Discussion

Rhinoviruses cause the majority of acute exacerbations of asthma and COPD. Current therapies for stable asthma and COPD show poor efficacy at controlling exacerbation rate and severity. Data from mouse models, ex vivo human cell culture models and in vivo human challenge models show that virus-induced type I and type III interferon response is protective for asthma exacerbations while the virus-induced inflammatory and pro-Th2 response is detrimental and drives asthma exacerbation pathogenesis. Future therapeutic targets aimed at surprising virus-induced asthma exacerbations should selectively suppress harmful mediators, while sparing beneficial anti-viral immunity. We have developed in vitro models using primary bronchial epithelial cells that have allowed us to identify novel targets that when targeted, suppress virus induced inflammation but spare anti-viral immunity. Early stage drug discovery studies have also identified novel inhibitors to these targets, but also new compounds with surprising interferon augmenting capacity.