The Bidirectional Relationship Between Gastroesophageal Reflux Disease (GERD) and Asthma in Pediatric and Adult...

Gastroesophageal reflux disease (GERD) and asthma are prevalent chronic conditions with a well-documented but complex bidirectional relationship. While previous studies have explored their association, a comprehensive synthesis of evidence across pediatric and adult populations is lacking. This systematic review examines the bidirectional relationship between GERD and asthma, focusing on epidemiological, mechanistic, and clinical aspects. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted across PubMed, Web of Science, Scopus, and Science Direct. Eight studies (cohort, case-control, cross-sectional, Mendelian randomization (MR), and bioinformatics analyses) were included after screening 329 records. Data were extracted on study design, population, diagnostic criteria, and key findings. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and Mendelian Randomization Quality (MR-Q) tool. Evidence supports a bidirectional association, with GERD increasing asthma risk (HR 1.62, 95% CI 1.21-2.18) and asthma elevating GERD risk (HR 1.36, 95% CI 1.20-1.54). MR confirmed genetic pleiotropy (OR 1.21 for GERD → asthma; OR 1.06 for asthma → GERD). Mechanistically, microaspiration, vagal reflexes, and shared pathways (e.g., renin-angiotensin system) were implicated. Pediatric studies highlighted GERD's role in poor asthma control, including increased nocturnal symptoms. However, heterogeneity in diagnostic criteria (ICD codes vs. endoscopy) and residual confounding (e.g., obesity) were limitations. GERD and asthma exhibit a bidirectional relationship driven by genetic, neural, and inflammatory mechanisms. Future research should prioritize randomized trials on combined therapies and deeper exploration of the gut-lung axis. Standardized diagnostics and prospective designs are needed to clarify causal pathways.