{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:39:09Z","timestamp":1790948349777,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1K23DC014082"],"award-info":[{"award-number":["1K23DC014082"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010836","name":"Triological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005301","name":"American College of Surgeons","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Objective\/Hypothesis<\/jats:title><jats:p>This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inflammation was assessed by histology and immunofluorescence (IF), quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>iLTS specimens showed increased inflammation versus normal controls (159\/high power field [hpf] vs. 119\/hpf, <jats:italic>P<\/jats:italic>\u2009=\u20090.038), and increased CD3\u2009+\u2009T\u2010cells, CD4\u2009+\u2009cells, and CD3+\/CD4\u2009+\u2009T\u2010helper (T<jats:sub>H<\/jats:sub>) cells (all <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT\u2010PCR showed a significant increase in interleukin (IL)\u20104 gene expression, indicating a T<jats:sub>H<\/jats:sub>2 phenotype. Murine IF revealed a dense CD4\u2009+\u2009T\u2010cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT\u2010PCR studies mirrored the human ones, with increased T\u2010helper cells and IL\u20104 in iLTS versus normal controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CD3\/CD4\u2009+\u2009T\u2010helper lymphocytes and the proinflammatory cytokine IL\u20104 are associated with iLTS. The association of a T<jats:sub>H<\/jats:sub>2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well\u2010developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL\u20104 by T\u2010helper lymphocytes may continue to propagate iLTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 129:177\u2013186, 2019<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.27321","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T09:02:52Z","timestamp":1542099772000},"page":"177-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["T\u2010Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-5449","authenticated-orcid":false,"given":"Alexander T.","family":"Hillel","sequence":"first","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Otolaryngology\u2013Head and Neck Surgery  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Otolaryngology\u2013Head and Neck Surgery  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idris","family":"Samad","sequence":"additional","affiliation":[{"name":"University of Ottawa Faculty of Medicine, Otolaryngology\u2013Head and Neck Surgery  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Murphy","sequence":"additional","affiliation":[{"name":"State University of New York Upstate Medical University, Otolaryngology and Communication  Syracuse NY U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Motz","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Department of Otolaryngology\u2013Head and Neck Surgery  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489414564249"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24410"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940911800312"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24956"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348948609500617"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-005-0929-y"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23771"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599816675323"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.22364"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489415608867"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000228006.21941.12"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2009.10.024"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599812466533"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348948309200417"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.127.10.1260"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20056"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-71665-2_1"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2277"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599810397750"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2014.1663"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1412"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599815589106"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599817706930"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.6A7119.2007"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26098"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2735"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22927"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108984"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1843.1999.00209.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.4049\/jimmunol.152.7.3606","article-title":"Subsets of murine lung fibroblasts express membrane\u2010bound and soluble IL\u20104 receptors. 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