Despite significant advances in the treatment of asthma, optimal clinical therapy for patients with this increasingly common and potentially debilitating disease is still in flux. Blacks and children bear a disproportionate burden of asthma morbidity and we are unable to stop the development and the progression of the disease in children. Several lines of evidence, including a recent FDA analysis, suggest that Blacks may experience increased serious adverse effects when using long-acting beta agonists (LABAs). Our retrospective analysis of the recently completed ACRN LARGE trial suggested that homozygosity at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) identifies a group of patients among Blacks that experience decreased benefit from LABA added to an inhaled corticosteroid (LABA/ICS). Our first trial, which includes both adults and children, prospectively examines whether B16 Arg/Arg identifies a group of Blacks who experience only marginal benefit from adding LABA to ICS therapy. Since 20% of Blacks are B16 Arg/Arg, this finding could alter therapy for a large proportion of the Black community. Our second proposal examines whether we can modify asthma in children. No current therapies available are able to produce long-lasting effects in asthma. Asthma in children is associated with a marked increase in IgE-mediated allergic sensitization in school-age children. Anti-IgE therapy has the potential to prevent allergic sensitization in these children and thus to alter the progression of disease. We therefore propose treating early school-age children with anti-IgE. In addition to examining outcomes during treatment, we will follow them for two years after cessation of therapy. In our mechanistic study of our anti-IgE proposal, we will explore how anti-IgE therapy may reprogram immune cells in the children participating in the trial. Airway inflammation is central to the pathobiology of asthma. In our proof of concept study we will examine whether newly discovered compounds that the body naturally produces to counter inflammation-resolvins, can be used to down regulate airway inflammation in allergic asthmatics exposed to allergens.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL098102-04
Application #
8301664
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
$989,393
Indirect Cost
$232,712
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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