Plasma Protein Biomarker-Based Diagnostics Of Outcome I*

基于血浆蛋白生物标志物的结果诊断 I*

• 批准号: 7090715
• 负责人: Stephen Francis Kingsmore
• 金额: $ 52.51万
• 依托单位: NATIONAL CENTER FOR GENOME RESOURCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090715
• 关键词: biomarker; clinical research; communicable disease diagnosis; cooperative study; diagnosis design /evaluation; diagnostic tests; early diagnosis; human subject; immunologic assay /test; mass spectrometry; patient oriented research; pneumonia; proteomics; septicemia

DESCRIPTION (provided by applicant): A multidisciplinary, collaborative effort involving investigators at 6 organizations is proposed to develop novel, in vitro diagnostic tests (IVD) for severe sepsis (SS) and community acquired pneumonia (CAP). Specific Aim 1: Early, accurate identification of sepsis patients who will develop organ dysfunction (SS) is critical for effective management and positive outcome. We propose to develop a rapid, point-of-care (POC) IVD for early diagnosis of SS. Our preliminary studies have identified candidate biomarkers of SS that we propose to validate in a prospective clinical study of sepsis at 3 tertiary care hospitals and emergency departments employing proteomic technologies (mass spectrometry and multiplexed immunoassays). Bivariable analyses will be performed to identify and validate biomarker differences between groups. Multivariable analyses will be performed on validated biomarkers to derive a biomarker panel for early diagnosis of SS. The biomarker panel will be compared with prognostic indices, such as metabolic endpoints and APACHE II score. The biomarker panel will be developed into an oligoplex IVD immunoassay performed on a single blood sample on the Biosite Triage platform, with a time-to-result of less than 30 minutes. Specific Aim 2: Complications of CAP are major determinants of morbidity and mortality. Early, accurate identification of patients with CAP who will have a complicated course or poor outcome (severe CAP) is critical for effective management and positive outcome. We propose to identify biomarkers for early diagnosis of severe CAP by separate analysis of CAP patients in the Aim 1 clinical study. Bi- and multivariable analyses will be performed to identify biomarker differences and derive a biomarker panel for early diagnosis of severe CAP. This panel will be compared with prognostic indices, such as PORT score. Specific Aim 3: Currently, initial antimicrobial treatment of sepsis and CAP is empiric. We propose to identify host biomarkers for early differentiation of common etiologic agents in sepsis and CAP, in order to allow more targeted initial therapy, thereby decreasing cost associated with ineffective therapy and lessening likelihood of antibiotic resistance. Bi- and multi-variable analyses will be performed on groups of patients from the Aim 1 study with confirmed sepsis and CAP pathogens (such as pneumococcus) in order to identify biomarkers and a biomarker panel for early differentiation of specific class agent in sepsis and CAP.

描述（由申请人提供）：提议为6个组织的调查人员进行跨学科的协作努力，以开发针对严重败血症（SS）和社区获得的肺炎（CAP）的新颖的体外诊断测试（IVD）。 具体目标1：对会发育器官功能障碍（SS）的败血症患者的早期准确鉴定对于有效的管理和积极结果至关重要。我们建议开发快速的，即保健（POC） IVD用于早期诊断Ss。我们的初步研究已经确定了SS的候选生物标志物，我们建议在3个三级护理医院和急诊部门的败血症中验证使用蛋白质组学技术（质谱和多重免疫测定）的临床研究。 将进行双变量分析，以识别和验证组之间的生物标志物差异。 将对经过验证的生物标志物进行多变量分析，以得出生物标志物面板以早期诊断Ss。生物标志物面板将与预后指数（例如代谢终点和Apache II得分）进行比较。生物标志物面板将发展为在生物材料分类平台上的单个血液样本上进行的寡聚IVD IVD免疫测定，其时间不到30分钟。 特定目的2：CAP并发症是发病率和死亡率的主要决定因素。早期，准确 鉴定CAP患者的病程复杂或结果不佳（严重的CAP）对于有效的管理和积极的结果至关重要。我们建议通过在AIM 1临床研究中对CAP患者的单独分析来鉴定生物标志物，以早期诊断出严重的CAP。将进行双重和多变量分析，以识别生物标志物差异并得出生物标志物面板以早期诊断出严重的CAP。该面板将与预后指数（例如端口分数）进行比较。 特定目标3：目前，败血症和CAP的初始抗菌治疗是经验性的。我们建议鉴定宿主生物标志物，以早日分化败血症和CAP中常见的病因学剂，以便允许更有针对性的初始治疗，从而降低与无效治疗相关的成本，并降低抗生素耐药性的可能性。将对来自AIM 1研究的患者组进行双重和多变量分析，并确认的败血症和CAP病原体（例如肺炎球菌），以识别 生物标志物和生物标志物面板，用于败血症和CAP中特定类药物的早期分化。