Transcriptomic Profile Changes in Benign Tracheal Stenosis: Wedge Resection vs. Radial Incision

Benign tracheal stenosis (BTS) is an uncommon but potentially life-threatening condition caused by fibroinflammatory scarring that narrows the airway. Etiologies include post-intubation, tracheostomy, and idiopathic disease. Bronchoscopic intervention is the first-line treatment; however, recurrence rates exceed 50%, and the optimal technique remains uncertain. Two widely used modalities-carbon dioxide (CO₂) laser wedge resection and radial incision with dilation-have never been directly compared in a randomized trial. Preliminary evidence, including our meta-analysis, suggests wedge resection may yield lower recurrence rates and longer recurrence-free intervals, but the biological mechanisms underlying these differences remain unknown. This project will conduct a randomized pilot study of 40 BTS patients comparing CO₂ laser wedge resection and radial incision with dilation. Endobronchial biopsies will be collected before and one month after intervention and analyzed using bulk ribonucleic acid (RNA) sequencing and spatial transcriptomics to capture both global and spatially resolved gene expression changes. This dual-modality approach will map molecular pathways involved in fibrosis resolution, immune cell dynamics, and epithelial repair. Patients will be followed for two years with standardized clinical, physiologic, and imaging assessments, and molecular signatures will be correlated with recurrence-free survival and other clinically meaningful outcomes. By combining prospective clinical data with high-resolution transcriptomic profiling, this study addresses critical gaps in mechanistic understanding and comparative effectiveness evidence for BTS management. The findings will establish a biologic framework for selecting optimal bronchoscopic approaches, identify candidate therapeutic targets to prevent recurrence, and generate effect-size estimates to power a future multicenter randomized controlled trial.