Systematic Review on Epidemiology of Gastroesophageal Reflux Disease in Asia

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006;4: REVIEWS Systematic Review on Epidemiology of Gastroesophageal Reflux Disease in Asia BENJAMIN C. Y. WONG* and YOSHIKAZU KINOSHITA *Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong; and the Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane, Japan Background & Aims: The epidemiology of gastroesophageal reflux disease (GERD) has been a subject of much interest in recent years. This review ascertains the prevalence of GERD in eastern and southeastern Asia, and reports on complications and risk factors. Methods: This qualitative systematic review of the epidemiology of GERD in eastern and southeastern Asia identified studies in adults reported in English in the Medline database (searched through April 2005), relevant reviews, and our own bibliographic databases. Results: Thirteen studies were included. The reported population prevalence of GERD in eastern Asia ranged from 2.5% to 6.7% for at least weekly symptoms of heartburn and/or acid regurgitation and may be increasing. No reliable data are available on the prevalence of esophagitis in the general population. In case studies, the prevalence of reflux esophagitis ranged from 3.4% to 16.3%. Well-established risk factors for GERD in Asian populations included hiatus hernia and obesity. Age and male sex also may be risk factors. Chest pain is the predominant extraesophageal manifestation of GERD in China, whereas in Japan, a link with asthma has been implicated in patients with severe esophagitis. Conclusions: There is a paucity of studies reporting the prevalence of GERD in eastern and southeastern Asia. These results highlight the need for further epidemiologic studies using representative study populations and a standardized methodology. Recognition and awareness of GERD need to increase concomitantly to ensure appropriate diagnosis and treatment of the disease. Gastroesophageal reflux disease (GERD) has been seen historically as a disease of Western countries, and was thought to be distinctly uncommon among Asians. 1 Endoscopic studies and, more recently, symptom-based surveys, however, have shown that reflux disease is more common in Asia than previously recognized. One of the difficulties when reviewing the prevalence of GERD in different countries is that symptom definitions and frequencies used to diagnose GERD are not standardized. A symptom-based definition of GERD, incorporating those with and without complications such as esophagitis, is the most appropriate means of including all GERD patients. Esophagitis is only present in a subset of patients with GERD, 2 and is viewed increasingly as a complication rather than a presentation of the disease. A panel of practicing gastroenterologists from the Asia-Pacific region recently discussed the definition of GERD during a consensus meeting on the management of GERD, which subsequently was presented at the Asia-Pacific Digestive Week This working group acknowledged the definition of GERD that was developed in Genval, Belgium, 4 and refined it, generating a more succinct version: GERD is a disorder in which gastric contents recurrently reflux into the esophagus causing heartburn and other symptoms. In Japan, however, the accepted definition of GERD extends to include damage to the esophageal mucosa. 5 The diagnosis of GERD depends on the frequency and severity of gastroesophageal reflux symptoms. Although occasional symptoms are experienced by a large proportion of the population, GERD patients experience an impaired health-related quality of life as a result of their disease. International consensus thus favors the use of at least twice-weekly symptoms of GERD to indicate disease. 4,6 Epidemiologic studies reporting the prevalence of GERD mostly refer to at least weekly symptoms, although lower symptom frequencies are sometimes used as a cut-off marker of disease. It is the aim of this qualitative systematic review to examine the epidemiology of GERD in eastern Asia. Published studies were assessed critically, including the methodologies, symptom definitions, and frequency cut offs used to diagnose the disease. The review also reports Abbreviation used in this paper: GERD, gastroesophageal reflux disease by the American Gastroenterological Association Institute /06/$32.00 doi: /j.cgh

