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）是重大健康问题的典型例子，一旦病情完全确立，治疗效果就会受到限制。大量的基础和临床研究工作已经导致支持性治疗的改善，但令人惊讶的是，针对预防这种破坏性综合征的研究却很少。直到进入 ICU 后才对有 ALI/ARDS 风险的患者进行延迟识别，这限制了临床试验只能招募已患有疾病的患者，超出了潜在预防策略的治疗窗口。我们最近描述的用于在发生呼吸衰竭和全面综合征之前识别高危患者的新系统（LIPS - 肺损伤预测评分）和重症监护重要方面的标准化方法（CLIP - 肺损伤预防清单）为制定合理策略以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生和进展的能力。我们的初步数据已确定 ASA 治疗与三组高危患者中 ALI 发展的减少之间存在独立关联，使这种简单的干预措施成为正式 II 期 ALI 预防试验的理想目标。来自 14 个学术医疗中心的多学科临床研究人员加入了美国危重疾病和损伤试验网络 LIPS-A 研究小组，将利用现有的急诊和重症监护临床研究基础设施，通过以下方式解决关键知识差距：a) 确定 ASA 对病程早期发现的高危患者预防 ALI 的功效，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的价值作为有风险的患者发生 ALI 的预后标志物，以优化未来 ALI 预防试验的设计和实施。更好地了解 ALI 风险以及潜在预防策略的有效性和安全性，是在限制这种严重疾病的破坏性并发症的影响方面取得进一步进展的重要步骤。相关性（参见说明）：每年 ALI 在美国造成 350 万住院天数和 75,000 人死亡。幸存者经常遭受生活质量的长期下降以及与重症监护和康复相关的巨额费用。因此，ALI 是一个重大的公共卫生问题，有效预防 ALI 将对危重病人和受伤患者的治疗结果以及相关的医疗费用产生重大影响。 （摘要完）

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)