Keywords

Introduction

Gastroesophageal reflux disease (GERD) is one of the most commonly encountered gastrointestinal disease in the world. GERD is a spectrum of disease which includes symptoms like heartburn or regurgitation to complications like erosive esophagitis, Barrett’s esophagus, and related neoplasia. GERD is a condition which develops when the reflux of the stomach contents causes troublesome symptoms and/or complication, as per Montreal definition of GERD [1]. GERD affects 10–20% of the adult population in the USA and Europe [1]. These figures are likely an underestimate of its true prevalence, since many patients self-medicate and/or do not seek medical advice. GERD is often perceived as a Western disease due to limited literature among the Asian population. The reported population prevalence of GERD in Eastern Asia ranges from 2.5 to 6.7% [2].

In the last decade, the Asia-Pacific region has carried out active research in GERD. Increasing incidence of GERD has been noted among various Asian countries in the last 10 years. The aim of this chapter, therefore, is to review the epidemiologic studies of GERD in Asia, including those of erosive esophagitis, and to provide a realistic understanding of the change of prevalence of GERD over time.

History of GERD in Asia

The regions of Asia include: Eastern (China, Japan, Korea, and Taiwan), Southeastern (Malaysia, Singapore, and Thailand), South Central (India, Iran, Pakistan, and Bangladesh) and Western (Israel and Turkey). The first report in the published English medical literature on GERD was by Kang and colleagues in 1993 [2]. Prior to that, in the late 1970s, two reports from Taiwan mentioned the presence of esophagitis among patients who had undergone gastroscopy [3, 4]. In 2005, Dent and colleagues estimated that the prevalence of GERD was 10–20% in Western countries and approximately 5% in Asia, in a systematic review of studies that defined GERD as symptoms of heartburn and/or regurgitation occurring on at least 1 day per week [1]. Similarly, in another systematic review, the prevalence of GERD in Asia was estimated to range between 2.5 and 6.7% [5]. However, recently many studies from Asia have shown an increasing trend in the prevalence of GERD. There are substantial differences in GERD prevalence among Asian regions. The prevalence is highest in West Asia (12.5–27.6%), less so in Central Asia (7.6–19.4%), and lowest in East Asia (2.5–9.4%) [7].

Measuring the Burden of GERD

The exact burden of GERD is difficult to measure, as endoscopy only measures erosive esophagitis. The true prevalence of GERD in the community with questionnaire or direct questioning will also provide vital information in estimating the prevalence, as a large number of people who suffer from GERD do not visit a physician for this complaint. There are also some language and cultural differences in symptom interpretation such as the lack of the exact word for heartburn in some Asian languages, making it difficult to accurately estimate the prevalence of GERD in these populations. For example, in Korean, Malay, and Chinese, there is no direct word describing the symptom, and a survey in the USA revealed that only 13.2% of East Asian patients understood the term [6]. There are only a few population-based studies from Asia that have used the Montreal definition or definitions that are close to it.

Prevalence of GERD: Symptom-Based Studies

Eastern Asia (China, Japan, Korea, and Taiwan)

In Eastern Asia, various large-scale population studies have been conducted. The prevalence of GERD was estimated between 6.6 and 20.7% among various populations. In a cross-sectional study by Fukujima et al., the prevalence of GERD was estimated at 6.6% among patients who visited physicians for a routine physical exam. In another survey of 1076 patients who presented with epigastric symptoms between April and August 2007 at 55 institutions in Japan, the prevalence of GERD was estimated at 15.6%, and in another study of 160,973 adults who presented for screening of gastric carcinoma and reported abdominal pain, the prevalence of GERD was between 15.8 and 20.7% [7,8,9].

The prevalence of GERD in China is estimated to be between 1.7 and 7.3%. The largest population-based study among 16,091 subjects by He et al., based on self-reported questionnaire, estimated the prevalence of GERD as 3.1%, varying between 1.7 and 5.1% in different regions [10]. Li et al., in a survey of more than 15, 000 outpatients attending hospitals in Zhejiang province, China, recorded a prevalence of 7.3% [11]. The prevalence of GERD in Shanghai (Weng et al.) and South China (Chen et al.) based on population-based studies was approximately 6.2% [12,13,14]. The prevalence was even lower in Hong Kong, where the prevalence rates of GERD, as estimated by telephonic interviews, were between 0.25 and 4.8% [15, 16].

