The association of eicosanoids with lung structure and function: Findings from the Multi-Ethnic Study of Atherosclerosis lung study and Framingham Heart Study

Mythri Ambatipudi; Jenna N McNeill; Athar Roshandelpoor; Mona Alotaibi; Louisa A Mounsey; Eric Hoffman; George O'Connor; Seung Hoan Choi; Norrina B Allen; R Graham Barr; Mohit Jain; Susan Cheng; Jennifer E Ho

doi:10.1371/journal.pone.0351692

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The association of eicosanoids with lung structure and function: Findings from the Multi-Ethnic Study of Atherosclerosis lung study and Framingham Heart Study

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The association of eicosanoids with lung structure and function: Findings from the Multi-Ethnic Study of Atherosclerosis lung study and Framingham Heart Study

Mythri Ambatipudi, Jenna N McNeill, Athar Roshandelpoor, Mona Alotaibi, Louisa A Mounsey, Eric Hoffman, George O'Connor, Seung Hoan Choi, Norrina B Allen, R Graham Barr, …

PloS one, Vol.21(6), e0351692

06/01/2026

DOI: 10.1371/journal.pone.0351692

PMID: 42378232

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Abstract

Eicosanoids are bioactive signaling lipids that have roles in airway remodeling, smooth muscle hypertrophy, emphysema and pulmonary fibrosis via mediation of pro- and anti-inflammatory pathways. Specific eicosanoids have been associated with lung diseases such as asthma and pulmonary fibrosis, yet their association with lung function more broadly is not completely understood. We aimed to investigate the association of eicosanoids and related metabolites with early changes in lung function and structure. We performed comprehensive profiling of over 250 eicosanoids and eicosanoid-related metabolites using directed non-targeted mass spectrometry in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study with independent validation in the Framingham Heart Study (FHS). We performed cross-sectional analysis of the associations between metabolites and lung function as assessed by spirometry and quantitative lung measures on computed tomography (CT). Among 3384 participants (mean age 63 ± 10 years, 51% women), 51 metabolites were associated with lung function in MESA Lung (22 with % predicted FEV1, 18 with % predicted FVC, and 25 with FEV1/FVC ratio), with 24 validated among FHS participants. Of these 51 metabolites, 27 were associated with obstructive lung physiology, including linoleic acid derivatives (9-HODE) and other long-chain fatty acids (hydroxyhexadecanoic acid, hydroxyoctadecanoic acid) associated with higher odds. Fourteen metabolites were associated with restrictive physiology, including putative dihydroxy-20:3 and an LTB3 analog associated with lower odds, and omega-3 fatty acids (EPA, stearidonic acid) associated with higher odds. Specific eicosanoids and eicosanoid-related metabolites including linoleic acid derivatives and long-chain fatty acids were associated with obstructive, and leukotrienes and omega-3 fatty acids with restrictive lung physiology. These findings highlight bioactive lipids involved in both pro- and anti-inflammatory pathways as potential influencers of lung function and may serve as future therapeutic targets early in lung disease development.

Aged

Atherosclerosis - ethnology

Atherosclerosis - metabolism

Atherosclerosis - physiopathology

Cross-Sectional Studies

Eicosanoids - metabolism

Female

Humans

Lung - metabolism

Lung - pathology

Lung - physiopathology

Male

Middle Aged

Details

Title: Subtitle: The association of eicosanoids with lung structure and function: Findings from the Multi-Ethnic Study of Atherosclerosis lung study and Framingham Heart Study
Creators: Mythri Ambatipudi - Beth Israel Deaconess Medical Center
Jenna N McNeill - Pulmonary and Allergy Associates
Athar Roshandelpoor - Beth Israel Deaconess Medical Center
Mona Alotaibi - University of California System
Louisa A Mounsey - Beth Israel Deaconess Medical Center
Eric Hoffman - University of Iowa
George O'Connor - Boston University School of Medicine
Seung Hoan Choi - Broad Institute
Norrina B Allen - Northwestern University
R Graham Barr - Columbia University Irving Medical Center
Mohit Jain - University of California San Diego
Susan Cheng - Cedars-Sinai Smidt Heart Institute
Jennifer E Ho - Broad Institute
Resource Type: Journal article
Publication Details: PloS one, Vol.21(6), e0351692
DOI: 10.1371/journal.pone.0351692
PMID: 42378232
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: PLoS
Grant note: National Institutes of Health: R01 HL140224
This work was partially supported by the National Heart, Lung, and Blood Institute (NHLBI) (Framingham Heart Study: contract N01-HC25195 and HHSN268201500001I; Multi-Ethnic Study of Atherosclerosis: contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169). The Multi-Ethnic Study of Atherosclerosis was also supported by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). A full list of participating Multi-Ethnic Study of Atherosclerosis investigators and institutions can be found at https://www.mesa-nhlbi.org. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the U.S. Department of Health and Human Services.
Language: English
Date published: 06/01/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9985179094602771

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