Clinical and Laboratory Core

这项建议的目的是阐明表面活性蛋白-A(SP-A)调节的机制 过敏性哮喘的炎症和免疫反应。我们假设SP-A功能障碍会导致 导致过敏性哮喘严重程度的异常免疫反应。三个相互关联的 在这项申请中提出了项目，每个项目都通过对人类受试者的研究得到加强 哮喘或使用从哮喘患者身上获得的生物标本。因此，我们提出一项 临床和实验室核心，促进安全和高效地收集研究数据和样本 从人类受试者身上。这样的设施有几个好处。一、巩固学科招生 防止每个研究项目中的人员工作重复。二、规范的学科评价 确保本项目中所有项目实验数据的一致性。第三，组装一个 经验丰富的临床研究团队在每个研究过程中帮助最大限度地提高受试者的安全性 协议。最后，合并的实验室设施允许建立统一的主题数据库和标准化 本计划中每个项目的生物标本的收集和处理。在目标1中，我们将招募和 在1-4年内筛选约140名受试者，招募120名受试者(60名哮喘，60名正常)参与 在项目1中概述的支气管镜检查中。我们还将对上皮细胞进行分型和确定 项目3中臭氧或过滤空气暴露后的渗透性表型。在目标2中，120名受试者(25/年) 将在项目1的1-5年接受支气管镜检查，以获得用于纯化SP-A和呼吸道的BAL液 上皮细胞用于SP-A功能的体外实验。80名受试者(16人/年)将接受 项目3中概述的研究的支气管镜检查。这些对象将在SP-A 223之间分配 正常组和哮喘组的多态和上皮通透性表型。在AIM 3中 生物标本(支气管肺泡灌洗液和细胞、支气管腔内活检和用于DMA的血液) 在筛查和支气管镜检查过程中获得的信息将被处理和分析，以用于 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.