A39-29 Association of Daily Zinc Use and Progression to Respiratory Failure Among Patients With Idiopathic Pulmonary Fibrosis

Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive, incurable lung disease with limited therapeutic options. Antifibrotic drugs are expensive and only slow disease progression, highlighting the need for new, affordable therapies. Evidence suggests zinc’s potential role in IPF. Zinc deficiency in mice increases oxidative stress and inflammation, leading to lung fibrosis. Furthermore, a zinc metabolism defect, characterized by reduced levels of the zinc transporter ZIP8, has been identified in the alveolar progenitor cells of patients with IPF playing a potential role on pulmonary fibrosis. Our study investigates whether oral zinc supplementation can reduce disease progression in patients with IPF in a real-world setting. Methods We retrospectively analyzed data from 70 US healthcare organizations in the TriNetX database from 2015 to 2025. We included patients over 18 with an IPF diagnosis (ICD-10.J84.112) who were using either pirfenidone or nintedanib. We stratified patients into two cohorts based on zinc supplementation use (cohort 1) or no zinc use (cohort 2) 12 months before an outpatient visit while on active antifibrotic therapy. Using propensity score matching for demographics and comorbidities, we compared the two groups. The primary outcome was new-onset chronic respiratory failure (CRF) (ICD-10.J96.1) at five year follow-up. We report data using hazard ratios (HR), proportions, and 95% confidence intervals (CI). A two-sided P-value 0.05 was statistically significant. Results Cohort 1 included 407 IPF patients (zinc cohort) and Cohort 2 included 7,563 IPF patients (no-zinc cohort). After propensity matching, 407 patients in each group were compared. The age at index (73.9 vs. 73.9), male proportion (62.7% vs. 62.9%), race not hispanic or latino (87.7% vs. 87.7%), malnutrition prevalence (3.9% vs. 2.5%), zinc deficiency prevalence (0% vs. 0%), and body mass index (28.1 vs. 28 Kg/m2) were not significantly different for cohort 1 and 2, respectively. Cohort 1 had significantly more hypertension (51.6% vs. 34.9%), heart failure (18.9% vs. 11.5%), emphysema (11.3% vs. 7.1%), hyperlipidemia (38.1% vs. 28.7%), and neoplasms (28.3% vs. 13.8%) prevalence. After excluding patients with prior CRF, 45 of 400 (11.25%) in cohort 1 and 62 of 394 (15.73%) in the cohort 2 developed new-onset CRF within five years. The HR was 0.69 (CI 0.47-1.01; p = 0.06). Conclusions Zinc supplementation might be associated with slower progression to CRF in patients with IPF. Further prospective research with larger same size is needed to better understand the role of zinc supplementation in IPF patients. This abstract is funded by: None