Associations of Plasma Omega-3 Fatty Acids With Progression and Survival in Pulmonary Fibrosis

Preclinical experiments suggest protective effects of omega-3 fatty acids and their metabolites in lung injury and fibrosis. Whether higher intake of omega-3 fatty acids is associated with disease progression and survival in humans with pulmonary fibrosis is unknown.What are the associations of plasma omega-3 fatty acid levels (a validated marker of omega-3 nutritional intake) with disease progression and transplant-free survival in pulmonary fibrosis?.Omega-3 fatty acid levels were measured from plasma samples of patients with clinically diagnosed pulmonary fibrosis from the Pulmonary Fibrosis Foundation (PFF) Patient Registry (n = 150), University of Virginia (UVA) (n = 58), and University of Chicago (UC) (n = 101) cohorts. The N-3 index (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]) was the primary exposure variable of interest. Linear-mixed effects models with random intercept and slope were used to examine associations of plasma omega-3 fatty acid levels with changes in FVC and diffusing capacity for carbon monoxide (Dlco) over a period of 12 months. Cox proportional hazards models were used to examine transplant-free survival. Stratified analyses by telomere length were performed in the UC cohort.Most of the cohort were patients with idiopathic pulmonary fibrosis (IPF) (88%) and men (74%). One-unit increment in log-transformed N-3 index plasma level was associated with a change in Dlco of 1.43 mL/min/mm Hg per 12 months (95% CI, 0.46-2.41) and a hazard ratio for transplant-free survival of 0.44 (95% CI, 0.24-0.83). Cardiovascular disease history, smoking, and antifibrotic usage did not significantly modify associations. Omega-3 fatty acid levels were not significantly associated with changes in FVC. Higher EPA plasma levels were associated with longer transplant-free survival among UC participants with shorter telomere length (P-value for interaction = .02).Further research is needed to investigate underlying biological mechanisms and whether omega-3 fatty acids are a potential disease-modifying therapy.