Associations of Omega-3 Fatty acids with Interstitial Lung Disease and Lung Imaging Abnormalities Among Adults.

Gunnar Guðmundsson, John S. Kim, Brian T. Steffen, Anna J. Podolanczuk, Steven M. Kawut, Imre Noth, Ganesh Raghu, Erin D. Michos, Eric A. Hoffman, Gisli Thor Axelsson, Vilmundur Gudnason, Elias Freyr Gudmundsson, Rachel A. Murphy, Josée Dupuis, Hanfei Xu, Ramachandran S. Vasan, George T. O'Connor, William S. Harris, Gary M. Hunninghake, R. Graham BarrMichael Y. Tsai, David J. Lederer, Vilmundur G. Guðnason

Research output: Contribution to journalArticlepeer-review


Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000-2012; n = 6,541), the Framingham Heart Study (2005-2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002-2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.

Original languageEnglish
Pages (from-to)95-108
Number of pages14
JournalAmerican Journal of Epidemiology
Issue number1
Early online date17 Aug 2020
Publication statusPublished - 2020

Bibliographical note

The Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 with the National Heart, Lung, and Blood Institute (NHLBI), US National Institutes of Health (NIH). MESA was also funded by National Center for Advancing Translational Sciences (NIH) grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. The MESA Lung Study was supported by grants R01-HL077612 and R01-HL093081 from the NHLBI. The MESA Lung Fibrosis Study was funded by grants RC1-HL100543, R01-HL-103676, T32-HL-105323, and K24-HL-131937 from the NHLBI. This work was partially supported by NIH grants NHLBI-N01-HC-25195, HHSN268201500001I, and 75N92019D00031 awarded to the Framingham Heart Study. The Age, Gene/Environment Susceptibility-Reykjavik Study was funded by National Institute on Aging (NIH) grants N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program (NIH), the Hjartavernd (Icelandic Heart Association), and the Althingi (Icelandic Parliament). Fatty acid levels were analyzed through an ancillary study (ICELAND-MI) supported by the Office of Dietary Supplements (NIH) and the NIH. J.S.K. was supported by a Pulmonary Fibrosis Foundation Scholars Award. A.J.P. was supported by grant K23-HL-140199 from the NHLBI. R.A.M. was supported by the Canadian Cancer Society (grant 704735) and the Michael Smith Foundation for Health Research (grant 17644). R.S.V. was supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. G.M.H. and this study were supported by grants P01-HL114501 and R01-HL-111024 from the NHLBI and a project grant (grant 141513-051) from the Icelandic Research Fund.

S.M.K. reports receipt of nonfinancial support from the American Thoracic Society, the Cardiovascular Medical Research and Education Fund, and the Pulmonary Hypertension Association and receipt of grants from the Cardiovascular Medical Research and Education Fund, Actelion, United Therapeutics, Gilead, Lung Biotech, Bayer, and Mallinkrodt outside the scope of this work. He has served in an advisory capacity (for grant review and other purposes) for United Therapeutics, Akros Pharma, GlaxoSmithKline, and Complexa, without financial support or in-kind benefits. I.N. reports receipt of personal fees and other support from Boehringer Ingelheim, HLR/Genentech, Sanofi Aventis, Global Blood Therapeutics, and Veracyte outside the scope of this work. E.A.H. is a founder of VIDA Diagnostics, Inc., a company that is commercializing lung image analysis software developed, in part, at the University of Iowa. W.S.H. reports ownership of stock in and laboratory employment with OmegaQuant Analytics, LLC, during the conduct of the study. R.G.B. reports receipt of grants from the Alpha-1 Foundation and the COPD Foundation outside the scope of this work. D.J.L. completed this work while employed at Columbia University; this study was not performed at Regeneron Pharmaceuticals, Inc., nor does this article represent any research, products, or processes pertaining to Regeneron Pharmaceuticals. D.J.L. reports receipt of grants and personal fees from Boehringer Ingelheim, Veracyte, Fibrogen, Global Blood Therapeutics, the Pulmonary Fibrosis Foundation, Philips Respironics, Sanofi Genzyme, Roche, Galapagos, Galecto, Bristol-Myers Squibb, and Pliant outside the scope of this work.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail:

Other keywords

  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • Epidemiologic Studies
  • Fatty Acids, Omega-3/blood
  • Fatty Acids, Unsaturated/blood
  • Female
  • Hospitalization/statistics & numerical data
  • Humans
  • Lung Diseases, Interstitial/blood
  • Male
  • Middle Aged
  • Risk Factors
  • Tomography, X-Ray Computed


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