Abstract
To evaluate pulmonary function analysis in murine respiratory disease models mostly, airway resistance (Rn) and compliance are used. Here, we aimed to validate FEV and correlate it to changes in Rn and compliance in different mouse models of lung disease and .
Using the flexiVent (Scireq, EMKA Technologies), we performed a forced oscillation perturbation to determine airway resistance (Rn), tissue elastance (E) and tissue damping (resistance, G), followed by a negative pressure forced expiration (NPFE), resulting in: FEV0.1, FEF0.1, FVC, PEF and FEV0.1/FVC to determine baseline indicators of disease. Next, airway hyperreactivity was assessed using methacholine (0 to 20 mg/ml), and both Rn and FEV0.1 were measured. The measurements were performed in three asthma models (house dust mite, chemical-induced and ovalbumin), an elastase emphysema model, a bleomycin fibrosis model, an LPS acute lung injury model and compared to healthy control mice.
In the lung fibrosis model, mice showed significantly decreased FEV0.1, FEF0.1 and FVC, along with increased H and G. In the emphysema model, mice showed significantly increased FEV0.1 and FVC, along with decreased H and G. The asthma models, showed no change at baseline Rn, but we found a significant decrease in FEV0.1. During the airway hyperreactivity provocation, FEV0.1 significantly decreased, while Rn significantly increased, as expected.
FEV0.1 measurements in mice show similarly results as described in human lung function assessment, both as descriptor of disease, as during airway hyperreactivity assessment. Especially for pre-clinical testing in mice, FEV0.1 is a promising alternative for classical airway resistance (Rn) measurements.
- Copyright ©the authors 2016