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

Chest. 2024 Mar;165(3):621-631. doi: 10.1016/j.chest.2023.09.035. Epub 2023 Oct 20.


Background: 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.

Research question: 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?

Study design and methods: 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 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.

Results: 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 1.43 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).

Interpretation: Further research is needed to investigate underlying biological mechanisms and whether omega-3 fatty acids are a potential disease-modifying therapy.

Keywords: omega-3 fatty acids; pulmonary fibrosis; telomere length.

MeSH terms

  • Carbon Monoxide
  • Disease Progression
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3*
  • Humans
  • Idiopathic Pulmonary Fibrosis*
  • Male


  • Fatty Acids, Omega-3
  • Eicosapentaenoic Acid
  • Carbon Monoxide