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）： 慢性阻塞性肺疾病（COPD）的发病率、死亡率、健康状况影响和护理成本的重要因素是间歇性加重，COPD的当前最佳治疗仅预防40%的加重，并且多达25%的具有加重的患者在1个月内显示不完全消退或复发。大多数急性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急性加重的管理，重要的是要准确阐明COPD中细菌和病毒感染的程度及其与气道炎症的关系，正如本研究申请中所提出的那样。该提案的核心是继续对50例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Merit综述的支持。受试者每4周一次在研究诊所和急性加重时就诊。在每次访视时，对患者进行临床评估，并采集痰液和血清样本。具体目的和计划的实验如下。 分子技术将用于表征COPD中的细菌感染，并将结果与培养进行比较。将从COPD研究诊所每月采集的痰液样本中提取DNA，并用作真实的时间PCR（RT-PCR）的模板，以定量测定4种主要病原体H. influenzae、S. pneumoniae、M.卡他菌和铜绿假单胞菌。为了确定病原体检测的意义，将对气道炎症进行定量，并检查急性加重后对细菌病原体的免疫应答。新的观察将包括分子诊断技术与COPD培养的比较，以及对仅通过分子技术检测病原体的意义的理解。 将使用经验证的患者报告结局指标EXACT-PRO客观评估急性加重的症状缓解。将评估该临床缓解是否通过根除致病病原体（细菌或病毒）以及通过缓解气道和全身炎症来确定。当在门诊访视中诊断为急性加重时，将在28天内采集总计5份痰液样本和3份血清样本，并每日电子记录EXACT-PRO。将对痰液标本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急性加重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为这些如何与急性加重联系提供新的信息。它还将告知是否需要更好的抗菌或抗炎治疗来改善结果。 将系统检查肠杆菌科和金黄色葡萄球菌新菌株的获得与急性加重的关系。将系统评估对分离菌株的全身免疫应答和菌株获得的气道炎症。将通过REP-PCR对肠杆菌科菌株进行分型。色葡萄金黄色葡萄球菌菌株将通过SPA分型来表征。在将菌株表征为新菌株或既存菌株后，将确定新菌株采集与急性加重之间的关系。将研究与这些病原体的新菌株相关的急性加重中的炎症和免疫应答。这将为肠杆菌科革兰阴性杆菌和沙门氏菌的作用提供严格的评价。金黄色葡萄球菌在急性加重，并告知我们需要治疗这些病原体在急性加重。 公共卫生关系： 慢性阻塞性肺疾病（COPD）患者经常发生急性加重，称为急性加重。COPD是VA人群的常见问题，COPD加重是退伍军人住院的主要原因。急性加重通常由细菌和/或病毒引起的气道感染引起。在这项研究中，基于DNA的新技术与培养的比较将提供COPD细菌感染的更好图像，也有助于我们解释这些新的测试。确定急性加重症状与气道感染和炎症的关系将有助于了解为什么多达25%的急性加重在一个月内复发。我们还将确定某些抗生素耐药性细菌是否会导致病情加重。更好地了解COPD急性加重将使我们更有效地预防和治疗它们，这无疑将使大量患有这种疾病的退伍军人受益。