Clinical and Laboratory Core

本研究的目的是阐明表面活性蛋白A（SP-A）调节 过敏性哮喘的炎症和免疫反应。我们假设SP-A功能障碍导致 导致过敏性哮喘严重程度的异常免疫反应。三个相互关联 在这项申请中提出了一些项目，每个项目都通过对人类受试者的研究得到加强， 哮喘或使用从哮喘受试者获得的生物样本。因此，我们建议 临床和实验室核心，以促进安全和有效地收集研究数据和标本 从人类实验对象身上。这种设施有几个优点。第一，巩固学科招聘 防止每个研究项目中的人员重复工作。第二，规范学科考核 确保该计划中所有项目的实验数据的一致性。第三，组装一个 经验丰富的临床研究团队有助于在每次研究过程中最大限度地提高受试者安全性 议定书最后，统一的实验室设施允许统一的主题数据库和标准化 本项目中每个项目的生物标本采集和处理。在目标1中，我们将招募和 在第1-4年筛选约140例受试者，招募120例受试者（60例哮喘，60例正常）参与研究 在项目1中概述的支气管镜检查研究中。我们还将进行基因分型， 项目3中臭氧或过滤空气暴露后的渗透表型。在目标2中，120例受试者（25例/年） 将在项目1的第1-5年接受支气管镜检查，以获得用于SP-A和气道纯化的BAL液 上皮细胞用于SP-A功能的离体实验。80例受试者（16例/年）将接受 用于项目3中概述的研究的支气管镜检查。这些科目将分为SP-A 223 多态性和上皮通透性表型之间的正常和哮喘组。在aim 3中 生物标本（支气管肺泡灌洗液和细胞、支气管内活检和DMA血液） 将对筛选和支气管镜检查程序期间获得的数据进行处理和分析， 项目1-3。

The purpose of this proposal is to elucidate the mechanisms by which surfactant protein-A (SP-A) modulates inflammatory and immunologic responses in allergic asthma. We hypothesize that SP-A dysfunction leads to abnormal immunologic responses that contribute to the severity of allergic asthma. Three inter-related projects are proposed in this application, each of which is strengthened by studies in human subjects with asthma or the use of biologic specimens obtained from subjects with asthma. Therefore, we propose a Clinical and Laboratory Core to facilitate the safe and efficient collection of research data and specimens from human 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 and processing of biologic specimens for each project in this program. In aim 1, we will recruit and screen approximately 140 subjects in years 1-4 to recruit 120 subjects (60 asthma, 60 normal) to participate in the bronchoscopy studies outlined in Project 1. We will also genotype and determine the epithelial permeability phenotype following ozone or filtered air exposure in Project 3. In aim 2, 120 subjects (25/year) will undergo bronchoscopy in years 1-5 in Project 1 to obtain BAL fluid for purification of SP-A and airway epithellial cells for ex vivo experiments of SP-A function. Eighty subjects (16/year) will undergo bronchoscopy for studies outlined in Project 3. These subjects will be divided between the SP-A 223 polymorphism and epithelial permeability phenotype within the normal and asthmatic groups. In aim 3 biologic specimens (bronchoalveolar lavage fluid and cells, endobronchial biopsies, and blood for DMA) obtained during the screening and bronchoscopy procedures will be processed and analyzed for use in Projects 1-3.