Association Between Gastroesophageal Reflux Disease and Frequency of Asthma Exacerbations: A Systematic Review and Meta-Analysis
Abstract
Gastroesophageal reflux disease (GERD) is common in patients with asthma; however, its role in asthma exacerbations remains unclear due to inconsistent study findings. This systematic review and meta-analysis aimed to synthesize the available evidence on the relationship between GERD and asthma exacerbations through two complementary objectives: (1) to assess the association between the presence of GERD and the frequency of asthma exacerbation in observational studies, and (2) to evaluate the effect of anti-reflux therapy (primarily proton pump inhibitors) on asthma exacerbations in randomized controlled trials (RCTs). Five research databases were searched up to December 2025 for RCTs and observational studies. A total of 10 studies were included, comprising six RCTs and four observational studies. Risk of bias was assessed using Risk of Bias 2 (ROB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tools. A random-effects model was used to pool the data, and heterogeneity was explored through subgroup analyses. The overall pooled effect was not statistically significant (standardized mean difference (SMD) = -0.12, 95% confidence interval (CI): -0.41 to 0.16, p = 0.323), with high heterogeneity (I² = 77.87%). Subgroup analysis revealed a statistically significant difference based on symptom status. Anti-reflux therapy significantly reduced asthma exacerbations in patients with symptomatic GERD (SMD = -0.41, 95% CI: -0.72 to -0.10), whereas no…
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