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Gastroesophageal reflux disease (GERD) has been reported to be uncommon among Asians. Although prevalence rates of reflux esophagitis and symptoms of GERD in Asian patients vary, most of the recently published studies have shown an increasing trend, likely due to better awareness and diagnosis as well as to a true increase in the prevalence of the disease. The exact reasons for this increase in prevalence are unclear but must be linked in some way to the dramatic socioeconomic development taking place in the region. Changes in dietary patterns and body mass index have been suggested as underlying reasons. On the other hand the high prevalence of Helicobacter pylori infection in Asia and its association with decreased acid secretion and a low prevalence of GERD have also been noted. Another interesting observation is differing rates of GERD among different Asian ethnic groups, indicating a possible genetic susceptibility to GERD. Diagnosis of GERD is usually based on symptoms; many Asian patients, however, do not understand the term “heartburn,” as there is no equivalent term in the major Asian languages. Patients therefore describe their symptoms variously, such as chest discomfort or wind and soreness in the chest. Nonerosive reflux disease appears to be common among Asians. Atypical manifestations of GERD, including noncardiac chest pain, asthma, and laryngitis, appear to be common among Asian patients as well.
Gastroesophageal reflux disease (GERD) has long been thought to be uncommon among Asians.1 The first published report on GERD in Asia to appear in English, in 1993, reported a very low frequency of esophagitis.2 More and better designed studies have now been carried out, giving us a clearer understanding of what appears to be an emerging disease in Asia.
Endoscopy-based studies give the most objective evidence of GERD and comprise the earliest studies on the disease in Asia. These studies are summarized in Table 1.2-13 The early studies reported a low prevalence of reflux esophagitis (RE). Kang and colleagues2 in a retrospective survey of 11,943 patients undergoing gastroscopy for various indications, reported a rate of 3.3%. A 1997 prospective endoscopy survey by Goh3 focusing primarily on the prevalence of Helicobacter pylori in dyspeptic patients reported a very low prevalence of 0.9%. Two studies from Taiwan published in 1997 gave contrasting prevalence rates of RE of 5% and 14.5%.4,5 Better standardization of the diagnosis of RE has come about with the wider use of the Los Angeles classification.14 Recent studies using this classification have generally confirmed a higher prevalence of RE than previously believed. Large prospective surveys in Japan reported a prevalence of RE of 13.8–16.3%.7,9,10 Rosaida and Goh11 from Malaysia found a prevalence of 13.4%. However, in a very large review of 22,628 computerized records of esophagogastroduodenoscopies (EGDs) in their center in Hong Kong, Wong and colleagues8 found the rate of RE to be 3.8%; similarly, Wai and associates12 recorded a prevalence of 5% in a large review of EGDs in Singapore. In general, prospective studies that have been designed to specifically study RE have found higher prevalence rates compared to retrospective reviews of endoscopy records.
Not all studies have reported on the severity of esophagitis, complications, or the presence of hiatus hernia and Barrett’s esophagus. The severity of RE in various Asian studies are shown in Table 2. Although RE is predominantly of the milder grades, the finding in two studies of up to 20% of patients having grade C or D esophagitis is quite alarming. Strictures were, however, uncommonly reported. No patients with strictures were reported by Rosaida and Goh,11 and in the study by Wong et al,8 strictures were found in only 14 patients (0.08%). Hiatus hernia has been shown to have a close association with RE. In the study by Kang and Ho,15 hiatus hernia was found in 5% of the Asian patients (compared to 24% in the comparative English population). In the Rosaida and Goh study,11 hiatus hernia was found in 6.7% of patients, and the odds ratio of RE in the presence of hiatus hernia was 10.23 (95% confidence interval: 5.59–18.82).
The findings of Barrett’s esophagus have been clouded by the variability in the definition used over the years. In earlier studies, diagnosis was made based purely on endoscopic findings.5,15 More recent published studies have used histologic demonstration of specialized intestinal metaplasia for the diagnosis of Barrett’s esophagus.8,11 Wong and coworkers8 in Hong Kong reported a prevalence of only 0.06%, while Rosaida and Goh11 reported a prevalence of 2% among dyspeptic Malaysian patients. Two large prospective studies from Japan reported rates of 0.9–1.2%.16 In contrast, Rajendra et al,13 in another study from Malaysia, reported a dramatically high prevalence of Barrett’s metaplasia of 6.2% among patients who had undergone endoscopy for dyspeptic and reflux symptoms, which, if confirmed by other studies from the same area, would certainly give rise to great concern.
