Acid suppressors linked to worse outcomes in biologic-treated asthma

Clinical takeaway: Reassess the ongoing need for PPIs in patients with difficult-to-treat asthma receiving biologic therapy, particularly when there is no clear ulcer-related indication. Chronic PPI use may represent a modifiable risk factor associated with poorer asthma outcomes.

Proton pump inhibitors (PPIs) are commonly prescribed and often continued long after the original indication has resolved. Although they may benefit some patients with asthma and concomitant reflux, concerns have grown about potential infectious and systemic adverse effects associated with long-term acid suppression.

Findings from a large retrospective cohort study presented at the CHEST 2026 Annual Meeting, but not yet peer reviewed, suggest that chronic empiric PPI use may be associated with worse outcomes among patients with difficult-to-treat asthma treated with biologics.

Using data from the TriNetX US Collaborative Network, investigators identified adults with asthma who received biologic therapies between 2014 and 2025, including omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab. To isolate empiric PPI use, researchers excluded patients with established ulcer-related indications such as gastroesophageal reflux disease, Barrett esophagus, peptic ulcer disease, eosinophilic esophagitis, or esophageal varices.

After propensity-score matching across 105 clinical and demographic variables, 1,228 chronic PPI users were compared with 1,228 nonusers. Over 1 year of follow-up, asthma exacerbations occurred in 31.9% of PPI users versus 22.6% of nonusers, representing an approximately 40% higher likelihood of exacerbation. Rescue systemic corticosteroid use was reported in 72% versus 40% of patients, while respiratory infections occurred in 8.4% versus 2.3%.

Healthcare utilization was also higher among PPI users. ICU admissions occurred in 4.3% versus 1.2% of patients, and emergency department visits occurred in 15.6% versus 8.4%. All-cause mortality did not differ significantly between groups.

“The findings suggest that long-term acid suppression may represent a modifiable risk factor in biologic-treated patients with difficult-to-treat asthma,” said presenting author Joshua Le, MD. “Proactive medication reconciliation, clear documentation of indication, and structured deprescribing strategies may reduce unnecessary long-term exposure and help mitigate preventable morbidity in this vulnerable population.”

Source: Le JP, et al. (2026 Oct 20) CHEST 2026 Annual Meeting. Empiric Chronic Proton Pump Inhibitor Use Is Associated With Increased Exacerbations in Biologic-Treated Difficult-to-Treat Asthma: A Propensity-Matched US Cohort Study