A Mechanistic Study Of Cigarette Smoke-Induced COPD And Cessation Effects In C57BL/6 Mice


Authored by  B Phillips, E Veljkovic, M Peck, A Buettner*, G Vuillaume

Presented at ICT 2013 Seoul     
* This author is not affiliated with PMI.

Abstract

Cigarette smoke is the primary etiological risk factor in the development and progression of Chronic Obstructive Pulmonary Disease (COPD). Smoking cessation, however, results in a continued higher risk of pulmonary disease in humans compared to never smokers. This study analyzed the progression of emphysema over a 7-month period of exposure to cigarette smoke (CS, 750 μg/l total particle matter from 3R4F cigarettes) or to CS followed by up to 5 months cessation (fresh air) in C57BL/6 mice. A battery of markers of disease progression was investigated, focusing on lung inflammation (cell infiltration, lung cytokines and oxysterol analysis), pulmonary function, and emphysematous changes to the lungs at the histopathological and morphometric level. Exposure of C57BL/6 mice to mainstream CS induced acute inflammatory changes in the lung and airways in a time-dependent manner. The changes include the infiltration of inflammatory cells into the lungs, whereby the total cell count was significantly increased with CS, with notable neutrophilopenia. This was mirrored by increased levels of inflammatory cytokines and oxysterols. Lung function analysis identified characteristic emphysematous changes to lung physiology and function in response to Cigarette Smoke, accompanied by histopathological and morphometric changes in the lung. Smoking cessation resulted in the rapid reversion back to sham control group levels for most of the measured parameters. The recovery typically occurred between 1 and 3 months after cessation. This model, and related downstream molecular analysis, will provide an excellent platform to examine the efficacy of smoking cessation as a benchmark for Modified Risk Tobacco Product assessment. 

a-mechanistic-study-of-cigarette-smoke-induced-copd-and-cessation-effects-in-c57bl-6-mice