A translational value of pulmonary function tests in a mouse model of bleomycin-induced pulmonary fibrosis: effects of approved therapies Nintedanib and Pirfenidone

Abstract

Pulmonary function tests (PFT’s) routinely implemented in clinics are the first step in the diagnosis of idiopathic pulmonary fibrosis. Evaluation of PFT’s in the mouse model of pulmonary fibrosis accompanied by histological readouts may improve clinical predictability of new therapeutic candidates. Forced expiration (FE) parameters are considered as the most predictive for restrictive pulmonary disorders. The aim of the study was to estimate the translational value of the PFT technique in the established mouse model by evaluating the effects of two approved therapies, pirfenidone and nintedanib. C57BL/6 mice were administered with bleomycin (BLM) intranasally and treated with pirfenidone or nintedanib from day 0 to day 14. Fourteen days after BLM challenge, PFT’s were assessed by using in vivo invasive lung function measurements. Histological evaluation was performed as modified Ashcroft score and digital analysis of de novo collagen deposition (CO1A1) and alpha-smooth muscle actin (αSMA) expression. Bleomycin challenge induced a significant decrease of forced vital capacity (FVC) and forced expiratory volume (FEV). Nintedanib treatment induced significant improvement of FE parameters, specifically 30% improvement of FVC and FEV100 in comparison to the vehicle control. Pirfenidone treatment showed no effect. These findings were confirmed with histological analysis. In conclusion, a good correlation of functional test results and clinical effect of nintedanib and pirfenidone was shown. Based on our findings, implementation of PFT could be a good platform to increase the translational value of the model.