Grant: Project Grant

Asthma is a lung disorder caused by diverse environmental triggers, such as allergens, viruses and pollutants. Asthma can be debilitating for many patients and can progress into more severe forms, especially when not treated properly. It also represents a serious burden for the society in terms of direct medical costs, as well as indirect costs, such as the loss of productivity at school or at work. Medications that are currently approved to treat asthma fall short, as it is estimated that symptoms are not adequately controlled in as much as 50% of patients. In fact, some patients are poorly responsive and sometimes totally refractory to these medications. Plus, some of these medications can engender side effects. Together, this suggests that there is a serious need to keep improving treatments for asthma. Asthma is also highly prevalent in Canada. It currently touches approximately 8% of the Canadian population. While it is more prevalent in boys than girls, its incidence at adulthood is higher in women than men. Although the underlying mechanism liable for this sexual switch in prevalence during adolescence is not fully understood, sex hormones, especially testosterone, is suspected to contribute. The goal of this research project is to investigate the role of testosterone in asthma. More specifically, the effect of testosterone will be studied on the contraction of a muscle that is encircling airways. This muscle is known to contribute to asthma symptoms because when it contracts, it narrows the passage of air and thereby causes breathing difficulty. The effect of testosterone on this airway muscle will be tested on large and small airways from female and male mice and human patients. The effect of testosterone deprivation and supplementation will also be tested in female and male mice in a mouse model of asthma. The hope is to identify key pathways for which targeting will improve asthma treatment for afflicted patients of both sexes and all ages.