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.


METHODS
Thirty-four New Zealand white rabbits underwent anterior cricothyroidotomy. Subglottic stenosis (SGS) was created by carbon dioxide laser injury.


METHODS
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).


CONCLUSIONS
Short-duration, anti-inflammatory therapy resulted in reduced stenosis and fibrosis with correlation of PGE2 levels in subglottic mucosal secretions.
Division of Pediatric Otolaryngology, Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Selma
S
Cetin
Allison B
AB
Tobey
Vlad C
VC
Sandulache
Tianbing
T
Yang
Mark
M
Barsic
Yan
Y
Lin
Joseph E
JE
Dohar
Patricia A
PA
Hebda
D000818:Animals; D000068579:Celecoxib; D002921:Cicatrix / Q000517:prevention & control; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D007829:Laryngostenosis / Q000517:prevention & control*; D009092:Mucous Membrane / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000627:therapeutic use; D011817:Rabbits; D013449:Sulfonamides / Q000627:therapeutic use; D014945:Wound Healing / Q000502:physiology
D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015232:Dinoprostone