Innate and adaptive immunity in COPD exacerbations

描述(由申请人提供)： 吸烟引起的慢性阻塞性肺疾病(COPD)是最常见的与肺部相关的死亡原因，因此也是我国面临的最紧迫的医疗保健问题之一。慢性阻塞性肺疾病急性加重(AE-COPD)是COPD的大部分医疗费用以及与健康相关的生活质量下降和发病率的主要原因。由于目前的治疗方法不足以预防频繁加重者的AE-COPD，因此必须更好地了解AE-COPD的潜在原因。目前还没有公认的AE-COPD的计算机或动物模型。因此，必须对从COPD患者身上获得的样本进行研究。该项目的长期目标是了解先天和适应性免疫系统的要素在遇到呼吸道病毒、细菌病原体或空气中的颗粒物时是如何相互作用的，以诱发AE-COPD症状。这个项目将把AE-COPD的频率、严重程度和病程与先天和适应性肺免疫功能的分析联系起来。中心假说认为，AE-COPD是肺泡巨噬细胞过度活跃、招募未成熟树突状细胞和已存在于肺实质的持续活跃的T细胞相互作用的结果。受试者将是有频繁加重病史的GOLD 3-4期COPD患者的预期队列，他们将接受纵向跟踪，病情恶化时确诊的COPD患者，以及对照受试者(GOLD 0-1现任和既往吸烟者，以及从不吸烟者)。样本将包括临床指征手术时取出的诱导痰、外周血、肺组织，以及在选定的受试者中进行的支气管肺泡灌洗。这些样本将通过酶联免疫吸附试验、实时定量聚合酶链式反应、流式细胞仪和免疫组织化学进行分析。 相关性：慢性阻塞性肺疾病(COPD)是吸烟者的常见问题，会导致间歇性呼吸急促、咳嗽和排痰增加(“恶化”)。这项研究的目的是了解免疫系统的特定部分如何导致这些症状。这些信息是寻找更有效的治疗方法来预防和治疗COPD恶化的第一步。

DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) due to smoking is the most common lung-related cause of death, and thus one of the most pressing healthcare problems facing our nation. Acute exacerbations of COPD (AE-COPD) are responsible for most of the healthcare costs and much of morbidity and decline in health-related quality of life in COPD. Because current therapies are inadequate to prevent AE-COPD in frequent exacerbators, the underlying reasons for AE-COPD must be better understood. There is no currently accepted computer or animal models of AE-COPD. Hence, samples obtained from human subjects with COPD must be studied. The long-term objective of this project is to understand how elements of the innate and adaptive immune system interact on encountering respiratory viruses, bacterial pathogens, or airborne particulates to induce the symptoms of AE-COPD. This project will correlate the frequency, severity and duration of AE-COPD with analysis of innate and adaptive pulmonary immune functions. The Central Hypothesis is that AE-COPD result from the interaction of hyperactive alveolar macrophages, recruited immature dendritic cells, and persistently-active T cells already resident in the lung parenchyma. Subjects will be a prospective cohort of GOLD stage 3-4 COPD patients with a history of frequent exacerbation who will be followed longitudinally, COPD patients identified at the time of an exacerbation, and control subjects (GOLD 0-1 current and ex-smokers, and never-smokers). Samples will include induced sputum, peripheral blood, lung tissue removed at the time of clinically-indicated surgery, and in selected subjects, bronchoalveolar lavage. These samples will be analyzed by ELISA, realtime PCR, flow cytometry, and immunohistochemistry. RELEVANCE: Chronic Obstructive Pulmonary Disease (COPD) is a common problem in smokers that causes intermittent periods of worsened shortness of breath, cough and increased sputum production ("exacerbations"). The goal of this study is to learn how specific parts of the immune system cause these symptoms. This information is a first step to finding more effective treatments to prevent and treat COPD exacerbations.