Plasma Protein Biomarker-Based Diagnostics Of Outcome In Sepsis and CAP

基于血浆蛋白生物标志物的脓毒症和 CAP 结果诊断

• 批准号: 7492246
• 负责人: Stephen Francis Kingsmore
• 金额: $ 49.12万
• 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/7492246
• 关键词: APACHE II; Accident and Emergency department; Acute; Acute Kidney Failure; Acute Physiology and Chronic Health Evaluation; Algorithms; American; Antibiotic Resistance; Antigens; Bacteremia; Biological Assay; Biological Markers; Blood; Blood Coagulation Disorders; Blood specimen; Candida; Cessation of life; Chest; Class; Clinical; Clinical Research; Communities; Consensus; Critical Care; Data Set; Detection; Development; Diagnostic; Diagnostic tests; Early Diagnosis; Early identification; Effectiveness; End Point; Enrollment; Enterobacter; Escherichia coli; Etiology; Event; Failure; Functional disorder; Genus staphylococcus; Goals; Gold; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitalization; Hospitals; Human; Immunoassay; In Vitro; Infection; Intensive Care Units; Klebsiella; Legionella pneumophila; Lobar; Mass Spectrum Analysis; Measures; Medical; Medicine; Metabolic; Methods; Monitor; Morbidity - disease rate; Mycoplasma; Newborn Respiratory Distress Syndrome; Numbers; Organ; Outcome; Outcomes Research; Patient Selection; Patients; Physicians; Plasma Proteins; Pneumonia; Principal Investigator; Proteins; Proteomics; Recombinants; Research Personnel; Resource Allocation; Respiratory Failure; Score; Sepsis; Sepsis Syndrome; Septic Shock; Severities; Societies; Sputum; Standards of Weights and Measures; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae; Technology; Testing; Time; Triage; Urine; Validation; Virus; activated Protein C; antimicrobial; atypical pneumonia; base; body system; candidemia; cohort; college; concept; cost; fungus; indexing; mortality; multidisciplinary; novel; outcome forecast; pathogen; point of care; predictive modeling; prognostic; programs; prospective; symposium; tertiary care

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（由申请方提供）：拟开展一项涉及6个组织的研究者的多学科协作研究，以开发用于严重脓毒症（SS）和社区获得性肺炎（CAP）的新型体外诊断试验（IVD）。 具体目标1：早期、准确地识别将发展为器官功能障碍（SS）的脓毒症患者对于有效的管理和积极的结局至关重要。我们建议开发一种快速的即时护理（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学技术（质谱和多重免疫测定）进行的脓毒症前瞻性临床研究中验证。 将进行双变量分析，以识别和验证组间生物标志物差异。 将对经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。将生物标志物组与预后指标（如代谢终点和APACHE II评分）进行比较。生物标志物组将开发为在Biosite Triage平台上对单个血液样本进行的寡聚物IVD免疫测定，获得结果的时间小于30分钟。 具体目标2：CAP的并发症是发病率和死亡率的主要决定因素。早，准 鉴别出有复杂病程或不良结局（严重CAP）的CAP患者对于有效管理和积极结局至关重要。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，并推导出用于早期诊断重度CAP的生物标志物组。将该面板与预后指标（如PORT评分）进行比较。 具体目标3：目前，败血症和CAP的初始抗菌治疗是经验性的。我们建议确定宿主生物标志物，用于早期区分脓毒症和CAP中常见的病原体，以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，并减少抗生素耐药性的可能性。将对Aim 1研究中确诊脓毒症和CAP病原体（如肺炎球菌）的患者组进行双变量和多变量分析，以确定 用于脓毒症和CAP中特定类别试剂的早期区分的生物标志物和生物标志物组。