Animal models of cigarette smoke-induced chronic obstructive pulmonary disease.
Chronic exposure of laboratory animals to cigarette smoke reproduces many of the anatomic/physiologic lesions (emphysema, small-airway remodeling and pulmonary hypertension) of human chronic obstructive pulmonary disease, although smoke-exposed laboratory animals are not good models of chronic bronchitis or acute exacerbations, as these are conditions based upon symptoms that are not recapitulated in animals. Many types of antiproteolytic and anti-inflammatory interventions, such as use of drugs or genetic modifications, are highly effective in preventing emphysema in these models, and some also prevent small-airway remodeling and pulmonary hypertension. However, the few attempts to translate these therapies into humans have been unsuccessful, probably because the animal models typically start therapy from day 1 of smoke exposure, whereas most humans are treated late in the course of their disease. Recent data from our laboratory suggest that the parenchyma can repair smoke-induced damage for some period, but then switches to a mode where it fails to repair; these observations suggest that the timing of an intervention in humans may be crucial to its success. The various different anatomic lesions induced by smoke appear to be largely independent effects and may require different therapeutic approaches.
Department of Pathology, University Hospital, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. jlwright@interchange.ubc.ca
Joanne L
JL
Wright
Andrew
A
Churg
D056151:Airway Remodeling; D000818:Animals; D029481:Bronchitis, Chronic / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000209:etiology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013045:Species Specificity; D013997:Time Factors
D012906:Smoke