2 April 2006 EPIDEMIOLOGY OF GERD IN ASIA 399 Table 1. Prevalence of GERD in Eastern and Southeastern Asia Study Wong et al, ; follow-up study Year in which study was conducted Target population Selection criteria Sample size Questionnaire 2002; followup 2003 Hong Kong Automatic dialing of random telephone numbers; member with most recent birthday interviewed Hu et al, Hong Kong Automatic dialing of random telephone numbers; member with most recent birthday interviewed Pan et al, Beijing and Shanghai Residents enrolled in proportion to the population of their district or county Wang et al, Not specified Xi an residents (northwestern China) Residents chosen randomly from urban, suburban, and rural regions based on census data Cho et al, Asan-si (Korea) Residents chosen randomly from 200 households in each of the 10 largest districts Fujiwara et al, Watanabe et al, Hirakawa et al, Stanghellini, Ho et al, and ; follow-up study Kansai area of Japan Employees taking part in an obligatory annual health screening 2001 Kansai area of Japan Male employees taking part in an obligatory annual health screening Japan Citizens over the age of 35 taking part in annual screening program for gastric cancer Not specified Japan (part of Random house-to-house international study) recruitment Not specified Jurong near Singapore Registered electors chosen by an ethnicity-stratified disproportionate random sampling procedure 2209; (follow-up, 712) GERQ; validated and specific for GERD 1649 Bowel Symptom Questionnaire; validated; not specific for GERD 4992 Not validated 2789 Not validated 1902 GERQ; validated and specific for GERD 6035 Not validated 4095 Not validated 911 Not validated 500 DIGEST; validated 696; (follow-up, 237) Bowel Symptom Questionnaire; validated, but not specific for GERD HB, heartburn; AR, acid regurgitation; FR, food regurgitation; GERQ, Gastroesophageal Reflux Questionnaire; DIGEST, Domestic/International Gastroenterology Surveillance Study. a At least twice weekly symptoms. b At least twice monthly symptoms. c Data obtained by reading off graph in referenced publication. d Symptoms experienced at any frequency in previous 3 months. on complications of GERD and risk factors associated with disease development. Data Selection A computerized literature search was performed in the PubMed and Medline databases for relevant articles through April The search terms were selected to identify studies describing the epidemiology of GERD in eastern Asia and southeastern Asia. Three inclusive searches were conducted and combined using the following search terms in full Medline and Medical Subject Headings (MeSH): (Asia, China, Taiwan, Japan, North Korea, South Korea, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, or Vietnam) and (GERD, GORD, reflux, heartburn, esophagitis or oesophagitis) and (epidemiology, epidemiological, prevalence, incidence, observational study or observational studies). As additional sources of potential studies for inclusion, recent reviews of the epidemiology of GERD 1,7 9 and our existing bibliographic databases also were examined for appropriate publications. Results Our initial search identified 301 results, of which 17 evaluated the prevalence or incidence of GERD or heartburn in eastern and southeastern Asia. Four of these

3 400 WONG AND KINOSHITA CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 4 Table 1 (continued). Symptom descriptors included Response rate (%) Yes 61.3; (follow-up, not specified) Prevalence of reflux symptoms (%) Daily At least weekly At least monthly At least yearly 2.5 (follow-up, 2.7) 8.9 (follow-up, 10.1) 29.8 (follow-up, 34.1) Not reported Yes Not specified HB, 2.5 HB, 3.1 HB, 7.0 Yes 91.8 HB, 1.7 AR, 3.5 FR, 1.4 HB, 4.1 AR, 7.8 FR, 3.3 HB, 11.0 AR, 21.0 FR, 8.6 Yes 75 GERD, 3.5 HB, 2.0 AR, 2.0 HB, 4.7 AR, 4.4 Not reported a 19.4 b 44.1 Not reported a Not reported N/A 3 10 c 9 24 c Not reported 27 HB, 9.8 d AR, 3.6 d Not reported 93; (follow-up, 34) 1.6; (follow-up, 10.6) HB, 4.6 were excluded: 2 because they described only data from infants and/or children 10,11 and 2 because they were not available in English. 12,13 This left 13 studies for review (Table 1): 5 were from China (including 1 follow upstudy 14 ), from Japan, from Singapore (2 on the same study, 1 follow-up study), and 1 from Korea. 26 All were full primary articles except 1, which was a meeting abstract. 