Cyclooxygenase-2 Inhibition for the Prevention of Subglottic Stenosis

Objective To evaluate the role of targeted cyclooxygenase-2 inhibition in reducing scarring associated with a subglottic airway mucosal injury. Design Thirty-four New Zealand white rabbits underwent anterior cricothyroidotomy. Subglottic stenosis (SGS) was created by carbon dioxide laser injury. Intervention Treatment consisted of intraperitoneal injection of celecoxib or vehicle for 4 days. Endoscopies were performed to assess injury and healing. Subglottic mucosal secretions were collected with Gelfoam swabs (Pfizer Inc) before and after injury and at subsequent time points. Animals were humanely killed at 3 or 8 weeks after injury and airways were excised, followed by gross examination and histologic analysis to assess the severity of SGS. Secretions were analyzed for interleukin-1β, prostaglandin E2 (PGE2), and matrix metalloproteinase-8 by enzyme-linked immunosorbent assays. Results Endoscopy showed mild to moderate stenosis in the celecoxib group, but mild to severe stenosis in the vehicle group. Histologic assessment confirmed and quantified reduction in stenosis and scarring as well as advanced reepithelialization. In the healing tissue, mucosal thickening (stenosis) was reduced significantly (P = .02) in celecoxib-treated animals compared with those treated with vehicle, at 3 and 8 weeks (decrease in thickness by 32% and 49%, respectively). Collagen density (fibrosis) was also reduced 25% at both 3 and 8 weeks but the difference was not statistically significant (P = .20). Reduced level of PGE2 in the subglottic mucosal secretions was correlated with mucosal thickness at 8 weeks (P = .02). Conclusion Short-duration, anti-inflammatory therapy resulted in reduced stenosis and fibrosis with correlation of PGE2 levels in subglottic mucosal secretions.