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

描述(由申请人提供)：尽管哮喘的治疗取得了重大进展，但对这种日益常见并可能使人虚弱的疾病患者的最佳临床治疗仍在不断变化中。黑人和儿童承受着不成比例的哮喘发病率负担，我们无法阻止这种疾病在儿童中的发展和发展。包括FDA最近的一项分析在内的几条证据表明，黑人在使用长效β-激动剂(LABA)时可能会经历更严重的不良反应。我们对最近完成的ACRN大型试验的回顾分析表明，β2-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。我们的第一个试验，包括成人和儿童，前瞻性地检查B16Arg/Arg是否识别出一组黑人，他们在ICS治疗中加入LABA只有轻微的好处。由于20%的黑人是B16精氨酸/精氨酸，这一发现可能会改变很大一部分黑人社区的治疗。我们的第二个建议是检查我们是否可以改变儿童哮喘。目前还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中IgE介导的过敏性致敏作用显著增加有关。抗IgE治疗有可能预防这些儿童的过敏反应，从而改变疾病的进展。因此，我们建议用抗-IgE治疗早期学龄儿童。除了检查治疗期间的结果外，我们还将在治疗停止后对其进行两年的跟踪调查。在我们的抗IgE方案的机制研究中，我们将探索抗IgE疗法如何重新编程参与试验的儿童的免疫细胞。呼吸道炎症在哮喘的病理生物学中处于中心地位。在我们的概念验证研究中，我们将检查新发现的化合物是否可以用来下调暴露于过敏原的过敏性哮喘患者的呼吸道炎症。这些化合物是人体自然产生的抗炎物质。

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.