Cigarette Smoke-Induced Translational Animal Models of Chronic Obstructive Lung Disease
Pp. 196-216 (21)
Andrew Churg and Joanne L. Wright
Animal models of chronic obstructive lung disease (COPD) are complicated by
the fact that COPD encompasses 4 different anatomic entities: emphysema, small airway
remodeling, pulmonary hypertension, increased mucin secretory alterations (the pathology
found in the clinical process, chronic bronchitis) and one clinical entity without distinct
pathological association (acute exacerbations). Models using chronic cigarette smoke
exposure can reproduce mild forms of some, but not all, of these lesions; however, cigarette
smoke exposure never causes the disabling/lethal GOLD stage III or IV lesions associated
with human COPD. Further complications of chronic smoke models relate to species
differences, and, for mice, strain differences, as well as developmental abnormalities
caused by genetic manipulation, abnormalities that can mimic changes of COPD.
Numerous drug/genetic modification models using chronic smoke exposure appear to
protect partially or completely against the changes of COPD, but trials of these same agents
in humans have been disappointing, perhaps because animals are typically treated from day
1 of smoke exposure whereas treatment in humans is always a late intervention; this
conclusion suggests that animal models should use late interventions and humans should be
treated much earlier in the course of their disease.
Animal model, cigarette smoke, COPD, drug discovery, drug
development, emphysema, inflammation, pulmonary hypertension, small airway
remodeling, translational model.
Department of Pathology, University of British Columbia, Vancouver, BC, Canada