Microbiome in Chronic Obstructive Pulmonary Disease

慢性阻塞性肺疾病中的微生物组

• 批准号: 7713377
• 负责人: Rubin M. Tuder
• 金额: $ 7.68万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-11 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7713377
• 关键词: Accounting; Acute; Ally; Antibiotics; Apoptosis; Arts; Bacteria; Bacterial Infections; Breathing; Bronchial Tree; Bronchoalveolar Lavage; Cessation of life; Characteristics; Chronic; Chronic Obstructive Airway Disease; Clinical; Cystic Fibrosis; Data; Deterioration; Disease; Disease Progression; Genes; Goals; Haemophilus influenzae; Immune response; Immune system; Immunity; Immunofluorescence Immunologic; Infection; Infectious Agent; Lasers; Lead; Lung; Lung diseases; Lymphoid Follicle; Methods; Molecular; Moraxella (Branhamella) catarrhalis; Morbidity - disease rate; Outcome; Pathogenesis; Pathology; Patients; Population; Ribosomal RNA; Risk; Role; Sampling; Severities; Severity of illness; Shortness of Breath; Smoker; Sputum; Staging; Streptococcus pneumoniae; Structure of parenchyma of lung; Techniques; Tissues; Translating; Tube; Viral; abstracting; advanced disease; airway inflammation; airway remodeling; base; cigarette smoking; inflammatory marker; insight; microbial community; microbiome; mortality; novel; public health relevance; rRNA Genes; repository; superinfection

DESCRIPTION (provided by applicant): Bacterial infection of lung airways underlies some of the main complications of COPD, which impact significantly in disease progression and outcome. Acute exacerbations (AE) represent one of the major contributing factors of morbidity, clinical deterioration, and morbidity among patients with COPD. Most importantly, AE and severity of COPD are mutually interrelated as AE are more frequent with patients with more severe COPD and, conversely, cause further deterioration of the degree of airflow limitation and disease severity. Lower airway bacterial infection or colonization may be the triggering mechanism of these immunological and structural abnormalities. Novel techniques aimed at amplification and sequencing of the gene encoding the bacterial small subunit ribosomal RNA (SSU-rRNA) allow for a molecular interrogation of species of bacteria present in lung diseases, such as demonstrated in cystic fibrosis. This technique offers significant potential advantages over traditional approaches including bacterial culture of sputum, induced sputum, or bronchoalveolar lavaged sampling. In this proposal, we hypothesize that the airways of COPD patients will contain defined microbiota, which is different from that of smokers with minimal/mild disease. Furthermore, we propose that the microbiota in COPD lungs changes throughout the bronchial tree and it correlates with markers inflammation. Specific Aim 1 will determine the lung microbiota along the airways and in the parenchyma in patients with COPD, smokers with minimal or mild disease, and in normal lungs using laser-capture microdissected LTRC samples based on high throughput amplification and sequencing of the gene encoding the SSU-rRNA. Specific Aim 2 will correlate specific microbiota with tissue markers of inflammation and apoptosis in lungs of patients COPD, smokers with minimal or mild disease and normal lungs using immunofluorescence allied to quantification by planimetry and/or stereology. This proposal may lead to highly relevant data with potential impact on fundamental aspects of the normal airway microenvironment on lung immunity and the role of bacterial in the pathogenesis of COPD, with potential applications to non-COPD lung diseases. PUBLIC HEALTH RELEVANCE: Bacterial infection of lung airways underlies some of the main complications of COPD, which is a disease caused by cigarette smoke and characterized by progressive difficulty in breathing. Patients with severe COPD are at risk of getting worse and acquiring viral and bacterial infections. These are called exacerbations, which oblige patients to be hospitalized and received antibiotics and drugs that suppress the immune system. These patients are then at significantly increased risk of death and marked clinical worsening of the shortness of breath. The proposed study is a novel way to find out whether there are bacteria present in small airway tubes in patients with COPD. We propose to use the lung tissues collected by the LTRC and translate a novel and state of the art method to perform a large scale screen of the bacteria that may present in normal and diseased lungs. (End of Abstract)

描述（由申请人提供）： 肺气道的细菌感染是慢性阻塞性肺病的一些主要并发症的基础，对疾病的进展和结果有显着影响。急性加重 (AE) 是 COPD 患者发病、临床恶化和发病的主要影响因素之一。最重要的是，AE 和 COPD 的严重程度是相互关联的，因为 AE 在 COPD 较严重的患者中更常见，相反，会导致气流受限程度和疾病严重程度进一步恶化。下呼吸道细菌感染或定植可能是这些免疫和结构异常的触发机制。旨在对编码细菌小亚基核糖体 RNA (SSU-rRNA) 的基因进行扩增和测序的新技术，可以对肺部疾病中存在的细菌种类进行分子研究，例如囊性纤维化中所证实的细菌种类。与传统方法（包括痰细菌培养、诱导痰或支气管肺泡灌洗取样）相比，该技术具有显着的潜在优势。在这项提议中，我们假设慢性阻塞性肺病患者的气道将含有特定的微生物群，这与患有轻微/轻度疾病的吸烟者的微生物群不同。此外，我们认为慢性阻塞性肺病肺部的微生物群在整个支气管树中发生变化，并且与炎症标志物相关。具体目标 1 将基于编码 SSU-rRNA 的基因的高通量扩增和测序，使用激光捕获显微解剖 LTRC 样本来确定 COPD 患者、患有轻微或轻度疾病的吸烟者以及正常肺部的气道和实质中的肺部微生物群。具体目标 2 将使用免疫荧光与平面测量和/或体视学定量相结合，将特定微生物群与慢性阻塞性肺病患者、患有轻微或轻度疾病的吸烟者以及正常肺部的炎症和细胞凋亡的组织标志物关联起来。该提议可能会产生高度相关的数据，对正常气道微环境对肺部免疫的基本方面以及细菌在慢性阻塞性肺病发病机制中的作用产生潜在影响，并可能应用于非慢性阻塞性肺病肺部疾病。 公共卫生相关性：肺部气道细菌感染是慢性阻塞性肺病（COPD）的一些主要并发症的基础，慢性阻塞性肺病是一种由香烟烟雾引起的疾病，其特征是进行性呼吸困难。严重慢性阻塞性肺病患者有病情恶化和感染病毒和细菌的风险。这些被称为病情加重，患者必须住院并接受抗生素和抑制免疫系统的药物。这些患者的死亡风险显着增加，并且呼吸急促的临床症状明显恶化。这项拟议的研究是一种查明慢性阻塞性肺病患者小气道管中是否存在细菌的新方法。我们建议使用 LTRC 收集的肺组织，并转化一种新颖且最先进的方法，对正常和患病肺部中可能存在的细菌进行大规模筛查。 （摘要完）