Transfusion Related Lung Injury in the Critically Ill

描述(由申请人提供)： 这项申请是为了支持Gajic博士作为一名独立临床调查员的职业发展。Gajic博士最近在梅奥临床医学院完成了临床研究硕士项目。在获奖期间，Gajic博士将推进他的研究培训，特别是医学信息学，并将教学课程和应用生理学、实验室方法和临床结果评估方面的实践经验应用于一个全面的临床研究项目。在一项对机械通气患者的观察性队列研究中，Gajic博士最近发现，输血产品和呼吸机设置是急性肺损伤发生的主要风险因素。拟议的前瞻性研究建立在这些观察的基础上。输血相关的急性肺损伤(TRALI)由于缺乏敏感和特异的诊断标准，在很大程度上被低估和报告。根据病例系列，已提出供者血液中的抗白细胞抗体和炎症介质在预置或易感宿主中触发肺免疫反应。然而，到目前为止，这一假设还没有在前瞻性临床试验中得到验证。Gajic博士的长期目标是阐明输血和机械力在急性肺损伤发病机制中的作用，并开发有效的预防策略。在一个未来的危重病人队列中，他的目标是 (1)确定在医疗重症监护病房输血时发生的急性肺损伤的发生率和转归；(2)确定供者性别、血液产品类型和储存年限是否与TRALI风险增加相关；(3)比较有和没有TRALI相合事件的患者供体血液样本中抗白细胞抗体(抗粒细胞、抗HLAI和II类)的患病率以及炎性细胞因子(IL 6、IL 8和TNF)的数量。这些结果将为未来具有重大公共卫生影响的试验奠定基础。(摘要结束)

DESCRIPTION (provided by applicant): This application is in support of Dr Gajic's career development as an independent clinical investigator. Dr Gajic has recently completed a Master's Program in Clinical Research at the Mayo Clinic College of Medicine. During the award period, Dr Gajic will advance his research training with particular focus on medical informatics and apply the lessons of didactic teaching and practical experiences in applied physiologic, laboratory methods and clinical outcome assessment towards a comprehensive clinical research project. In an observational cohort study of mechanically ventilated patients, Dr. Gajic has recently identified transfusion of blood products and ventilator settings as major risk factors for the development of acute lung injury. The proposed prospective research builds on these observations. Transfusion Related Acute Lung Injury (TRALI) has been largely under-diagnosed and under-reported because of a lack of sensitive and specific diagnostic criteria. Based on case series, it has been proposed that anti-leukocyte antibodies and mediators of inflammation in donor blood trigger a pulmonary immune response in primed or susceptible hosts. However, to date this hypothesis has not been validated in a prospective clinical trial. It is Dr Gajic's long-term objective to delineate the role of blood transfusions and mechanical forces in the pathogenesis of acute lung injury and to develop an effective preventive strategy. In a prospective cohort of critically ill medical patients he aims to (1) determine the incidence and outcome of acute lung injury which develops in temporal association with blood transfusion in the medical intensive care unit; (2) determine if donor gender, type of blood product and storage age are associated with an increased risk of TRALI; and (3) to compare the prevalence of anti-leukocyte antibodies (anti-granulocyte, anti-HLA class I and II) and the amount of inflammatory cytokines (IL 6, IL 8 and TNF) in donor blood samples of patients with and without a TRALI compatible event. These results will form the basis for future trials with major public health implications. (End of Abstract)