The prevalence of GERD in South Korea was estimated to be similar to the Western countries at 7.1%, based on telephone interviews among the general population. Based on another population-based study [17] and telephone survey [18] in Korea, its prevalence was estimated at 3.5 and 8.5%, respectively. In Taiwan, using a modified GERD questionnaire, Lu et al. recorded prevalence of 6.6% as once-weekly symptoms [19]. A recent review of changing GERD trends showed that prevalence of symptom-based GERD in Eastern Asia was 5.2–8.5% [4,5,6,7,8,9, 20, 21] from 2005 to 2010, whereas it was 2.5–4.8% [11, 13, 14] before 2005. However, it has stricter criteria for GERD definition for inclusion of the studies.

Southeastern Asia (Malaysia, Singapore, and Thailand)

In Singapore, Ho et al. showed the highest prevalence among Indians (7.5%) and Malays (3%) [22]. In another study that surveyed the same cohort in 1994 and in 1999, the prevalence of GERD was 5.5% ± 1.5% initially, but increased to 10.5% ± 2.0% after 5 years [23]. In Malaysia, Rajendra and Alahuddin in 2004 showed symptomatic prevalence of 9.7% based on patients having monthly symptoms [24]. In Thailand, a study by the Thai motility club (using questionnaire) reported a 7.4% prevalence of GERD in community (unpublished data) (esophagitis 4–6%) [26].

South Central Asia (India, Iran, Pakistan, and Bangladesh)

Most studies in South Central Asia were conducted in Iran. The prevalence of GERD in Iran was 6.3–18.3% from 2005 to 2010, and higher than in Eastern Asia [25,26,27]. The prevalence of GERD in Bangladesh ranged from 5.3 to 19.4% [28, 29]. Jafri et al. reported a prevalence of 24% in Pakistan in 2005 [30]. The prevalence of GERD in India was estimated at 7.6% in a large prospective multicenter study involving 12 centers and 3224 subjects in 2011 [31]. The prevalence of GERD in other questionnaire-based cross-sectional studies ranged between 10.6 and 18.7% [32,33,34].

West Asia (Israel and Turkey)

The prevalence of GERD in West Asia was found to be the highest in all of Asia. The prevalence was found to be 20–27.6% in Turkey [35,36,37]. However, the symptom profile of the Turkish people was said to differ considerably; they have a relatively lower occurrence of heartburn and a higher incidence of regurgitation and dyspepsia. In Israel, Moshkowitz et al. reported prevalence of 12.5% of GERD symptoms [38]. Another population-based study in 2007 also reported a high prevalence of GERD symptoms, including retrosternal burning in 6.5%, retrosternal pain in 5.2%, acid taste in the mouth in 10.4%, and reflux of gastric contents in 7.9% of subjects [39]. Prevalence of GERD in population-based studies is higher in Central and West Asia than in East Asia [38].

Selected studies highlighting the prevalence of reflux symptoms in Asia after year 2000

Study, year [reference]

Country

Method

Sample size

Prevalence of reflux symptoms (%)

Daily/at least weekly/at least monthly/at least yearly

Eastern Asia

Stanghellini 1999 [21]

Japan (part of international study

Digest

500

Prevalence of 9.8% for heartburn and of 3.6% for regurgitation

Random house-to-house recruitment

Fujiwara et al. 2005 [7]

Kansai, Japan

Questionnaire

6035 (clinic based)

Prevalence of 12.8% (> 2 per month)

He et al. 2010 [10]

China

Self-reported questionnaires

16,091

At least weekly, 5.2%; at least twice a week, 3.1% (2.4% in urban and 3.8% in rural area)

Pan et al. 2000 [40]

China

Assisted self-completed questionnaire (GERQ)

4992

HB 2.5/HB 3.1/HB 7.0

Hu et al. 2002

China

Telephone interview (bowel symptom questionnaire)

