Bacterial Infection in COPD

慢性阻塞性肺病的细菌感染

• 批准号: 8391088
• 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 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8391088
• 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.

描述（由申请人提供）： 间歇性加重是慢性阻塞性肺病 (COPD) 发病率、死亡率、健康状况影响和护理费用的一个重要因素，目前 COPD 的最佳治疗只能预防 40% 的急性加重，而多达 25% 的急性加重患者要么表现出不完全缓解，要么在 1 个月内复发。大多数病情加重是由细菌和病毒气道感染引起的。因此，为了改善 COPD 急性加重的管理，准确阐明 COPD 中细菌和病毒感染的程度及其与气道炎症的关系非常重要，正如本研究申请中提出的那样。该提案的核心是继续对 50 名 COPD 患者进行纵向前瞻性队列研究，该研究自 1994 年以来一直得到本次优点审查的支持。参与者每 4 周在研究诊所就诊一次，并在病情加重时进行一次观察。每次就诊时，都会对患者进行临床评估并获取痰液和血清样本。具体目标和计划的实验如下。 分子技术将用于表征慢性阻塞性肺病的细菌感染，并将结果与​​培养物进行比较。将从慢性阻塞性肺病研究诊所每月获得的痰样本中提取DNA，并用作实时PCR（RT-PCR）的模板，以定量测定4种主要病原体：流感嗜血杆菌、肺炎链球菌、卡他莫拉菌和铜绿假单胞菌的存在。为了确定病原体检测的重要性，将量化气道炎症，并检查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培养的慢性阻塞性肺病进行比较，以及了解仅通过分子技术检测病原体的含义。 将通过经过验证的患者报告结果测量 EXACT-PRO 客观评估病情加重的症状缓解情况。将评估这种临床解决是否取决于致病病原体（细菌或病毒）的根除以及气道和全身炎症的解决。当临床诊断出病情加重时，28天内将获得总共5份痰样本和3份血清样本，以及EXACT-PRO的每日电子记录。痰标本将进行细菌和病毒检测。还将对痰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全身炎症。将分析 EXACT-PRO 恶化的缓解是否与微生物根除和炎症缓解相关。对感染、炎症和临床症状的仔细研究将提供关于这些因素如何与病情恶化相关的新信息。它还将告知是否需要更好的抗菌或抗炎疗法来改善结果。 将系统地研究肠杆菌和金黄色葡萄球菌新菌株的获得与病情加重的关系。将系统评估对分离菌株的全身免疫反应以及菌株获得时的气道炎症。肠杆菌科菌株将通过 REP-PCR 进行分型。金黄色葡萄球菌菌株将通过 spa 分型来表征。在将应变表征为新应变或预先存在的应变之后，将确定新应变的获得和恶化之间的关系。将研究与这些病原体的新菌株相关的恶化中的炎症和免疫反应。这将为肠杆菌科革兰氏阴性杆菌和金黄色葡萄球菌在病情加重中的作用提供严格的评估，并告知我们在病情加重时需要治疗这些病原体。