7–9], such as elderly subjects [2], pregnant women [3], and subjects with type 2 diabetes [4], asthma [5], or depressive disorder [6]. Many questionnaires used to assess the prevalence of GERD are not reproducible or have not been previously validated [2–4, 9–17]. Also, the survey approach, including telephone interviews, postal questionnaires, and self- completed instruments, has methodological limitations [3, 11, 12, 14, 16–25]. Therefore, to overcome these limitations, we conducted a population-based study to assess the prevalence of GERD in the general adult population of Temuco, a city in southern Chile, using a validated and reliable questionnaire specific for reflux disease [26]. Data of previous prevalence studies of GERD using face-to-face interviews were compared with findings of our study. The objective of our study was to determine GERD preva- lence in a general adult population from Temuco in southern Chile and its association with demographic variables. Figure 1. Map of Temuco used for further cluster randomization. Temuco was divided into four sectors properly representing the various economic and cul- tural areas of the city. Cluster randomization of sector 1 can be seen. The boxes Materials and methods in bold represent the subsectors studied. Data source tobacco and alcohol consumption, medications used for the The source population consisted of all individuals 18 years or control of GERD symptoms, and use of healthcare resources for older living in the urban area of Temuco, Chile, between 1 GERD-related consultations. March 2017 and 31 December 2017. According to Chile’s Institute of Statistics (INE), the total urban population of the city Sampling and administration of the questionnaire was 232,528 inhabitants, of whom 172,116 subjects were adults (>18 years of age) [27]. The urban area of Temuco was divided into four sectors, which were representative of different economic and cultural areas of the city, e.g. sectors 1 and 2 are of medium social and economic Study design and participants status, sector 3 of high status, and sector 4 of low status A cross-sectional survey was designed, the primary objective of (Figure 1). The downtown district was excluded because most of which was to determine the prevalence of GERD in the adult ur- the buildings were commercial properties or office spaces. ban population of Temuco. Secondary objectives were: (i) to de- Sectors were then divided into 12 subsectors of approximately scribe clinical features and associated factors of patients with clusters of 10 blocks each. A two-stage cluster random-sampling GERD and (ii) to assess demographic, anthropometric, and so- method was used, in which a subset of households within each ciocultural factors of respondents to the survey. Subjects of selected conglomerate of blocks was randomly selected for in- both sexes, aged 18 years or older who gave written informed clusion in the study (Figure 2). A team of six previously trained consent, were included in the study. Exclusion criteria were as medical students performed face-to-face interviews in the se- follows: morbid obesity, scleroderma, pulmonary disease, pres- lected households. They also confirmed the eligibility criteria, ence of neoplasms, esophageal motor disorders, diseases capa- obtained the written informed consent, and administered the ble of causing GERD or alterations in esophageal motility as part questionnaire. Interviewers were totally familiar with the in- of its natural history, benign and malignant gastroduodenal dis- strument and knew how to explain better any eventual ques- eases, history of surgery of the upper gastrointestinal tract, and tion that has not been fully understood by the subjects caustic injury. Pregnant women and subjects with cognitive im- interviewed. When no one fulfilled the inclusion criteria, the pairment or mental illness were also excluded. household on the right of the index home was selected. When no one lived in the household, the interviewer returned Study procedures 24 hours later and, if it was still uninhabited, it was replaced by A validated and reliable specific questionnaire for the diagnosis the contiguous household on the right. Respondents who, of GERD was used [26, 28]. The questionnaire consists of seven according to the scale, were found to suffer from GERD were re- items: heartburn, regurgitation, chest pain, dry cough, dyspha- ferred to the healthcare center for further consultation. gia, dysphonia, and asthma. Heartburn, regurgitation, chest pain, and dry cough are scored from 0 to 3 (0: none; 1: at least Ethical consideration once a month; 2: at least once a week; 3: every day) and