2640

4.8

Wong et al. 2003 [16]

China

Telephone interview (GERQ)

3605

2.5/8.9/29.8

Cho et al. 2005 [17]

Korea

Face-to-face interview (GERQ)

1902

GERD 3.5/HB 4.7/AR 4.4

2.0/AR 2.0

Fujiwara et al. 2005 [7]

Japan

Face-to-face interview

6035

2.1/6.6/19.4/44.1

Western & Southern Asia

Bor et al. 2005 [35]

Turkey

Face-to-face interview (GERQ)

630

4.9/GERD 20/HB GERD 37.6/HB 10/AR 15.6, 15.9/AR 32.7 9, AR 32.7

Nouraie et al. 2007

Iran

Face-to-face interview

2561

GERD 21.2/HB 12.2/AR 16.8

Pourshams et al. 2007

Iran

Face-to-face interview

1000

12.3

Sperber et al. 2007 [39]

Israel

Telephone interview (RDQ)

1221

0.3/9.3

Bhatia et al. 2011 [85]

India

Questionnaire

3224

Heartburn 2.7/3.2/12.7

Regurgitation 2.0/2.3/9.2

  1. GERQ gastroesophageal reflux questionnaire, HB heartburn, AR acid regurgitation, RDQ reflux disease questionnaire

Prevalence of Esophagitis

Most endoscopy-based studies were conducted on subjects with upper gastrointestinal symptoms in tertiary care hospitals.

Eastern Asia (China, Japan, Korea, and Taiwan)

Using the Los Angeles classification, the prevalence was estimated between 6.6 and 15.0% [41,42,43,44,45] from nine studies between 2000 and 2005 and 4.3–15.7% [46,47,48,49] after 2005. Several studies were conducted in retrospective manner and may have under- or overestimated the exact prevalence of endoscopic reflux esophagitis. SILC study, [50] a population-based endoscopy study conducted in China, showed symptomatic GERD to be more prevalent among patients who agreed to endoscopy (4.7% vs. 1.7%). Among patients who underwent endoscopy, the prevalence of erosive esophagitis was 6.4% (Los Angeles grade A 4.1%, grade B 2.1%, grade C 0.2%, and grade D 0%, respectively). Erosive esophagitis was also more prevalent among patients with symptomatic GERD (12.5% vs. 6.1%).

Southeastern Asia (Malaysia, Singapore, and Thailand)

In Malaysia, the prevalence of erosive esophagitis was estimated at 13.4% among 1000 patients with upper abdominal discomfort [51]. Similarly, Rajendra et al. showed prevalence of erosive esophagitis as 6.1% in 1985 patients with abdominal discomfort or reflux [52]. In Singapore, several studies showed prevalence of reflux esophagitis between 5 and 6.9% [53, 52].

Western Asia (Israel and Turkey)

In Saudi Arabia, Al-Humayed et al. reported a prevalence of 15% in 1607 patients who underwent endoscopy for evaluation of dyspepsia [54]. A retrospective analysis of 18,766 endoscopies by Yilmaz et al. in Turkey between 1996 and 2001 reported prevalence of erosive esophagitis as 12.8% [54].

Prevalence of Extra-Esophageal Syndromes

Extra-esophageal syndromes include respiratory symptoms, such as chronic cough, asthma, or laryngitis, dental erosions, noncardiac chest pain (NCCP), and sleep disturbance [55]. In a study by Shimizu et al. [56], the proportion of endoscopic reflux esophagitis in patients with asthma was higher than in controls (39.3% vs. 0.6%). The proportion of sleep dysfunction was 52.5–56.6% among the patients with GERD [57,58,59]. In tertiary hospitals in China, dental erosions were found in 64.5% among patients with frequent reflux symptoms (three to five times per week), 44.4% among subjects with occasional symptoms (one to two times per week), and 36.7% among controls (p < 0.05) [60]. The prevalence of GERD among patients with NCCP was 66.7% and 20%, respectively, in Malaysia [61] and Turkey [35].

