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Noninvasive and Invasive Pulmonary Function in Mouse Models of Obstructive and Restrictive Respiratory Diseases

¹ Lung Toxicology Research Unit, ² Respiratory Muscle Research Unit, ³ Clinical Immunology, and ⁴ Morphology and Molecular Pathology Section, Katholieke Universiteit Leuven, Leuven, Belgium

Correspondence and requests for reprints should be addressed to Jeroen A.J. Vanoirbeek, Ph.D., Katholieke Universiteit Leuven, Lung Toxicology Research Unit, Herestraat 49 bus 706, 3000 Leuven, Belgium. E-mail: jeroen.vanoirbeek{at}med.kuleuven.be

Pulmonary function analysis is an important tool in the evaluation of mouse respiratory disease models, but much controversy still exists on the validity of some tests. Most commonly used pulmonary function variables of humans are not routinely applied in mice, and the question of which pulmonary function is optimal for the monitoring of a particular disease model remains largely unanswered. Our study aimed to delineate the potential and restrictions of existing pulmonary function techniques in different respiratory disease models, and to determine some common variables between humans and mice. A noninvasive (unrestrained plethysmography) and two invasive pulmonary function devices (forced maneuvers system from Buxco Research Systems [Wilmington, NC] and forced oscillation technique from SCIREQ [Montreal, PQ, Canada]) were evaluated in well-established models of asthma (protein and chemical induced): a model of elastase-induced pulmonary emphysema, and a model of bleomycin-induced pulmonary fibrosis. In contrast to noninvasive tests, both invasive techniques were efficacious for the quantification of parenchymal disease via changes in functional residual capacity, total lung capacity, vital capacity, and compliance of the respiratory system. Airflow obstruction and airflow limitation at baseline were only present in emphysema, but could be significantly induced after methacholine challenge in mice with asthma, which correlated best with an increase of respiratory resistance. Invasive pulmonary functions allow distinction between respiratory diseases in mice by clinically relevant variables, and should become standard in the functional evaluation of pathological disease models.

Key Words: BALB/c mice • forced maneuvers technique • forced oscillation technique • asthma • emphysema • fibrosis

CLINICAL RELEVANCE Pulmonary function analysis is an important tool in the evaluation of mouse respiratory disease models but much controversy still exists on the usefulness and validity of some of the tests. Most commonly used pulmonary function variables of humans are not measured in mice, which complicates the search for an optimal pulmonary function assessment in corresponding disease models. This study is the first to evaluate the current leading technologies for pulmonary function measurements in three different and contrasting laboratory models of respiratory diseases. The study offers reference values and a better insight in the variables that are appropriate to describe lung diseases in mice.