Phenotypic Epithelial Changes in Laryngotracheal Stenosis

Ioan A. Lina, Hsiu Wen Tsai, Alexandra J. Berges, Rafael A. Ospino, Ruth J. Davis, Kevin M. Motz, Samuel Collins, Baishakhi Ghosh, Venkataramana Sidhaye, Alexander Gelbard, Alexander T. Hillel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2194-2201
Number of pages8
JournalLaryngoscope
Volume132
Issue number11
DOIs
StatePublished - Nov 2022

Keywords

  • Laryngotracheal stenosis
  • epithelium
  • iLTS
  • iSGS
  • iatrogenic
  • idiopathic subglottic stenosis
  • subglottic stenosis

ASJC Scopus subject areas

  • Otorhinolaryngology

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