Bacterial Infection in COPD

慢性阻塞性肺病的细菌感染

• 批准号: 8586872
• 负责人: Sanjay Sethi
• 金额: --
• 依托单位: VA WESTERN NEW YORK HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8586872
• 关键词: Acute; Adrenal Cortex Hormones; Age; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Therapy; Antibiotics; Antigens; Antiviral Agents; Bacillus (bacterium); Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; Biological; Caring; Cause of Death; Chronic; Chronic Obstructive Airway Disease; Clinic; Clinic Visits; Clinical; Clinical Research; Cohort Studies; Culture Techniques; DNA; Detection; Development; Diagnosis; Disease; Electronics; Enterobacteriaceae; Evaluation; Fibrinogen; Goals; Gold; Haemophilus influenzae; Health Status; Hospitalization; Immune response; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Lead; Learning; Link; Measures; Methods; Molecular; Molecular Diagnostic Techniques; Moraxella (Branhamella) catarrhalis; Morbidity - disease rate; Outcome; Outcome Measure; Participant; Pathogen detection; Pathogenesis; Pathogenicity; Patient Outcomes Assessments; Patients; Polymerase Chain Reaction; Population; Prospective Studies; Proteins; Pseudomonas aeruginosa; Relapse; Research; Resolution; Role; Running; Sampling; Serum; Specimen; Sputum; Stable Disease; Staphylococcus aureus; Streptococcus pneumoniae; Symptoms; Techniques; Testing; Therapeutic; Time; United States; Veterans; Viral; Virus; Virus Diseases; Visit; Work; aging population; airway inflammation; antimicrobial; base; clinical application; cost; disease characteristic; experience; improved; innovation; insight; methicillin resistant Staphylococcus aureus; microbial; mortality; novel; pathogen; prevent; prospective; public health relevance; receptor; research study; respiratory; treatment strategy; viral detection

DESCRIPTION (provided by applicant): A significant contributor to the morbidity, mortality, health status impact and cost of care of chronic obstructive pulmonary disease (COPD) are intermittent exacerbations, Current optimal treatment of COPD prevents only 40% of exacerbations and as many as 25% of patients with an exacerbation either display incomplete resolution or relapse within 1 month. Most exacerbations are caused by bacterial and viral airway infection. Therefore, to improve our management of COPD exacerbations, it is important to elucidate precisely the extent of bacterial and viral infection in COPD and its relation to airway inflammation, as proposed in this research application. Central to the proposal is continuation of a longitudinal prospective cohort study in 50 patients with COPD that has been supported by this Merit Review since 1994. Participants are seen every 4 weeks in the Study Clinic and at exacerbation. At each visit the patient is evaluated clinically and sputum and serum sample are obtained. Specific Aims and planned experiments are as follows. Molecular techniques will be used to characterize bacterial infection in COPD and results will be compared with culture. DNA will be extracted from sputum samples obtained on a monthly basis in the COPD study clinic and used as template in real time PCR (RT-PCR) to make a quantitative determination of the presence of the 4 major pathogens, H. influenzae, S. pneumoniae, M. catarrhalis and P. aeruginosa. In order to determine the significance of pathogen detection, airway inflammation will be quantified and immune response to bacterial pathogens following exacerbations will be examined. Novel observations will include a comparison of molecular diagnostic techniques to COPD with cultures, and an understanding of the implication of detecting a pathogen only by molecular techniques. Symptomatic resolution of exacerbations will be assessed objectively with a validated patient reported outcome measure, the EXACT-PRO. Whether this clinical resolution is determined by eradication of the offending pathogen (bacteria or virus) and by resolution of airway and systemic inflammation will be assessed. When an exacerbation is diagnosed in a clinic visit, a total of 5 sputum samples and 3 serum samples will be obtained within 28 days, as well as daily electronic recording of the EXACT-PRO. Sputum specimens will be subjected to bacterial and viral detection. A comprehensive assessment of airway inflammation in sputum will also be made. Serum c-reactive protein and fibrinogen will be used to measure systemic inflammation. Whether EXACT-PRO resolution of exacerbation is related to microbial eradication and inflammatory resolution will be analyzed. A careful study of infection, inflammation and clinical symptoms will provide new information as to how these are linked in exacerbations. It would also inform whether better antimicrobial or anti-inflammatory therapies are needed to improve outcomes. The relationship of acquisition of new strains of Enterobacteriaceae and Staphylococcus aureus with exacerbations will be systematically examined. Systemic immune response to the isolated strains and airway inflammation with strain acquisition will be systematically assessed. The Enterobacteriaceae strains will be typed by REP-PCR. The S. aureus strains will be characterized by spa typing. Following strain characterization as new or pre-existing, the relationship between new strain acquisition and exacerbation will be determined. Inflammatory and immune response in exacerbations associated with new strains of these pathogens will be studied. This will provide a rigorous evaluation of the role of Enterobacteriaceae gram negative bacilli and S. aureus in exacerbations and inform us of the need for treatment of these pathogens in exacerbations. PUBLIC HEALTH RELEVANCE: Patients with chronic obstructive pulmonary disease (COPD) experience frequent acute episodes of worsening known as exacerbations. COPD is a common problem in the VA population and COPD exacerbations are a major cause of hospitalization among veterans. Exacerbations are usually caused by airway infection, with a bacteria and/or a virus. In this study, comparison of new DNA based techniques with cultures will provide a better picture of bacterial infection in COPD and also help us interpret these new tests. Determination of the relation of symptoms of exacerbation with airway infection and inflammation will provide insight in to why as many as 25% of exacerbations relapse within a month. We will also determine if certain antibiotic resistant bacterial species cause exacerbations. A better understanding of COPD exacerbations will make our efforts to prevent and treat them more effective, which will undoubtedly benefit the large number of veterans afflicted with this disease.

