Measuring severe lung disease in mice - a cautionary tale

Background: The flexiVent small animal ventilator (SCIREQ, Canada) allows measurement of detailed respiratory mechanics on animals as small as 10g. It uses the forced oscillation technique (FOT) to measure respiratory system impedence (Zrs) by applying a signal containing 19 mutually prime sinusoidal frequencies ranging from 0.25 to 19.625 Hz at the airway opening. The constant phase model (CPM) is fit to Zrs to calculate airway resistance (Raw) tissue damping (G) and tissue elastance (H). The default settings of flexiVent apply an unweighted (absolute) fitting of the CPM to the Zrs spectra. This may not be appropriate for mice with severe lung disease.

Methods: Adult female BALB/c mice with influenza-induced lung disease were challenged with methacholine (MCh). Data were analysed using the default “primewave” settings of flexiVent v5.1. These same data were then adjusted to remove the two lowest frequencies (0.25 and 0.625 Hz) and a relative (weighted) fitting of the CPM was applied.

Results: The default analysis produced a poor model fit and uninterpretable measurements of Raw, G and H, especially at higher MCh concentrations. Applying the weighted fitting improved the application of the CPM to Zrs spectra. A better partitioning of the CPM into airway and tissue compartments was achieved by removing the lowest two frequencies from the analysis.

Conclusion: The default flexiVent settings provided by SCIREQ are not suitable for accurate measurement of lung mechanics in mouse models of severe lung disease.