Association Between Proton Pump Inhibitors and Asthma: A Population-Based Cohort Study

OBJECTIVE: The relationship between proton pump inhibitors (PPIs) and asthma is controversial. The goal of this study was to determine the association between PPI use in non-asthma subjects and their subsequent asthma prevalence. DESIGN: Nationwide, population-based cohort study. METHODS: We conducted a nationwide, population-based retrospective cohort study using data from the National Health Insurance Research Database (NHIRD) of Taiwan from 1999 to 2013. We identified 24,077 adult patients with PPI use for more than 3 months and 24,077 controls matched by propensity score on a one-to-one ratio for age, gender, comorbidities (hypertension, hyperlipidemia, gastroesophageal reflux disease, allergic rhinitis, atopic dermatitis, peptic ulcer disease, diabetes, and sleep apnea syndrome), and medications (histamine 2 receptor antagonists [H2RA], nonsteroidal anti-inflammatory drugs [NSAIDs], and acetaminophen). The cumulative asthma incidence for the two cohorts in the follow-up period was estimated with the Kaplan–Meier method, and the difference was examined using the log-rank test. Multivariate Cox regression models were used to calculate the adjusted hazard ratios (HR). RESULTS: The overall incidence of asthma was 1.58-fold greater in the PPI cohort than in the non-PPI cohort (13.3 versus 8.4 per 1,000 person-years), with an adjusted HR of 1.76 (95% confidence interval [CI], 1.64–1.88). In patients without previous peptic ulcer disease, the adjusted HR of asthma associated with PPIs was higher than in the non-PPI group (1.95; 95% CI, 1.80–2.11). The risk of asthma due to PPI use was also more significant in patients not receiving H2RA (1.81; 95% CI, 1.66–1.96), NSAIDs (1.93; 95% CI, 1.73–2.15), and acetaminophen (1.88; 95% CI, 1.70–2.08). CONCLUSIONS: This population base study demonstrated that patients with long-duration of PPI use are at a higher risk of developing asthma, regardless of age, gender, comorbidities, and medications.