{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:09:49Z","timestamp":1777493389423,"version":"3.51.4"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) is a severe organ failure occurring mainly in critically ill patients as a result of different types of insults such as sepsis, trauma or aspiration. Sepsis is the main cause of ARDS, and it contributes to a high mortality and resources consumption both in hospital setting and in the community. ARDS develops mainly an acute respiratory failure with severe and often refractory hypoxemia. ARDS also has long term implications and sequelae. Endothelial damage plays an important role in the pathogenesis of ARDS. Understanding the mechanisms of ARDS presents opportunities for novel diagnostic and therapeutic targets. Biochemical signals can be used in concert to identify and classify patients into ARDS phenotypes allowing earlier effective treatment with personalised therapies. This is a narrative review where we aimed to flesh out the pathogenetic mechanisms and heterogeneity of ARDS. We examine the links between endothelium damage and its contribution to organ failure. We have also investigated future strategies for treatment with a special emphasis in endothelial damage.<\/jats:p>","DOI":"10.3389\/fmed.2023.1203827","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T13:35:21Z","timestamp":1685712921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Endothelial dysfunction triggers acute respiratory distress syndrome in patients with sepsis: a narrative review"],"prefix":"10.3389","volume":"10","author":[{"given":"Rachael","family":"Cusack","sequence":"first","affiliation":[]},{"given":"Lieuwe D.","family":"Bos","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Povoa","sequence":"additional","affiliation":[]},{"given":"Ignacio","family":"Martin-Loeches","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","article-title":"Acute respiratory distress syndrome","volume":"5","author":"Matthay","year":"2019","journal-title":"Nat Rev Dis Primer"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1001\/jama.2012.5669","article-title":"Acute respiratory distress syndrome","volume":"307","author":"Ranieri","year":"2012","journal-title":"JAMA"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.ccm.2014.08.002","article-title":"Evolving epidemiology and definitions of the acute respiratory distress syndrome and early acute lung injury","volume":"35","author":"Sweatt","year":"2014","journal-title":"Clin Chest Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/s13054-022-04211-w","article-title":"Longitudinal phenotypes in patients with acute respiratory distress syndrome: a multi-database study","volume":"26","author":"Chen","year":"2022","journal-title":"Crit Care Lond Engl"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1164\/rccm.202002-0347OC","article-title":"Machine learning classifier models can identify acute respiratory distress syndrome phenotypes using readily available clinical data","volume":"202","author":"Sinha","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s13054-021-03578-6","article-title":"Latent class analysis to predict intensive care outcomes in acute respiratory distress syndrome: a proposal of two pulmonary phenotypes","volume":"25","author":"Wendel Garcia","year":"2021","journal-title":"Crit Care"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/s2213-2600(14)70097-9","article-title":"Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials","volume":"2","author":"Calfee","year":"2014","journal-title":"Lancet Respir Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.vph.2008.06.009","article-title":"Endothelial pathomechanisms in acute lung injury","volume":"49","author":"Maniatis","year":"2008","journal-title":"Vasc Pharmacol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.ccm.2014.08.004","article-title":"Clinical and biological heterogeneity in ARDS: direct versus indirect lung injury","volume":"35","author":"Shaver","year":"2014","journal-title":"Clin Chest Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"C799","DOI":"10.1152\/ajpcell.00555.2022","article-title":"The role of the alveolar epithelial glycocalyx in acute respiratory distress syndrome","volume":"324","author":"Rizzo","year":"2023","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1378\/chest.14-2454","article-title":"Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies","volume":"147","author":"Calfee","year":"2015","journal-title":"Chest"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"48s","DOI":"10.1183\/09031936.03.00420803","article-title":"Pulmonary and extrapulmonary acute respiratory distress syndrome are different","volume":"22","author":"Pelosi","year":"2003","journal-title":"Eur Respir J"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1078\/0344-0338-00266","article-title":"Acute remodeling of parenchyma in pulmonary and extrapulmonary ARDS. 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