• John S Kim, Shwu-Fan Ma, Jennie Z Ma, Yong Huang, Catherine A Bonham, Justin M Oldham, Ayodeji Adegunsoye, Mary E Strek, Kevin R Flaherty, Emma Strickland, Inemesit Udofia, Joshua J Mooney, Shrestha Ghosh, Krishnarao Maddipati, and Imre Noth.
• Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA; Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY. Electronic address: Jk6jb@virginia.edu.
• Chest. 2024 Mar 1; 165 (3): 621631621-631.

BackgroundPreclinical 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.Research QuestionWhat 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?Study Design And MethodsOmega-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 12 months. Cox proportional hazards models were used to examine transplant-free survival. Stratified analyses by telomere length were performed in the University of Chicago cohort.ResultsMost 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 1.43 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 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).InterpretationFurther research is needed to investigate underlying biological mechanisms and whether omega-3 fatty acids are a potential disease-modifying therapy.Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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