Association Between Gastroesophageal Reflux Disease and Frequency of Asthma Exacerbations: A Systematic Review and Meta-Analysis

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 significant benefit was observed in patients without GERD symptoms. No significant differences were found across subgroups based on study design or diagnostic method. Overall, no significant association between GERD and asthma exacerbations was identified. However, symptom status appeared to act as a clinically significant effect modifier. Anti-reflux therapy may benefit asthmatic patients with symptomatic GERD, but empirical treatment of all asthmatic patients with evidence of reflux is not supported. These findings favor a symptom-driven treatment approach rather than routine empirical therapy.