Grant: Chair: GlaxoSmithKline Partnered - Operating Component

Infections with the common cold virus (human rhinovirus) are a frequent cause of wheezing illnesses during early childhood. Studies indicate that wheezing illnesses due to human rhinovirus (HRV) infections are associated with an increased risk of developing asthma by the age of 6 years. Asthma symptoms are due to an underlying abnormality of the airways, termed airway hyperresponsiveness (AHR), in which the airways contract too much and too quickly in response to stimuli that have little or no effect on healthy subjects. The airways of asthmatic patients have chronic structural changes (scarring) present, which is termed airway remodeling, and there is now good evidence that this airway remodeling contributes to AHR. Airway remodeling changes are seen in childhood, and may predate the onset of asthma symptoms. Given these observations, and the association between childhood HRV infections and the subsequent development of asthma, we hypothesize that HRV infections play an important role in the development of airway remodeling. We have shown that HRV infection of the cells lining the airways, known as airway epithelial cells, results in increased production of mediators involved in the development of airway remodeling. We now plan to build on these published observations by studying the effects of commonly prescribed asthma medications on HRV-induced remodeling mediators. We will also study how these mediators affect other types of cells in the airways that are also involved in airway remodeling. Finally, we will perform a clinical study in which we will give experimental cold infections to asthmatic and healthy volunteers to see whether there are differences in airway remodeling mediators in these subjects before and after infection. These studies should lead to a better understanding of how common cold virus infections lead to the development of asthma. See also: http://www.cihr-irsc.gc.ca/e/41658.html