Innate and adaptive immunity in COPD exacerbations

描述（由申请人提供）： 由吸烟引起的慢性阻塞性肺疾病（COPD）是最常见的与肺相关的死亡原因，因此也是我国面临的最紧迫的医疗保健问题之一。COPD急性加重（AE-COPD）是造成COPD患者大部分医疗保健费用和大部分发病率以及健康相关生活质量下降的原因。由于目前的治疗不足以预防AE-COPD频繁加重患者，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计算机或动物模型。因此，必须研究从患有COPD的人类受试者获得的样本。该项目的长期目标是了解先天性和适应性免疫系统的元素如何在遇到呼吸道病毒，细菌病原体或空气中的颗粒物时相互作用，以诱导AE-COPD的症状。本项目将AE-COPD的频率、严重程度和持续时间与先天性和适应性肺免疫功能的分析相关联。中心假说认为AE-COPD是由过度活跃的肺泡巨噬细胞、募集的未成熟树突状细胞和已经驻留在肺实质中的持续活性T细胞相互作用引起的。受试者将是一个前瞻性队列，包括有频繁急性加重史的GOLD 3-4期COPD患者（将对其进行纵向随访）、急性加重时确定的COPD患者和对照受试者（GOLD 0-1级，当前吸烟者和既往吸烟者以及从不吸烟者）。样本将包括诱导痰、外周血、在临床指征手术时取出的肺组织，以及选定受试者的支气管肺泡灌洗。将通过ELISA、实时PCR、流式细胞术和免疫组织化学分析这些样本。 相关性：慢性阻塞性肺疾病（COPD）是吸烟者的常见问题，其导致呼吸短促、咳嗽和痰产生增加的间歇期恶化（“恶化”）。这项研究的目的是了解免疫系统的特定部分如何引起这些症状。这些信息是寻找更有效的治疗方法来预防和治疗COPD急性加重的第一步。

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.