Biomarkers in Patients with Sepsis or Acute Respiratory Distress Syndrome

脓毒症或急性呼吸窘迫综合征患者的生物标志物

• 批准号: 9352012
• 负责人: ANTHONY F. SUFFREDINI
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9352012
• 关键词: ATP phosphohydrolase; Acute; Adrenal Cortex Hormones; Adult Respiratory Distress Syndrome; American; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Archives; Autoantibodies; Autoantigens; Biological Assay; Biological Markers; Blood Cells; Blood specimen; Bronchoalveolar Lavage; Carboxy-Lyases; Caring; Categories; Chest; Clinical; Clinical Trials; Coagulation Process; Collaborations; Complication; Diffuse; Enrollment; Etiology; Fever; Functional disorder; Goals; Growth Factor Gene; Healthcare; Hemostatic Agents; Hypotension; Immunoassay; Infection; Inflammation; Inflammatory Response; Injury; Institutional Review Boards; Interleukin-6; International; Ischemia; Lead; Leukocytes; Life; Lung; Manuscripts; Measures; Mediating; Mediator of activation protein; Methods; Methylprednisolone; MicroRNAs; Morbidity - disease rate; Organ; Outcome; Pathogenesis; Patients; Plasma; Play; Pneumonia; Potassium Channel; Protein Array; Protein C; Proteins; Pulmonary Inflammation; Pulmonary aspiration of gastric contents; Research; Respiratory Failure; Role; Rosa; Sampling; Sepsis; Septic Shock; Shock; Site; Societies; Stomach; Syndrome; TNF gene; Tachycardia; Technology; Tennessee; Time; Time Study; Tissues; Universities; Vascular Endothelial Growth Factors; Vasodilation; Viscera; White Blood Cell Count procedure; Work; base; candidate marker; chemokine; cytokine; high risk; insight; lung injury; microbial; mortality; pathogen; procalcitonin; response; septic; symposium; treatment as usual

We are evaluating biomarkers in patients with severe infections that lead to shock and lung dysfunction. Samples are being analyzed in collaboration with collaborators at the University of Tennessee Memphis who have conducted a trial prospectively evaluating the effects of corticosteroids on outcome from septic shock or severe respiratory failure. Our goals are to evaluate biomarkers at the time of study entry and during the course of the illness to determine if there are molecules that will help characterize the patients who are likely to have a beneficial response from corticosteroid therapy. During the last year we have screened samples from patients with documented infection and ARDS for chemokines, cytokines, hemostatic, and growth factors that have been suggested to play a role in the pathogenesis of lung injury. We utilized a highly sensitive antibody profiling technology to study autoantibodies in 48 patients with either acute respiratory distress syndrome (ARDS) or severe sepsis. 57% of ARDS and 46% of septic patients without ARDS had elevated autoantibodies compared to the healthy controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that titers of low autoantibodies at early time points rose precipitously and peaked between days 7-14. The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self-proteins and may contribute to late term sequela of systemic inflammation. (J Transl Med 2010; 8:97) We studied biomarkers in 79 patients receiving methylprednisolone or usual care during early ARDS. Interleukin-6, tumor necrosis factor, vascular endothelial growth factor, protein C, procalcitonin and proadrenomedullin were measured in archived plasma. We found that the changes in biomarkers changes varied with the precipitating cause of ARDS (infectious vs. noninfectious and pulmonary vs. non-pulmonary etiologies), suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of ARDS. (Crit Care Med 2012; 40:495) We are currently evaluating the differential effects of anti-inflammatory therapy on the expression of microRNA species associated with archived samples of peripheral blood cells from patients with ARDS. These molecules may provide insight into mechanisms that are engaged with the initiation of this therapy for severely ill patients. Preliminary analysis of this work has been presented (microRNA Expression in Peripheral Blood Cells from Patients with Acute Respiratory Distress Syndrome Treated with Corticosteroids. American Thoracic Society International Conference, May 16-24, 2014, San Diego, CA ). The following manuscript has been submitted to Crit Care "Temporal Changes in MicroRNA Expression in Blood Leukocytes from Patients with the Acute Respiratory Distress Syndrome".

我们正在评估严重感染的患者的生物标志物，导致休克和肺功能障碍。样本正在与田纳西大学孟菲斯大学的合作者合作进行分析，后者已经进行了试验，该试验前瞻性地评估了皮质类固醇对败血性休克或严重呼吸衰竭结果的影响。我们的目标是在研究进入时和疾病过程中评估生物标志物，以确定是否有分子有助于表征可能对皮质类固醇治疗有益反应的患者。在过去的一年中，我们筛选了来自趋化因子，细胞因子，止血和生长因子的病历和ARDS患者的样品，这些样本被认为在肺部损伤的发病机理中起作用。 我们利用高度敏感的抗体分析技术来研究48例急性呼吸窘迫综合征（ARDS）或严重败血症患者的自身抗体。与健康对照组相比，无需ARD的ARDS和46％的ARDS和46％的自身抗体升高。针对包括钾通道调节剂，胃ATPase，谷氨酸脱羧酶-65和几种细胞因子（包括钾通道调节剂）的频谱检测到频繁的高滴度抗体。对系列样品的分析表明，早期时间点低自身抗体的滴度急剧上升，并在第7-14天之间达到峰值。 ARDS和严重败血症中自身抗体的快速诱导表明，持续的系统性炎症和相关的组织破坏介导了对这些自我蛋白质的耐受性的破裂，并可能导致全身炎症的后期后遗症。 （J Transf Med 2010; 8:97） 我们研究了79例在早期ARDS期间接受甲基促甲硅龙或经常护理的患者的生物标志物。白介素6，肿瘤坏死因子，血管内皮生长因子，蛋白质C，促脂蛋白素和原肾上腺素蛋白在存档的血浆中测量。我们发现，生物标志物变化的变化随ARD的降水原因而变化（传染性，非感染和肺与非肺病因），这表明基本机制以及对抗炎疗法的反应可能随ARDS的原因而变化。 （Crit Care Med 2012; 40：495） 我们目前正在评估抗炎疗法对与ARDS患者外周血细胞的存档样品相关的microRNA物种表达的差异作用。这些分子可能会深入了解与严重患者开始这种疗法的机制。 已经进行了对这项工作的初步分析（已通过皮质类固醇治疗的急性呼吸窘迫综合征患者的外周血细胞中的microRNA表达。美国胸腔协会国际会议，2014年5月16日至24日，加利福尼亚州圣地亚哥，加利福尼亚州）。 以下手稿已提交给CRIT护理“急性呼吸窘迫综合征患者的血清细胞中microRNA表达的时间变化”。