Childhood Asthma in Urban Settings Clinical Research Network - Leadership Center

项目概要/摘要 我们城市环境中的儿童哮喘（原因）领导中心提案的总体目标是 提供行政领导和支持，以开发和开展合作研究，以解决高 城市社区儿童哮喘未得到满足的优先需求，包括：a) 制定预防战略 哮喘，b) 改善治疗并抑制进展，c) 减少严重恶化，以及 d) 定义 呼吸系统健康和疾病的内型。提出了四个假设来实现这些目标。首先， 在婴儿期补充免疫调节细菌将预防早期肠道紊乱 与过敏和哮喘发生风险相关的微生物组，以及 将促进气道粘膜免疫发育。二、鉴于蟑螂（CR）过敏的重要性 以及城市儿童哮喘发病率的增加，CR 免疫疗法将改善哮喘控制和 减少疾病进展。第三，我们建议气道细胞的转录分析将定义 T2-low 导致非特应性和特应性哮喘的机制，并为治疗提供了新的见解。 最后，对严重恶化期间获得的气道细胞和分泌物进行多组学评估，导致 急诊就诊和住院治疗将揭示新的机制途径，为改善治疗和治疗提供信息 预防。我们提出了五种协议来测试这些假设： 1. 城市环境与儿童哮喘研究（URECA） 2. 微生物补充剂 (STMC-103H) 对微生物定植和免疫发育的影响 3. 城市中重度哮喘儿童的蟑螂（CR）免疫治疗（IT） 奥马珠单抗 4. T2-低（非特应性）哮喘的发病机制和机制 5. 急诊科 (ED) 和医院的哮喘严重急性加重：确定治疗目标 预防和治疗 我们期望我们提出的 CAUSE 研究计划将提供所需的关键信息 识别城市儿童哮喘表型和内型，改善哮喘治疗并建立 预防方向。总的来说，这些研究将继续严格的计划方法 NIAID 哮喘网络致力于实现疾病改变和预防的长期目标 居住在城市社区的低收入家庭的高危儿童的疾病。

PROJECT SUMMARY/ABSTRACT The overall goals of our Childhood Asthma in Urban Settings (CAUSE)-Leadership Center proposal are to provide administrative leadership and support to develop and conduct collaborative research to address high priority unmet needs for childhood asthma in urban communities, including: a) developing strategies to prevent asthma, b) improving treatment and inhibiting progression, c) reducing severe exacerbations, and d) defining endotypes of respiratory health and disease. Four hypotheses are proposed to accomplish these goals. First, supplementation with immune modulating bacteria in infancy will prevent the early life perturbations in the gut microbiome that have been associated with risk for the development of allergic sensitization and asthma, and will promote airway mucosal immune development. Second, given the importance of cockroach (CR) allergy and exposure to asthma morbidity in urban children, CR immunotherapy will improve asthma control and reduce disease progression. Third, we propose that transcriptional analysis of airway cells will define T2-low mechanisms that contribute to both non-atopic and atopic asthma and provide new insights into treatment. Finally, multi-omics evaluation of airway cells and secretions obtained during severe exacerbations leading to ED visits and hospitalizations will reveal novel mechanistic pathways to inform improved treatment and prevention. We propose five protocols to test these hypotheses: 1. Urban Environment and Childhood Asthma study (URECA) 2. Effects of a Microbial Supplement (STMC-103H) on Microbial Colonization and Immune Development 3. Cockroach (CR) Immunotherapy (IT) in Urban Children with Moderate-Severe Asthma Protected by Omalizumab 4. Pathogenesis and Mechanisms of T2-low (Non-Atopic) Asthma 5. Severe Asthma Exacerbations in the Emergency Department (ED) and Hospital: Identifying Targets for Prevention and Treatment It is our expectation that our proposed CAUSE research program will provide critical information needed to recognize asthma phenotypes and endotypes in urban children, improve treatment of asthma and establish direction for prevention. Collectively, these studies will continue the rigorous programmatic approach of the NIAID Asthma Networks towards achieving the long-term goals of disease modification and prevention of disease in high-risk children of low-income families living in urban communities.