Human Sample Core

人体样本核心

• 批准号: 8403441
• 负责人: Monica Kraft
• 金额: $ 44.19万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8403441
• 关键词: Asthma; Biopsy; Biopsy Specimen; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Bronchoscopy with Bronchoalveolar Lavage; Cataloging; Catalogs; Cell Surface Receptors; Clinical Research; Collaborations; Collection; Data; Databases; Development; Epithelial Cells; Extrinsic asthma; Fibroblasts; Fibrosis; Generations; Hamman-Rich syndrome; Host Defense; Human; Human Resources; Human Subject Research; Hyaluronan; Immunologics; Inflammatory; Instruction; Integration Host Factors; Interleukin-13; Laboratory Personnel; Lung; Lung Inflammation; Lung diseases; Phenotype; Process; Production; Proteins; Protocols documentation; Pulmonary Surfactant-Associated Protein A; Recruitment Activity; Regulation; Research; Research Personnel; Research Project Grants; Safety; Sampling; Screening procedure; Signal Transduction; Specimen; Study Subject; System; Transplantation; data management; experience; human subject; laboratory facility; lung injury; macrophage; prevent; programs; receptor; research study; response; sample collection; success; surfactant

The purpose of this proposal is to elucidate the mechanisms by which production of endogenous matrix components in the context of non-infectious lung injury drives unremitting lung inflammation and fibrosis by interacting with cognate receptors leading to the development of an invasive pro-fibrotic fibroblast phenotype. The primary insult of a noninfectious challenge such as that which occurs in idiopathic pulmonary fibrosis or asthma, leads to the generation of endogenous matrix breakdown products that are recognized by a variety of cell surface receptors including TLRs. Critical host defense systems such as surfactant proteins commence to thwart the pro-inflammatory signals produced by the interaction of matrix fragments with cognate receptors. Three inter-related projects are proposed in this application to investigate these mechanisms, two of which employ studies in human subjects with asthma or two which employ studies of subjects with idiopathic pulmonary fibrosis (IPF). Therefore, we propose a Human Sample Core to facilitate the safe and efficient collection of research data and specimens from human subjects and assure adequate phenotyping of subjects. There are several advantages to such a facility. First, consolidating subject recruitment prevents duplication of personnel effort in each research project. Second, standardized subject assessment assures uniformity of experimental data across all projects in this program. Third, assembling an experienced clinical research team helps to maximize subject safety through the course of each research protocol. Finally, the consolidated laboratory facility allows for a uniform subject database and standardized collection, processing and storage of biologic specimens for each project in this program. In aim 1, we will recruit and screen approximately 100 subjects (20/year) with IPF and 150 subjects with asthma (50 mild, 50 severe) and 50 normal subjects to participate in the studies outlined in Projects 1-3. In aim 2, subjects with severe IPF (20/year) receiving lung transplant will undergo bronchoscopy with bronchoalveolar lavage (BAL) in the operating suite for experiments outlined in Projects 1 and 2; 150 subjects (30/year) asthmatic and normal subjects will undergo bronchoscopy with BAL, endobronchial biopsy and brushing to obtain ainway macrophages and epithelial cells, and airway fibroblasts for ex vivo experiments outlined in Projects 2 and 3. In aim 3, lung specimens from 100 subjects with idiopathic pulmonary fibrosis undergoing lung transplant will be obtained for fibroblast invasion studies outlined in Project 1 and specimens obtained from bronchoscopy will be processed for experiments in Projects 2 and 3.

该提案的目的是阐明在非感染性肺损伤的情况下内源性基质成分的产生通过与同源受体相互作用导致侵袭性促纤维化成纤维细胞表型的发展而驱动持续的肺部炎症和纤维化的机制。非感染性挑战的主要损伤，例如特发性肺纤维化或哮喘中发生的损伤，导致内源性基质分解产物的产生，这些产物被包括 TLR 在内的多种细胞表面受体识别。关键的宿主防御系统，如表面活性剂蛋白，开始阻止基质片段与同源受体相互作用产生的促炎信号。本申请提出了三个相互关联的项目来研究这些机制，其中两个项目采用了对患有哮喘的人类受试者的研究，或者两个项目采用了以下研究： 患有特发性肺纤维化（IPF）的受试者。因此，我们提出了人类样本核心，以促进安全有效地收集人类受试者的研究数据和标本，并确保受试者的充分表型分析。这种设施有几个优点。首先，整合受试者招募可以防止每个研究项目中人员工作的重复。二、标准化科目 评估确保该计划中所有项目的实验数据的一致性。第三，组建经验丰富的临床研究团队有助于在每个研究方案的过程中最大限度地提高受试者的安全性。最后，综合实验室设施允许该计划中的每个项目有一个统一的主题数据库以及生物标本的标准化收集、处理和存储。在目标 1 中，我们将招募并筛查大约 100 名 IPF 受试者（20 名/年）和 150 名哮喘受试者（50 名轻度，50 名哮喘）。 严重）和 50 名正常受试者参加项目 1-3 中概述的研究。在目标 2 中，接受肺移植的严重 IPF（20/年）受试者将在手术室中接受支气管镜检查和支气管肺泡灌洗 (BAL)，以进行项目 1 和 2 中概述的实验； 150 名受试者（30 名/年）哮喘患者和正常受试者将接受 BAL 支气管镜检查、支气管内活检和刷牙以获取所有信息 巨噬细胞和上皮细胞以及气道成纤维细胞用于项目 2 和 3 中概述的离体实验。 在目标 3 中，将从 100 名接受肺移植的特发性肺纤维化受试者中获取肺标本，用于项目 1 中概述的成纤维细胞侵袭研究，并处理从支气管镜检查中获得的标本，用于项目 2 和 3 中的实验。