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Chronic proton pump inhibitor use carried 60% greater odds of asthma exacerbation and nearly 4-fold odds of rescue corticosteroid use in a matched cohort of 2456 patients.
Empiric chronic proton pump inhibitor (PPI) use was associated with more asthma exacerbations, rescue systemic corticosteroid use, and respiratory infections in adults with biologic-treated, difficult-to-treat asthma, according to data presented at the American College of Chest Physicians (CHEST) 2026 Annual Meeting in Phoenix.¹,²
“Clinicians should carefully reassess the necessity of chronic PPI therapy in biologic-treated asthma patients without clear ulcer-related indications,” said investigator Joshua Le, MD, a resident physician at Allegheny Health Network.² “Chronic PPI use frequently persists as an act of omission, with therapy continued beyond its initial short-term indication despite resolution of symptoms or lack of objective need.”
PPIs have shown modest benefit in a small subset of patients with asthma, particularly those with nocturnal symptoms and coexisting reflux.¹ A growing body of evidence links long-term PPI exposure to infectious and systemic adverse events.¹ However, data in patients receiving empiric therapy without ulcer-related indications remain limited, especially among those treated with biologics.¹
Le and colleagues conducted a retrospective propensity score–matched cohort study using the TriNetX US Collaborative Network, which includes 65 health care organizations.¹ The analysis included adults aged ≥ 18 years with asthma treated between 2014 and 2025 with omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, or tezepelumab. Investigators excluded patients with gastroesophageal reflux disease, eosinophilic esophagitis, Barrett esophagus, peptic ulcer disease, or esophageal varices to isolate empiric PPI use.¹
Persistent exposure was defined by repeated PPI prescriptions at 3 to 6 months and 6 to 12 months. PPI users were older (mean, 58.3 vs 48.1 years) and carried a greater burden of hypertension (21.1% vs 13.9%) and diabetes (10.8% vs 5.3%).¹
Matching (1:1) on 105 covariates balanced demographics, comorbidities, asthma severity markers, prior exacerbations, medication exposure, IgE, eosinophils, body mass index, and health care utilization.¹ After matching, 1228 patients remained in each cohort, with outcomes assessed from 1 to 365 days after the index prescription. During 1 year of follow-up, asthma exacerbations occurred in 31.9% of PPI users vs 22.6% of nonusers (OR, 1.60; 95% CI, 1.34–1.92; P <.0001).¹
Rescue systemic corticosteroid use was nearly twice as common among PPI users (72% vs 40%; OR, 3.88; 95% CI, 3.27–4.59; P <.0001).¹ Respiratory infections occurred in 8.4% of PPI users compared with 2.3% of nonusers (OR, 3.83; 95% CI, 2.52–5.82; P <.0001).¹
Chronic PPI use was also associated with more intensive care unit admissions (4.3% vs 1.2%; OR, 3.65; 95% CI, 2.04–6.50; P <.0001) and emergency department visits (15.6% vs 8.4%; OR, 2.00; 95% CI, 1.56–2.58; P <.0001).¹ All-cause mortality did not differ significantly between groups.¹
Investigators concluded long-term acid suppression may represent a modifiable risk factor in this population. They noted the association may be mediated by microbiome alteration and increased susceptibility to respiratory pathogens.¹
“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,” Le said.²
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