Grant: CIHR/Regional Partnership Program/Operating Grants

Asthma is a chronic inflammatory airway disease that affects ~12% of children and ~6% of adults in Canada where disease occurrence has nearly doubled in the past two decades. In most patients symptoms can be controlled by common therapies such as steroids. However, 15% of patients are "difficult-to-treat", being resistant to steroid control, and exhibit a severe asthma phenotype. Notably this patient subpopulation accounts for well over 50% of asthma health care costs. Our project examines a unique protein complex called S100A8/A9 released by neutrophils, which are the main inflammatory cells that escape the bloodstream and populate the bronchial airways of severe asthmatics. We will study the effects of the S100A8/A9 protein on human airway cells that contribute to disease worsening over time. We will use human lung cell cultures and mouse models of "asthma" to assess the role of S100A8/A9 in airway inflammation, lung function, and cell responses. We will also determine how these effects occur by examining whether a specific receptor for S100A9/A9, called RAGE, is involved. Ours will be the first study examining these proteins in allergic airway inflammation, thus they have potential to uncover new means for future treatment of asthma, particularly in those patients that suffer from difficult-to-treat severe disease.