Selected Studies Highlighting the Prevalence of Erosive Esophagitis in Asia

Study, year [reference]

Country

Target population

Sample size

Prevalence of esophagitis (%)

Southern Asia

Khuroo et al., 1989

India

Patients with dyspepsia

239

5.60

Nasseri-Moghaddam et al., 2003

Iran

Patients with dyspepsia referred for upper endoscopy

269

76.90

Southeastern Asia

Kang et al., 1993 [2]

Singapore

Patients with upper GI symptoms (inpatients and outpatients)

11,943

4.50

Rosaida et al., 2004 [51]

Malaysia

Patients with upper abdominal discomfort

1000

13.40

Eastern Asia

Yeh et al., 1997 [62]

Taiwan

Patients with upper GI symptoms (heartburn, regurgitation, epigastric pain, and GI bleeding)

464

14.50

Yeom et al., 1999

Korea

Patients with GI tract symptoms

1010

5.30

Furukawa et al., 1999 [63]

Japan

Patients requiring routine physical examinations

6010

16.30

Inamori et al., 2003 [64]

Japan

First time endoscopy in patients with heartburn, dyspepsia, noncardiac chest pain

392

13.80

Western Asia

Turkey

Patients with dyspepsia referred for upper endoscopy

395

15.40

Toruner et al., 2004

Prevalence of Barrett’s Esophagus

Barrett’s esophagus is histologically confirmed by specialized intestinal metaplasia in biopsies from a columnar-lined distal esophagus. Epidemiologic studies have consistently reported that the prevalence of Barrett’s esophagus-associated adenocarcinoma is very rare in Asia [65, 66]. Among 19,812 consecutive Chinese patients undergoing upper endoscopy for routine health examination between June 2003 and December 2006, Barrett’s esophagus (BE) was confirmed only in 0.06% [45]. In another large Korean retrospective analysis of 70,103 patients undergoing upper endoscopy, 1% had suspected CLE. Of these patients, BE was histologically confirmed in 0.22% [67]. In the earliest study on Barrett’s esophagus from Asia confirmed on histopathology, Yeh et al. reported a prevalence of 2% [65].

The prevalence of Barrett’s esophagus was reported between 0.3 and 2% [62, 68,69,70,71,72,73] in tertiary hospitals from various regions of Asia. Recent large studies from Korea and Taiwan have yielded prevalence rates of 0.01 and 0.03% for LSBE and 0.14 and 2.4% for SSBE, respectively [45, 67]. In India, Amarapukar et al. showed prevalence of 2.6% [74]. It has been commented previously that Japanese studies report a higher prevalence of Barrett’s owing to a different definition of the gastroesophageal junction [73].

Changing GERD Trends in Asia

The prevalence rates of both GERD symptoms and erosive esophagitis in a majority of recent reports have, in general, been higher than in earlier studies. This may be due to better diagnosis and recording of cases, but consistently higher rates from many centers in Asia are more likely to reflect a true increase in the prevalence of GERD.

A recent survey of 221 gastroenterologists, 205 primary care physicians, and 159 otolaryngologists across seven nations in Asia revealed that most (gastroenterologists, 90%; primary care physicians, 67%; otolaryngologists, 65%) perceive a rising occurrence of GERD [75]. Although there is a lack of longitudinal studies on the same source population to determine absolute change of GERD prevalence over time, recent reports from cross-sectional studies conducted across Asia indicate a general upward trend in the prevalence of GERD, [23, 43] with a rising proportion of patients presenting with reflux esophagitis [23, 43] and Barrett’s esophagus or metaplasia [43, 75].

In a longitudinal five-year follow-up study looking at reflux symptoms, Lim et al. from Singapore reported a rise in the prevalence of reflux symptoms from 1.6 to 9.9% [23]. In another study from a small town in Western Japan over a 6-year period, 15.4% of GERD cases were identified as new cases [76]. More studies on changes in prevalence of reflux esophagitis with time have been carried out. Ho et al. from Singapore tracked the prevalence of esophagitis in their endoscopy records over a nine-year period and recorded an increase from 3.9 to 9.8% [53]. A study of 23,870 upper gastrointestinal endoscopies in a single Japanese center provides support for the Singapore results, showing the prevalence of reflux esophagitis increased from 0.8% in 1975–1977 to 2.3% in 1995–1997 [77].

