Rodent Models of Lung Disease: A Road Map for Translational Research.

Abstract

Animal models provide a controlled and reproducible environment for investigating the pathogenesis of human lung diseases. In many cases, the morphological changes associated with a particular model may resemble those seen in their human counterparts, but the corresponding biochemical events may differ, and their timeframe may be significantly reduced. Nevertheless, gaining insight into human disease mechanisms may be possible by employing experimental approaches that minimize the problems associated with extrapolating data from animal studies. Such strategies include using more than one model of a particular disease, employing different routes of administration of the injurious agent, using a variety of animal strains or species, or focusing on biochemical mechanisms common to both the animal model and its human counterpart. For example, rodent models that replicate elastic fiber injury in human pulmonary emphysema have been used to test aerosolized hyaluronan's ability to slow the disease's progression. The same models facilitated the identification of a new biomarker for pulmonary emphysema that may be a real-time indicator of therapeutic efficacy in clinical trials. Therefore, the appropriate use of these models can provide a necessary road map for designing appropriate dosages, delivery routes, timeframes, and endpoints in clinical trials of novel agents for the treatment of lung disease.