Childhood Asthma in Urban Settings Clinical Research Network - Leadership Center

项目摘要/摘要 我们在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，以开发和进行协作研究，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)改进治疗和抑制进展，c)减少严重恶化，d)确定 呼吸系统健康和疾病的内型。为了实现这些目标，本文提出了四个假设。第一, 在婴儿期补充免疫调节菌将防止肠道早期的生命紊乱 与过敏性致敏和哮喘的风险相关的微生物群，以及 会促进呼吸道粘膜免疫功能的发展。其次，考虑到蟑螂(CR)过敏的重要性 和暴露于城市儿童的哮喘发病率，CR免疫疗法将改善哮喘控制和 减少疾病进展。第三，我们认为，对呼吸道细胞的转录分析将定义T2-LOW 有助于非特应性哮喘和特应性哮喘的机制，并为治疗提供新的见解。 最后，对严重恶化期间获得的呼吸道细胞和分泌物进行多组学评估，从而导致 急诊就诊和住院将揭示新的机械途径，以告知改善治疗和 预防。我们提出了五个协议来验证这些假设： 1.城市环境与儿童哮喘研究(URECA) 2.微生物添加剂(STMC-103H)对微生物定植和免疫发育的影响 3.蟑螂(CR)免疫疗法(IT)对中重度哮喘儿童的保护作用 奥马珠单抗 4.低T_2(非过敏性)哮喘的发病机制 5.急诊科和医院的严重哮喘恶化：确定目标 预防和治疗 我们期望，我们提议的原因研究计划将提供所需的关键信息 认识城市儿童哮喘表型和内型，改进哮喘治疗，建立 预防的方向。总的来说，这些研究将继续采用严格的方案方法 NIAID哮喘网络为实现疾病改进和预防的长期目标而努力 生活在城市社区的低收入家庭的高危儿童罹患疾病。

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.