The use of plethysmography in determining the severity of lung pathology in a mouse model of minimally lethal influenza virus infection.

To characterize the impact on lung function, we assessed plethysmography parameters in a course of infection with mouse-adapted A/Pennsylvania/14/2010 (H3N2) influenza virus. Several parameters, represented by enhanced pause (penh) and ratio of inspiratory/expiratory time (Ti/Te), were observed that had early (1-7dpi) and robust changes regardless of virus challenge dose. Other parameters, characterized by tidal volume (TV), breathing frequency (freq) and end inspiratory pause (EIP), changed later (7-15dpi) during the course of infection and had a virus challenge dose effect. A third category of lung function parameters, such as peak inspiratory flow, had early, virus challenge-independent changes followed by later changes that were challenge dependent. These parameters changed in a similar manner after infection with a non-mouse adapted virus, although the time-course of many parameters was delayed somewhat when compared with mouse-adapted virus. Histopathological assessment of lung samples corresponded with changes in lung function parameters. This study demonstrates the utility of plethysmography in assessing disease in a mouse model of mild influenza virus infection.