描述（由申请人提供）： 导致发病率，死亡率，健康状况的影响和慢性阻塞性肺部疾病（COPD）的护理成本的重要原因是间歇性加重，当前对COPD的最佳治疗只能阻止40％的加重，并且在1个月内表现出不满的分辨率或复发的患者中只有多达25％的患者。大多数加重是由细菌和病毒气道感染引起的。因此，为了改善我们对COPD加重的管理，如本研究应用中所提出的那样，精确阐明COPD中细菌和病毒感染的程度及其与气道炎症的关系。该提案的核心是在50例COPD患者中继续进行一项纵向前瞻性队列研究，自1994年以来一直受到此优点审查的支持。研究诊所和恶化。在每次访问时，临床评估患者，并获得痰液和血清样品。具体目标和计划实验如下。 分子技术将用于表征COPD中的细菌感染，并将结果与​​培养结果进行比较。 DNA将从每月在COPD研究诊所每月获得的痰液样本中提取，并在实时PCR（RT-PCR）中用作模板，以定量确定4种主要病原体，H。h. h. h. phynzae，S。pneumoniae，M。Cartarrhalis和P. eruginosa。为了确定病原体检测的显着性，将检查气道炎症，并将检查对恶化后对细菌病原体的免疫反应。新的观察结果将包括将分子诊断技术与COPD与培养物进行比较，以及仅通过分子技术检测病原体的意义的理解。 通过有效的患者报告的结果指标，确切的PRO，将对恶化的症状分辨率进行客观评估。该临床分辨率是否取决于消除有害病原体（细菌或病毒）以及气道和全身炎症的分辨率确定。当诊断出诊所的诊所诊断时，将在28天内获得总共5个痰样品和3个血清样品，以及确切PRO的每日电子记录。痰标本将经过细菌和病毒检测。还将对痰液中的气道炎症进行全面评估。血清C反应蛋白和纤维蛋白原将用于测量系统性炎症。将分析与微生物消除和炎症分辨率有关的精确PRO分辨率。对感染，炎症和临床症状的仔细研究将提供有关在恶化中如何联系的新信息。它还将告知是否需要更好的抗菌或抗炎疗法来改善预后。 肠杆菌科和金黄色葡萄球菌的新菌株的获取与恶化的关系的关系将受到系统的检查。将系统地评估对孤立菌株和气道炎症的全身免疫反应。肠杆菌科菌株将由REP-PCR键入。金黄色葡萄球菌菌株将以水疗键入为特征。在应变表征为新的或预先存在的应变表征之后，将确定新的应变获取和加重之间的关系。将研究与这些病原体的新菌株相关的加重中的炎症和免疫反应。这将对肠杆菌科的作用进行严格的评估，在恶化中的作用，并告知我们需要治疗这些病原体在加剧的情况下。 公共卫生相关性： 慢性阻塞性肺疾病（COPD）的患者经常出现被称为加重的恶化。 COPD是VA人口中的一个常见问题，COPD加剧是退伍军人住院的主要原因。加剧通常是由气道感染，细菌和/或病毒引起的。在这项研究中，将新的基于DNA的技术与培养物进行比较将为COPD中的细菌感染提供更好的了解，并帮助我们解释这些新测试。确定恶化与气道感染和炎症的关系的确定将为为什么在一个月内复发多达25％的病情。我们还将确定某些抗生素耐药物种是否引起恶化。对COPD加剧的更好理解将使我们努力预防和对待它们更有效，这无疑将使大量患有这种疾病的退伍军人受益。