Core B Clinical Core

这项哮喘和过敏性疾病合作研究中心(AADCRC)提案的总体目标是 阐明先天免疫系统保护机体免受病毒感染的机制 哮喘的恶化。在更新我们的AADCRC计划时，我们将继续专注于关键的 而且通常对天然免疫因素研究不足，表面活性物质的阴离子脂类(棕榈酰-油酰基- 磷脂酰甘油(POPG)和磷脂酰肌醇(PI))和Toll相互作用蛋白(Tollip)和 表面活性蛋白-A(SP-A)。在本申请中提出了三个相互关联的项目；该计划将 使用从表型良好的患者体内获得的生物呼吸道和外周系统样本 患有和不患有2型哮喘和过敏症的参与者通过临床核心B核心进行研究。我们假设 POPG/PI、Tollip和SP-A作为独特的免疫调节剂减弱病毒的影响 2型哮喘的感染，特别是轮状病毒-C、甲型流感和SARS-CoV-2。补充 功能性POPG/PI、SP-A和IL-33诱骗受体Sst2提供了新的替代方案 因病毒感染而加重的哮喘。使用人类样本是至关重要的，因为SARS的动物模型- CoV-2、流感和RVC是有限的，研究结果对人类疾病的翻译可能是不同的。因此， 临床核心的目标是为我们的AADCRC调查人员提供服务，以安全、一致地执行 研究参与者的表型和标准化、高质量的生物呼吸道采集程序 和外围系统标本，具有成本效益的样本处理和数据收集，具有稳健的数据 管理和统计分析，以检验每个项目中提出的假设。这一临床核心将 广泛表型100名参与者包括60名哮喘患者(30名轻度哮喘患者和30名重度哮喘患者)和40名对照组 (25例特应性，15例非特应性)用于肺功能测试、2型表型、基因分型、鼻腔采样以及 参与支气管镜检查研究，以了解这些天然免疫调节剂在 哮喘和特应性哮喘，以及轻度和重度哮喘。临床核心将协调和执行支气管镜检查 对所有参与者进行支气管肺泡灌洗、鼻腔和上皮细胞刷检以及支气管内膜活检。 临床核心将负责处理、存储和分发从 这三个项目中的每一个都是参与者。在这一能力下，核心将允许每个临床样本被利用 充分发挥其潜力，平等地为所有项目服务。在AADCRC内利用人类对象进行的所有研究 除了样本，临床核心还将负责确保患者的安全、数据保密性和 监管合规性。在这个核心中嵌入了一个生物统计单元，以将临床数据与 分子/生物标记物数据，以有效地模拟细胞特征和临床表型之间的关系 哮喘。

The overall goal of this Asthma and Allergic Diseases Cooperative Research Center (AADCRC) proposal is to elucidate the mechanisms by which the innate immune system affords protection against viral-induced exacerbations in asthma. In the renewal of our AADCRC program, we will continue to focus on the critical and often understudied innate immune factors the anion lipids of surfactant, (palmitoyl-oleoyl- phosphatidylglycerol (POPG) and phosphatidylinositol (PI)) and Toll interacting protein (Tollip) and surfactant protein-A (SP-A). Three inter-related projects are proposed in this application; the program will employ use of biologic airway and peripheral systemic specimen samples obtained from well-phenotyped participants with and without type 2 asthma and atopy through Core B, the Clinical Core. We hypothesize that POPG/PI, Tollip and SP-A function as unique immune modulators which attenuate the effects of viral infections in type 2 asthma, specifically RV-C, influenza A and SARS-CoV-2. Supplementation of functional POPG/PI, SP-A and the IL-33 decoy receptor sST2 offer novel alternatives to reduce exacerbations due to viral infections in asthma. Use of human samples is critical as animal models of SARS- CoV-2, influenza and RVC are limited, and translational of findings to human disease can be variable. Therefore, the goal of the Clinical Core is to provide services for our AADCRC investigators to perform safe, consistent procedures in research participants for phenotyping and standardized, high quality collection of biologic airway and peripheral systemic specimens, cost effective sample processing and data collection, with robust data management and statistical analysis to test the hypotheses presented in each project. This Clinical Core will extensively phenotype 100 participants comprised of 60 asthma (30 mild, and 30 severe) patients and 40 controls (25 atopic, 15 non-atopic) for lung function testing, type 2 phenotyping, genotyping, nasal sampling, and to participate in the bronchoscopy studies to understand the effectiveness of these innate immune modulators in asthma and atopy, and in mild and severe asthma. The Clinical Core will coordinate and perform bronchoscopy with bronchoalveolar lavage, nasal and epithelial cell brushings, and endobronchial biopsy on all participants. The Clinical Core will be responsible for processing, storing, and distributing all samples collected from participants, to each of the three projects. In this capacity, the Core will allow each clinical sample to be utilized to its full potential and serve all projects equally. For all of the studies within the AADCRC utilizing human subject samples, the Clinical Core will also be responsible for assuring patient safety, data confidentiality and full regulatory compliance. A Biostatistics Unit is embedded in this core to integrate the clinical data with the molecular/biomarker data to effectively model relationships between cellular features and clinical phenotypes in asthma.