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)是一个重大健康问题的典型例子，一旦病情完全确定，其治疗效果就会受到限制。巨大的基础和临床研究努力促进了支持性治疗的改进，但令人惊讶的是，在预防这种毁灭性综合征方面所做的研究很少。对有ALI/ARDS风险的患者的延迟识别，直到进入ICU后，临床试验仅限于招募已确诊疾病的患者，超出了潜在预防策略的治疗窗口。我们最近描述的在发生呼吸衰竭和全面发展综合征之前识别高危患者的新系统(LIPS-肺损伤预测评分)和危重护理分娩重要方面的标准化方法(CLIP-Checklist for肺损伤预防)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发生发展中的关键作用，以及阿司匹林(ASA)有效阻止ALI的发生和发展的能力。我们的初步数据已经在三个大的高危患者队列中确定了ASA治疗与ALI发生减少之间的独立关联，使这一简单的干预成为正式的第二阶段ALI预防试验的理想目标。由来自14个学术医学中心的多学科临床研究人员组成的团队共同参与了美国危重病和创伤试验网络LIPS-一个研究小组将利用急诊和重症监护环境中成熟的临床研究基础设施来解决关键知识缺口问题，方法是a)确定ASA对在疾病早期被发现的高危患者预防ALI的有效性，b)评估血小板激活及其抑制影响ALI发生的机制，以及c)评估肺损伤生物标志物作为ALI高危患者预后标志物的价值，以便优化未来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，是在限制这种毁灭性的危重疾病并发症的影响方面取得进一步进展的关键步骤。相关性(参见说明)：在美国，每年ALI的住院日为350万天，死亡人数为7.5万人。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，有效地预防ALI将对危重伤员的转归和相关的医疗成本产生重大影响。(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)