Core B Clinical Core

核心 B 临床核心

• 批准号: 10261954
• 负责人: Tara F Carr
• 金额: $ 25.04万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10261954
• 关键词: 2019-nCoV; ACE2; Alleles; Allergic Disease; Alveolar Macrophages; Animal Model; Anions; Asthma; Attenuated; Biological; Biological Response Modifiers; Biometry; Biopsy; Blood; Bronchoalveolar Lavage Fluid; Bronchoscopy; Bronchoscopy with Bronchoalveolar Lavage; Brush Cell; Cells; Clinical; Clinical Data; Clinical Research; Collaborations; Collection; Consent; DNA; Data; Data Analyses; Data Collection; Effectiveness; Epithelial; Epithelial Cells; Future; Genetic Transcription; Genotype; Goals; Heterogeneity; Human; Human Subject Research; Immune response; Immunologic Factors; Immunomodulators; Individual; Infection; Inflammation; Inflammatory Response; Influenza; Influenza A virus; Innate Immune System; Interleukin-6; Leadership; Lipids; Liquid substance; Mediator of activation protein; Modeling; Nasal Epithelium; Natural Immunity; Nose; Participant; Patient Recruitments; Patients; Peripheral; Phase; Phenotype; Phosphatidylglycerols; Phosphatidylinositols; Procedures; Process; Production; Protocols documentation; Pulmonary Surfactant-Associated Protein A; Pulmonary function tests; RIPK1 gene; Research; Research Personnel; Rhinovirus; SARS-CoV-2 infection; Safety; Sampling; Services; Signal Transduction; Specimen; Standardization; Statistical Data Interpretation; Supplementation; TOLLIP gene; Testing; Tissues; Toll-like receptors; Viral; Virus Diseases; Work; airway epithelium; asthma exacerbation; asthmatic; atopy; biobank; clinical phenotype; cost effective; cytokine; data management; experience; experimental study; human disease; human subject; influenzavirus; molecular marker; novel; patient safety; programs; receptor; receptor binding; recruit; sample collection; screening; surfactant; synergism

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.

哮喘和过敏性疾病合作研究中心（AADCRC）提案的总体目标是 阐明先天性免疫系统提供针对病毒诱导的免疫缺陷的保护的机制。 哮喘的恶化。在更新我们的AADCRC计划时，我们将继续关注关键的 和经常未充分研究的先天免疫因子，表面活性剂的阴离子脂质，（棕榈酰-油酰- 磷脂酰甘油（POPG）和磷脂酰肌醇（PI））和Toll相互作用蛋白（Tollip），以及 表面活性蛋白-A（SP-A）。本申请提出三个相互关联的项目;该计划将 使用从表型良好的 通过Core B（临床核心），有和没有2型哮喘和特应性的参与者。我们假设 POPG/PI、Tollip和SP-A作为独特的免疫调节剂起作用，其减弱病毒的作用。 感染2型哮喘，特别是RV-C，甲型流感和SARS-CoV-2。补充 功能性POPG/PI、SP-A和IL-33诱饵受体sST 2提供了新的替代方案， 哮喘中病毒感染引起的急性发作。使用人类样本作为SARS动物模型至关重要- CoV-2，流感和RVC是有限的，并且将发现转化为人类疾病可能是可变的。因此，我们认为， 临床核心的目标是为我们的AADCRC研究者提供服务， 在研究参与者中进行表型分型和标准化高质量生物气道采集的程序 和外周系统标本，具有成本效益的样本处理和数据收集，数据可靠 管理和统计分析，以测试每个项目中提出的假设。该临床核心将 100名参与者包括60名哮喘患者（30名轻度和30名重度）和40名对照者 (25特应性，15例非特应性）进行肺功能检测、2型表型分型、基因分型、鼻采样，并 参与支气管镜检查研究，以了解这些先天免疫调节剂在 哮喘和特应性，以及轻度和重度哮喘。临床中心将协调并进行支气管镜检查 对所有参与者进行支气管肺泡灌洗、鼻和上皮细胞刷检以及支气管内活检。 临床中心将负责处理、储存和分发从 参与者，三个项目的每一个。在这种能力下，核心将允许使用每个临床样本 充分发挥其潜力，平等地为所有项目服务。对于AADCRC中使用人类受试者的所有研究 样本，临床中心还将负责确保患者的安全性，数据保密性和完整性。 合规性。生物统计单元嵌入该核心，将临床数据与 分子/生物标志物数据，以有效地模拟细胞特征和临床表型之间的关系， 哮喘