25 Prevalence of Gastroesophageal Reflux Disease Wong et al 15 reported a prevalence of 2.5% of frequent reflux symptoms, defined as heartburn and/or acid regurgitation occurring at least once a week, in a population study in Hong Kong (n 2209). Random telephone interviews were performed using the Chinese version of the well-validated Gastroesophageal Reflux Questionnaire, 27 and the response rate was 61%. In a 1-year follow-up investigation of the above study, Wong et al 14 showed an increased prevalence of weekly GERD symptoms from 2.5% to 2.7%, and an increased prevalence of monthly symptoms from 8.9% to 10.1%. However, only 32% (712 of 2209) of study participants completed both the original and the follow-up survey. In this subgroup, the prevalence of GERD symptoms was more stable over the 1-year follow-up period, with a monthly prevalence of 9.8% in 2002 and 10.1% in 2003, and a weekly prevalence of 2.7% in both years. Hu et al 16 reported a higher prevalence of 4.8% for at least weekly heartburn and/or acid regurgitation in an earlier population study in Hong Kong (n 1649). The questionnaire used in this study was a translated version

4 April 2006 EPIDEMIOLOGY OF GERD IN ASIA 401 of the validated Bowel Symptom Questionnaire. 28 Random telephone interviews were conducted, and the response rate was 62%. The approximately 2-fold difference in the prevalence rate of GERD between these 2 studies of the same source population (conducted only 6 years apart) may be owing to the different questionnaires used to assess prevalence. Although both questionnaires were validated, the Gastroesophageal Reflux Questionnaire used by Wong et al 14,15 was developed specifically to assess the prevalence of GERD in population-based studies, whereas the Bowel Symptom Questionnaire used in the study by Hu et al 16 was developed as a diagnostic tool for dyspepsia, irritable bowel syndrome, and functional gastrointestinal symptoms and is not specific for GERD. All 3 studies from Hong Kong used random telephone numbers to select interviewees. The telephone density in Hong Kong is among the highest in the world, 29 making it likely that the study populations were representative of the Hong Kong population as a whole. Two studies from mainland China identify patients with GERD using nonvalidated symptom scores. Pan et al 17 reported a population prevalence of 3.1% for at least weekly heartburn in a study conducted in Beijing and Shanghai (n 4992). Participants completed a symptom questionnaire, which was scored from 0 (symptom-free) to 18. Participants with a score of 6 or greater usually had more than 1 symptom, with a high degree of intensity or frequency. This score thus was chosen as the lower limit to identify GERD, and was reached by 8.9% of the study population. However, neither the symptom scale nor the cut-off value used to identify disease had been validated, which, together with the lack of a reported response rate in this study, makes its findings hard to interpret with confidence. Wang et al 18 reported a prevalence of 4.1% of at least weekly heartburn in a further population-based survey conducted in Xi an in northwest China (n 2789). Study participants were interviewed face-to-face by medical students, and an excellent response rate (92%) was achieved. Wang et al used a modified version of the questionnaire developed by Pan et al. 17 A total symptom score of 3 or greater (of a possible 18) was chosen as the lower limit to identify individuals with GERD and was reached by 16.9% of responders. Acid regurgitation was the most common symptom and was experienced at least weekly by 7.8% of the study population; 3.3% experienced food regurgitation at least weekly. As was the case in the study by Pan et al, 17 neither the symptom scale nor the cut-off value used to identify disease were validated in this study. Figure 1. The risk factors for (A) GERD and its main esophageal complication (B) reflux esophagitis. Odds ratios with 95% confidence intervals. Data from Rosaida et al. 39 dx diagnosis. In Korea, a prevalence of 3.5% was reported by Cho et al 26 for at least weekly heartburn and/or acid regurgitation in the combined city and farming area of Asan-si (n 1417). The prevalence of GERD, when defined as the presence of heartburn or acid regurgitation at least twice a week or causing impairment of health-related wellbeing, was 2.7%. Interviews were conducted face-to-face using a translated version of the well-validated Gastroesophageal Reflux Questionnaire, 27 and the response rate was good at 78%. The prevalence of symptoms of GERD in Japanese populations has been assessed in 3 separate studies. A large study of employees in the Kansai area reported a prevalence of 6.6% for at least twice weekly heartburn and/or acid regurgitation (n 6035). 