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: 6961210
• 负责人: Lorraine B Ware
• 金额: $ 145.51万
• 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/6961210
• 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，除保护性通气策略外没有其他特定治疗。对ARDS患者的小型单中心研究中的个体生物学标记的研究表明，细胞因子级联反应，炎症级联反应和肺中的凝血级联反应在肺中和全身性ARDS中发生了重大改变。尽管从这些生物标志物研究中获得了丰富的信息，但没有一个单一的生物标志物可以明确诊断ARDS或将幸存者与非活生生区分开。由于ARDS的复杂性，需要采用新的方法和方法，以更全面地解决ARDS的临床病理生理学。临床蛋白质组学是一种有希望的方法，NHLBI最近推荐了ARDS研究中的重要未来方向。可以识别可以诊断ARD和预测结果的独特等离子体蛋白谱的识别，有可能成为临床使用的强大工具，促进适当的疗法和分层在临床试验中的应用。此外，在大量具有新统计算法的患者中，对蛋白质生物标志物的分析将提高我们对临床ARDS发病机理的理解。基于我们在识别有良好特征的患者组中特定生物标志物或患有既定ARDS的特定生物标志物方面取得的重大进展，我们假设可以使用新的和现有的蛋白质生物标志物来诊断风险患者的ARDS既可以诊断ARDS，又可以识别患有不良临床临床抗病风险的ARDS患者。为了解决这些假设，我们将利用一种多学科的临床蛋白质组学方法，该方法借鉴了我们在测量和解释生物学标记，高吞吐量蛋白质测定设计，生物信息和生物统计学以及削减边缘质量光谱质谱蛋白质体发现工作方面的专业知识。这种多学科团队的方法，结合经过证明的持续访问大型临床试验数据集的访问将用于针对ARDS临床实践和临床研究中未满足的主要需求领域。