Setting, sampling and study design

As previously described [9], 18 000 residents of China aged 18-80 years were selected randomly using a stratified, multi-stage sampling methodology. Urban and rural populations, which have distinct socioeconomic characteristics (Additional File 1), were sampled in a ratio of 1:1 (n = 1800 from each stratum in each region) in proportion to the overall age and sex distribution of each region.

All respondents completed a survey consisting of a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire (RDQ) [7]. A random sub-sample of 20% of the respondents in each region was asked to undergo a physical examination that included measurement of weight, height, and waist and hip circumference. The residents of Shanghai were also invited to undergo endoscopy, the results of which are described elsewhere [10, 11].

The general information questionnaire collected self-reported information on age, height, weight, sex, marital status, education, income, occupation, lifestyle habits, health status, family history of gastrointestinal diseases, and medical history (current and previous medical problems and related treatment).

The RDQ was used to determine the frequency and severity of heartburn (defined as 'burning behind the breastbone' and/or 'pain behind the breastbone') and regurgitation (defined as 'acid taste in the mouth' and/or 'unpleasant movement of materials upwards from the stomach') during a 1-month recall period. The frequency and severity of each RDQ item are scored on a 6-point Likert scale (0-5; where 0 is no symptoms, 1 is symptoms on less than 1 day a week or very mild symptoms, and 5 is daily or severe symptoms) (Additional File 2). The validity and reliability of the RDQ as a diagnostic tool has been previously demonstrated [12]. The Chinese version of the RDQ used in the present study underwent extensive linguistic validation including forward and backward translation, cognitive debriefing of patients with GERD, and expert input from gastroenterologists. The pilot study showed that a version with a 1-week recall period had credible reliability and construct validity [7]. Applying the Montreal Definition, symptom-defined GERD was defined as mild symptoms of heartburn and/or regurgitation occurring on at least 2 days a week (a frequency score ≥3 and a severity score of ≥2 for any of the relevant symptoms), or moderate-to-severe symptoms of heartburn and/or regurgitation occurring on at least 1 day a week (a frequency score ≥2 and a severity score ≥3 for any of the relevant symptoms).

Participants filled out the questionnaires themselves, either in local residential committee offices or in their own home, with trained and supervised facilitators available to explain any questions that were unclear. Informed consent was obtained, and individuals were free to discontinue their participation in the study at any time. The study was approved by the Ethics Committee of the Second Military Medical University, Shanghai, China.

Data collection and analysis

Data were collected and validated as previously described, with the SAS 9.1.3 program (SAS Institute, Cary, NC, USA) used to complete data analyses [9]. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by univariate and multivariate logistic regression in order to examine factors that are potentially associated with symptom-defined GERD. The Cochran-Armitage test was used for trend testing and the Cochran-Mantel-Haenszel test was used to compare the baseline characteristics of respondents in the different study centres.

Response rate and sample characteristics

In total, 16 091 individuals completed the survey (a response rate of 89.4%) and 16 078 responses (99.9%) were suitable for analysis. In the 20% sub-sample, the response rate was 89.4% and 3214 responses were suitable for analysis (99.8%). The mean (SD) age of participants in the total study sample was 42.5 (15.2) years; 52.2% of participants were female. Body mass index (BMI) ranged from 11.8 kg/m² to 41.0 kg/m², with a mean (SD) of 22.6 kg/m² (3.3). The majority of participants reported that they did not drink alcohol (79.7%) or smoke cigarettes (69.9%). The baseline characteristics of each study centre are detailed in Additional File 3. Approximately half of all respondents lived in the rural areas of each of the studied provinces.

Prevalence of reflux symptoms

Most reflux symptoms were experienced less often than 1 day a week, and most were very mild in severity (Figures 1a and 1b).

Prevalence of GERD

The prevalence of symptom-defined GERD was 3.1% overall (2.4% in urban areas and 3.8% in rural areas), and varied among the five regions studied, from 1.7% in Guangzhou to 5.1% in Wuhan (Table 3). The prevalence of symptom-defined GERD in the 20% sub-sample was 3.4%.

Factors associated with the presence of GERD

When separated into individuals who reported heartburn of any frequency or severity (n = 638) and those who reported regurgitation of any frequency or severity (n = 1738), a number of differences were found in the factors associated with regurgitation and heartburn. Alcohol consumption was significantly associated with the presence of regurgitation (OR: 1.34; 95% CI: 1.15-1.55) but not heartburn (OR: 1.15; 95% CI: 0.91-1.45). Conversely, a BMI of ≥27.5 kg/m² was significantly associated with the presence of heartburn (OR: 1.47; 95% CI: 1.14-1.91) but not regurgitation (OR: 1.10; 95% CI: 0.92-1.33). Compared with participants aged 30-39 years, those aged 70-80 years had a significantly higher risk of heartburn (OR: 1.45; 95% CI: 1.02-2.07) but a significantly lower risk of regurgitation (OR: 0.70; 95% CI: 0.55-0.90). Living in a rural area, decreasing health status and a family history of gastrointestinal disease were associated with a significant increase in the risk of both heartburn and regurgitation (data not shown).