19 A further large study of male employees in the Kansai area reported a prevalence of 6.7% for at least twice weekly heartburn and/or acid regurgitation (n 4095). 20 The response rates were high in both studies at 86%, but neither study used a validated questionnaire. In a smaller, age-stratified study of Japanese individuals (n 911), less than 5% of those younger than the age of 50 reported at least weekly symptoms of heartburn and/or acid regurgitation, although this increased to almost 10% in the group aged years (Figure 1). 21 Standardized, nonvalidated questions were asked to assess the prevalence of GERD symptoms, and neither the response rates nor the prev-

5 402 WONG AND KINOSHITA CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 4 alence rates for the study population as a whole were specified. Additional studies are needed to assess the prevalence of GERD in the general population in Japan using a validated symptom questionnaire. All 3 available studies recruited individuals from those undergoing their annual medical health checks; 2 studies assessed prevalence only in employed individuals, and 1 of these studies assessed the prevalence only in men, making them less representative of the general population. An international study on the prevalence of GERD symptoms reported a 3-month prevalence of 9.8% for heartburn and of 3.6% for regurgitation in a Japanese population. 22 The interviews were conducted using translations of a validated Domestic/International Gastroenterology Surveillance Study questionnaire. The overall response rate was very low at 27%, making the results less applicable to the population as a whole. The very low frequency threshold of any symptoms in the previous 3 months also makes it likely that the study captured healthy individuals with occasional reflux symptoms as well as those with GERD, making the Domestic/International Gastroenterology Surveillance Study less useful in assessing the prevalence rates of GERD. However, the standardized methodology may allow for some comparison between countries, and it is interesting that the reported prevalence for 3-monthly symptoms was lower in Japan than in most Western geographic areas assessed. An overall prevalence of 1.6% was obtained for at least monthly heartburn and/or reflux in a Singapore study by Ho et al 23 (n 696). Face-to-face interviews were conducted using a validated modified version of the validated Bowel Symptoms Questionnaire by Talley et al, 28 and the response rate was extremely high at 93%. Compared with Chinese individuals (a prevalence of.4% for both heartburn and acid regurgitation), Malay and Indian interviewees were significantly more likely to report heartburn (a prevalence of 3% and 5%, respectively) and Indian individuals were significantly more likely to report acid regurgitation (5% prevalence). The study did not assess the prevalence of weekly symptoms, which generally are taken as the cut-off level for reflux disease. Also, because the study population was controlled for race, it is possible that it was not truly representative of the general population as a whole, of which 71% are Chinese, 20% are Malays, and 8% are Indians. A 5-year follow-up investigation of the study by Ho et al 24 identified an increase from 1.6% to 10.6% in the prevalence of at least monthly symptoms of heartburn and/or acid regurgitation. 