Grant: Project Grant

We are all routinely exposed to air pollution derived from transport and power generation, or occupationally in industries that underpin the Canadian economy (forestry, mining, oil & gas), with many Canadians exposed to unacceptable levels. The Government of Canada notes "air pollution costs Canadians and the Canadian economy billions of dollars per year". Much of these costs derive from pollution-induced worsening of respiratory diseases, including asthma (which affects 1 in 10 Canadians at a cost of nearly $3 billion annually). The primary medications for controlling asthma are inhaled corticosteroids, which reduce the inflammation that increases airways muscle contraction, mucus and, consequentially, difficulty breathing. Our preliminary data suggest that exposure to air pollution can reduce the effectiveness of corticosteroids, which then may compromise asthma control and increase the risk of 'lung attacks' that cause hospitalization or even death. The current proposal will validate and build on our early results and, additionally, elucidate the underlying mechanisms therein. To do this, we will conduct a novel, controlled crossover trial of diesel exhaust (DE) and an inhaled corticosteroid in mild asthmatics. We will collect lung samples and assess how air pollution may alter the expression of genes and proteins in the lung. In parallel, we will grow lung epithelial cells and use them to examine mechanisms underlying the effects of air pollution on corticosteroid responsiveness and determine the effectiveness of interventions. This study has the potential to enhance both prevention and therapy for Canadian asthmatics. Our results can inform physician practices and drive regulatory policies to protect vulnerable groups. Additionally, understanding how the effects of corticosteroids on lung gene expression are modified by air pollution could lead to the development of improved medications for the millions of Canadians suffering from airways disease.