{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T09:36:39Z","timestamp":1793957799432,"version":"4.8.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"American Heart Foundation","award":["24SCEFIA1262494"],"award-info":[{"award-number":["24SCEFIA1262494"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["KO8HL153953"],"award-info":[{"award-number":["KO8HL153953"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Child Health and Human Development","award":["R01HD09382"],"award-info":[{"award-number":["R01HD09382"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Inflamm"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although studies have evaluated the presence of cell-free DNA and neutrophil extracellular traps (NETs) in acute respiratory distress syndrome (ARDS), the kinetics of NET formation during the early ICU admission and whether plasma NET markers correlate with clinical outcomes in patients with moderate-to-severe hypoxemia remain unknown. We sought to determine whether serial plasma NET marker levels in study participants collected over 48\u00a0h post enrollment predict disease severity and mortality in non-COVID-19 ARDS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We obtained previously collected plasma samples (trial enrollment, 24\u00a0h, 48\u00a0h) from 200 randomly selected ARDS participants in the completed Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) Trial, as well as from 20 healthy control donors. We determined plasma levels of surrogate biomarkers for NETs using a cell-free DNA fluorescence assay and a plasma myeloperoxidase (MPO)-DNA complex ELISA. We correlated these surrogate biomarker levels with clinical outcomes from the ROSE trial study participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ROSE plasma samples demonstrated significantly higher NET levels compared to healthy donor controls. Individual study participant NET levels did not change over the forty-eight hours after trial enrollment. Higher levels of both surrogate markers correlated with fewer ventilator-free days, but only cell free-DNA correlated with mortality and higher illness severity scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Surrogate markers for plasma NET levels measured in patients with moderate or severe ARDS correlate directly with adverse clinical outcomes and may serve as biomarkers for predicting severe disease. Further studies of surrogate biomarkers for NET formation in moderate-to-severe ARDS are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12950-025-00448-8","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T06:37:05Z","timestamp":1749796625000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Plasma surrogate markers of neutrophil extracellular traps correlate with disease severity in patients with moderate to severe acute respiratory distress syndrome"],"prefix":"10.1186","volume":"22","author":[{"given":"Joni A.","family":"Aoki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Denorme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Cody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Rustad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Middleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian C.","family":"Yost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle S.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the NHLBI Prevention and Early Treatment of Acute Lung Injury (PETAL) Network Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"448_CR1","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1001\/jama.2017.21907","volume":"319","author":"E Fan","year":"2018","unstructured":"Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA. 2018;319:698\u2013710.","journal-title":"JAMA"},{"key":"448_CR2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","volume":"5","author":"MA Matthay","year":"2019","unstructured":"Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5:18:1\u201322.","journal-title":"Nat Rev Dis Primers"},{"key":"448_CR3","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1056\/NEJMra1608077","volume":"377","author":"BT Thompson","year":"2017","unstructured":"Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. N Engl J Med. 2017;377:562\u201372.","journal-title":"N Engl J Med"},{"key":"448_CR4","doi-asserted-by":"publisher","first-page":"3783","DOI":"10.1172\/JCI83873","volume":"126","author":"CC Yost","year":"2016","unstructured":"Yost CC, Schwertz H, Cody MJ, Wallace JA, Campbell RA, Vieira-de-Abreu A, Araujo CV, Schubert S, Harris ES, Rowley JW, Rondina MT, Fulcher JM, Koening CL, Weyrich AS, Zimmerman GA. Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation. J Clin Invest. 2016;126:3783\u201398.","journal-title":"J Clin Invest"},{"key":"448_CR5","doi-asserted-by":"crossref","unstructured":"Denorme F, Portier I, Rustad JL, Cody MJ, de Araujo CV, Hoki C, Alexander MD, Grandhi R, Dyer MR, Neal MD, Majersik JJ, Yost CC, Campbell RA. Neutrophil extracellular traps regulate ischemic stroke brain injury. 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J Thorac Oncol. 2021;16:537\u201345.","journal-title":"J Thorac Oncol"}],"container-title":["Journal of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12950-025-00448-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12950-025-00448-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12950-025-00448-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T06:37:08Z","timestamp":1749796628000},"score":1,"resource":{"primary":{"URL":"https:\/\/journal-inflammation.biomedcentral.com\/articles\/10.1186\/s12950-025-00448-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["448"],"URL":"https:\/\/doi.org\/10.1186\/s12950-025-00448-8","relation":{},"ISSN":["1476-9255"],"issn-type":[{"value":"1476-9255","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]},"assertion":[{"value":"13 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki, ensuring the protection of all human participants through informed consent, risk\u2013benefit analysis, and appropriate safeguards for vulnerable populations.The PETAL Pathogenesis Committee approved this study as an ancillary NET study in October of 2020, and provided the samples to the University of Utah in July of 2021. We obtained plasma samples from 200 randomly chosen study participants who survived for at least forty-eight hours. The PETAL Pathogenesis Committee ensured that all ROSE trial plasma samples and clinical information were de-identified prior to arrival at the University of Utah. We also collected plasma from twenty healthy donors enrolled by our laboratory using our institutional protocol at the University of Utah for blood sampling of healthy volunteers (IRB# 0051506).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22"}}