Microbiome Displacement, Adaptive Immunity Contribute to Scar Progression in iSGS

Gelbard A, Shilts MH, Hoke A, et al. Idiopathic Subglottic Stenosis and the Epithelial Interface of Host and Environment. J Am Coll Surg. 2025, in press.

Rosow DE. Idiopathic Subglottic Stenosis, the Epithelial Mesenchymal Transition, and Adaptive Immunity. J Am Coll Surg. 2025, in press.

Idiopathic subglottic stenosis (iSGS) is a rare condition causing tracheal obstruction in White women. Progressive narrowing of the airway due to fibrotic scar formation leads to respiratory distress; treatments include pharmacologic therapy, endoscopic scar dilation, tracheostomy, and scar resection.

This study provided valuable data on the mechanisms leading to scar formation. The authors used tissue from an international iSGS patient cohort; they performed single cell RNA sequencing to characterize the cell types and molecular phenotypes within the scar.

The analysis showed that there was depletion of basal progenitor cells; residual epithelial cells acquired a mesenchymal phenotype. Organisms from the patients’ microbiome were displaced into the lamina propria, and this finding led to additional investigations that confirmed activation of an adaptive immune response.

The authors concluded that microbiome displacement and the adaptive immune response contributed to scar progression. This mechanism strongly suggested that surgical resection of the scar with restoration of normal mucosa will be the most effective treatment for iSGS. Data presented in the article compared outcomes of various treatments and showed that surgical resection of the scar had a durable treatment response and low recurrence rates.

The editorial by Rosow agreed with the findings and suggested further research to determine if post-intubation tracheal stenosis occurs because of similar cellular and molecular changes.