Transfusion Related Lung Injury in the Critically Ill

描述（由申请人提供）： 该申请是为了支持Gajic博士作为独立临床研究者的职业发展。 Gajic博士最近完成了马约临床医学院的临床研究硕士课程。 在获奖期间，Gajic博士将推进他的研究培训，特别关注医学信息学，并将教学教学和实践经验应用于应用生理学，实验室方法和临床结果评估的课程，以实现全面的临床研究项目。 在一项针对机械通气患者的观察性队列研究中，Gajic博士最近发现血液制品的输注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。由于缺乏敏感和特异性的诊断标准，输血相关急性肺损伤（TRALI）在很大程度上被诊断和报告不足。 基于病例系列，已经提出供体血液中的抗白细胞抗体和炎症介质在致敏或易感宿主中触发肺免疫应答。然而，迄今为止，这一假设尚未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，并制定有效的预防策略。 在一个危重医学患者的前瞻性队列中，他的目标是 (1)确定与重症监护室输血时间相关的急性肺损伤的发生率和结果;（2）确定供体性别、血液制品类型和储存年龄是否与TRALI风险增加相关;（3）比较抗白细胞抗体的患病率（抗粒细胞、抗HLA I类和II类）和具有和不具有TRALI相容性事件的患者的供体血液样品中炎性细胞因子（IL 6、IL 8和TNF）的量。 这些结果将成为未来具有重大公共卫生意义的试验的基础。 (End摘要）

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)