25 Only 237 individuals (34%) from the initial cohort of 696 responded to the second survey, thus suggesting that response bias may have contributed to this apparent increase in prevalence. Nevertheless, the scale of change does seem to imply a genuine increase in the prevalence of reflux disease. Esophageal Complications of Gastroesophageal Reflux Disease A number of esophageal complications are associated with GERD, with reflux esophagitis (Table 2) and Barrett s esophagus among the most extensively studied. The study by Pan et al 17 reported a prevalence for esophagitis of 21.4% (9 of 42) in individuals with symptoms of GERD. From this, Pan et al calculated an estimated population prevalence of 1.9% for reflux esophagitis in Beijing and Shanghai. However, the very small subgroup included in the second phase of the study suggests that additional data are required to confirm the general population prevalence of reflux esophagitis. All other available data on the prevalence of reflux esophagitis in eastern Asia originated from case series. These are likely to overestimate the true prevalence of reflux esophagitis because they depend on consultation behavior and also may include other forms of esophagitis not related to reflux. A large study was conducted in Hong Kong in patients undergoing routine or emergency upper endoscopy (n 16,606). 30 Of these patients, 3.8% had endoscopically evident esophagitis. A Taiwanese study identified esophagitis in 5% of individuals undergoing upper-gastrointestinal endoscopy (n 2044). 31 Most of the patients were free of symptoms and had been admitted for their yearly self-paid check-up. A smaller study in Taiwan reported esophagitis in 14.5% of 464 Chinese patients undergoing uppergastrointestinal endoscopy. 32 Patients had referred themselves for a variety of upper-gastrointestinal symptoms such as acid regurgitation, heartburn, epigastric pain, and upper-gastrointestinal bleeding. The higher rate of esophagitis reported in this second study from Taiwan probably is a result of a preselection for upper-gastrointestinal symptoms in the patient population and a lower threshold for identifying esophagitis at endoscopy. A large Japanese study reported esophagitis in 16.3% of patients visiting a hospital for routine physical examinations (n 6010). 33 A smaller Japanese study reported esophagitis in 13.8% of patients with heartburn, dyspepsia, and noncardiac chest pain undergoing endoscopy for the first time (n 392). 34 A retrospective Japanese study identified esophagitis in 9.8% of individuals more than 30 years old who had been endoscoped as part of a screening program for gastric cancer (n 2788). 35

6 April 2006 EPIDEMIOLOGY OF GERD IN ASIA 403 Table 2. Prevalence of Esophagitis in Eastern and Southeastern Asia Study Year(s) in which study was conducted Target population Selection criteria Sample size System for assessing and grading esophagitis Prevalence of esophagitis (%) Proportion of esophagitis patients with mild esophagitis a (%) Pan et al, Wong et al, Chang et al, Yeh et al, Furukawa et al, Inamori et al, Amano et al, Yeom et al, Lee et al, Kang et al, Rajendra et al, Rosaida and Goh, Beijing and Shanghai Residents; subgroup of GERD prevalence study Hong Kong Consecutive patients undergoing routine or emergency upper endoscopy Taiwan Individuals undergoing upper-gi endoscopy Taiwan Patients referring themselves for upper-gi symptoms including regurgitation, heartburn, epigastric pain and GI bleeding Japan Outpatients and subjects visiting a hospital for routine physical examinations 1999 Japan Patients with symptoms such as heartburn, dyspepsia, and noncardiac chest pain undergoing endoscopy for the first time Japan Individuals more than 30 years old who had been endoscoped as part of a screening program for gastric cancer Korea Patients referred because of symptoms related to the GI tract Korea Patients mostly free of symptoms coming for self-paid check-up 1993 Singapore Inpatients and outpatients undergoing upper-gi endoscopy Malaysia Patients undergoing elective gastroscopy for upper-abdominal or reflux complaints Malaysia Patients undergoing endoscopy for upperabdominal discomfort 42 S M ,606 LA S M (edema or diffuse rubor not classified as esophagitis) 464 S M (grade I defined as linear, nonconfluent lesions) 5 Not reported 14.5 Not reported 6010 LA LA LA S M (presence of red streaks with associated friability) 5.3 Not reported 7015 S M (grade defined as linear, nonconfluent lesions) 11,943 Red streaks and/or 4.5 Not reported erosions extending proximally from the squamocolumnar junction 1985 S M (grade I a defined as linear, nonconfluent lesions) 1000 LA GI, gastrointestinal; LA, Los Angeles classification of esophagitis; S M, Savary Miller classification of esophagitis. a Mild esophagitis was defined as LA grade A/B or S M grade I, except by Rajendra et al, 38 who defined mild esophagitis as Savary Miller grade IorII.

