Animal models of cigarette
smoke-induced
chronic obstructive pulmonary disease (
COPD) provide potentially useful ways to test
drug therapies, either by direct administration of the treatment of interest, or by use of genetically modified animals that mimic the actions of the
drug of interest. Evaluation of the potential effects of a
drug in animal models requires a long-term (generally 6-mo)
smoke exposure to produce/prevent lesions because acute models do not completely predict chronic events. There are now more than 30 chronic studies in the literature which, in aggregate, show that antiproteolytic
therapies, antiinflammatory
therapies, and
antioxidant therapies substantially or completely prevent
emphysema,
small airway remodeling, and
pulmonary hypertension in laboratory animals. However, the few corresponding trials in humans (anti-
TNF-alpha therapy,
PDE4 inhibitors) have produced only minor improvements or failed to prevent
disease progression. New data from our laboratory indicates that, at least for murine
emphysema, the development of disease goes through different phases, with early repair and late failure to repair
smoke-induced damage. These observations suggest that the potential effects of
drug treatment in humans may vary depending on the stage of the disease and that treatment may be more effective in relatively early disease. An additional complicating factor is that interventions that ameliorate
emphysema may or may not prevent
small airway remodeling and/or
pulmonary hypertension, suggesting that different therapeutic approaches may be needed for the various different anatomic lesions of
COPD.