BIOMARKERS OF OXIDANT STRESS IN ARDS

项目3的长期目标是开发新的干预措施， 有利地改变亚组中的氧化剂-抗氧化剂失衡， 有ARDS风险且以高氧化应激为特征的患者， 为了防止ARDS的发生，如果它确实发生在这些 患者，以降低其严重程度和相关的发病率和死亡率。 项目3有以下四个具体目标： 1.为了检验这一假设，选择的生物标志物的水平升高， 氧化应激是急性肺损伤发生的危险因素 (ALI)或创伤或脓毒症后的ARDS，两项巢式病例对照研究将 在创伤或脓毒症患者的前瞻性队列中进行。 三种生物标志物，血清蛋白3-硝基酪氨酸和羰基， 和尿异前列腺素（IPF 2 α-I），将与 多变量统计模型中随后发生的ALI或ARDS。 对照将从相同的目标人群和对照中选择 用于生物标志物分析的样本将根据以下因素与病例匹配： 是在创伤或败血症发作后的同一时间。 2.为了检验以下假设： 氧化应激与严重创伤后ALI/ARDS的发作一致， 严重脓毒症，将进行两项巢式病例对照研究， 具体目标1中描述的相同队列。水平相同 从发病后第一个48小时的生物标志物（如上所列） 病例中的ALI或ARDS将与从匹配的 对照 3.为了验证氧化剂生物标志物水平升高 由于创伤或败血症引起的ARDS发作时的应激是 长期呼吸衰竭、器官系统衰竭和死亡率， 患者ARDS发作时特定目标1中列出的相同生物标志物 由于创伤或脓毒症将进行比较（通过多变量统计 方法），有三个结果（均在ARDS发作后28天）：1. 无呼吸机天数，2.无器官衰竭天数和3. mortality. 4.为了验证一个假设，给予全身性抗氧化剂 降低ARDS患者氧化应激生物标志物的水平 由于创伤或败血症，随机、双盲、安慰剂对照 将进行研究以评估DL-α-生育酚对 Specific Aim 1中的生物标志物在创伤或脓毒症所致的早期ARDS中的作用。

Project 3's long term goal is to develop new interventions that can favorably change the oxidant-antioxidant imbalance in subgroups of patients at risk for ARDS and characterized by high oxidant stress in order to prevent ARDS from occurring and, if it does occur in these patients, to reduce its severity and associated morbidity and mortality. Project 3 has the following four Specific Aims: 1. To test the hypothesis that elevated levels of selected biomarkers of oxidant stress are risk factors for the development of acute lung injury (ALI) or ARDS after trauma or sepsis, two nested case-control studies will be conducted within prospective cohorts of patients with trauma or sepsis. Levels of three biomarkers, serum protein 3-nitrotyrosine and carbonyls, and a urinary isoprostane (IPF2 alpha-I), will be related to the subsequent occurrence of ALI or ARDS in a multivariate statistical model. Controls will be selected from the same target population and control samples for biomarker analysis will be matched with cases on the basis of being from the same time after onset of trauma or sepsis. 2. To test the hypothesis that elevations in selected biomarkers of oxidant stress coincide with the onset of ALI/ARDS after major trauma or severe sepsis, two nested case-control studies will be conducted within the same cohorts described in Specific Aim 1. Levels of the same biomarkers (as listed above) from the first 48 hours after the onset of ALI or ARDS in cases will be compared with those obtained from matched controls. 3. To test the hypothesis that elevated levels of biomarkers of oxidant stress at the onset of ARDS due to trauma or sepsis are risk factors for prolonged respiratory failure, organ system failure and mortality, the same biomarkers listed in Specific Aim 1 at the onset of ARDS in patients due to trauma or sepsis will be compared (by multivariate statistical methods) with three outcomes (all at 28 days after onset of ARDS): 1. ventilator-free days, 2. organ failure free days and 3. mortality. 4. To test the hypothesis that administering a systemic anti-oxidant decreases the levels of biomarkers of oxidant stress in patients with ARDS due to trauma or sepsis, a randomized, double-blinded, placebo controlled study will be conducted to assess the effects of dl-alpha-tocopherol on the biomarkers in Specific Aim 1 in early ARDS due to trauma or sepsis.