{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:43:44Z","timestamp":1791150224521,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labour, and Welfare, Japan"},{"name":"NPO Respiratory Disease Conference"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Drug\u2010induced lung injury (<jats:styled-content style=\"fixed-case\">DLI<\/jats:styled-content>) can result from a vast number of agents, and sometimes presents findings similar to those of acute respiratory distress syndrome (<jats:styled-content style=\"fixed-case\">ARDS<\/jats:styled-content>). Previous studies have reported that circulating levels of soluble thrombomodulin (<jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content>) reflect endothelial injuries, which play key roles in the development of <jats:styled-content style=\"fixed-case\">ARDS<\/jats:styled-content>. We hypothesized that endothelial injuries are an important aspect of pathogenesis in severe <jats:styled-content style=\"fixed-case\">DLI<\/jats:styled-content>. The primary aim of this study was to examine the associations between soluble <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> and disease severity in <jats:styled-content style=\"fixed-case\">DLI<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of the 2580 patients who underwent a bronchoalveolar lavage (<jats:styled-content style=\"fixed-case\">BAL<\/jats:styled-content>) procedure at Tosei General Hospital between May 2007 and February 2015, we retrospectively analysed the data of 68 <jats:styled-content style=\"fixed-case\">DLI<\/jats:styled-content> patients. Soluble <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> in plasma and <jats:styled-content style=\"fixed-case\">BAL<\/jats:styled-content> fluid (<jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content>), and other biomarkers were included in our analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the time of diagnosis, 39 patients (57%) had respiratory failure (partial pressure of oxygen\/inspiratory oxygen fraction ratio, <jats:styled-content style=\"fixed-case\">PaO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FiO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content> ratio\u2009&lt;\u2009300). There was a significant negative linear correlation between the <jats:styled-content style=\"fixed-case\">PaO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FiO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content> ratio and soluble <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content> (r\u2009=\u2009\u22120.448, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). In a stepwise multiple regression analysis, soluble <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content> and surfactant protein D (<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010D) were the only independent determinants of the <jats:styled-content style=\"fixed-case\">PaO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FiO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content> ratio. Additionally, in a multivariate logistic regression model, soluble <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content> (adjusted <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">aOR<\/jats:styled-content>): 7.48, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.60\u201334.98) and <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>\u2010D (<jats:styled-content style=\"fixed-case\">aOR<\/jats:styled-content>: 5.31, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 1.40\u201320.15) was an independent predictor of respiratory failure (<jats:styled-content style=\"fixed-case\">PaO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">FiO<jats:sub>2<\/jats:sub>\n<\/jats:styled-content> ratio\u2009&lt;\u2009300).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Soluble <jats:styled-content style=\"fixed-case\">TM<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">BALF<\/jats:styled-content> is an independent predictor of severe <jats:styled-content style=\"fixed-case\">DLI<\/jats:styled-content>. These findings underscore the importance of pulmonary endothelial injuries in the pathogenesis of severe <jats:styled-content style=\"fixed-case\">DLI<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.12965","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T08:09:14Z","timestamp":1481962154000},"page":"744-749","source":"Crossref","is-referenced-by-count":9,"title":["Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug\u2010induced lung injury"],"prefix":"10.1111","volume":"22","author":[{"given":"Atsushi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Tosei General Hospital  Seto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Tosei General Hospital  Seto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Kondoh","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Tosei General Hospital  Seto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Ando","sequence":"additional","affiliation":[{"name":"Center for Advanced Medicine and Clinical Research Nagoya University Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Tosei General Hospital  Seto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Tosei General Hospital  Seto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergy Tosei General Hospital  Seto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","unstructured":"KuboK AzumaA KanazawaM KamedaH KusumotoM GenmaA SaijoY SakaiF SugiyamaY TatsumiKet al.;Japanese Respiratory Society Committee for formulation of consensus statement for the diagnosis and treatment of drug\u2010induced lung injuries. Consensus statement for the diagnosis and treatment of drug\u2010induced lung injuries.Respir.Investig.2013;51:260\u201377.","DOI":"10.1016\/j.resinv.2013.09.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000079633"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874306401206010063"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.97.10020265"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-0851"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-13-39"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-133"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2103"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421806"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22782"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1055\/s-0038-1648199","article-title":"Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells","volume":"65","author":"Ishii H","year":"1991","journal-title":"Thromb. Haemost."},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.1.9612021"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00442.2002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","unstructured":"SapluA CalfeeCS LiuKD KangelarisK HansenH PawlikowskaL WareLB AlkhouliMF AbbottJ MatthayMA;NHLBI ARDS Network. Plasma soluble thrombomodulin levels are associated with mortality in the acute respiratory distress syndrome.Intensive Care Med.2015;41:470\u20138.","DOI":"10.1007\/s00134-015-3648-x"},{"key":"e_1_2_7_16_1","first-page":"717","article-title":"AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility \u2013 2002 revision & update","volume":"47","author":"Kallstrom TJ","year":"2002","journal-title":"Respir. Care"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-2746"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-5231(03)00143-6"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2008.01.005"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00138"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.11.983"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00061.2012"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.10.872"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/806014"},{"key":"e_1_2_7_25_1","first-page":"79","article-title":"Detection of thrombomodulin in human lung cancer cells","volume":"142","author":"Tamura A","year":"1993","journal-title":"Am. J. Pathol."}],"container-title":["Respirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fresp.12965","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fresp.12965","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/resp.12965","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T14:47:39Z","timestamp":1696171659000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/resp.12965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1111\/resp.12965"],"URL":"https:\/\/doi.org\/10.1111\/resp.12965","archive":["Portico"],"relation":{},"ISSN":["1323-7799","1440-1843"],"issn-type":[{"value":"1323-7799","type":"print"},{"value":"1440-1843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]}}}