{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:19:54Z","timestamp":1792095594444,"version":"4.4.0"},"reference-count":38,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K24 HL153669"],"award-info":[{"award-number":["K24 HL153669"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL140224"],"award-info":[{"award-number":["R01 HL140224"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL160003"],"award-info":[{"award-number":["R01 HL160003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL168889"],"award-info":[{"award-number":["R01 HL168889"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32HL116275"],"award-info":[{"award-number":["T32HL116275"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2025,8,31]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Eicosanoids are upstream lipid mediators of inflammatory pathways. Transpulmonary gradient (\u0394EIC) analysis using multisite sampling enables physiological assessment of metabolic flux across the lungs. While specific eicosanoids have been implicated in lung disease, the relationship between their metabolic flux and pulmonary physiology remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a cross-sectional study of patients with dyspnoea who underwent spirometry and right heart catheterisation with multisite (pulmonary artery, radial artery) sampling. Eicosanoids and eicosanoid-related metabolites were profiled\n                      <jats:italic>via<\/jats:italic>\n                      a directed nontargeted liquid chromatography\u2013mass spectrometry platform. We quantified \u0394EIC (\u0394EIC=radial artery concentration\u2212pulmonary artery concentration), indicating potential lung release or uptake, and examined associations of \u0394EIC with spirometry parameters and lung disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 516 participants (mean age 57\u00b115\u2005years, 59% female), 68% had normal spirometry values, 19% had obstructive physiology and 13% had restrictive physiology. 10% had COPD and 7% had interstitial lung disease. Of 887 eicosanoids, 194 (22%) demonstrated significant \u0394EIC, with 74% indicating pulmonary uptake (false discovery rate q&lt;0.05). 10 \u0394EIC were associated with lower odds of obstruction, including anti-inflammatory arachidonic acid derivatives (11\/15-hydroxyeicosatetraenoic acid; 11,12\/14,15-dihydroxyeicosatrienoic acid), prostaglandin G2 and leukotriene precursor 5S-hydroperoxyeicosatetraenoic acid, which were also associated with lower odds of COPD. Seven \u0394EIC were associated with restriction, including anti-inflammatory docosahexaenoic acid derivative 10,11\/13,14-dihydroxydocosapentaeonic acid, which was also associated with interstitial lung disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Using multisite sampling and molecular profiling, we identified specific eicosanoids with metabolic flux across the pulmonary circulation. Differential transpulmonary gradients of pro-inflammatory and anti-inflammatory eicosanoids were associated with abnormal lung function, underscoring potential relevance to chronic lung disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.01133-2025","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T13:50:16Z","timestamp":1761227416000},"page":"01133-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transpulmonary eicosanoid metabolite gradients: insights into metabolic flux of pro- and anti-inflammatory metabolites and lung function"],"prefix":"10.1183","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5244-0647","authenticated-orcid":false,"given":"Louisa A.","family":"Mounsey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8492-9930","authenticated-orcid":false,"given":"Mona","family":"Alotaibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhi K.","family":"Parekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7988-775X","authenticated-orcid":false,"given":"Sophie M.","family":"Nemeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna N.","family":"McNeill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8108-8240","authenticated-orcid":false,"given":"Gregory D.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"2026050510154315000_12.2.01133-2025.1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12931-023-02475-6","article-title":"Global, regional, and national burden of asthma and its attributable risk factors from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"24","author":"Wang","year":"2023","journal-title":"Respir Res"},{"key":"2026050510154315000_12.2.01133-2025.2","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1186\/s12889-024-20430-y","article-title":"Global health inequalities in the burden of interstitial lung disease and pulmonary sarcoidosis from 1990 to 2021","volume":"24","author":"Chen","year":"2024","journal-title":"BMC Public Health"},{"key":"2026050510154315000_12.2.01133-2025.3","unstructured":"World Health Organization (WHO). 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