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Separate specimens were used for epithelial cell expansion in vitro to assess average growth rate and functional capabilities using transepithelial\u2010electrical resistance (TEER), fluorescein isothiocyanate\u2010dextran flux permeability assay, ciliary coverage, and cilia beating frequency (CBF). Finally, epithelial tight junction protein expression of cultured cells was quantified using immunoblot assay (<jats:italic>n<\/jats:italic>\u2009=\u20094) and immunofluorescence (<jats:italic>n<\/jats:italic>\u2009=\u20096).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>scRNA\u2010seq analysis revealed a decrease in goblet, ciliated, and basal epithelial cells in the scar iSGS cohort. Furthermore, mRNA expression of proteins E\u2010cadherin, claudin\u20103, claudin\u201010, occludin, TJP1, and TJP2 was also reduced (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in scar epithelium. Functional assays demonstrated a decrease in TEER (paired 95% confidence interval [CI], 195.68\u2013890.83\u2009\u03a9\u2009\u00d7\u2009cm<jats:sup>2<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), an increase in permeability (paired 95% CI, \u22126116.00 to \u22121401.99 RFU, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), and reduced epithelial coverage (paired 95% CI, 0.1814\u20131.766, fold change <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in iSGS\u2010scar epithelium relative to normal controls. No difference in growth rate (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) or CBF was found (paired 95% CI, \u22122.118 to 3.820\u2009Hz, <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). Immunoblot assay (paired 95% CI, 0.0367\u20130.605, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and immunofluorescence (paired 95% CI, 13.748\u201359.191 mean grey value, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) revealed E\u2010cadherin reduction in iSGS\u2010scar epithelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>iSGS\u2010scar epithelium has a dysfunctional barrier and reduced structural protein expression. These results are consistent with dysfunctional epithelium seen in other airway pathology. Further studies are warranted to delineate the causality of epithelial dysfunction on the downstream fibroinflammatory cascade in iSGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 134:374\u2013381, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30951","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T12:20:56Z","timestamp":1691670056000},"page":"374-381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dysfunctional Epithelial Barrier Is Characterized by Reduced <scp>E\u2010Cadherin<\/scp> in Idiopathic Subglottic Stenosis"],"prefix":"10.1002","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-6291","authenticated-orcid":false,"given":"Alexandra J.","family":"Berges","sequence":"first","affiliation":[{"name":"Johns Hopkins Department of Otolaryngology\u2013Head and Neck 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Hopkins Department of Otolaryngology\u2013Head and Neck Surgery  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baishakhi","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataramana","family":"Sidhaye","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland U.S.A."},{"name":"Johns Hopkins Division of Pulmonary and Critical Care Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-7312","authenticated-orcid":false,"given":"Ioan","family":"Lina","sequence":"additional","affiliation":[{"name":"Johns Hopkins Department of Otolaryngology\u2013Head and Neck Surgery  Baltimore Maryland 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