7 404 WONG AND KINOSHITA CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 4 In Korea, 5.3% of patients were referred to the hospital because symptoms related to the gastrointestinal tract were reported to have esophagitis (n 1010). 36 A lower prevalence of 3.4% was reported in patients visiting a hospital for a self-paid check-up, most of whom were free of symptoms (n 7015). 37 The difference in prevalence rates of esophagitis in the 2 Korean studies is likely to be owing to differences in the study population. Patients in the first study had upper-abdominal complaints, whereas most individuals in the second study were symptom-free. In Singapore, a prevalence of 4.5% was reported for esophagitis in a large retrospective study (n 11,943). 2 The study was conducted among inpatients and outpatients undergoing diagnostic upper-gastrointestinal endoscopy. A study of a multi-ethnic Malaysian population reported a prevalence of 6.1% for esophagitis (n 1985). 38 Patients were undergoing elective gastroscopy for predominantly upper-abdominal or reflux complaints. Within this multi-ethnic population, Indians were reported to be at increased risk for esophagitis compared with Chinese or Malays (8.5% vs 4.5% and 5.6%, respectively). A higher prevalence of 13.4% was reported for esophagitis in a prospective survey of consecutive Malaysian patients by Rosaida and Goh 39 (n 1000). Patients in this study underwent endoscopy for upper-abdominal discomfort. The prevalence of esophagitis in Asia may be increasing. An increase in the prevalence of reflux esophagitis from 3% in the 1970s to 10% 15% in the late 1990s has been suggested by a Japanese comparative study of upper-gastrointestinal endoscopies. 40 An increase in the prevalence of erosive esophagitis from 2.7% in the early 1990s to 9.0% in also was observed in a Malaysian study by Rosaida and Goh. 41 Barrett s esophagus is characterized by a columnar epithelium replacing the squamous mucosa that normally lines the distal esophagus. 42 Long-segment Barrett s esophagus was reported in 1.6% and short-segment Barrett s esophagus in 4.6% of the multi-ethnic Malaysian population described earlier. 38 As was the case for esophagitis, Indians were at greater risk for having Barrett s esophagus than were Malays or Chinese. A prevalence of 2% for Barrett s esophagus was reported in the study of self-referred Chinese patients undergoing uppergastrointestinal endoscopy in Taipei. 32 A much lower prevalence was described for a sample of southern Chinese patients undergoing upper endoscopy, of whom only.06% were found to have Barrett s esophagus (n 22,628). 30 The lack of a standardized grading and assessment system for Barrett s esophagus may contribute to the wide range in its reported prevalence. Extraesophageal Manifestations of Gastroesophageal Reflux Disease A significant association of GERD with chest pain, chronic cough, hoarseness of voice, asthma, and pneumonia was reported in the general population of Hong Kong, although only chest pain remained significantly associated with GERD on multiple logistic regression analysis (odds ratio, 2.7; 95% confidence interval, ). 15 This association was supported by a second study conducted in Hong Kong in which abnormal gastroesophageal reflux was observed in 29% of chest pain patients with normal coronary angiograms who underwent 24-hour ph monitoring (n 78). 43 A further study of chest pain patients in Hong Kong reported that 92% of those with abnormal 24-hour ph monitoring responded to proton pump inhibitor treatment, compared with only 33% of those with normal 24-hour ph monitoring (P.003). 44 Although chest pain appears to be the predominant extraesophageal manifestation of GERD, associations have been observed with other chronic disorders such as asthma. The treatment of severe reflux esophagitis is reported to be associated with improvement in asthma symptoms in Japan (n 72). 45 A further Japanese study investigated the response to 8 weeks of proton pump inhibitor therapy in asthmatic patients with gastroesophageal reflux (n 22) and in controls (n 31). 