{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T16:06:12Z","timestamp":1771430772574,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["K23DC020988\u201002"],"award-info":[{"award-number":["K23DC020988\u201002"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC018567\u201004"],"award-info":[{"award-number":["R01DC018567\u201004"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R56DC020736\u201007"],"award-info":[{"award-number":["R56DC020736\u201007"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010836","name":"American Laryngological, Rhinological and Otological Society","doi-asserted-by":"publisher","award":["Triological Society Career Development Award 14102"],"award-info":[{"award-number":["Triological Society Career Development Award 14102"]}],"id":[{"id":"10.13039\/100010836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Iatrogenic Laryngotracheal Stenosis (iLTS) is a pathologic narrowing of the laryngotracheal airway secondary to intubation injury. Inflammation plays a critical role in iLTS pathogenesis. However, the local immune mediators promoting inflammation and subsequent fibrosis remain poorly understood. Transcriptomic analysis of iLTS specimens using single\u2010cell RNA sequencing has revealed increased expression of the damage\u2010associated molecular pattern (DAMP), S100A8\/A9. The goal of this study is to define the role of S100A8\/A9 in iLTS pathogenesis in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>S100A8\/A9 expression was assessed using single\u2010cell RNA sequencing and immunofluorescence in human iLTS and unaffected tracheal controls. To assess the fibrogenicity of S100A8\/A9, iLTS\u2010induced mice were treated with recombinant S100A8\/A9 (0.1\u2009mg\/kg) or a vehicle control. Fibrosis was assessed by measurement of tracheal lamina propria (LP) thickness and fibrosis\u2010related gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunofluorescence of human iLTS specimens demonstrated increased expression of S100A8\/A9 in the LP compared to controls. In iLTS\u2010induced mice, S100A8\/A9 treatment resulted in greater LP thickness compared to control\u2010treated mice (117.7\u2009\u00b1\u200923.72 vs. 67.7\u2009\u00b1\u200933.11\u2009\u03bcM,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). Gene expression analysis demonstrated a 4.42\u2009\u00b1\u20090.73 fold increase in\n                      <jats:italic>Col1a1<\/jats:italic>\n                      expression in S100A8\/A9\u2010treated iLTS mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). S100A8\/A9's downstream regulatory protein MYD88 is increased in human iLTS and in iLTS mice treated with S100A8\/A9.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>S100A8\/A9 is abundant in human iLTS and promotes fibrosis in a murine model. Targeting S100A8\/A9 and its downstream signaling protein MYD88 may be an effective treatment strategy to attenuate iLTS. Investigation into therapies that target S100A8\/A9 signaling is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>NA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70008","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T07:20:24Z","timestamp":1754637624000},"page":"251-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>S100A8<\/scp>\n                    \/\n                    <scp>A9<\/scp>\n                    Promotes Fibrosis in Iatrogenic Laryngotracheal Stenosis"],"prefix":"10.1002","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9319-5761","authenticated-orcid":false,"given":"Laura M.","family":"Mafla","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Abd\u2010Elazem","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-7606","authenticated-orcid":false,"given":"Raymond J.","family":"So","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel L.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-8776","authenticated-orcid":false,"given":"Yee","family":"Chan\u2010Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-5449","authenticated-orcid":false,"given":"Alexander T.","family":"Hillel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9255-7265","authenticated-orcid":false,"given":"Kevin M.","family":"Motz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24956"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000228006.21941.12"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archoto.2009.175"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599816675323"},{"key":"e_1_2_8_6_1","first-page":"1402","article-title":"Idiopathic Subglottic Stenosis","volume":"76","author":"Brandenburg J. 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