Azithromycin Prevents Subglottic Stenosis in Mice.

Area of Science:

• Otolaryngology
• Pulmonology
• Pharmacology

Background:

• Pediatric subglottic stenosis (SGS) involves airway narrowing due to pathological fibroblast activity and extracellular matrix deposition.
• Recent observations suggest azithromycin may reduce SGS, potentially by impacting airway infections and the microbiome.
• This study investigates azithromycin's therapeutic effects against SGS.

Purpose of the Study:

• To characterize the immunomodulatory and antibacterial protective effects of azithromycin against subglottic stenosis.
• To assess azithromycin's impact on fibroblast-mediated extracellular matrix production and myofibroblast differentiation.
• To evaluate azithromycin's efficacy in a murine model of SGS.

Main Methods:

• In vitro: Azithromycin's effects on TGF-β1-stimulated fibroblasts were assessed for gene expression (RT-qPCR) and myofibroblast differentiation (α-SMA immunostaining).
• In vivo: Mice were pretreated with intranasal azithromycin before SGS induction via wire brush injury.
• Disease severity and immune cell infiltration were analyzed using histology and immunostaining.

Main Results:

• Azithromycin significantly reduced extracellular matrix and myofibroblast gene expression (COL1A1, LOX, ACTA2) in vitro.
• α-SMA immunostaining showed decreased myofibroblast differentiation in azithromycin-treated fibroblasts.
• In vivo, azithromycin treatment led to reduced lamina propria thickness and altered T-cell infiltration, indicating decreased stenosis.

Conclusions:

• Azithromycin effectively prevents pro-fibrotic gene expression and myofibroblast differentiation.
• The study demonstrates azithromycin's protective effect against the development of subglottic stenosis in a murine model.
• Azithromycin is proposed as a potential therapeutic agent for treating pediatric subglottic stenosis.