Early Insulin Therapy and Development of ARDS

描述(由申请人提供)：对急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)的预防研究相对较少。最近，强化胰岛素治疗(NT)被证明可以降低重症患者的发病率和/或死亡率，但NT对预防早期危重疾病事件(如ALI/ARDS)的有效性尚不清楚。这项建议的广泛目标是评估早期IIT预防高危人群ALI/ARDS的潜力。在目标1中，早期胰岛素治疗和ARDS发展之间的联系将在一项基于ARDS分子流行病学的回溯性嵌套病例对照研究中进行检验，这是一项对有ARDS风险的患者进行的大型前瞻性研究。然而，任何预防ALI/ARDS的干预措施都必须及早进行，最好是在ICU入院之前，因为38%的ARDS患者在入院当天符合ARDS标准。因此，在AIM#2中，在一项随机对照试验中，将研究急诊科(ED)早期IIT在减少肺损伤和调节与脓毒症相关的ALI/ARDS相关的介质方面的潜力。在AIM#1中，将使用倾向评分分析和多变量Logistic回归模型来解释潜在的混杂因素。在AIM#2中，将在脓毒症的第一周连续记录以Murray肺损伤评分(LIS)衡量的肺损伤。此外，严重败血症患者在入院时、研究的第一天和第三天的血液样本将被采集，血浆中游离脂肪酸、肿瘤坏死因子-a、白细胞介素6和血管性血友病因子抗原的水平将通过液、气相色谱和酶联免疫吸附试验进行检测。协方差分析将用于比较在急诊室接受早期IIT的随机患者和在ICU入院48小时后接受IIT的标准ICU组之间LIS和血浆水平随时间的变化。这项提案与NHLBI的使命和公共卫生相关，具有重大的健康相关性。ALI/ARDS是一种毁灭性的肺损伤形式，具有显著的死亡率、发病率和医疗费用。任何能够降低ALI/ARDS发生率的干预措施都将在挽救生命和避免发病率方面产生重大的流行病学影响。

DESCRIPTION (provided by applicant): There has been relatively little focus on the prevention of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS). Recently, intensive insulin therapy (NT) have been shown to decrease morbidity and/or mortality in critically ill patients with prolonged intensive care unit (ICU) stays, but the utility of NT to protect against early critical illness events such as ALI/ARDS is unknown. The broad objective of this proposal is to assess the potential of early IIT to prevent ALI/ARDS in at-risk populations. In Aim #1, the association between early insulin therapy and development of ARDS will be examined in a retrospective nested case control study based on the Molecular Epidemiology of ARDS, a large prospective study of patients at risk for ARDS. However, any intervention to prevent ALI/ARDS must occur early, preferably prior to ICU admission, since 38% of ARDS patients fulfill ARDS criteria on the day of ICU admission. Thus in Aim #2, in a randomized control trial, the potential of early IIT initiated in the Emergency Department (ED) to reduce lung injury and modulate mediators implicated in sepsis-related ALI/ARDS will be examined. The method of propensity score analyses and multivariate logistic regression models will be used to account for potential confounders in Aim #1. In Aim #2, lung injury as measured by the Murray Lung Injury Score (LIS) will be recorded serially in the first week of sepsis. In addition, blood samples will be collected from patients with severe sepsis on admission to the ED and on Day 1 and 3 of the study and plasma levels of free fatty acids, tumor necrosis factor-a, interleukin-6 and Von Willebrand Factor antigen will be determined by liquid and gas chromatography and by ELISA. Analyses of covariance will be used to compare the change in LIS and plasma levels over time between patients randomized to receive early IIT in the ED versus the standard ICU group who receive IIT 48 hours after ICU admission. This proposal has significant health relatedness to the NHLBI's mission and relevance to public health. ALI/ARDS is a devastating form of lung injury with significant mortality, morbidity, and health care costs. Any intervention that can decrease the incidence of ALI/ARDS will have a significant epidemiologic impact in lives saved and morbidity averted.