Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease associated with high morbidity, mortality, and limited treatment options. Gastroesophageal reflux disease (GERD) and microaspiration have been hypothesized to contribute to IPF pathogenesis. Prior studies suggest that proton pump inhibitors (PPIs) may slow disease progression through anti-inflammatory and antifibrotic effects. However, current American Thoracic Society guidelines report insufficient evidence to recommend the routine use of PPIs in IPF. We evaluated whether PPI use in a large, multicenter IPF cohort was associated with all-cause mortality and adverse outcomes. Methods We conducted a retrospective cohort study using the TriNetX dataset, which contains de-identified electronic health records from over 100 healthcare organizations. Adults aged 18 years and older with a diagnosis of IPF between 1/1/2015 and 1/1/2024 were included. PPI users had documented PPI prescriptions within 3 months before and up to one year after IPF diagnosis; non-users had no PPI exposure during this period. Patients were propensity score-matched 1:1 by age, sex, race and ethnicity, body mass index (BMI), diffusing capacity of the lung for carbon monoxide (DLCO), smoking history, comorbidities, and antifibrotic use. Outcomes included all-cause mortality, emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, gastrointestinal (GI) bleeding, influenza and pneumonia, acute respiratory distress syndrome (ARDS), and mechanical ventilation. To evaluate the associations between PPI use and outcomes in IPF, hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards regression model. Results Among 39,095 patients, 11,358 PPI users were matched to 11,358 non-users. PPI users had a higher risk of all-cause mortality (HR 1.323, 95%CI 1.242-1.409), ED visits (HR 1.670, 95%CI 1.556-1.793), inpatient admissions (HR 2.587, 95%CI 2.439-2.744), ICU admissions (HR 3.248, 95%CI 2.930-3.601), GI bleeding (HR 3.294, 95%CI 2.705-4.010), influenza and pneumonia (HR 1.665, 95%CI 1.556-1.782), ARDS (HR 1.888, 95%CI 1.427-2.498), and mechanical ventilation (HR 3.842, 95%CI 2.998-4.923) relative to non-users. Conclusions In this large matched cohort of patients with IPF, PPI use was associated with unfavorable outcomes and greater healthcare utilization compared with patients not receiving PPIs. These findings contrast with earlier studies that suggested potential benefits or neutral effects of PPIs in IPF. Given these discrepancies, clinicians should carefully assess the indications for PPI therapy in this population. Further prospective, randomized controlled trials are warranted to clarify the risks, benefits, and underlying mechanisms linking PPI use to clinical outcomes in IPF. This abstract is funded by: None
Lee et al. (Fri,) studied this question.
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