AsthmaNet: Brigham and Women's Hospital & Children's Hospital Boston

AsthmaNet：布莱根妇女医院

基本信息

批准号：
8894548
负责人：
Elliot Israel
金额：
$ 39.05万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8894548
关键词：
12 year old ADRB2 gene Adolescent Adrenal Cortex Hormones Adrenergic Receptor Adult Adverse effects African American Age Agonist Allergens Allergic Amino Acids Arginine Asthma Black Bear Boston Breathing Caucasians Cells Cessation of life Child Childhood Asthma Clinical Clinical Research Clinical Trials Communities Data Death Rate Development Disease Disease Progression Double-Blind Method Elderly Enrollment Event Food Genetic Crossing Over Genetic Polymorphism Genotype Glycine Haplotypes Health Hospitalization Hospitals IgE Immune Incidence Inflammation Investigation Israel Life Mediating Meta-Analysis Morbidity - disease rate National Heart, Lung, and Blood Institute Nature Outcome Patients Peak Expiratory Flow Pediatric Hospitals Pharmaceutical Preparations Pharmacogenetics Phase Physiological Placebo Control Placebos Positioning Attribute Prospective Studies Randomized Relative Risks Research Research Personnel Resources Retrospective Studies Risk Running School-Age Population Signal Transduction Ursidae Family Woman adverse outcome aged airway inflammation alternative treatment anti-IgE arginylarginine asthmatic experience genome wide association study improved indexing instrument member prevent primary outcome programs receptor respiratory response secondary outcome treatment strategy treatment trial

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：尽管在治疗哮喘的治疗方面取得了重大进展，但对于这种日益常见且可能使人衰弱的患者的最佳临床治疗仍在不断变化。黑人和儿童承担着哮喘发病率的负担，我们无法阻止儿童疾病的发展和进展。包括最近的FDA分析在内的几条证据表明，使用长效β激动剂（LABAS）时，黑人可能会增加严重的不良影响。我们对最近完成的ACRN大型试验的回顾性分析表明，Beta2-肾上腺素能受体（B16 ARG/ARG）的第16个氨基酸位置的纯合性确定了黑人中的一组患者，这些患者的经验降低了LABA的益处，而LABA添加了添加到吸入性皮质类固醇（Laba/ICS/ICS）中。我们的第一次试验包括成人和儿童，前瞻性地检查了B16 ARG/ARG是否确定了一群仅在将LABA添加到ICS疗法中受益的黑人。由于20％的黑人是B16 ARG/ARG，因此这一发现可能会改变黑人社区中很大一部分的疗法。我们的第二个建议研究了我们是否可以改变儿童哮喘。目前没有可用的疗法能够在哮喘中产生长期效果。儿童的哮喘与学龄儿童IgE介导的过敏敏化的明显增加有关。抗IGE疗法有可能预防这些儿童过敏性敏化，从而改变疾病的进展。因此，我们建议治疗早期学龄儿童患有抗IGE的儿童。除了检查治疗期间的结局外，我们还将在停止治疗后两年。在我们对抗IGE提案的机理研究中，我们将探讨抗Ige治疗如何重新编程参加试验的儿童中的免疫细胞。气道炎症是哮喘病理生物学的核心。在我们的概念验证研究中，我们将研究身体自然产生的新发现的化合物是否可以抵抗炎症 - 溶质 - 可用于降低暴露于过敏原的过敏性哮喘患者中气道炎症。