Grant: Operating Grant

Severe asthma is found in 10% of asthmatics but is responsible for a disproportionately high fraction of the health care budget. We have recently developed a program to identify difficult to treat asthma and examined its pathophysiology. We have shown that biopsies from severe asthmatics compared to the ones from moderate and mild forms of the disease are associated with different type of inflammation and uncontrolled remodeling. A new subset of T cells was recently identified (Th-17). The major hypothesis of this proposal to be tested is that Th-17 is an important cell in the pathogenesis of severe asthma and that cytokines produced by this type of T cells are responsible for the steroid hypo- responsiveness and the uncontrolled increase in smooth muscle mass and subepithelial fibrosis. We will be using human tissue and cell lines in combination with advanced molecular techniques to test this hypothesis. Results from this proposal may explain the pathophysiology of severe asthma and open up new avenues in designing new therapeutic approaches to control or reverse the disease.