dyspha- The study was approved by the Ethics Committee of the gia, dysphonia, and asthma from 0 (absent) to 1 (present), with a Universidad de La Frontera. Written informed consent was total score from 0 to 15. The questionnaire has been previously obtained from all participants. Personal data were anonymized. validated against the results of 24-hour esophageal pH monitor- This manuscript was written following the STROBE statement. ing and showed an internal consistency of 0.75 and inter-ob- server reliability of 0.87 [28]. Using a cut-off score of 3, the sensitivity, specific, positive, and negative predictive values Sample size and statistical analysis were 92%, 95%, 98%, and 79%, respectively, with a correct classi- Considering that the urban adult population of Temuco is fication of subjects of 92.4% [26, 28]. Other data of interest were 172,116 inhabitants [27] and based on a prevalence of GERD of added to the questionnaire, including age and gender, anthro- 52.8% found in a previous pilot study of our group [29], with an pometric data (height, weight, and body mass index [BMI]), accuracy of 3.0%, a confidence interval of 95%, and a design 288 | C. Manterola et al. Figure 2. Sampling of subsector 8 of sector 1. Maps were raised to later randomize blocks and households. Table 1. Distribution of the prevalence of gastroesophageal reflux Table 2. Distribution of symptoms of gastroesophageal reflux dis- disease (GERD) in the population surveyed from the four sectors of ease (GERD) in the population surveyed (n ¼ 1,069) the city Symptom No. of subjects (%) Sector No. of subjects Presence of GERD, n (%) Heartburn 335 (31.3) 1 361 142 (39.3) Regurgitation 586 (54.8) 2 232 128 (55.2) Chest pain 258 (24.1) 3 231 114 (49.3) Dry cough 318 (29.8) 4 245 95 (38.8) Dysphagia 325 (30.4) Total 1,069 479 (44.8) Dysphonia 241 (22.5) Asthma 159 (14.9) effect of 1.15, a sample size of 1,057 subjects was calculated. Categorical variables are expressed as frequencies and percen- not statistically significant. On the other hand, regurgitation tages, and continuous variables as mean and standard devia- was the most frequently reported symptom (54.8%) followed by tion or as median and range. The prevalence of GERD and the heartburn (31.3%), cough (30.4%), and chest pain (29.8%) prevalence of individual symptoms of reflux disease were calcu- (Table 2). lated. The chi-square test and the Fisher’s exact test were used About one-third of respondents (n ¼ 353) with GERD scoring for the comparison of categorical variables, and the Mann– 3 in the questionnaire reported that they were using medica- Whitney U test or the Wilcoxon test for the comparison of con- tions to control GERD symptoms, including antacids in 41.9% of tinuous variables. Multiple logistic-regression analysis was cases, H2 antagonists in 30.9%, and PPIs in 26.9% (no relation- used to assess variable independently associated with GERD. ship between positivity questionnaire and PPIs use was veri- Statistical significance was set at P < 0.05. fied). Drugs had been prescribed by a healthcare professional in only 53.0% of subjects (n ¼ 187). Also, 68.0% of these subjects (n ¼ 240) never visited the public healthcare system (55.0% were Results visited in private practices, 27.5% self-medicated, 14.2% chose A total of 1,069 subjects were interviewed (47.9% women) with a alternative medicines, and the remaining 3.3% did not respond median age of 40 years (range 18–92 years). The average BMI was to this item). 25.7 6 4.4 kg/m2 (range 15.8–54.1 kg/m2). Education level in- In the bivariate analysis, the prevalence of GERD was higher cluded primary education in 18.1% of subjects, secondary edu- in women than in men (64.3% vs 26.9%, P < 0.001). Also, subjects cation in 47.0%, and university studies in 34.3%. Six people with GERD were older and shorter (Table 3). In the multivariate (0.6%) were illiterate. Current smoking was recorded in 5.5% of analysis, age (P < 0.001) and female gender (P ¼ 0.001) were the subjects and alcohol consumption in 3.0%. Working status in- variables independently associated with GERD. cluded active workers in 45.5% of subjects, housewives in 17.2%, pensioners/retired in 6.0%, unemployed in 3.0%, and students in Discussion 28.2%. The median overall score of the in-study population was 2 The present population-based study carried out in the city of (range 0–13) and the average score was 2.7 6 2.6. On the other Temuco, Chile has shown a prevalence of GERD of 44.8%. We hand, 590 subjects (55.2%) had a score of <3 (average 0.9 6 0.8) used a reliable and validated questionnaire for assessing esoph- and 479 subjects (44.8%) had a score of 3 (average 