The presence of symptom-defined GERD was associated with a self-reported history of dyspepsia (OR: 2.81; 95% CI: 2.20-3.59), dysphagia (OR: 4.56; 95% CI: 2.30-9.04), gastritis (OR: 3.06; 95% CI: 2.46-3.81) or peptic ulcer disease (OR: 2.05; 95% CI: 1.52-2.76). There was no significant association between GERD and self-reported irritable bowel syndrome (OR: 0.53; 95% CI: 0.12-2.42). Self-reported joint disorders (OR: 2.03; 95% CI: 1.58-2.61) and chronic cough (OR: 2.14; 95% CI: 1.39-3.28) were associated with GERD, whereas asthma (OR: 0.87; 95% CI: 0.39-1.94), hoarseness (OR: 0.76; 95% CI: 0.38-1.55) and non-cardiac chest pain (OR: 1.54; 95% CI: 0.72-3.31) were not.

Factors associated with GERD

The factors most strongly associated with symptom-defined GERD were declining self-reported health status and a family history of gastrointestinal disease. Self-reported health status is known to be an accurate predictor of morbidity and mortality in China and other Asian populations as well as worldwide [24, 25], and the association we observed may reflect the burden of symptoms and comorbidity in individuals with GERD. An association of GERD with a relevant family history has been seen in previous studies [5, 26], and the results of twin studies in Sweden and the UK have also provided evidence of a genetic component to the disease [27–29]. In support of this genetic association, a recent study found an association between GERD and the gene encoding collagen type III alpha 1 (COL3A1) [30].

We also found that individuals living in a rural area had a higher risk of GERD than those living in an urban area. The reasons for this are unclear, and previous studies in China do not provide consistent support for this association. Pan et al. found that GERD was more common in rural than urban areas in Beijing (12.5% vs 8.6%) but that the reverse was true in Shanghai (7.0% vs 8.6%) [20]. Wang et al. found that GERD was more common in urban (21.1%) than rural (17.4%) areas of Xi'an [16].

The current study found a significant association between obesity and heartburn, but not between obesity and symptom-defined GERD; however, the pilot study using a less stringent definition of GERD did find a positive association with obesity [6]. Previous population-based studies that looked at the association of GERD with BMI in China have also reported inconsistent results [6, 14–20]. This contrasts with the increasingly clear association between GERD and obesity that has been found in Western countries, particularly in the USA [31–34]. It is possible that this reflects differences in the prevalence of other etiological factors such as hiatus hernia or perhaps the low prevalence of obesity in China.

Association of GERD with self-reported medical history

The current results support an association of GERD with a history of peptic ulcer disease [16, 35–37], but do not support associations seen in Europe between GERD and irritable bowel syndrome or asthma [36, 38, 39] or a protective effect for gastritis against GERD [40]. It is, however, important to distinguish between objectively demonstrated gastritis and the patient-reported history of gastritis that is reported in the present study. In Asian countries 'gastritis' commonly denotes upper gastrointestinal discomfort and a diagnosis is unlikely to be based on endoscopic biopsy or serum pepsinogen measurement. GERD was associated with chronic cough in our study, supporting the established association with this extraesophageal syndrome [1].

The association we found between joint disorders (rheumatoid arthritis and osteoarthritis) and GERD may reflect the use of non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief in this population [41].

Strengths and limitations

This large, population-based, epidemiological study provides high-quality data on the prevalence of GERD in five geographically diverse regions of China. Key strengths are the large sample size, the use of a validated symptom questionnaire and survey methodology, and also the use of a symptom-based definition of GERD that was built on global consensus. Importantly, the population sampling and survey administration methods achieved a high response rate (89.4%) that minimized the potential for responder bias and generated representative adult population samples [9]. In addition, by gathering data on treatment history, it was possible to gain insight into how existing treatment of GERD may affect prevalence data.

Samples sizes were equal for rural and urban populations and for each population region, and were not weighted in proportion to the actual population size. However, available data indicate that the mean ratio of urban to rural people for all five study regions was approximately 0.81:1, ranging from 0.71:1 (in Wuhan) to 0.98:1 (in Beijing) [9] and in China overall this ratio was approximately 0.82:1 in 2007 [42]. Therefore we consider the urban and rural strata in this study to be sufficiently representative of the five study regions.

Language barriers and cultural differences are inevitable study limitations, although every effort was made to overcome these through the survey administration techniques and the linguistic validation of questionnaires [9]. Another potential limitation is that the medical history of participants was self-reported, although it should be noted that it is standard practice in China for patients to keep their own medical records which may reduce the impact of this limitation.

Further study

Further investigation into potential risk factors and comorbidities associated with GERD is warranted, ideally in relation to incident cases of GERD. Ascertaining details of the drug treatments used by participants for diagnosed conditions would be of value in future studies, particularly use of NSAIDs, acetylsalicylic acid, traditional herbal remedies and treatments for GERD. Further research is needed to clarify whether the prevalence of GERD is increasing in China, and the factors that may be associated with such an increase.