This application is for the continuation of the Asthma Clinical Research Network or ACRN . The ACRN is an interactive network of 6 research centers conducting studies of novel therapeutic approaches to asthma. The need for such a network was suggested by epidemiological data showing increases in the mortality, morbidity, prevalence, and costs of asthma, by clinical and basic research studies showing that asthma is linked to inflammation in the airways, and by the accelerating rate of development of potentially highly effective, but also potentially costly novel treatments for asthma. Defining the place of these new therapies was seen as requiring collaborative, multi-center studies examining large numbers of subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure to meet this need and has added a clinical research site at Harlem Hospital in New York, which serves a predominantly minority population. The ACRN completed and published trials of the effects of regular use of a beta-agonist in subjects with mild asthma ( BAGS ) and of the efficacy of the anti-inflammatory agent, colchicine, as an alternate to an inhaled corticosteriod in moderate asthma. It is now conducting two additional trials comparing the effects of a long-acting beta-agonist, an inhaled corticosteriod, and the combination of the two in altering clinical outcomes, physiologic outcomes, and airway inflammation in moderate or severe asthma. A fifth study, establishing doses of different inhaled corticosteriods with equivalent effects on cortisol secretion, is about to be started. Data from completed trials, and associated ancillary studies, has been presented at national meeting to the ATS, ACCP, and AAAAI. This application specifically outlines the goals of the ACRN over the next five years. The studies proposed include: 1) A comparison of the clinical efficacy of doses of different inhaled corticosteriods with equal systemic effects (as estimated from the study described above), 2) A prospective study of the effects of regular use of an inhaled beta- agonist in subjects stratified by genotype for the beta-adrenergic receptor, 3) A study analyzing the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteriod therapy in subjects with mild or moderate persistent asthma; and 4) six other studies from which 3 will be chosen for execution during the next five years. Other studies will be considered if new information becomes available suggesting the need for additional trials.
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