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This heterogeneity presents challenges for mechanistic and therapeutic research, as evidenced by conflicting results from trials of n\u22123 polyunsaturated fatty acid (PUFA) supplementation for ARDS. PUFAs and downstream oxylipins are important to pulmonary inflammation but are not well defined in ARDS. We hypothesized that differences in fatty acid metabolism, as measured by levels of n\u22123 and n\u22126 PUFAs and oxylipins, are associated with differences in ARDS outcomes, inflammation, and causes. To test this, PUFAs\/oxylipins were measured by LC MS\/MS in plasma samples from 90 patients with ARDS. Pro\u2010inflammatory cytokines and chemokines IL\u20106 and IL\u20108 were measured by ELISA. Multivariable linear regressions modeled the relationship between PUFAs\/oxylipins, inflammation, and ARDS mortality, severity, and cause. Multiple n\u22123 and n\u22126 PUFA\u2010derived oxylipins were decreased in severe ARDS. We did not detect differences in PUFAs\/oxylipins by mortality. PUFAs\/oxylipins varied by cause of ARDS, especially between patients with sepsis and those with trauma. Furthermore, specific oxylipins were associated with IL\u20106 and IL\u20108. As we observed that oxylipins varied by disease severity and underlying cause, these metabolites may function as biomarkers and suggest dysregulated mechanisms of lung repair. Furthermore, while oxylipins are derived from PUFAs, differences in PUFAs did not directly correlate with changes in oxylipins, suggesting altered lipid metabolism as a mechanism. Further consideration of differences in lipid metabolism in ARDS could identify subgroups with differential responses to n\u22123 PUFA supplementation or other therapies.<\/jats:p>","DOI":"10.1096\/fj.202504787rr","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:25:10Z","timestamp":1778685910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterogeneous Causes of Acute Respiratory Distress Syndrome Correlate With Distinct Peripheral Polyunsaturated Fatty Acid Metabolites"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-6554","authenticated-orcid":false,"given":"Laura A.","family":"Leuenberger","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine and The Davis Heart and Lung Research Institute The Ohio State University  Columbus Ohio 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