Grant: Operating Grant

Chronic obstructive pulmonary disease (COPD) refers to two diseases- emphysema and chronic bronchitis- that restricts normal breathing. COPD is the forth leading cause of death in the Canada, and although current therapies can slow disease progression, COPD is incurable. Cigarette smoking is the most important risk factor for COPD, a disease associated with chronic inflammation and irreversible loss of the air sacs where oxygen is exchanged. Lung cells such as fibroblasts and epithelial cells contribute to inflammation, and their death may account for loss of air sacs in emphysema. Our studies are aimed at understanding how lung cells stop inflammation and survive repeated exposure to cigarette smoke. Using our cell-based (lung fibroblasts, epithelial cells) and preclinical mouse model of cigarette smoke exposure, we will assess the therapeutic potential of a cellular protein called the aryl hydrocarbon receptor (AhR) in reducing inflammation (cytokine, chemokines, lipid mediators) and a cell death process called apoptosis. Using techniques like western blot, histological staining and polymerase chain reaction (PCR), we will also determine in lung samples obtained from Canadians with COPD, the expression of the aryl hydrocarbon receptor. Even though quitting smoking reduces the likelihood of developing COPD, it does not warrant that chronic inflammation and damage associated with long-term tobacco use will not progress to lung disease. The research conducted here has the potential to lead to new approaches that would block some of the untoward health consequences of tobacco smoke. These might include increasing AhR expression or activity in an individual with COPD to prevent additional lung destruction and improve airflow by attenuating inflammation. Given that nearly half of the Canadian population is composed of current and former smokers, the inherent benefits in terms of new and more selective therapies to treat tobacco smoke-associated lung disease is enormous.