A Novel Nonhuman Primate Model of Cigarette Smoke–Induced Airway Disease

摘要: Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers human COPD. These include a anatomy that differs from humans, the limited airway pathologies lymphoid aggregates develop in smoke-exposed mice, challenges associated with serial biological sampling. Thus, we assessed utility cigarette smoke (CS)–exposed cynomolgus macaque as nonhuman primate (NHP) large model Twenty-eight NHPs were exposed to air or CS 5 days per week up 12 weeks. Bronchoalveolar lavage function tests performed at intervals. After weeks, measured pathologies, inflammation, airspace enlargement. CS-exposed developed robust mucus metaplasia, submucosal gland hypertrophy hyperplasia, peribronchial fibrosis, increases bronchial aggregates. Although did not emphysema over study time, they exhibited precede development, including following: i) matrix metalloproteinase-9 proinflammatory mediator levels bronchoalveolar fluid, ii) lung parenchymal leukocyte counts aggregates, iii) oxidative stress levels, iv) alveolar septal cell apoptosis. can be used occurring COPD patients. Unlike rodents, safely undergo longitudinal sampling, which could useful assessing novel therapeutics