Clinical Question: Does proton pump inhibitor (PPI) use increase the risk of obstructive lung disease exacerbation?
Background: Previous studies have shown inconsistent results, yielding an unclear correlation between PPI use and risk of exacerbation of obstructive lung diseases. Some trends have been established, but little is known about dose-dependent responses.
Study Design: Retrospective cohort study
Setting: Belgian nationwide claims data incorporating outpatient pharmacy dispensing and hospital care records.
Synopsis: Using Belgian nationwide claims data of 932,135 adult patients with long-term medication use for chronic obstructive airway disease in both inpatient and outpatient settings, this study established an increased risk of exacerbation with concurrent use of PPI. Specifically, after adjustment for age, sex, smoking, socioeconomic status, exacerbation history, frailty, comorbidities, and gastroesophageal reflux disease (GERD), they found an 18% increased risk of exacerbation with PPI use (adjusted HR, 1.18; 95% CI, 1.17 to 1.19). Further, this study showed the risk of exacerbation increased with cumulative PPI use, from an HR of 1.09 at up to 28 defined daily doses, to 1.25 at over 365. Notably, exposure of one week or less was not associated with exacerbation, and neither was short-term use in patients with a GERD diagnosis, suggesting the signal reflects chronic use rather than appropriate short courses. Confounding by indication remains a concern, as PPI users were older, sicker, and more frequent exacerbators at baseline, though propensity weighting did not meaningfully change the estimate. Though no clear causal relationship can be established from this data, physicians prescribing PPIs should consider shorter treatment duration and reassessment of PPI indication in patient populations receiving long-term medications for chronic obstructive airway disease.
Bottom Line: Long-term PPI use is associated with increased exacerbation risk in chronic obstructive airway disease; short courses for clear indications appear safe.
Citation: Dehondt V, et al. Exacerbation risk by chronic proton pump inhibitor use in obstructive lung diseases. Chest. 2026;169(5):1218-1227. https://doi.org/10.1016/j.chest.2026.01.002.
Dr. Herring
Dr. Herring is a PGY-2 internal medicine resident at the University of Tennessee Health Sciences College of Medicine and Erlanger Hospital, both in Chattanooga, Tenn.