Repeated lung function measurements do not accentuate experimental lung fibrosis in mice

Besides imaging techniques, assessment of lung function is an important clinical tool for the diagnosis and monitoring of chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). In mice, lung function maneuvers are usually performed using algorithm-based ventilation strategies including forced oscillation technique (FOT), negative pressure-driven forced expiratory (NPFE) and pressure-volume (PV) maneuvers via the FlexiVent system. Lung function tests (LFTs) in mice require a tracheotomy and therefore are performed as end-point measurement only. For this reason, several mice are needed for each time point to be analyzed. Repeated LFT would allow monitoring of a disease process in one and the same individual while reducing numbers of laboratory animals. However, its feasibility in mice and impact on developing lung fibrosis has not been studied so far. Using orotracheal cannulation without surgical exposure of the trachea, we examined the tolerability to repeated LFT (up to four times) in one and the same mouse, both under healthy conditions and in a model of AdTGF-β1 induced lung fibrosis. Together, our data show that repeated LFTs were feasible and well tolerated in the same mice with developing lung fibrosis and allowed a detailed longitudinal evaluation of lung mechanics. Implementation of reproducible, repeated lung function analyses will help to reduce numbers of animals in experimental studies.