Acute and chronic changes in the subglottis induced by graded carbon dioxide laser injury in the rabbit airway

Objective: To investigate the repair process following carbon dioxide laser injury to the upper airway mucosa (UAM) during the development of chronic subglottic stenosis (SGS). Design: Animals were assigned to either sham control (cricothyroidotomy only) or injured (cricothyroidotomy and posterior subglottic laser) groups using various carbon dioxide laser exposures (8, 12, and 16 W) for 4 seconds. Subjects: Twenty-four New Zealand white rabbits. Interventions: The subglottis was approached via cricothyroidotomy. Sham control airways were immediately closed, whereas injured air-ways were subjected to graded carbon dioxide laser exposures prior to closure. Airways were endoscopically monitored preoperatively, postoperatively, and on postoperative days 7, 14, 28, 42, 56, 70, and 84. Animals were killed at 14 and 84 days. Subglottic tissue was harvested for histologic evaluation (reepithelialization, extracellular matrix, vascularity, and inflammation). Main Outcome Measures: Endoscopic visualization and histologic analysis. Results: (1) Increases in UAM thickness (up to 5 times the thickness of normal mucosa) were observed but were limited primarily to the lamina propria. The mucosal epithelium regenerated without chronic changes. Focal areas of cartilage repair were encountered acutely after injury and to a greater extent in the chronic phases of repair. (2) Acutely, the thickened lamina propria comprised poorly organized extracellular matrix components and demonstrated increases in blood vessel size and number. (3) Histologic changes present in the acute phase only partially resolved in progression to chronic SGS. Chronic SGS was characterized by thick collagen fiber bundles extending into the remodeled subglottic cartilage. Conclusions: The carbon dioxide laser induces acute changes to lamina propria architecture and vascularity that persist chronically. Elucidating responsible signaling pathways may facilitate the development of therapeutic agents to prevent or reduce the formation of SGS.