5.1 6 2.1). So, ageal reflux disease according to the presence and frequency of the prevalence of GERD was 44.8%. The prevalence of GERD var- seven common symptoms of GERD. The prevalence found in ied according to areas surveyed (Table 1), but differences were the present study is lower than that observed in a previous Gastroesophageal reflux disease prevalence | 289 Table 3. Association between demographic variables and gastro- subgroups were 25.6 6 3.9 and 26.8 6 4.9 kg/m2, respectively esophageal reflux disease (GERD) (P ¼ 0.1619). Related to any dietary elements in this geographical area of Chile that could lead to obesity, we can argue that effec- Variable No GERD (n ¼ 590) GERD (n ¼ 479) P-value tively there are some, e.g. the fruit of the araucarias (La Age, years 40.7 6 18.0 45.7 6 18.0 <0.001 ~ ones’; however, there Araucanı́a Region typical tree), called ‘pin Sex, n (%) <0.001 is not enough evidence to asseverate it. Female 183 (35.7) 329 (64.3) We did not find differences in other factors that have been Male 407 (63.1) 150 (26.9) related to the disease, such as smoking or alcohol consumption Height, cm 164.1 6 13.6 161.6 6 12.5 0.047 [48, 49]. The small percentage of smokers and alcohol users in Weight, kg 68.7 6 12.5 68.6 6 12.7 0.942 our study may account for this finding. On the other hand, the Body mass index, kg/m2 25.6 6 3.9 26.8 6 4.9 0.162 proportion of subjects with university studies was 34.3%—a high rate that can be explained by the presence of numerous ed- ucation centers in two areas of the city. The percentage of un- cross-sectional survey (52.8%) in 2002–2003 in the same city, al- employed patients was also high because students accounted though, in this case, only 364 persons were interviewed [29]. A for 28.0% of the study sample. An influence of the education review of prevalence studies of GERD in adult populations using level or working status on the development of GERD was not face-to-face interviews and published from 2000 is summarized established. After logistic-regression analysis, only age and fe- in Table 4 [15, 29, 30, 32–36, 38–40]. Prevalence rates are highly male gender were significantly associated with GERD. variable from 3.5% to 52.8% as well as the number of subjects in- The potential effect of indigenous elements in the popula- cluded in the surveys (from 364 to 13,959) and the geographical tion samples is difficult to determine precisely because, al- origin of the study samples. In these studies, the GerdQ ques- though the self-declared indigenous population in urban tionnaire developed by Jones et al. [41] and the GERD question- naire developed by Locke et al. [31] were the tools most Temuco in the 2017 census was 24.7% (including different races frequently used for diagnosing GERD. In some surveys, how- of original peoples) [50], there is no form to determine the pro- ever, the prevalence of GERD was defined as the presence of portion of indigenous elements in the different in-study sectors acid regurgitation and/or heartburn at least once a week [33, 37]. (possibly this value can be even higher, because there are peo- Marked differences in the prevalence rates of GERD have been ple with indigenous ancestry who are not considered as such). reported in populations from Asia (between 1.7% and 27.5%) [25, On the other hand, regarding the potential influence of 32–37, 40], Europe (between 14.8% and 28.7%) [16, 20, 42], and migrants from rural communities around introducing higher Latin America (between 4.7% and 52.8%) [22, 29, 30]. Helicobacter pylori rates and hence less GERD, there is evidence The comparison across studies is limited, for different rea- supporting no relationship between GERD and H. pylori pres- sons: the heterogeneity of the in-study populations and the use ence; also, successful eradication therapy does not have an im- of different scales and instruments with the same purpose, but pact on the emergence or exacerbation of GERD [51–54]. only some of them valid and reliable [26, 31, 41]. On the other Another interesting point to comment on is the potential as- hand, there are a lot of studies using different definitions of sociation between the high rates of GERD and esophageal can- GERD and utilizing ‘unknown questionnaires’ as measurement cer (Barrett’s-related) rates in the community. First of all, we do instruments. The majority of published instruments (almost 40) not know the reasons to explain the high prevalence of GERD did not fulfill all relevant diagnostic criteria [43]. Finally, other found, but it is similar to a previous study published in 2005 reasons that may be associated are the form of applying the [29]. On the