Effect of pirfenidone injection on ferret vocal fold scars: A preliminary in vivo study

OBJECTIVES: This study examined the antifibrotic effect of pirfenidone (PFD), which has received regulatory approval in the United States and Japan for treatment of idiopathic pulmonary fibrosis, on the scarred ferret vocal fold (VF) in vivo. METHODS: Eight male ferrets were divided into two groups: saline and PFD. All animals underwent unilateral scarring under anesthesia. The right VF was electrocauterized with ablation of the entire lamina propria. PFD (1.0 mg/mL) or saline injections into right-side scarred VFs were performed (under an operating microscope) 4 weeks later. After an additional 4 weeks, the larynges were harvested for histological analysis. Prior to harvesting, the ferrets were re-anesthetized, and the VFs were observed and recorded using a rigid video laryngoscope. We immunohistochemically evaluated the expression of collagen types I and III, alpha-smooth muscle actin (alpha-SMA), and fibronectin in the entire lamina propria. We compared the affected areas (calculated using ImageJ software) between the treated (right) and untreated (left) sides within the same animals and between groups. RESULTS: Collagen type I (P = 0.0021) and alpha-SMA (P = 0.0021) expression levels were lower in the PFD group, but the collagen type III and fibronectin levels did not differ significantly between the two groups. CONCLUSION: PFD injection into the scarred VF is a potentially promising novel antifibrotic treatment. LEVEL OF EVIDENCE: NA Laryngoscope, 130:726-731, 2020.