Noninvasive and invasive pulmonary function in mice with obstructive and restrictive respiratory diseases

Pulmonary function analysis has become an important tool in the evaluation of different murine respiratory disease models. It is still unclear however, which test is optimal for a particular disease as the most commonly used pulmonary function variables of humans are not routinely applied in mice. With this study we wanted to delineate the potential and restrictions of several existing pulmonary function techniques and validate some common variables between humans and mice.We therefore evaluated one noninvasive (whole body plethysmography) and two invasive pulmonary function setups (forced maneuvers system from Buxco and forced oscillation technique-FlexiVent from Scireq) in different mouse models. Two models of asthma (occupational and allergic), a model of pulmonary emphysema and a model of pulmonary fibrosis were compared with healthy controls. We found that noninvasive tests were not useful for our purpose. However, invasive forced expiratory flow-volume curves adequately measured hyper-responsiveness to methacholine, airflow limitation and airway obstruction, which best correlated with the invasive measurement of respiratory resistance. Both invasive techniques were efficacious for the quantification of restriction or hyperinflation via changes in total lung capacity or vital capacity, and compliance of the respiratory system was proven to be useful and specific in this setting. Forced oscillation variables may have less clinical value but were shown to be additional for the further description of the underlying lung disease. We conclude that invasive pulmonary functions are very useful in the description of respiratory disease models and may bring murine models more close to human pathology.

Publication year:2009