Chicago Community-Acquired Pneumonia Consortium II

描述(申请人提供)：社区获得性肺炎(CAP)和流感是美国第八大最常见的主要死亡原因和重要的次要死亡原因。信息表明，自上次疾控中心赞助的基于人群的研究以来，CAP的病因和可能的频率发生了变化。甚至CAP的定义也进行了修订，排除了新定义的医疗保健相关肺炎(HCAP)。不幸的是，缺乏适当的基于人群的病原体特异性研究来定义HCAP，现在已经导致了很大的争议。相反，分子诊断技术的发展，如尿抗原检测和细菌和病毒基因的聚合酶链式反应(PCR)检测，不仅使病原学记录比基于培养的方法更准确，而且在更大比例的病例中确定了病原学。所有这些因素都要求在准确的病因学诊断的基础上，对CAP的发病率进行基于人群的当代评估。为了应对这一需求和疾控中心的筹资机会，我们发展了一个由三家芝加哥市区医院组成的联盟，在18个月内招募1500名成年CAP患者。结合之前在相同中心使用几乎相同的方案进行的一项研究，将可以在3年内进行准确的估计。准确的基于人群的发病率估计需要包括在这些医院住院的患者中看到的具有各种种族/民族、社会经济和获得医疗保健特征的城市人口。目前疾控中心的研究排除了肺炎患者的几个亚组，例如最近出院的患者。由于这些患者通常使用ICD-9 CAP代码进行编码，它们将影响我们的发病率计算。因此，我们将扩大这项提议的纳入标准，以招募这些患者，期望分子诊断工具将证明他们的肺炎有很高比例是由常见的CAP病原体引起的。我们还将解决社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)肺炎发病率增加的问题。微生物病原学将通过广泛的诊断测试来确定，包括常规使用尿抗原检测、配对血清学和CDC批准的一系列聚合酶链式反应分析。流感和细菌混合感染的作用将通过聚合酶链式反应、培养和配对血清学来积极探索。肺炎球菌基因和普通细菌16S核糖体基因的全血定量聚合酶链式反应(QPCR)将提高诊断的敏感性。确认qPCR与死亡率、感染性休克和器官衰竭相关，将挑战这些并发症是由宿主反应而不是细菌因素引起的传统教条。我们的数据与其他参与中心的数据相结合，将提供对肺炎发病率和病原学更准确的当代评估。结果将为未来关于诊断检测、经验性抗生素治疗、疫苗接种机会和其他预防策略的决定提供信息。

DESCRIPTION (provided by applicant): Community-acquired pneumonia (CAP) and influenza are the 8th most frequent primary and an important secondary cause of death in the US. Information suggests that etiology and possibly frequency of CAP have changed since the last CDC-sponsored population-based study. Even the definition of CAP has undergone revision, with exclusion of a group with the newly-defined healthcare-associated pneumonia (HCAP). Unfortunately, lack of an appropriate population-based pathogen-specific study to define HCAP has now resulted in significant controversy. Conversely, developments in molecular diagnostic techniques, such as urinary antigen testing and polymerase chain reaction (PCR) detection of bacterial and viral genes, have not only made documentation of etiology more accurate than culture-based methods but define etiology in a greater proportion of cases. All these factors coalesce on the need for a contemporary population-based estimate of CAP incidence based on an accurate etiologic diagnosis. In response to this need and the resultant CDC Funding Opportunity, we developed a consortium of three urban Chicago hospitals to recruit 1500 adult CAP patients over an 18 month period. Combining with a previous study at the same centers using a nearly identical protocol will allow accurate estimates over >3years. An accurate population-based estimate of incidence requires inclusion of an urban population with the variety of racial/ethnic, socioeconomic, and access to healthcare characteristics seen in patients admitted to these hospitals. Several subgroups of patients presenting to the hospital with pneumonia are excluded from the current CDC study, such as recent hospital discharges. Since these patients are routinely coded with ICD-9 CAP codes, they will impact our incidence calculations. We will therefore expand inclusion criteria for this proposal to recruit these patients, expecting that molecular diagnostic tools will demonstrate that a high percentage of their pneumonias are caused by usual CAP pathogens. We will also address concern regarding an increased incidence of community-acquired methicillin-resistant S. aureus (CA-MRSA) pneumonia. Microbial etiology will be determined by extensive diagnostic testing, including routine use of urinary antigen detection, paired serology, and a battery of CDC-approved PCR assays. The role of influenza and bacterial co- infection will be aggressively explored with PCR, culture, and paired serology. Whole blood quantitative PCR (qPCR) of a pneumococcal gene and a generic bacterial 16s ribosomal gene will increase diagnostic sensitivity. Confirmation that qPCR correlates with mortality, septic shock, and organ failure will challenge the conventional dogma that these complications are due to the host response rather than bacterial factors. Our data combined with that of other participating centers will provide a more accurate contemporary assessment of pneumonia incidence and etiology. Results will inform future decisions regarding diagnostic testing, empirical antibiotic therapy, and the opportunities for vaccination and other prevention strategies.