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 is incurable. Cigarette smoking is the most important risk factor for developing COPD, a disease associated with chronic inflammation and irreversible loss of the air sacs where oxygen is exchanged. Lung structural cells such as fibroblasts and epithelial cells contribute to inflammation, and death of these cells may account for loss of air sacs associated with emphysema. Our studies are aimed at understanding how lung structural cells stop inflammation and survive repeated exposure to cigarette smoke. Using our cell-based (lung fibroblasts, epithelial cells) and preclinical mouse models 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. We will also determine in lung samples obtained from Canadians with COPD, if low expression of the AhR is associated with more inflammation and cell death. 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.