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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL074204-03
Application #
6931576
Study Section
Special Emphasis Panel (ZHL1-CSR-B (M1))
Program Officer
Smith, Robert A
Project Start
2003-09-15
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$860,696
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lugogo, Njira; Green, Cynthia L; Agada, Noah et al. (2018) Obesity's effect on asthma extends to diagnostic criteria. J Allergy Clin Immunol 141:1096-1104
Nyenhuis, Sharmilee M; Krishnan, Jerry A; Berry, Alalia et al. (2017) Race is associated with differences in airway inflammation in patients with asthma. J Allergy Clin Immunol 140:257-265.e11
Peters, Stephen P; Bleecker, Eugene R; Kunselman, Susan J et al. (2013) Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol 132:1068-1074.e1
Fuhlbrigge, Anne; Peden, David; Apter, Andrea J et al. (2012) Asthma outcomes: exacerbations. J Allergy Clin Immunol 129:S34-48
Szefler, Stanley J; Chinchilli, Vernon M; Israel, Elliot et al. (2012) Key observations from the NHLBI Asthma Clinical Research Network. Thorax 67:450-5
Calhoun, William J; Ameredes, Bill T; King, Tonya S et al. (2012) Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA 308:987-97
Sutherland, E Rand; Goleva, Elena; King, Tonya S et al. (2012) Cluster analysis of obesity and asthma phenotypes. PLoS One 7:e36631
McGrath, Kelly Wong; Icitovic, Nikolina; Boushey, Homer A et al. (2012) A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med 185:612-9
Huang, Yvonne J; Nelson, Craig E; Brodie, Eoin L et al. (2011) Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol 127:372-381.e1-3
Peters, Stephen P; Kunselman, Susan J; Icitovic, Nikolina et al. (2010) Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 363:1715-26

Showing the most recent 10 out of 24 publications