other hand, the crude mortality rate of esophageal measurement instruments (face to face, by phone, mail, etc.), cancer per 100,000 inhabitants in Chile in 2015 was 3.7. the accuracy of the sample-size estimation, the type of sam- However, in La Araucanı́a Region (Capital Temuco), it was 9.5 pling strategies utilized, etc. for men and 6.2 for women (the highest in the country) [55], so A high prevalence of main GERD symptoms was found in is a fascinating issue for further investigation. However, Barrett our study, particularly heartburn and regurgitation, although esophagus in our city has unknown incidence. this finding is consistent with the high number of subjects who The present findings should be interpreted taking into ac- reported taking anti-reflux medications for the control of symp- count the limitations of the study, particularly the generalizabil- toms, generally prescribed by the public healthcare system. ity of the results to different target populations. The strengths Also, age, female gender, and height were associated with of the study include the use of a validated and reliable question- GERD. A relationship of GERD with increasing age has also been naire for assessment of GERD symptoms, trained interviewers, reported in other studies [20, 33, 40]. It has been shown that the face-to-face approach for administering the questionnaire, non-erosive reflux disease is more common in women, whereas and the cluster random sampling for the selection of Barrett’s esophagus and esophageal adenocarcinoma are more participants. frequent in men [44]. The estrogen-related endocrine milieu is In conclusion, using a population-based cross-sectional reported to modulate the metabolism of fat and obesity is a main risk for GERD [45]. study and a validated questionnaire, the prevalence of GERD in Obesity and BMI are well-known risk factors for reflux dis- an urban area of southern Chile was 44.8%. An independent as- ease (especially in the Western population). This association is sociation of GERD with female gender and age was observed. not coincidental because GERD pathophysiology is, in part, con- Further studies using endoscopic examination would be neces- nected with overweight and obesity [17, 38, 45–47]. A relation- sary to ascertain the association between a positive question- ship between BMI and GERD was not observed probably because naire score for GERD and endoscopic esophagitis. In addition, it one of the exclusion criteria of our study was obesity, in spite of would be advisable to carry out education campaigns to detect which, the study population was slightly overweight (the BMI and treat patients with GERD in order to prevent complications average was 25.7 6 4.4 kg/m2, with a fairly similar distribution and to contribute to reducing the economic burden of the across the four sectors). The average of <3 and 3 points disease. 290 | Table 4. Summary of GERD-prevalence studies in adult population using face-to-face interviews since 2000 Reference Year No. of Country Population Sampling method Instrument Validity Reliability Heartburn Regurgitation GERD C. Manterola et al. subjects prevalencea prevalencea prevalence (%) (%) (%) Dacoll [30] 2000 1,141 Uruguay Urban population Systematic sampling GerdQ [31] Yes NR 10.7 8.1 4.7 Wang [32] 2004 2,789 China Adults of Xi’an Stratified sampling Unknown No No 4.1 7.8 17.4 questionnaire Cho [33] 2005 1,902 Korea Asan-si residents Simple random Unknown Yes Yes 2.0 2.0 3.5 questionnaire Manterola [29] 2005 364 Chile Urban adult population of Cluster sampling Manterola [26] Yes Yes 46.4 59.6 52.8 Temuco Moraes-Filho [15] 2005 13,959 Brazil Urban adult population of NR Unknown No No 11.9 NR 7.3 22 cities questionnaire Mungan [34] 2012 8,143 Turkey Turkish general population Simple random GerdQ [31] Yes Yes NR NR 27.6 Shaha [35] 2012 2,000 Bangladesh Urban and rural areas of Simple random Manterola [26] Yes Yes 5.25 5.25 5.5 northeastern Bangladesh Yönem [36] 2013 1,345 Turkey Adults living in Sivas Simple random Locke [37] Yes NR 8.0 8.9 19.3 Bor [38] 2016 1,065 Russia Adults in Moscow Simple random Locke [37] Yes NR 17.5 17.6 23.6 Wang [30] 2016 1,072 India People in southern India Multi-stage cluster GerdQ [31] Yes NR 26.4 18.1 22.2 Bor [39] 2017 3,214 Turkey Subjects aged 20 years or Three-stage stratified Locke [37] Yes Yes 12.7 18.7 22.8 older from 17 cities cluster Manterola 2020 1,069 Chile Urban adult population of Two-stage cluster ran- Manterola [26] Yes Yes 31.3 54.8 44.8 Temuco dom sampling aSymptom present at least once a week; GERD: gastroesophageal reflux disease; NR: not reported. 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