Grant: Project Grant

Asthma is a major public health problem that is caused by environmental conditions associated with westernization of society. Irritants and allergens trigger airway inflammation and over time the symptoms of asthma develop. Periods of vulnerability may determine the onset of symptoms and disease so that asthma may occur at any time of life. Inflammation is a key feature of asthma but even when controlled, symptoms and lung function disturbances often persist. Airway structural changes, such as the growth of airway smooth muscle, termed airway remodeling likely account for much of the problem. The current proposal is a translational one that proposes to evaluate one of the most promising pathways for airway remodeling, namely the epidermal growth factor receptor (EGFR) and the molecules (EGFR ligands) that stimulate it, in the causation of asthma. The levels of EGFR ligands in the airway tissues and secretions of asthmatic subjects with and without airway remodeling will be examined. The focus will be on the lining cells (epithelium) and T lymphocytes as sources of EGFR ligands. Asthmatic subjects will be studied for the release of EGFR ligands into the airways following challenge with allergens, irritants or methacholine that may cause bronchoconstriction. Understanding the details of how the EGFR is causing airway remodeling will be examined in cell culture models as well as through the use of genetically altered mice lacking one of the principal molecules that activates the EGFR in the airways.