LIPS-A: Lung Injury Prevention Study with Aspirin

描述（由申请人提供）：急性肺损伤（ALI）及其更严重的形式，急性呼吸窘迫综合征（ARDS）是主要健康问题的典型例子，一旦病情完全确定，治疗效果就会受到限制。大量的基础和临床研究工作已经改善了支持性治疗，但令人惊讶的是，关于预防这种毁灭性综合症的研究很少。对ALI/ARDS风险患者的延迟识别直到进入ICU后，限制了临床试验纳入已经确定疾病的患者，超出了潜在预防策略的治疗窗口。我们最近描述了在呼吸衰竭和全面综合征发展之前识别高危患者的新系统（LIPS -肺损伤预测评分）和危重病护理重要方面的标准化方法（CLIP -肺损伤预防检查表），为制定合理的策略来限制甚至预防这种危及生命的综合征奠定了基础。越来越多的证据支持抗炎脂质介质、血小板和血小板-中性粒细胞相互作用在ALI发展中的关键作用，以及阿司匹林（ASA）有效预防该综合征发展和进展的能力。我们的初步数据已经在三个大队列的高危患者中确定了ASA治疗与降低ALI发展之间的独立关联，使这种简单的干预成为正式的II期ALI预防试验的理想目标。一个由来自14个学术医疗中心的临床研究人员组成的多学科团队已经加入了美国危重疾病和损伤试验网络lip -A研究小组，他们将利用现有的基础设施进行急诊和危重护理环境的临床研究，以解决关键的知识空白：A)确定ASA对在病程早期发现的高风险患者预防ALI的疗效；b)评估血小板活化及其抑制影响ALI发展的机制，以及c)评估肺损伤生物标志物作为高危患者ALI发展的预后标志物的价值，以优化未来ALI预防试验的设计和实施。更好地了解急性呼吸道感染风险，以及潜在预防策略的有效性和安全性，是在限制这一严重疾病的毁灭性并发症影响方面取得进一步进展的必要步骤。相关性（见说明）：在美国，每年急性脑损伤造成350万住院日和7.5万人死亡。幸存者经常遭受生活质量的长期下降和与重症监护和康复有关的巨额费用。因此，急性呼吸道感染是一个重大的公共卫生问题，有效预防急性呼吸道感染将对危重病人和受伤病人的预后和相关的医疗费用产生重大影响。（摘要结束）

DESCRIPTION (provided by applicant): Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are typical examples of a major health problem for which the efficacy of treatment is limited once the condition is fully established. Enormous basic and clinical research efforts have lead to improvements in supportive treatment, but surprisingly little research has been done into prevention of this devastating syndrome. Delayed recognition of patients at risk for ALI/ARDS until after admission to the ICU has limited clinical trials to enrolling patients with already established disease, beyond the therapeutic window of potential prevention strategies. Our recently described novel system for identification of patients at high risk before the development of respiratory failure and the full blown syndrome (LIPS - Lung Injury Prediction Score) and the standardized approach to important aspects of critical care delivery (CLIP - Checklist for Lung Injury Prevention) have laid the groundwork for developing rational strategies to limit or even prevent this life-threatening syndrome. Increasing evidence supports the critical role of anti-inflammatory lipid mediators, platelets and platelet- neutrophil interactions in the development of ALI and the ability of aspirin (ASA) to effectively prevent the development and progression of this syndrome. Our preliminary data has identified an independent association between ASA therapy and decreased development of ALI in three large cohorts of at risk patients, making this simple intervention an ideal target of a formal, phase II ALI prevention trial. A multidisciplinary team of clinical investigators from fourteen academic medical centers who have joined together in the US Critical Illness and Injury Trials Network LIPS-A study group will utilize the established infrastructure for clinical research in the emergency and critical care setting to address critical knowledge gaps by a) determining the efficacy of ASA for prevention of ALI in patients at high risk identified early in the course of their illness, b) evaluating the mechanisms by which platelet activation and its inhibition affect ALI development, and c) assess the value of lung injury biomarkers as prognostic markers of ALI development in patients at risk in order to optimize the design and conduct of future ALI prevention trials. The better understanding of ALI risk, and the efficacy and safety of potential prevention strategies, are essential steps for further progress in limiting the impact of this devastating complication of critical illness. RELEVANCE (See instructions): Each year ALI accounts for 3.5 million hospital days and 75,000 deaths in the USA. Survivors frequently incur long-term decrease in quality of life and enormous costs related to intensive care and rehabilitation. Therefore, ALI represents a major public health problem and effective prevention of ALI will have a major impact on outcomes of critically ill and injured patients and associated healthcare cost. (End of Abstract)