Abstract
There have been conflicting mechanisms that proton pump inhibitors (PPIs) may promote or prevent asthma development. However, the evidence on the association of PPI use with the risk of asthma and its exposure-response relationship has been limited. We aim to identify the association between the use of PPIs and the incidence of asthma, compared with use of histamine 2 receptor antagonists (H2RAs). A nationwide, prevalent new-user cohort study was conducted using Korea's National Sample Cohort database. Patients were defined as PPI or H2RA users between 2003 and 2019. PPI users matched to H2RA users based on time-conditional propensity score. Cox proportional hazards model was used to estimate adjusted hazard ratios with 95% confidence intervals of incident asthma associated with PPI use by duration of use, cumulative dose, and average dose per duration. Among the 250,041 pairs, PPI users (51.3% male; mean [SD] age, 42.6 [16.5]; mean follow-up, 6.7 years) showed a higher incidence rate of asthma (7.94 events per 1000 person-year) compared to H2RA users (3.70 events per 1000 person-year) with adjusted hazard ratio of 2.15 (95% confidence interval = 2.08-2.21). The risk of asthma was significantly increased across all observed groups of duration of use, cumulative dose, and average dose per duration. This study suggested that PPI use is associated with an increased risk of developing asthma compared to H2RA use.