District of Columbia Childhood Asthma in Urban Settings - Clinical Research Center

利用我们机构多样化和经验丰富的调查人员基础，我们在领导合作伙伴方面的成功 和单部位随机临床试验(RCT)以及机械性和观察性研究，以及我们获得 对于大量患有哮喘的城市、弱势群体和主要是少数族裔的年轻人，我们建议设立 哥伦比亚大学城市儿童哮喘临床研究中心(DC CARE-CRC)。它将实施 网络范围内的研究项目，由高级和初级调查人员组成的多学科团队带来多样化的 背景：儿童哮喘、过敏和免疫学、呼吸道多组学和计算生物学。这个 被提议的临床领导多次成功地成为多地点哮喘研究的顶级参与者 合作，我们的机构拥有必要的基础设施，以促进事业的合作研究。 对于我们的特定地点项目，我们将建立在内城哮喘联盟(ICAC)和 探索单剂量奥马珠单抗范式转换的机制和临床方面 秋季，以防止病情恶化。具体地说，在为未来可能的RCT提供试点临床数据的同时， 我们将研究鼻部微生物群和鼻部炎症反应在病毒感染过程中的相互作用。 使用和不使用单剂抗IgE的上呼吸道感染(URI)。协同工作 易加重的城市青年、过敏性过敏、过敏原暴露、鼻病毒(和其他病毒性)尿毒症 引发强烈的Th2反应和哮喘加重，最常发生在开学后(The “九月疫情”)。廉政公署已经证明，当整个秋季都在执行时， 奥马珠单抗可将病情恶化的几率降低50%。考虑到该方法的成本和复杂性， 然而，并注意到皮下注射后在一段时间内奥马珠单抗的血清水平上升 足以防止病毒引起的恶化(7-8天)，我们提出了一个全新的策略： 发作前的奥马珠单抗(双簧管)。它是一种试验性的、非治疗性的、机械性的RCT 在URI发病72小时内给予奥马珠单抗或安慰剂。在三个秋季，双簧管将 将至少100名6-17岁患有持续性哮喘、高度特应性疾病和最近病情恶化的青年随机分组。 我们将在开学后的90天内“捕获”他们的URI，对他们的鼻腔呼吸道进行两次采样(72小时内 在URI开始之后的7-10天之间在窗口中再次出现)。我们的具体目标是：(1)成为 合作研究事业网络中的领导者，同时培养下一代地方 DC事业的机构领导-CRC；(2)确定鼻腔呼吸道之间的关系 单剂量奥马珠单抗治疗儿童的微生物组、宿主转录组和Th2反应 安慰剂在病毒性尿路感染发病时的作用；(3)确定宿主鼻气道抗病毒的关系 病毒URI开始时给予和不给予奥马珠单抗的干扰素-α反应；和(4-探索性)：至 确定干预组和对照组之间临床结果的差异。

Leveraging our institution’s diverse and experienced investigator base, our success in leading collaborative and single-site randomized clinical trials (RCTs) and mechanistic and observational studies, and our access to a large population of urban, disadvantaged, and largely minority youth with asthma, we propose the District of Columbia’s Childhood Asthma in Urban Settings Clinical Research Center (DC CAUSE-CRC). It will implement network-wide research projects with a multi-disciplinary team of senior and junior investigators bringing diverse backgrounds in pediatric asthma, allergy and immunology, airway multi-omics, and computational biology. The proposed clinical leadership has repeatedly succeeded as top enrollers in multi-site asthma research collaboratives, and our institution houses the required infrastructure to facilitate CAUSE’s collaborative studies. For our site-specific project, we will build on the prior work of the Inner City Asthma Consortium (ICAC) and explore the mechanistic and clinical aspects of the paradigm-shifting use of a single dose of omalizumab in the fall season to prevent exacerbations. Specifically, while providing pilot clinical data for a possible future RCT, we will examine the interaction of the nasal microbiome and the nasal inflammatory responses during viral upper respiratory infections (URIs) with and without a single dose of anti-IgE. Working synergistically in exacerbation-prone urban youth, allergic sensitization, allergen exposure, and rhinovirus (and other viral) URIs trigger a strong Th2 response and asthma exacerbations that occur most frequently after school begins (the “September epidemic”). The ICAC has demonstrated that when administered across the entire fall season, omalizumab reduces the odds of exacerbations by >50%. Given the cost and complexity of this approach, however, and noting that serum levels of omalizumab rise following subcutaneous injection within a time frame sufficient to prevent a virally induced exacerbation (7-8 days), we propose an entirely new strategy: Omalizumab Before Onset of Exacerbations (OBOE). It is a pilot, non-therapeutic, mechanistic RCT of omalizumab or placebo administered within 72 hours of onset of an URI. Over three fall seasons, OBOE will randomize at least 100 youth aged 6-17 years with persistent asthma, high atopy, and a recent exacerbation. We will “capture” their URIs for 90 days after school starts, sampling their nasal airways twice (within 72 hours of URI onset and again in a window between 7-10 days after URI onset). Our specific aims are: (1) to be leaders in the collaborative studies of the CAUSE network while fostering the next generation of local institutional leadership for DC CAUSE-CRC; (2) to determine the relationship among the nasal airway microbiome, host transcriptome, and Th2 responses in children treated with single dose omalizumab or placebo at the onset of viral URIs; (3) to determine the relationship between host nasal airway antiviral interferon-α response with and without omalizumab given at the onset of a viral URI; and (4-exploratory): to determine the differences in clinical outcomes between intervention and control participants.