Core B Clinical Core

核心 B 临床核心

基本信息

批准号：
10473851
负责人：
Tara F Carr
金额：
$ 25.29万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
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/10473851
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

项目摘要

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免疫系统提供针对病毒诱导的保护的机制哮喘恶化。在更新我们的 AADCRC 计划时，我们将继续关注关键的问题并且经常研究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) 和表面活性蛋白-A (SP-A)。本申请提出了三个相互关联的项目；该计划将采用从表型良好获得的生物气道和外周系统样本通过核心 B（临床核心）患有或不患有 2 型哮喘和过敏症的参与者。我们假设 POPG/PI、Tollip 和 SP-A 作为独特的免疫调节剂，可减弱病毒的影响 2 型哮喘感染，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 sST2 提供了新的替代方案来减少哮喘因病毒感染而加重。使用人类样本作为 SARS 的动物模型至关重要 CoV-2、流感和 RVC 的作用有限，并且研究结果对人类疾病的转化可能存在差异。所以，临床核心的目标是为我们的 AADCRC 研究人员提供安全、一致的服务研究参与者的表型分析程序和标准化、高质量的生物气道采集和周围系统标本，具有成本效益的样本处理和数据收集，具有可靠的数据管理和统计分析来测试每个项目中提出的假设。该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，30 名重度）和 40 名对照（25 种特应性，15 种非特应性）用于肺功能测试、2 型表型分析、基因分型、鼻腔取样以及参与支气管镜检查研究，以了解这些先天免疫调节剂的有效性哮喘和特应性，以及轻度和重度哮喘。临床核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、鼻腔和上皮细胞刷检以及支气管内活检。临床核心将负责处理、存储和分发从三个项目中每一个项目的参与者。以此能力，核心将允许利用每个临床样本充分发挥其潜力并平等地服务于所有项目。对于 AADCRC 内所有使用人类受试者的研究样本，临床核心还将负责确保患者安全、数据机密性和全面监管合规性。生物统计单元嵌入该核心，将临床数据与分子/生物标志物数据可有效模拟细胞特征与临床表型之间的关系哮喘。