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

描述（由申请人提供）：尽管哮喘治疗取得了重大进展，但对这种日益常见且可能使人衰弱的疾病患者的最佳临床治疗仍在不断变化。黑人和儿童在哮喘发病率方面承担着不成比例的负担，我们无法阻止儿童疾病的发展和进展。包括最近FDA分析在内的多项证据表明，黑人在使用长效β受体激动剂（LABA）时可能会遇到严重的不良反应。我们对最近完成的ACRN LARGE试验的回顾性分析表明，β 2-肾上腺素能受体（B16 Arg/Arg）第16位氨基酸的纯合性确定了一组黑人患者，这些患者在吸入性皮质类固醇（LABA/ICS）中加入LABA后获益减少。我们的第一项试验包括成人和儿童，前瞻性地检查B16 Arg/Arg是否识别出一组在ICS治疗中添加LABA仅获得边际获益的黑人。由于20%的黑人是B16 Arg/Arg，这一发现可能会改变大部分黑人社区的治疗。我们的第二个建议是研究我们是否可以改变儿童哮喘。目前没有可用的治疗方法能够对哮喘产生持久的影响。儿童哮喘与学龄儿童IgE介导的过敏性致敏显著增加相关抗IgE治疗有可能预防这些儿童的过敏性致敏，从而改变疾病的进展。因此，我们建议用抗IgE治疗学龄前儿童。除了检查治疗期间的结果外，我们还将在停止治疗后随访两年。在我们的抗IgE方案的机制研究中，我们将探索抗IgE治疗如何重新编程参与试验的儿童的免疫细胞。气道炎症是哮喘病理学的核心。在我们的概念验证研究中，我们将检查身体自然产生的新发现的化合物是否可以用于下调暴露于过敏原的过敏性哮喘患者的气道炎症。

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.