46 Excluding the 4 participants who withdrew from the study because of an adverse drug reaction, an improvement in asthma symptoms (defined as 20% increase in peak expiratory flow) was observed in 38% of participants with gastroesophageal reflux but none of those without. Risk Factors for Gastroesophageal Reflux Disease and Its Complications Alcohol consumption and the presence of a hiatus hernia were identified as risk factors for GERD and esophagitis in the Malaysian study by Rosaida and Goh 39 (Figure 1). A body mass index greater than 25 also was found to be a risk factor for GERD, but not for esophagitis. Cigarette smoking and alcohol consumption were identified as risk factors for GERD in the study of male Japanese employees by Watanabe et al 20 (controls, n 3819; GERD, n 276). There may be an effect of age and male sex (particularly in older patients) on the risk for GERD symptoms. 15,17 Of Japanese individuals visiting clinics for

8 April 2006 EPIDEMIOLOGY OF GERD IN ASIA 405 Figure 2. Prevalence of GERD (defined as heartburn and/or acid regurgitation at least once a week or at least once a month) in Japan., at least monthly;, at least weekly. Reprinted with permission from Hirakawa et al. 21 their annual medical health check, at least weekly GERD symptoms were experienced by less than 5% of individuals younger than the age of 50, but by almost 10% of individuals aged between 50 and 59 years (Figure 2). 21 There is also some evidence to suggest that age and male sex are associated with a higher incidence of esophagitis, 38,39 although at least 1 Asian study found no association between these factors and the disease. 2 Much recent discussion has focused on the role of Helicobacter pylori infection in GERD. The prevalence of H pylori infection is decreasing in eastern Asia. In Japan, the prevalence of H pylori infection is higher in the elderly than in young individuals (Figure 3), and most individuals currently infected with H pylori probably acquired the infection in childhood. 47 Raghunath et al 48 recently conducted a systematic review of 20 studies and identified a significantly lower prevalence of H pylori infection in patients with GERD than in controls (38% vs 49%). The overall prevalence of H pylori in the general population was found to be higher in the East (Japan and Hong Kong) than in Europe and North America. In patients with GERD, however, the prevalence of H pylori was lower in Eastern countries than in the West. Whether H pylori infection protects against reflux esophagitis nevertheless remains uncertain. Discussion There is a paucity of data available on the prevalence of GERD in Asia. Our search identified only 13 studies for review (Table 1), 9 of which were from mainly urban areas in China or Japan. These results highlight the pressing need for additional GERD prevalence studies in Asia, using a representative study population and standardized, well-validated questionnaires. The diagnosis of GERD depends on the frequency and severity of gastroesophageal reflux symptoms. For adults with at least weekly symptoms of heartburn and/or acid regurgitation, the reported prevalence of GERD across eastern and southeastern Asia ranged from 2.5% to 6.7%. Focusing on studies using validated symptom questionnaires only, the reported prevalence ranged from 2.5% to 4.8%. No reliable data were available on the prevalence of esophagitis in the general population, although the study by Pan et al 17 calculated an estimate of 1.9%. The prevalence of GERD seems lower in Asian countries than in the West, where it ranges from 10% 20%. 9 In addition, results from the Domestic/International Gastroenterology Surveillance Study suggest a lower 3-month prevalence of heartburn and regurgitation in a Japanese population compared with most of Europe and the United States. 22 The prevalence of reflux esophagitis in Asia also seems lower than in Europe, 17,49 but higher than in Africa, 40 although data are sparse because endoscopy is not amenable to population-based studies. Reflux esophagitis also tends to be of a lower grade in Asia compared with Europe and the United States. The vast majority of Chinese patients with esophagitis seem to have low-grade esophagitis, 31 whereas this proportion is only just over half in the United States. 50 The classification of symptoms and esophageal complications of GERD are not standardized globally, and this makes the comparison of prevalence studies difficult. Differences in reported prevalence also may arise because of language and cultural differences in symptom perception and interpretation. There is no direct translation of Figure 3. The prevalence of H pylori infection in Japan., 1974;, 1984;, Reprinted with permission from Fujisawa et al. 47