Although the presence of RE provides the most objective evidence of GERD, methodological problems arise with reports of RE. These include differences in systems of classification and grading, differences in the population studied (all patients endoscoped vs healthy subjects vs dyspeptic patients), and whether the studies were prospective or retrospective or whether they were planned to look for RE by designated investigators or merely a review of endoscopy records.
There have been fewer population- or community-based studies, compared with endoscopy studies, reported from the Asian-Pacific region (Table 3).17-24 In a community survey, Ho and colleagues17 noted frequent reflux symptoms, defined as heartburn or acid regurgitation occurring more than once per month, in 1.6% of patients. In a second study, Ho et al18 reported a prevalence of heartburn of 4.6% over a 1-year period. Further subanalysis showed that only 2.1% of respondents reported symptoms of at least once per month. Pan and associates,19 using cluster sampling and a GERD symptom scoring system in a study of residents in Shanghai and Beijing, reported a prevalence of 9%, similar to the prevalence of heartburn occurring at least once per month (8.9%) noted by Wong and coworkers,20 also in a Chinese population. In a recent study, Rajendra and Alahuddin21 reported a monthly prevalence of heartburn among Malaysian patients of 9.7% and weekly symptoms of 6%. Two recently published studies from Japan and China show a high prevalence of GERD symptoms—12.8% and 17%, respectively.22,23 By contrast, Cho and coworkers,24 in a well-conducted survey in a farming/city district in South Korea, recorded a prevalence of reflux symptoms of only 4.7%.
While symptoms of predominant heartburn and acid regurgitation are considered to be predictive of GERD,25 this does not exclude other upper gastrointestinal disease. In a study from Hong Kong, a significant proportion—18% (82 of 460)—of patients with typical reflux symptoms who had undergone EGD were found to have concomitant peptic ulcer disease.26 The authors concluded that empirical treatment based on reflux symptoms was therefore not appropriate. Reflux symptoms may be secondary to peptic ulcer disease in countries with a high prevalence of H. pylori gastritis.
Asia is a disparate geographical region with many different ethnic groups. In Malaysia, where three major Asian races coexist, significant differences have been observed in the prevalence of RE and nonerosive reflux disease (NERD).11 These observations are very interesting. RE is more common among Indians compared to the Chinese and Malays; however NERD is more common among both the Indians and Malays compared to the Chinese (Table 4). These ethnic differences suggest that genetic factors in addition to environmental factors may play a part in the pathogenesis of the disease. The genetic basis of GERD is supported by a recent paper by Rajendra and associates27 that shows a predominance of the HLA B7 subtype among Indians with Barrett’s esophagus in a subgroup of Malaysian patients.
There have been few studies looking at time trends of GERD. Ho and colleagues17 reported a prevalence of GERD symptoms of 1.6% in their original survey carried out in 1994. In a re-survey in 2001, the rate of heartburn was reported to have increased to 10.6%.28 A similar study by the same authors also showed a significant increase in the incidence of endoscopic esophagitis from 3.9% in 1992 to 9.8% in 2001 in Singapore.29 In our own study from Malaysia,30 the incidence of RE increased from 2.7% to 9.0% during the time period from 1991–1992 to 2000–2001. Interestingly, during the same time period there was a significant decrease in the prevalence of duodenal ulcer disease, from 24.3% to 10.4%. These changes mirror the experience that has already occurred in the West,31 and demonstrate a time-lag phenomenon with the Asian experience.
