Clinical Centers (CC) for the NHLBI Prevention and Early Treatment of Acute Lung

描述(由申请人提供)：该项目的目标是在有早期ARDS风险或患有ARDS的患者中采用新的治疗方法，以降低显著的归因性死亡率，并改善短期和长期发病率(1，2)。作为预防和早期治疗急性肺损伤(PEAL)网络的参与者，我们的具体目标是： 1.建立一个两个地点的多学科网络，以征聘花瓣研究人员。来自密歇根大学肺和重症监护医学部、急性监护外科和急诊科重症监护病房(ED-ICU)的首席调查人员和合作调查人员将合作，确保研究对象的早期识别和强有力的招募。此外，亨利福特健康系统的急诊科和肺部和重症监护医学部的研究人员也加入了我们在这个网络中的第二个网站，为招募患者进行花瓣研究创造了一个丰富的环境。通过纳入完全整合的急诊ICU，在这些机构为危重患者提供独特的连续护理，使这些患者能够及早招募和干预，这种环境得到了加强。 2.通过继续和启动多种重叠的招募战略，每年至少招募40名高素质的参与者参加PEATAL方案，包括通过电子病历建立新的警报机制、计算肺损伤预防分数、有针对性地捕获特定的高危人群和传统的协调员筛选。 3.ARDS的预防：观察GM-CSF对有ARDS危险的严重脓毒症患者相关临床结局的影响。主要的结果衡量标准是28天和90天的死亡率。主要次要终点包括ARDS和其他器官衰竭的发展/进展、脓毒症的解决、ICU持续时间和住院时间以及长期功能恢复。生物学结果包括单核细胞先天反应和全身炎症反应。 4.急性呼吸窘迫综合征的早期干预：观察阿奇霉素对早发性急性呼吸窘迫综合征患者相关临床结局的影响。主要的结果衡量标准是28天和90天的死亡率。主要次要终点包括无呼吸机天数、无器官衰竭天数、感染并发症、ICU和住院时间以及长期功能恢复。需要评估的一个重要生物学结果是阿奇霉素治疗对肺微生物组时间变化的影响。这些极具新颖性的研究将由一位在这一领域拥有杰出专业知识的联合调查员领导。

DESCRIPTION (provided by applicant): The goal of this project is to employ novel therapies in patients who are at risk for or who have early ARDS in order to reduce the significant attributable mortality and to improve both short term and long term morbidities (1,2). As a participant in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, our specific aims are: 1. The creation of a two site multi-disciplinary network for recruitment into PETAL studies. Principal Investigators and Co-investigators from the Divisions of Pulmonary and Critical Care Medicine, Acute Care Surgery, and the Emergency Department Intensive Care Unit (ED-ICU) at the University of Michigan will collaborate to insure early identification and robust recruitment o study subjects. Additionally, investigators from the Emergency Department and the Division of Pulmonary and Critical Care Medicine of Henry Ford Health System, our second site in this network, have joined to create a rich environment in which to recruit patients for PETAL studies. This environment is strengthened by the inclusion of a fully integrated ED-ICU, providing a unique continuum of care for critically ill patients at these institutions, permitting early recruitment and intervention in these patients. 2. The annual recruitment of at least 40 high quality enrollees into PETAL protocols through the continuation and initiation of multiple overlapping recruitment strategies, including a novel alert mechanism through the electronic medical record, calculation of lung injury prevention scores, targeted capture of select at risk populations and traditional coordinator screening. 3. Prevention of ARDS: To determine the effect of GM-CSF administration on relevant clinical outcomes in patients with severe sepsis who are at risk for ARDS. The primary outcome measures are 28- and 90-day mortality. Major secondary end-points include the development/progression of ARDS and other organ failures, resolution of sepsis, duration of ICU and hospital stay, and long term functional recovery. Biological outcomes include monocyte innate responses and systemic inflammatory responses. 4. Early intervention in ARDS: To determine the effect of azithromycin administration on relevant clinical outcomes in patients with early onset ARDS. The primary outcome measures are 28- and 90-day mortality. Major secondary end-points include ventilator-free days, organ failure free days, infectious complications, duration of ICU and hospital stay, and long term functional recovery. An important biological outcome to be assessed is the influence of azithromycin therapy on temporal changes in the lung microbiome. These highly novel studies are to be led by a Co-Investigator with outstanding expertise in this arena.