To address new treatment approaches through AsthmaNet, National Jewish Health will contribute expertise under the direction of Drs. Richard Martin and Stanley Szefler along with experienced investigators from the ACRN and CARE Networks, and Dr. Lisa Cicutto as leader in the Education, Training and Career Development Core and the Community Engagement Core of the Colorado Clinical and Translational Sciences Institute. To understand the relationship of asthma, vitamin D deficiency and obesity in adults, we will examine the role of vitamin D supplementation to enhance inhaled corticosteroid (ICS) response. After a run-in period of ICS, based on evidence of vitamin D deficiency and stratified for body mass index, subjects with asthma, ages 18 to 70 years, will be randomized to ICS plus vitamin D or placebo for a 6-month period in a double-blind, parallel, placebo controlled design to evaluate change in asthma control. An associated mechanistic study will examine cellular mechanisms of steroid response related to the MAP kinase-1 pathway. To improve asthma management in young children, we will evaluate three treatments: low dose ICS delivered via nebulizer/face mask, low dose ICS via metered dose inhaler/spacer/face mask, or an oral leukotriene antagonist. After a placebo run-in, children with asthma, ages 1 to less than 5 years, will be randomized to one treatment in a double-blind, parallel design for a one-year study period. We will measure symptom control and exacerbations and also determine whether therapy can be individualized based on patient characteristics including biomarkers and genetics. To evaluate a novel treatment strategy, we will examine the role of an omega3/antioxidant nutritional formula on exercise-induced bronchospasm in adolescents, ages 12 to 18 years, using a double-blind, placebo controlled, parallel design over a three month treatment period. We will also implement a Clinical Research Skills Development Core Plan and contribute expertise in quality control of physiological clinical outcomes to develop independent academic clinical investigators in asthma. The National Jewish site will contribute collaborative experience, leadership skills and commitment for recruitment of adults and children to participate in AsthmaNet trials.

Public Health Relevance

To improve asthma patient outcomes for both adults and children by innovative and practical clinical trials. Also, to understand mechanisms as to the improvement in asthma status. The Denver group will furthermore contribute to the leadership of the AsthmaNet group.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL098075-04
Application #
8294815
Study Section
Special Emphasis Panel (ZHL1-CSR-U (S1))
Program Officer
Taggart, Virginia
Project Start
2009-09-30
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$875,082
Indirect Cost
$314,132
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Sutherland, E Rand; Busse, William W; National Heart, Lung, and Blood Institute's AsthmaNet (2014) Designing clinical trials to address the needs of childhood and adult asthma: the National Heart, Lung, and Blood Institute's AsthmaNet. J Allergy Clin Immunol 133:34-8.e1
Castro, Mario; King, Tonya S; Kunselman, Susan J et al. (2014) Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA 311:2083-91
Szefler, Stanley J; Chmiel, James F; Fitzpatrick, Anne M et al. (2014) Asthma across the ages: knowledge gaps in childhood asthma. J Allergy Clin Immunol 133:3-13; quiz 14
Szefler, Stanley J (2014) Advances in pediatric asthma in 2013: coordinating asthma care. J Allergy Clin Immunol 133:654-61
Raissy, Hengameh H; Kelly, H William; Harkins, Michelle et al. (2013) Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med 187:798-803
Szefler, Stanley J (2013) Advances in pediatric asthma in 2012: moving toward asthma prevention. J Allergy Clin Immunol 131:36-46
Szefler, Stanley J (2012) Advances in pediatric asthma in 2011: moving forward. J Allergy Clin Immunol 129:60-8
Szefler, Stanley J (2011) Is it time to revise the asthma guidelines? J Allergy Clin Immunol 128:937-8