Subglottic stenosis examined as a fibrotic response to airway injury characterized by altered mucosal fibroblast activity.
OBJECTIVE
To investigate the association between mucosal fibroblast activity and subglottic stenosis (SGS) development.


METHODS
Prospective study of an animal model of SGS.


METHODS
Academic research laboratory.


METHODS
New Zealand white rabbits were assigned to either the cricothyroidotomy and carbon dioxide laser injury group or the cricothyroidotomy and silver nitrate injury group. Airways were excised for histologic analysis and the establishment of primary fibroblast cultures. Lesions from surgical excision of established SGS and subglottic tissue were used to analyze SGS recurrence.


METHODS
The subglottis was approached via cricothyroidotomy and was subjected to either carbon dioxide laser or silver nitrate injury before closure. The SGS lesions were excised at 8 to 10 weeks and were used to establish explants for fibroblast culture. The animals underwent recovery for an additional 14 days to follow recurrence of SGS. After 14 days, all the animals were killed humanely, and subglottic tissue was harvested for histologic evaluation. Rates of migration and contraction of SGS and normal airway fibroblasts were assayed using established in vitro methods under basal conditions and with prostaglandin E(2) treatment.


METHODS
For in vivo studies, injury, healing, and scarring of the mucosa and cartilage were the primary measures. For cultured fibroblast experiments, cellular responses of fibroblasts from normal and stenosed mucosa were compared and contrasted.


RESULTS
Mucosal injury resulted in acute fibroplasia and chronic SGS, surgical excision of mature SGS at 8 weeks resulted in rapid recurrence of stenosis, and SGS-derived fibroblasts were relatively refractory to the effects of prostaglandin E(2) on migration and contraction.


CONCLUSIONS
Subglottic stenosis represents a fibrotic airway repair process that involves fibroblasts that produce recurrent, excessive scar formation. We suggest that SGS development and recurrence may be partially dictated by altered fibroblast responsiveness to antifibroplastic signals during mucosal repair.
Singh
Tripti
T
Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, PA 15224, USA.
Sandulache
Vlad C
VC
Otteson
Todd D
TD
Barsic
Mark
M
Klein
Edwin C
EC
Dohar
Joseph E
JE
Hebda
Patricia A
PA
D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology*; D005355:Fibrosis; D005931:Glottis / Q000473:pathology*; D007829:Laryngostenosis / Q000473:pathology* / Q000503:physiopathology; D011817:Rabbits; D020545:Respiratory Mucosa / Q000293:injuries / Q000473:pathology*; D014945:Wound Healing