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。黑人和儿童承担着不成比例的哮喘发病率负担，我们无法阻止儿童疾病的发展和进展。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受体激动剂（LABAs）时可能会经历更严重的副作用。我们对最近完成的ACRN LARGE试验的回顾性分析表明，β -肾上腺素能受体（B16 Arg/Arg）第16个氨基酸位置的纯合性确定了一组黑人患者从吸入皮质类固醇（LABA/ICS）中添加LABA获益减少。我们的第一项试验包括成人和儿童，前瞻性地研究了B16精氨酸/精氨酸是否能识别一组黑人，这些黑人在ICS治疗中加入LABA后只获得了边际效益。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方法。我们的第二个建议是研究我们是否可以改变儿童哮喘。目前没有一种可用的治疗方法能够对哮喘产生持久的影响。儿童哮喘与学龄期儿童ige介导的过敏性致敏的显著增加有关。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他们进行为期两年的随访。在我们抗ige提案的机制研究中，我们将探索抗ige治疗如何在参与试验的儿童中重新编程免疫细胞。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，我们将研究新发现的身体自然产生的对抗炎症的化合物，是否可以用来降低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.