Biomarker Profiles in the Diagnosis/Prognosis of ARDS

ARDS 诊断/预后中的生物标志物概况

• 批准号: 7110356
• 负责人: Lorraine B Ware
• 金额: $ 154.8万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-12 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110356
• 关键词: adult respiratory distress syndrome; bioinformatics; biomarker; blood proteins; clinical research; clinical trials; cooperative study; diagnosis design /evaluation; disease /disorder proneness /risk; high throughput technology; human data; human subject; mass spectrometry; medical complication; pathologic process; patient oriented research; prognosis; protein quantitation /detection; proteomics; respiratory disorder diagnosis; statistics /biometry

DESCRIPTION (provided by applicant): The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure characterized by severe lung inflammation, a high mortality and no specific therapy other than a protective ventilatory strategy. Studies of individual biological markers in small single center studies of patients with ARDS have revealed major alterations in the cytokine cascade, the inflammatory cascade and the coagulation cascade both in the lung and systemically in ARDS. Despite the wealth of information gained from these biomarker studies, no single biomarker can unequivocally diagnose ARDS or differentiate survivors from non-survivors. Because of the complexity of ARDS, new approaches and methods are needed that can address the clinical pathophysiology of ARDS at a more comprehensive level. Clinical proteomics is a promising approach that has recently been recommended by the NHLBI as an important future direction in ARDS research. The recognition of unique plasma protein profiles that can diagnose ARDS and predict outcome has the potential to be a powerful tool for clinical use, facilitating application of appropriate therapies and stratification in clinical trials. Furthermore, the analysis of a panel of protein biomarkers in a large population of patients with new statistical algorithms will improve our understanding of the pathogenesis of clinical ARDS. Based on the remarkable progress that we have made in identifying specific biomarkers in large well characterized groups of patients either at risk for or with established ARDS, we hypothesize that panels of new and existing protein biomarkers can be used both to diagnose ARDS in at risk patients and to identify patients with ARDS who are at highest risk of adverse clinical outcomes. To address these hypotheses, we will utilize a multi-disciplinary clinical proteomics approach that draws on our expertise in measurement and interpretation of biological markers, high throughput protein assay design, bioinformatics and biostatistics and cutting edge mass spectroscopy proteomic discovery efforts. This multidisciplinary team approach, combined with proven ongoing access to large clinical trial datasets will be used to target major areas of unmet need in both clinical practice and clinical research in ARDS.

描述（由申请人提供）： 急性呼吸窘迫综合征（ARDS）是急性呼吸衰竭的常见原因，其特征是严重的肺部炎症、高死亡率，并且除了保护性通气策略外没有其他特殊治疗方法。在针对 ARDS 患者的小型单中心研究中，对个体生物标志物的研究揭示了 ARDS 患者肺部和全身细胞因子级联、炎症级联和凝血级联的重大改变。尽管从这些生物标志物研究中获得了大量信息，但没有任何一种生物标志物可以明确诊断 ARDS 或区分幸存者和非幸存者。由于 ARDS 的复杂性，需要新的方法和方法来更全面地解决 ARDS 的临床病理生理学问题。临床蛋白质组学是一种很有前途的方法，最近被 NHLBI 推荐为 ARDS 研究的重要未来方向。识别独特的血浆蛋白谱可以诊断 ARDS 并预测结果，有可能成为临床使用的强大工具，促进在临床试验中应用适当的疗法和分层。此外，使用新的统计算法对大量患者的一组蛋白质生物标志物进行分析将提高我们对临床 ARDS 发病机制的理解。基于我们在大量特征明确的有 ARDS 风险或已确诊的患者群体中识别特定生物标志物方面取得的显着进展，我们假设新的和现有的蛋白质生物标志物组合可用于诊断高危患者的 ARDS并确定出现不良临床结果风险最高的 ARDS 患者。为了解决这些假设，我们将利用多学科临床蛋白质组学方法，该方法利用我们在生物标记物测量和解释、高通量蛋白质测定设计、生物信息学和生物统计学以及尖端质谱蛋白质组学发现工作方面的专业知识。这种多学科团队方法，加上经过验证的对大型临床试验数据集的持续访问，将用于针对 ARDS 临床实践和临床研究中未满足需求的主要领域。