9 406 WONG AND KINOSHITA CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 4, No. 4 the word heartburn in Chinese or in Korean, and the term was understood by only 13% of Asian patients in a multiethnic study in Boston (compared with 35% of Caucasian patients and 54% of African American patients). 51 In the study by Wong et al, 15 the description a burning pain or discomfort behind the breastbone rising up towards the neck was used for heartburn. Nevertheless, heartburn was reported in only 50% of Chinese patients with GERD, which is considerably lower than in studies of Western populations. In contrast, a feeling of acidity in the stomach 15 was a common complaint found in Chinese patients with GERD. Similarly, in Malaysia, many Chinese and Malay patients use wind as an all-encompassing term for upper-gastrointestinal symptoms, 1 while this term has a much more narrow definition in the West. Apart from perceived differences in GERD prevalence caused by language and cultural differences, an undetermined portion of actual differences in prevalence may be explained by genetic variations in Asia and the West. 52 There are indications that the prevalence of GERD and esophagitis are increasing in Asia. 14,23,24,40,41 Socioeconomic changes have led to an increased adoption of a Western way of life and its associated stresses in Asian countries. In Japan, gastric acid secretion has increased notably since the 1970s, irrespective of H pylori infection, 53 possibly leading to an increased GERD prevalence. In addition, the dietary fat intake has increased markedly in Japan. 53 The incidence of obesity is also increasing in Asia, 54 and obesity is a known risk factor for GERD. 39 Further research is required to verify the effect of a Western diet and way of life on GERD prevalence, possibly in Asians who have moved to Western countries. Nevertheless, these data suggest that the prevalence of GERD in Asia is likely to increase further in the future. The increasing awareness and recognition of GERD emphasizes the need for a global definition and a standardized symptom assessment of the disease. It also necessitates an increased level of recognition of the full spectrum of GERD by primary care physicians and gastroenterologists to ensure that patients are diagnosed and managed appropriately. Further research is needed to establish the wider prevalence of GERD in Asia, using representative study populations and a standardized, well-validated methodology. References 1. Goh K. Changing epidemiology of gastroesophageal reflux disease in the Asian-Pacific region: an overview. J Gastroenterol Hepatol 2004;19:S22 S Kang JY, Tay HH, Yap I, et al. Low frequency of endoscopic esophagitis in Asian patients. J Clin Gastroenterol 1993; 16: Fock KM, Talley N, Hunt R, et al. Report of the Asia-Pacific consensus on the management of gastroesophageal reflux disease. J Gastroenterol Hepatol 2004;19: Dent J, Brun J, Fendrick AM, et al, on behalf of the Genval Workshop Group. An evidence-based appraisal of reflux disease management the Genval Workshop Report. Gut 1999;44(Suppl 2):S1 S Hongo M, Nomura T. Modern perspectives on pathophysiology and treatment of gastroesophageal reflux disease. J Clin Exp Med 2001;198: Dent J, Armstrong D, Delaney B, et al. Symptom evaluation in reflux disease: workshop background, processes, terminology, recommendations, and discussion outputs. Gut 2004;53(Suppl 4):iv Ho KY. Gastroesophageal reflux disease is uncommon in Asia: evidence and possible explanations. World J Gastroenterol 1999; 5: Lim LG, Ho KY. Gastroesophageal reflux disease at the turn of millennium. World J Gastroenterol 2003;9: Dent J, El-Serag HB, Wallander MA, et al. Epidemiology of gastrooesophageal reflux disease: a systematic review. 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