Innate Immunity in the Pathogenesis of Virus-induced Asthma Exacerbations

The major asthma morbidity, mortality, and health care costs are a result of acute exacerbations. However, exacerbations are only partially responsive to current therapies and new approaches to treatment are needed. The great majority of acute asthma exacerbations are associated with respiratory viral infections and, of viruses implicated, approximately 60% are human rhinoviruses (RVs). The mechanisms of RV-induced asthma exacerbations are poorly understood. We have previously shown that adults with asthma have increased susceptibility to naturally occurring RV infections. Our recent studies have investigated mechanisms of innate host defense against RV infection. First, primary bronchial epithelial cells from subjects with asthma were shown to replicate RV in vitro to several logs, whereas those of normal control subjects were resistant to infection. This resistance was a result of rapid induction of apoptosis and of interferon (IFN)-β in the normal cells, whereas these responses were deficient in asthma...