This application proposes to continue the participation of investigators at Thomas Jefferson University in an interactive network of six centers (the Asthma Clinical Research Network or ACRN ) in conducting studies of novel therapeutic approaches to asthma and in disseminating findings to the practicing community. The need for such a network was suggested by epidemiological data showing increases in 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 effective, but also potentially costly treatments for asthma. Defining the place of these 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 infrastructure to meet this need and has added another center at Harlem Hospital in New York, which serves a predominantly minority population. The ACRN has completed studies of the effects of regular beta-agonist use in mild asthma ( BAGS ) and of the efficacy of the anti-inflammatory agent, colchicine, as an alternative to an inhaled corticosteroid in moderate asthma. Now underway are two additional trials comparing the effects of a long-acting beta-agonist, an inhaled corticosteriod, and the combination of the two in altering clinical and physiologic outcomes, and airway inflammation in moderate or severe asthma. A fifth study, establishing doses of different inhaled corticosteroids with equivalent effects on cortisol secretion, is imminent. Completed trials as well as 10-12 ancillary studies designed to improve the performance of clinical research have been presented at meetings of the ATS, ACCP, and AAAAI. Three of these studies have thus far been published in peer- reviewed journals. The ACRN has also reported the results of a subgroup analysis of subjects in the BAGS study showing 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 Jefferson Center in the multicentered, collaborative trials of the ACRN. Proposed studies include a comparison of the efficacy of doses of different inhaled corticosteriods with equal systemic effects (as estimated from the study described above), a prospective study of the effects of regular use of an inhaled beta-agonist in subjects stratified by genotype for the beta-adrenergic receptor, and a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteriods in subjects with mild or moderate persistent asthma. Other planned studies are also briefly discussed, with the understanding that they could be modified or replaced in response to new information, new therapies, or changing clinical research priorities.
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| 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 |
| 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 |
| 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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