Proton Pump Inhibitor Use and Its Association With Asthma: A Systematic Review and Meta-Analysis

Background: Asthma is a prevalent chronic respiratory condition marked by airway inflammation and hyperresponsiveness, significantly impacting quality of life. Emerging evidence suggests a potential association between proton pump inhibitor (PPI) use and an increased risk of asthma. This systematic review and meta-analysis assessed the relationship between PPI use and the development or exacerbation of asthma. Methods: A systematic search of PubMed, Web of Science, and Embase databases was conducted, covering studies published from the inception of the database to July 12, 2024. Observational studies examining the association between PPI use and asthma risk were included. Two reviewers independently extracted data using Nested Knowledge software, with study quality assessed via the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed, pooling odds ratios (ORs) and hazard ratios (HRs) to assess the association, with heterogeneity evaluated via the I2 statistic. Results: Fourteen studies, conducted between 2009 and 2024 and involving over 1.7 million participants, met the inclusion criteria. The pooled HR showed a 38% increased risk of asthma among PPI users compared to nonusers (HR, 1.38; 95% CI, 1.14-1.62). OR analysis indicated a 29% higher risk (OR, 1.29; 95% CI, 1.23-1.35). PPI users had an 81% higher risk compared to histamine H2 receptor antagonist (H2RA) users (HR, 1.81; 95% CI, 1.09-2.53), and asthma patients using PPIs were 61% more likely to experience exacerbations (OR, 1.61; 95% CI, 1.42-1.80). Conclusion: PPI use is associated with an increased risk of asthma. These findings underscore the need for cautious prescribing and further investigation into underlying mechanisms.