PMID- 35141889 OWN - NLM STAT- MEDLINE DCOM- 20221018 LR - 20221230 IS - 1531-4995 (Electronic) IS - 0023-852X (Print) IS - 0023-852X (Linking) VI - 132 IP - 11 DP - 2022 Nov TI - Phenotypic Epithelial Changes in Laryngotracheal Stenosis. PG - 2194-2201 LID - 10.1002/lary.30040 [doi] AB - OBJECTIVE: Characterize and quantify epithelium in multiple etiologies of laryngotracheal stenosis (LTS) to better understand its role in pathogenesis. STUDY DESIGN: Controlled in vitro cohort study. METHODS: Endoscopic brush biopsy samples of both normal (non-scar) and scar were obtained in four patients with idiopathic subglottic stenosis (iSGS) and four patients with iatrogenic LTS (iLTS). mRNA expression of basal, ciliary, and secretory cell markers were evaluated using quantitative PCR. Cricotracheal resection tissue samples (n = 5 per group) were also collected, analyzed using quantitative immunohistochemistry, and compared with rapid autopsy tracheal samples. RESULTS: Both iSGS and iLTS-scar epithelium had reduced epithelial thickness compared with non-scar control epithelium (P = .0009 and P = .0011, respectively). Basal cell gene and protein expression for cytokeratin 14 was increased in iSGS-scar epithelium compared with iLTS or controls. Immunohistochemical expression of ciliary tubulin alpha 1, but not gene expression, was reduced in both iSGS and iLTS-scar epithelium compared with controls (P = .0184 and P = .0125, respectively). Both iSGS and iLTS-scar had reductions in Mucin 5AC gene expression (P = .0007 and P = .0035, respectively), an epithelial goblet cell marker, with reductions in secretory cells histologically (P < .0001). CONCLUSIONS: Compared with non-scar epithelium, the epithelium within iSGS and iLTS is morphologically abnormal. Although both iSGS and iLTS have reduced epithelial thickness, ciliary cells, and secretory cells, only iSGS had significant increases in pathological basal cell expression. These data suggest that the epithelium in iSGS and iLTS play a common role in the pathogenesis of fibrosis in these two etiologies of laryngotracheal stenosis. SETTING: Tertiary referral center (2017-2020). LEVEL OF EVIDENCE: NA Laryngoscope, 132:2194-2201, 2022. CI - (c) 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc. FAU - Lina, Ioan A AU - Lina IA AUID- ORCID: 0000-0002-8619-7312 AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Tsai, Hsiu-Wen AU - Tsai HW AUID- ORCID: 0000-0002-2837-6769 AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Berges, Alexandra J AU - Berges AJ AUID- ORCID: 0000-0002-0890-6291 AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Ospino, Rafael A AU - Ospino RA AUID- ORCID: 0000-0002-8501-1934 AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Davis, Ruth J AU - Davis RJ AUID- ORCID: 0000-0001-9592-932X AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Motz, Kevin M AU - Motz KM AUID- ORCID: 0000-0002-9255-7265 AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Collins, Samuel AU - Collins S AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. FAU - Ghosh, Baishakhi AU - Ghosh B AD - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, U.S.A. FAU - Sidhaye, Venkataramana AU - Sidhaye V AD - Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, U.S.A. AD - Department of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, U.S.A. FAU - Gelbard, Alexander AU - Gelbard A AD - Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A. FAU - Hillel, Alexander T AU - Hillel AT AUID- ORCID: 0000-0001-8471-5449 AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. LA - eng GR - R01 DC018567/DC/NIDCD NIH HHS/United States GR - R21 DC017225/DC/NIDCD NIH HHS/United States GR - R01 HL124099/HL/NHLBI NIH HHS/United States GR - R01 HL151107/HL/NHLBI NIH HHS/United States GR - 1R01HL146401-01/HL/NHLBI NIH HHS/United States GR - T32DC000027/DC/NIDCD NIH HHS/United States GR - T32 DC000027/DC/NIDCD NIH HHS/United States GR - R01 HL146401/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220210 PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 0 (Keratin-14) RN - 0 (Mucin 5AC) RN - 0 (RNA, Messenger) RN - 0 (Tubulin) SB - IM MH - Cicatrix/pathology MH - Cohort Studies MH - Constriction, Pathologic/complications MH - Humans MH - Keratin-14 MH - *Laryngostenosis/surgery MH - Mucin 5AC MH - RNA, Messenger MH - *Tracheal Stenosis/pathology MH - Tubulin PMC - PMC9363526 MID - NIHMS1818459 OTO - NOTNLM OT - Laryngotracheal stenosis OT - epithelium OT - iLTS OT - iSGS OT - iatrogenic OT - idiopathic subglottic stenosis OT - subglottic stenosis EDAT- 2022/02/11 06:00 MHDA- 2022/10/19 06:00 PMCR- 2022/12/25 CRDT- 2022/02/10 05:42 PHST- 2021/12/13 00:00 [revised] PHST- 2021/09/15 00:00 [received] PHST- 2022/01/19 00:00 [accepted] PHST- 2022/02/11 06:00 [pubmed] PHST- 2022/10/19 06:00 [medline] PHST- 2022/02/10 05:42 [entrez] PHST- 2022/12/25 00:00 [pmc-release] AID - LARY30040 [pii] AID - 10.1002/lary.30040 [doi] PST - ppublish SO - Laryngoscope. 2022 Nov;132(11):2194-2201. doi: 10.1002/lary.30040. Epub 2022 Feb 10.