Chronic PPI Use Linked to Increased Asthma Exacerbations and Corticosteroid Use,suggests study

The safety of persistent acid suppression in high-risk asthma patients was tested through a retrospective propensity score-matched cohort study using the TriNetX U.S. Collaborative Network, which is made up of 65 healthcare organizations. The subjects of this study were adults above 18 years old who had asthma treated between 2014 and 2025 by biologics such as omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, or tezepelumab.

To establish the use of empiric PPIs, those who had an established ulcers or esophagitis indication, such as GERD, eosinophilic esophagitis, Barrett’s esophagitis, peptic ulcers or esophageal varices, were excluded. Persistence of PPI treatment was established based on repeat prescriptions of 3-6 months and 6-12 months and compared between the PPI users and non-users. The 1:1 propensity score-matching was done for 105 covariates (demographics, co-morbidities, exacerbations, lab results, such as IgE and eosinophils and healthcare utilization).

Key findings:

• After propensity score matching of the TriNetX database, 1,228 well-matched patients were retained in each group (unmatched PPI users were of greater age [58.3 ± 17.4 vs. 48.1 ± 19.3 years] with higher prevalence of comorbidities), demonstrating significant differences in outcomes during 1-year follow-up period.
• Chronic use of PPIs was related to a significantly increased number of acute asthma exacerbations (31.9% vs. 22.6%; OR 1.60, 95% CI 1.34–1.92; p < 0.0001) and significantly increased rates of rescue use of systemic corticosteroids (72% vs. 40%; OR 3.88, 95% CI 3.27–4.59; p < 0.0001).
• The diagnosis of respiratory infections was significantly more prevalent among chronic PPI users than among non-PPI users (8.4% vs. 2.3%; OR 3.83, 95% CI 2.52–5.82; p < 0.0001).
• ICU admissions and ED visits were significantly more common in the chronic PPI cohort than in the control group (4.3% vs. 1.2%; OR 3.648, 95% CI 2.04–6.50; p < 0.0001 and 15.6% vs. 8.4%; OR 2.00, 95% CI 1.56–2.58; p < 0.0001), while there were no statistically significant differences in all-cause mortality.

In summary, the clinical reality as observed from the registry-based study indicates an independent association between chronic empirical PPI use in biologic treatment of difficult-to-treat asthma and increased exacerbations, infections, and healthcare utilization. The results obtained from the study show that prolonged acid suppression is a modifiable risk factor.

Reference:

Le JP, Gupta N, Malode A, et al. Empiric chronic proton pump inhibitor use is associated with increased exacerbations in biologic-treated difficult-to-treat asthma: a propensity-matched US cohort study. CHEST. 2026;170(4S). https://doi.org/10.1016/j.chest.2026.07.3902