This application proposes to continue the participation of investigators at UCSF 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 UCSF 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 genotypes 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.
| 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 |
| Lambert, Allison; Drummond, M Bradley; Wei, Christine et al. (2015) Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients. J Allergy Clin Immunol 136:649-653.e4 |
| Wang, Y; Tong, C; Wang, Z et al. (2015) Pharmacodynamic genome-wide association study identifies new responsive loci for glucocorticoid intervention in asthma. Pharmacogenomics J 15:422-9 |
| Dunn, Ryan M; Lehman, Erik; Chinchilli, Vernon M et al. (2015) Impact of Age and Sex on Response to Asthma Therapy. Am J Respir Crit Care Med 192:551-8 |
| 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 |
| Szefler, Stanley J; Chinchilli, Vernon M; Israel, Elliot et al. (2012) Key observations from the NHLBI Asthma Clinical Research Network. Thorax 67:450-5 |
| Wechsler, Michael E; Castro, Mario; Lehman, Erik et al. (2011) Impact of race on asthma treatment failures in the asthma clinical research network. Am J Respir Crit Care Med 184:1247-53 |
| Sutherland, E Rand; Lehman, Erik B; Teodorescu, Mihaela et al. (2009) Body mass index and phenotype in subjects with mild-to-moderate persistent asthma. J Allergy Clin Immunol 123:1328-34.e1 |
| Qian, Zhengmin; Lin, Hung-Mo; Chinchilli, Vernon M et al. (2009) Associations between air pollution and peak expiratory flow among patients with persistent asthma. J Toxicol Environ Health A 72:39-46 |
| Qian, Zhengmin; Lin, Hung-Mo; Chinchilli, Vernon M et al. (2009) Interaction of ambient air pollution with asthma medication on exhaled nitric oxide among asthmatics. Arch Environ Occup Health 64:168-76 |
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