Chicago Community-Acquired Pneumonia Consortium II

描述（由申请人提供）：社区获得性肺炎（CAP）和流感是美国第八大最常见的主要和重要的次要死亡原因。信息表明，自上次cdc发起的基于人群的研究以来，CAP的病因学和可能的频率发生了变化。即使是CAP的定义也经过了修订，排除了新定义的卫生保健相关性肺炎（HCAP）组。不幸的是，目前缺乏适当的基于人群的病原体特异性研究来定义HCAP，这导致了重大争议。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反应（PCR）检测，不仅使病因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病因。所有这些因素结合在一起，需要在准确的病因诊断的基础上，以当代人群为基础的CAP发病率估计。为了响应这一需求和由此产生的CDC资助机会，我们建立了一个由芝加哥三家城市医院组成的联盟，在18个月的时间内招募1500名成年CAP患者。结合之前在同一中心使用几乎相同的方案进行的研究，将可以准确估计30年后的情况。准确的以人口为基础的发病率估计需要纳入城市人口，这些人口具有各种种族/民族、社会经济和获得这些医院收治的患者所具有的医疗保健特征。一些因肺炎就诊的患者亚组被排除在当前的CDC研究之外，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，因此它们将影响我们的发病率计算。因此，我们将扩大本提案的纳入标准以招募这些患者，期望分子诊断工具将证明其肺炎的高比例是由通常的CAP病原体引起的。我们还将关注社区获得性耐甲氧西林金黄色葡萄球菌（CA-MRSA）肺炎发病率的增加。微生物病因将通过广泛的诊断检测来确定，包括常规的尿抗原检测、配对血清学和一系列cdc批准的PCR检测。流感和细菌共感染的作用将通过PCR、培养和配对血清学积极探索。全血定量PCR （qPCR）检测肺炎球菌基因和细菌16s核糖体基因可提高诊断敏感性。证实qPCR与死亡率、感染性休克和器官衰竭相关，将挑战传统的教条，即这些并发症是由于宿主反应而不是细菌因素。我们的数据与其他参与中心的数据相结合，将提供更准确的肺炎发病率和病因的当代评估。结果将为今后关于诊断检测、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.