This application proposes to continue the participation of investigators at National Jewish Medical and Research Center in an interactive network of six centers, the Asthma Clinical Research Network (ACRN) in conducting studies of novel therapies for asthma and in disseminating findings to the practicing community. The need for such a network was suggested by increases in the mortality, morbidity, prevalence, and costs of asthma, by research studies showing that asthma is linked to airway inflammation, and by the accelerating rate of development of potentially effective, but also potentially costly treatments. Defining the place of these new therapies was seen as requiring collaborative, multi-center studies examining subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure and added a research site at Harlem Hospital, 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 mild asthma (""""""""BAGS"""""""") and of the efficacy of colchicine as an alternate to an inhaled corticosteroid (ICS) in moderate asthma. It is now conducting trials comparing a long-acting Beta-agonist, an ICS, and the combination of the two in moderate to severe asthma. We are about to start a 5th study to establish doses of different ICS with equivalent effects on cortisol secretion. These studies have been presented at meetings of the ATS, ACCP, and AAAAI, as have 10-12 ancillary studies analyzing the performance of clinical research. The ACRN has also reported its findings from subgroup analysis of the """"""""BAGS"""""""" study: that subjects with different genotypes for the Beta-adrenergic receptor are differently affected by regular use of albuterol. This application proposes continued participation of the National Jewish Asthma Clinical Research group in the multicentered, collaborative trials of the ACRN. The studies proposed include a comparison of the clinical efficacy of doses of different inhaled corticosteroids with equal systemic effects, a prospective study of regular use of an inhaled Beta-agonist in subjects stratified by genotype for the Beta-adrenergic receptor, a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteroid therapy in subjects with mild or moderate persistent asthma, and other studies illustrated briefly in this application, but modified or replaced by the ACRN Steering Committee in response to new information or the release of new forms of therapy.
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| Brehm, John M; Ramratnam, Sima K; Tse, Sze Man et al. (2015) Stress and Bronchodilator Response in Children with Asthma. Am J Respir Crit Care Med 192:47-56 |
| Israel, Elliot; Lasky-Su, Jessica; Markezich, Amy et al. (2015) Genome-wide association study of short-acting ?2-agonists. A novel genome-wide significant locus on chromosome 2 near ASB3. Am J Respir Crit Care Med 191:530-7 |
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| Szefler, Stanley J (2012) Advances in pediatric asthma in 2011: moving forward. J Allergy Clin Immunol 129:60-8 |
| Szefler, Stanley J; Busse, William W (2012) The long-acting ?-adrenergic agonist controversy in asthma: troublesome times! J Allergy Clin Immunol 130:1256-9 |
| Tantisira, Kelan G; Damask, Amy; Szefler, Stanley J et al. (2012) Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus. Am J Respir Crit Care Med 185:1286-91 |
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