Grant: CIHR New Investigator

Asthma is common, within Canada and worldwide, and has major health and economic consequences. The airways ("breathing tubes") of people with asthma are inflamed and will react to irritants by narrowing and making it more difficult to breathe. This typically results in an "asthma exacerbation" whereby the asthmatic will notice shortness of breath and may need urgent medical attention. Diesel exhaust (DE) is associated with asthma exacerbations, but how and why this occurs is unclear. One hypothesis (or "educated guess") has been that DE causes "oxidative stress", which is damage to cells and body tissues due to certain chemical characteristics classically, this is due to an "unpaired electron"). Therefore, we want to test the idea that DE creates oxidative stress and that this is responsible for airway narrowing in human asthmatics. We also want to know if this is made worse by the addition of a typical allergen (for example, pollen from the alder tree). In our laboratory, we create DE and we finely control its concentration while volunteers inhale it for 2 hours. The concentration of DE is typical of that in a mining operation or on the streets of Mexico City. Such a short exposure time has no permanent effects but should show mild changes in the airways and blood (which return completely back to normal within hours) to help us decide if our hypothesis is correct. Each volunteer subject is exposed, on different days, to DE and to clean air. Before and after each exposure, we perform tests to see how much oxidative stress and airway narrowing is occurring. In some subjects, we add alder pollen to see if that worsens the effect of DE. This research will allow a better understanding of DE-related airways disease, and this may should lead to measures to protect Canadians exposed to traffic-related pollution. This research may support a recommendation for or against changes in fuel composition or personal measures to bolster anti-oxidant levels.