The global burden of gastro-oesophageal reflux disease: more than just heartburn and regurgitation
Authors: Rami Sweis, Mark Fox
Journal: The Lancet. Gastroenterology & hepatology (2020)

Gastro-oesophageal reflux disease is a common condition caused by the reflux of stomach contents into the oesophagus, leading to uncomfortable symptoms and complications.1Hampel H Abraham NS El-Serag HB Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications.Ann Intern Med. 2005; 143: 199-211Crossref PubMed Scopus (896) Google Scholar, 2Eusebi LH Ratnakumaran R Yuan Y Solaymani-Dodaran M Bazzoli F Ford AC Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.Gut. 2018; 67: 430-440Crossref PubMed Scopus (220) Google Scholar The prevalence of this disorder is increasing and this increase has been linked to population ageing and the obesity epidemic worldwide.1Hampel H Abraham NS El-Serag HB Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications.Ann Intern Med. 2005; 143: 199-211Crossref PubMed Scopus (896) Google Scholar As these trends continue, especially in countries such as India and China, we need to consider their impact on the global burden of gastro-oesophageal reflux disease. In The Lancet Gastroenterology & Hepatology, the GBD 2017 Gastro-oesophageal Reflux Disease Collaborators used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and applied statistical tools that incorporate predictive covariates and adjustments for differences in study design to assess the global burden of gastro-oesophageal reflux disease.3GBD 2017 Gastro-oesophageal Reflux Disease CollaboratorsThe global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; (published online March 13.)https://doi.org/10.1016/S2468-1253(19)30408-XGoogle Scholar The global age-standardised prevalence of gastro-oesophageal reflux disease was stable over time, at 8791 (95% UI 7772–9834) cases per 100 000 population in 1990 and 8819 (7781–9863) cases per 100 000 population in 2017, and the disease was responsible for an estimated 0·7% (95% UI 0·4–1·1) of all years lived with disability globally in 2017. Furthermore, although the age-standardised prevalence appeared to be stable between 1990 and 2017, all-age prevalence increased by 18·1% between 1990 and 2017, while years lived with disability increased by 67·1% between 1990 and 2017, reflecting the increased prevalence in older age groups and population ageing over time. As with any such analysis, the results depend on the quality of data and assumptions made by the authors about the disease. In this study the prevalence of gastro-oesophageal reflux disease was defined by the presence or absence of typical reflux symptoms, specifically heartburn and acid regurgitation. However, there is an important difference between symptoms (which are based on a subjective description), and disease (diagnosis of which is based on objective evidence of reflux). Patients with typical symptoms and reflux oesophagitis or Barrett's oesophagus on endoscopy have gastro-oesophageal reflux disease; however, about half of patients with pathological acid exposure in the oesophagus do not have mucosal disease (ie, non-erosive reflux disease). Ambulatory reflux monitoring also identifies individuals with symptoms related to reflux events that have normal levels of acid exposure (reflux hypersensitivity). All three groups are classified as forms of gastro-oesophageal reflux disease; however, the same symptoms are reported by individuals with functional heartburn in whom there is no pathological reflux and no association of reflux events with symptoms.4Herregods TV Troelstra M Weijenborg PW Bredenoord AJ Smout AJ Patients with refractory reflux symptoms often do not have GERD.Neurogastroenterol Motil. 2015; 27: 1267-1273Crossref PubMed Scopus (61) Google Scholar, 5Gyawali CP Kahrilas PJ Savarino E et al.Modern diagnosis of GERD: the Lyon Consensus.Gut. 2018; 67: 1351-1362Crossref PubMed Scopus (576) Google Scholar Additionally, typical reflux symptoms can be reported by patients with other conditions including eosinophilic oesophagitis, motility disorders (eg, achalasia), and other functional disorders (eg, rumination). The prospective Diamond study showed that, for gastroenterologists, the sensitivity of symptom-based diagnosis of gastro-oesophageal reflux disease compared to objective pH studies was only 67%, and specificity was 70%, with no improvement if a validated questionnaire was applied.6Dent J Vakil N Jones R et al.Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond Study.Gut. 2010; 59: 714-721Crossref PubMed Scopus (219) Google Scholar Furthermore, symptom response to proton pump inhibitor therapy was neither sensitive nor specific to the diagnosis.6Dent J Vakil N Jones R et al.Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond Study.Gut. 2010; 59: 714-721Crossref PubMed Scopus (219) Google Scholar Conversely, not all patients with pathological acid exposure complain of typical symptoms. Up to a third of individuals with Barrett's oesophagus are asymptomatic, probably because metaplastic columnar mucosa has reduced sensitivity to acid.7Fox M Forgacs I Gastro-oesophageal reflux disease.BMJ. 2006; 332: 88-93Crossref PubMed Scopus (62) Google Scholar In other patients, gastro-oesophageal reflux disease presents with non-cardiac chest pain or laryngo-pharyngeal complaints (eg, chronic cough or hoarseness).7Fox M Forgacs I Gastro-oesophageal reflux disease.BMJ. 2006; 332: 88-93Crossref PubMed Scopus (62) Google Scholar, 8Heinrich H Sweis R The role of oesophageal physiological testing in the assessment of noncardiac chest pain.Ther Adv Chronic Dis. 2018; 9: 257-267Crossref PubMed Scopus (4) Google Scholar Atypical symptoms are less often triggered by reflux events (approximately 25% compared to approximately 50%). Nonetheless, excluding these presentations will systematically underestimate the burden of gastro-oesophageal reflux disease. These findings make it clear that clinical history and response to therapy are insufficient to identify this condition. An international working group published the Lyon Classification, an approach to diagnosis of gastro-oesophageal reflux disease that uses objective information from endoscopy and physiological investigation.5Gyawali CP Kahrilas PJ Savarino E et al.Modern diagnosis of GERD: the Lyon Consensus.Gut. 2018; 67: 1351-1362Crossref PubMed Scopus (576) Google Scholar Conclusive evidence for the diagnosis includes severe mucosal disease on endoscopy or oesophageal acid exposure time longer than 6% on ambulatory reflux studies (even where endoscopy is normal). When endoscopy and pH-impedance monitoring are inconclusive (ie, acid exposure time 4–6%), then supportive evidence including the presence of a positive reflux-symptom association or ineffective oesophageal motility on manometry add confidence to confirm or refute the diagnosis. The present study confirms that the prevalence of reflux symptoms increases with age;9Lee J Anggiansah A Anggiansah R Young A Wong T Fox M Effects of age on the gastroesophageal junction, esophageal motility, and reflux disease.Clin Gastroenterol Hepatol. 2007; 5: 1392-1398Summary Full Text Full Text PDF PubMed Scopus (133) Google Scholar however, age-standardised prevalence was stable over the past 25 years. This implies that the increase in obesity during this time has had no effect on the risk of gastro-oesophageal reflux disease, which seems unlikely in the face of consistent evidence to the contrary.1Hampel H Abraham NS El-Serag HB Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications.Ann Intern Med. 2005; 143: 199-211Crossref PubMed Scopus (896) Google Scholar, 2Eusebi LH Ratnakumaran R Yuan Y Solaymani-Dodaran M Bazzoli F Ford AC Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.Gut. 2018; 67: 430-440Crossref PubMed Scopus (220) Google Scholar, 9Lee J Anggiansah A Anggiansah R Young A Wong T Fox M Effects of age on the gastroesophageal junction, esophageal motility, and reflux disease.Clin Gastroenterol Hepatol. 2007; 5: 1392-1398Summary Full Text Full Text PDF PubMed Scopus (133) Google Scholar The authors themselves question whether this result "is driven more by measurement error than underlying epidemiology". One technical reason for this discrepancy is that bodyweight increases with age,10Anggiansah R Sweis R Anggiansah A Wong T Cooper D Fox M The effects of obesity on oesophageal function, acid exposure and the symptoms of gastro-oesophageal reflux disease.Aliment Pharmacol Ther. 2013; 37: 555-563Crossref PubMed Scopus (47) Google Scholar making it difficult to detect independent effects of these variables in the model. Another confounding factor is that, at any given level of reflux severity, older patients are less likely to report symptoms,10Anggiansah R Sweis R Anggiansah A Wong T Cooper D Fox M The effects of obesity on oesophageal function, acid exposure and the symptoms of gastro-oesophageal reflux disease.Aliment Pharmacol Ther. 2013; 37: 555-563Crossref PubMed Scopus (47) Google Scholar a pattern observed in many disorders. Determining the burden of diseases in an ageing population is important in planning health-care services. This study provides up to date information about the prevalence of typical reflux symptoms and the level of disability that is associated with gastro-oesophageal reflux disease; however, the results are conservative because the analysis did not include the full spectrum of symptoms and disease caused by this condition. Nevertheless, it will be of interest to compare results for gastro-oesophageal reflux disease against those for other common conditions that affect both young and old populations, in developed and developing regions worldwide. We declare no competing interests. The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017Gastro-oesophageal reflux disease is common worldwide, although less so in much of eastern Asia. The stability of our global age-standardised prevalence estimates over time suggests that the epidemiology of the disease has not changed, but the estimates of all-age prevalence and YLDs, which increased between 1990 and 2017, suggest that the burden of gastro-oesophageal reflux disease is nonetheless increasing as a result of ageing and population growth. Full-Text PDF Open Access