Cross-sectional studies in Asia have also shown rising prevalence of GERD. In Korea, a study around 2005–2007 showed a GERD prevalence of 8.2% based on weekly symptoms of heartburn and/or acid regurgitation; this compares with the mere 3.5% based on the same criteria reported in a 2000–2001 study [17, 43]. Similarly, a 2003 study from South China estimated the prevalence of GERD based on weekly symptoms of heartburn and/or acid regurgitation at 6.2%, [12] in contrast to the modest 3.1% based on weekly heartburn reported by a study conducted in Beijing and Shanghai approximately a decade ago [78].

Erosive esophagitis prevalence has also shown a similar trend. The prevalence of endoscopic reflux esophagitis in Eastern Asia was 3.4–5.0% [77, 78] before 2000, and 6.6–15.0% [41,42,43,44,45] from 2000 to 2005. Japan witnessed an almost fivefold increase in the prevalence of esophagitis (latest figures are 13.8% of patients who underwent their first upper gastrointestinal endoscopy and 16.3% of patients on routine physical examinations) since the 1970s [63, 82].

Rising prevalence is also evident in Korea where the most recent (2004–2005) study reported finding reflux esophagitis in 18.8% of all dyspeptic patients undergoing EGD; [79] this is more than fivefold that reported a decade ago (3.4% during the period 1996–1998) [77] and is the highest esophagitis rate reported in Southeast and East Asia thus far.

On the heels of this rising trend are Malaysia and Taiwan, where esophagitis was seen in 13.4% (patients who underwent endoscopy) [51] and 14.5% (patients with upper gastrointestinal symptoms) [62]. The study, conducted at a single center in Malaysia, saw an almost fivefold increase within the decade encompassing the 1990s and early 2000s. On a smaller scale, the Philippines witnessed a twofold increase in esophagitis prevalence (6.3% vs. 2.9%, based on endoscopic diagnoses) within a span of approximately 10 years from 1992 [80]. However, despite the remarkable upsurge in prevalence, the esophagitis cases seen in the region remain largely mild; more than 80% of the cases in the above-mentioned Japanese and Malaysian studies were grade A type according to Los Angeles classification.

Why is GERD Increasing in Asia?

Most Asian patients have nonerosive GERD; erosive esophagitis is less commonly seen than in the Western population. Asians are known to be less predisposed to GERD than Caucasians due to their inherent smaller gastric parietal cell mass and lower acid output, low body mass index, lower obesity, lower consumption of alcohol, and probably also their traditional low-fat diet [81]. A high prevalence of H. pylori in Asia is also accounted as a reason for low GERD predisposition [53]. There is evidence to suggest that changing dynamics in various risk and protective factors contribute to both an increased incidence and severity of GERD in Asia. Despite these theories, the exact reason for the increasing trend in GERD in Asia is difficult to determine. This has been proposed as a result of interaction of environmental and genetic factors. The increase in prevalence occurring over a relatively short period of time (10–20 years) points to the predominant role of environmental factors. The growing affluence and socioeconomic development in Asia has resulted in consequent lifestyle changes. A change in diet and physical activity and an increase in BMI and obesity have often been thought to be putative. Also, life expectancy has now increased markedly, and a higher prevalence of GERD could also reflect the aging of the population.

Summary

There is evidence to suggest that changing dynamics in various risk and protective factors contribute to both an increased incidence and severity of GERD in Asia. It is therefore of utmost importance for both primary care physicians and specialists to increase vigilance for this emerging disease. General public awareness is required to facilitate early intervention for risk factors, more accurate diagnoses, and appropriate treatment. The development and validation of diagnostic questionnaires that are universally applicable in Asian countries of different ethnic and cultural origins are challenging tasks, but it is necessary to facilitate research into the epidemiology of GERD in Asia. Further studies are required to elucidate the clinical course of GERD and the time trend of its complications, such as Barrett’s esophagus and adenocarcinoma of the esophagus. Differences may also be attributed to referral patterns, diagnostic practices, and physician recognition.