The Impact of Gastro-esophageal Reflux on the Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung condition characterised by chronic airflow obstruction that interferes with normal respiration and which is not entirely reversible. Gastroesophageal reflux disease (GERD) is a condition that occurs when the volume of gastric content exceeds its physiological removal from the oesophagus and causes difficulties with or without associated damage to the oesophageal mucosa and troubling symptoms. Self-reported questionnaires set the prevalence of GERD in COPD patients at around 17% to 54%. This review sought to conduct a meta-analysis of available studies that compare the likelihood of COPD exacerbation in individuals with and without GERD. Methods: This meta-analysis was performed in a manner consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic search was conducted to identify relevant studies published up to July 2020 in PubMed, Medline and Embase using the Ovid platform. The following were deemed eligible for inclusion: 1) articles reporting the rate of COPD exacerbations; 2) articles enrolling patients with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease criteria; 3) articles enrolling patients with GERD; 4) articles comparing two groups of patients (COPD with GERD vs. COPD without GERD); 5) articles reporting exacerbation rates with corresponding 95% confidence intervals (CIs) or sufficient data for further calculations; and 6) articles reporting the mean, standard deviation or odds ratio (OR) values for COPD and GERD. The quality of the selected studies was assessed using the Critical Appraisal Skills Programme checklist for cohort studies and the Appraisal Tool for Cross-sectional Studies. Results: This systematic review and meta-analysis of 10 observational studies included a total of 13,245 patients and indicated that 1) GERD increased the likelihood of COPD patients being exacerbated (OR: 5.37; 95% CI: 2.71–10.64) and 2) that COPD patients with GERD reported more exacerbations (weighted mean difference: 0.48 times/year; 95% CI: 0.31–0.65). The sensitivity analysis showed that I2 ranged from 47% to 61%. Conclusion: Overall, this meta-analysis revealed a significant relationship between GERD and the exacerbation of COPD. Moreover, the present findings imply that medical professions need to educate patients, especially those without an obvious aetiology or who are refractory to anti‐acid treatment, to recognise and control not only COPD symptoms but also GERD symptoms so as to correctly identify the cause of their symptoms, treat them effectively and obtain medical treatment when needed. Objectively assessing GERD's existence using endoscopy or pH monitoring in such patients, which may reveal potential strategies for reducing or managing GERD and thereby decrease the frequency of acute exacerbation of COPD, should be considered.