Investigators at the University of California, San Francisco here apply to participate in a cooperative research network examining current and novel therapies and management strategies for adult asthma and disseminating its findings to the medical community. The need for this network is demonstrated by asthma's rising morbidity and cost, by advances in basic research on its pathogenesis, and by the development of potentially effective but also potentially costly new therapies. Defining the place of these therapies will require large collaborative, multi-center studies. This application proposes two studies that address issues of current clinical importance and that incorporate new approaches to examining mechanisms of disease. The first project examines whether the effects of an inhaled corticosteroid on """"""""airway remodeling"""""""" are dose-dependent, whether they are enhanced by the addition of a long-acting beta-agonist, and whether changes in measures of remodeling are related to changes in the levels of expression of genes for products thought to regulate collagen deposition and mucus production. The new technologies used in this study include design-based stereology for quantitative morphometry of bronchial biopsies and transcription profiling of gene expression in bronchial epithelial cells. The second project examines whether the addition of a macrolide antibiotic to usual care alters important outcomes in asthma exacerbations, especially in the subgroups currently most often treated, like those with purulent sputum or symptoms of sinusitis. This study will offer an opportunity to examine the validity of a microarray-based approach to detecting respiratory pathogens, developed in the UCSF Department of Biochemistry/Biophysics. To conduct these and other Asthma Clinical Research Network studies, we propose to draw from an established database of > 5000 patients with asthma who have participated in - or expressed an interest in participating in - clinical trials. Finally, we propose a Clinical Research Skills Development program for new appointees to the Pulmonary and Allergy Divisions, to foster their skills in clinical research and in genomic-based technologies.
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