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

Abstract

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 (avalidated 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 Patient Registry (n= 150), University of Virginia (n= 58), and University of Chicago (n= 101) cohorts. The N-3 index (docosahexaenoic acid+ eicosapentaenoic acid) 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 over a period of 12months. Cox proportional hazards models were used to examine transplant-free survival. Stratified analyses by telomere length were performed in the University of Chicago cohort. Most of the cohort were patients with idiopathic pulmonary fibrosis (88%) and male patients (74%). One-unit increment in log-transformed N-3 index plasma level was associated with a change in diffusing capacity for carbon monoxide of 1.43mL/min/mmHg per 12months (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 eicosapentaenoic acid plasma levels were associated with longer transplant-free survival among University of Chicago 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.