Core B Clinical Core

核心 B 临床核心

• 批准号: 10661661
• 负责人: Tara F Carr
• 金额: $ 25.5万
• 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/10661661
• 关键词: 2019-nCoV; ACE2; Alleles; Allergic Disease; Alveolar Macrophages; Animal Model; Anions; Asthma; Attenuated; Biological; Biological Markers; 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 Cells; Epithelium; 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; Modeling; Molecular; 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; inflammatory modulation; influenzavirus; 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.

这种哮喘和过敏性疾病合作研究中心（AADCRC）的总体目标是 阐明先天免疫系统可保护病毒引起的机制 哮喘加重。在续签AADCRC计划中，我们将继续关注关键 并且经常研究的先天免疫因子表面活性剂的阴离子脂质 磷脂酰甘油（POPG）和磷脂酰肌醇（PI））和TOLL相互作用蛋白（Tollip）和 表面活性剂蛋白A（SP-A）。在本申请中提出了三个相互关联的项目；该程序将 采用生物气道和外围系统样品样品的使用 通过有或没有2型哮喘的参与者和特应特应通过Core B（临床核心）。我们假设这一点 POPG/PI，TOLLIP和SP-A充当独特的免疫调节剂，可衰减病毒的影响 2型哮喘的感染，特别是RV-C，流感和SARS-COV-2。补充 功能性POPG/PI，SP-A和IL-33诱饵受体SST2提供新颖的替代品来减少 由于哮喘的病毒感染而加重。使用人类样品作为SARS的动物模型至关重要 COV-2，流感和RVC受到限制，发现人类疾病的发现可能是可变的。所以， 临床核心的目标是为我们的AADCRC调查人员提供服务，以执行安全，一致 研究参与者的表型和标准化，高质量的生物气道的程序 以及周围的全身标本，具有成本效益的样品处理和数据收集，并具有强大的数据 管理和统计分析测试每个项目中提出的假设。这个临床核心将 广泛的表型100参与者由60名哮喘（30个轻度和30例严重）患者和40例对照组成 （25 Atopic，15个非原子）用于肺功能测试，2型表型，基因分型，鼻抽样和TO 参加支气管镜研究，以了解这些先天免疫调节剂在 哮喘和特应特纳，以及轻度和严重的哮喘。临床核心将协调和进行支气管镜检查 带有支气管肺泡灌洗，鼻和上皮细胞刷，以及所有参与者的支气管调查。 临床核心将负责处理，存储和分发从 参与者，三个项目中的每个项目。以这种能力，核心将允许使用每个临床样本 具有全部潜力，并同等地服务于所有项目。对于使用人类主题的AADCRC中的所有研究 样本，临床核心还将负责确保患者的安全性，数据机密性和完整 法规合规性。生物统计学单元嵌入了该核心，以将临床数据与 分子/生物标志物数据有效地模拟细胞特征与临床表型之间的关系 哮喘。