Ear, Nose and Throat Disorders

Biography

Biography: Natasha Mirza

Abstract

Objective: Acquired Subglottic stenosis (SGS) is a pathologic process driven by airway epithelial injury. There is a lack of functional animal models of this condition.  The aims of this study were to (1) develop and (2) validate an animal model (3) identify inflammatory mediators associated with granulation formation and finally to (4) Identify the change in inflammatory profile using pulse steroid therapy.

Methods: Laryngotracheal complexes (LTCs) from C57BL/6 mice were divided into 3 groups: uninjured,  mechanically injured and chemically injured groups.  LTCs were harvested and then transplanted in to the backs of recipient mice. These transplanted LTCs) were harvested at 3 weeks, sectioned and stained with H & E and the lamina propria thickness was measured. PCR was then performed to study the levels of cytokines and a therapeutic intervention with intraperitoneal pulsed steroid injections was performed.  Validation of this mouse model was performed by studying the granulation tissue from human samples and similarly measuring the cytokines levels.

Results: A significant increase in the lamina propria was observed with formation of granulation tissue at week 3. Inflammatory mediators in the mechanical and chemical trauma groups showed that the levels of TGF beta, IL-1 and MMP9 were elevated. Validation of this animal model was achieved by examining tissue specimens taken from 10 patients with subglottic stenosis. Using PCR the same wound healing markers were elevated in both humans and mice. Finally the use of pulsed intraperitoneal steroid injections resulted in a significant decrease in the cytokines in the treated animals. 

Conclusion: This is a novel, validated animal model to study the development of Subglottic Stenosis.  Chemical and Mechanical Injury mimic pathologic processes and therapeutic interventions in this model allow a better understanding of the processes involved in aberrant wound healing.