The exact reasons for the changes in disease prevalence are difficult to determine but reflect in general the dramatic socioeconomic development and consequent lifestyle changes that are rapidly taking place in Asia. For example, there have been changes in diet from a predominantly carbohydrate-based diet to one that contains more protein and fat, with a corresponding increase in the body mass index. Genetic predisposition to GERD among different ethnic groups would mean that such an increase would be more prominent among certain racial groups.28 The high rate of H. pylori infection in Asia with consequent lowered acid secretion has been postulated as a reason for the low prevalence of GERD in the region.1 Studies from Japan have provided the most persuasive evidence for this hypothesis. Japan has overall a high rate of H. pylori infection and atrophic gastritis. Shirota et al32 showed that the prevalence of H. pylori was lower in patients with RE. Other studies have also shown an inverse correlation between the severity of RE and H. pylori infection.33 Hamada and colleagues demonstrated a high incidence of RE after H. pylori eradication, especially in patients who had corpus gastritis and a predisposition to reflux hiatus hernia.34 Previous studies from the same group showed an increase in gastric acidity following H. pylori eradication in patients with atrophic gastritis35 and in an animal experiment postulated that ammonia produced by H. pylori infection protects against esophagitis.36
Heartburn, the cardinal symptom of GERD, is well recognized in the West; however, the situation is distinctly different in our part of the world. For example, there is no word in the Chinese vernacular language to describe this symptom. Spechler and coworkers,37 in a survey of outpatients attending clinics in the Boston area, discovered that the majority of patients of East Asian origin did not understand the symptom of heartburn. Doctors (or interviewers carrying out population surveys) will be better served if they explain in words what they mean by heartburn and acid regurgitation rather than assuming that the patient or respondent understands these terms. In Malaysia, many Chinese and Malay patients complain of “wind” with reference to dyspepsia and reflux symptoms as an all encompassing term. To clarify the situation, researchers from Hong Kong have come out with a simple, locally validated GERD questionnaire,38 which has been recommended for use in routine clinical practice.
The concept of NERD has gained wider acceptance among doctors in recent years, and its definition and natural history have been clarified.41 Patients with NERD obviously are not exposed to the complications of RE, however, they do not necessarily suffer from milder symptoms.
In the Western population, NERD has been reported in more than 50% of the population.42 The first study specifically looking at the prevalence of NERD in the Asia-Pacific region has recently been published. Rosaida and Goh11 found in a carefully studied prospective study in a multiracial Asian population that 65.5% of their patients had NERD. In another endoscopy study of patients with typical reflux symptoms, a subanalysis of data showed that 215 of 460 patients (46.7%) without RE changes would be deemed to have NERD.25 In a survey of medical practitioners, respondents reported that they diagnosed NERD in more than 50% of their patients with GERD.43
There have been few studies done in Asia looking at atypical and extraesophageal manifestations of GERD. Lau and colleagues44 reported a prevalence rate of GERD of 30% using prolonged pH monitoring while Ho and colleagues39 reported a 40% rate using a battery of tests including pH monitoring, acid perfusion tests, and manometry. In a population-based telephone survey done in Hong Kong, Wong and coworkers40 found the prevalence of GERD in patients with noncardiac chest pain to be 51%.
In a hospital-based study from Thailand, 57% of asthmatic patients also experienced symptoms of GERD.45 GERD symptoms were reported in 19.1% of 141 consecutive patients attending an asthma clinic in Malaysia.46 An earlier report from the same center detected a prevalence rate of 56.7% for GERD using pH monitoring, a symptom questionnaire, and endoscopy in patients with difficult-to-control asthma.47 In a study from India, 74.3% of asthmatics screened gave a history of GERD48 while in a detailed study from Taiwan, 51% of asthmatic patients were found to have gastroesophageal reflux on pH monitoring and 41.1% showed ineffective esophageal motility on manometry.49
Ear, nose, and throat symptoms are also common extraesophageal manifestations of GERD. In a study from the West, GERD was diagnosed in 60% of patients with posterior laryngitis using 24-hour esophageal pH testing.50 There have been no full published reports regarding the relationship between chronic laryngitis and GERD in Asian patients; however, two studies have recently been presented and published in abstract form. Qua et al51 studied a group of Malaysian patients who had chronic idiopathic laryngitis and found, using a clinical symptom questionnaire, endoscopy, and 24-hour esophageal pH testing, that 65.6% of them had GERD. A study from the Philippines using prolonged pH monitoring found that 52.6% of patients with chronic laryngitis had abnormal acid reflux although they were asymptomatic.52
Atypical or extraesophageal manifestations of GERD appear to be common in Asian patients and should be recognized and treated appropriately in clinical practice.
GERD is clearly an emerging disease in Asia. Although NERD is by far the most common form of GERD in Asia, the incidence of RE is increasing among certain populations and ethnic groups. Complicated GERD, particularly Barrett’s esophagitis, is still uncommon, while atypical manifestations of GERD, including asthma, chronic laryngitis, and noncardiac chest pain, are increasingly diagnosed. Rapid socioeconomic development and the westernization of Asian lifestyles, including changes in diet and an increase in average body mass index, are likely key factors in this changing epidemiology.