Plasma Protein Biomarker-Based Diagnostics Of Outcome In

基于血浆蛋白生物标志物的结果诊断

• 批准号: 6999564
• 负责人: Stephen Francis Kingsmore
• 金额: $ 51.75万
• 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/6999564
• 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）：提议由 6 个组织的研究人员参与多学科协作，开发针对严重败血症 (SS) 和社区获得性肺炎 (CAP) 的新型体外诊断测试 (IVD)。 具体目标 1：早期、准确地识别将出现器官功能障碍 (SS) 的脓毒症患者对于有效管理和积极结果至关重要。我们建议开发一种快速的护理点 (POC) IVD 用于 SS 的早期诊断。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 家三级医院和急诊科采用蛋白质组技术（质谱和多重免疫分析）进行脓毒症前瞻性临床研究中对其进行验证。 将进行双变量分析来识别和验证组间生物标志物的差异。 将对经过验证的生物标志物进行多变量分析，以获得用于 SS 早期诊断的生物标志物组。生物标志物组将与代谢终点和 APACHE II 评分等预后指数进行比较。该生物标志物组合将开发为寡聚体 IVD 免疫测定，在 Biosite Triage 平台上对单个血液样本进行检测，得出结果的时间不到 30 分钟。 具体目标 2：CAP 并发症是发病率和死亡率的主要决定因素。早、准 识别病程复杂或预后不良（严重 CAP）的 CAP 患者对于有效管理和积极结果至关重要。我们建议通过对 Aim 1 临床研究中的 CAP 患者进行单独分析来确定早期诊断严重 CAP 的生物标志物。将进行双变量和多变量分析，以确定生物标志物差异，并得出用于早期诊断严重 CAP 的生物标志物组。该面板将与预后指数（例如 PORT 评分）进行比较。 具体目标 3：目前，脓毒症和 CAP 的初始抗菌治疗是经验性的。我们建议确定宿主生物标志物，用于脓毒症和CAP常见病因的早期分化，以便进行更有针对性的初始治疗，从而降低与无效治疗相关的成本，并减少抗生素耐药性的可能性。将对 Aim 1 研究中确认患有脓毒症和 CAP 病原体（例如肺炎球菌）的患者组进行双变量和多变量分析，以确定 用于早期区分脓毒症和 CAP 特定类别药物的生物标志物和生物标志物组。