Bosma Karen J, Lewis James F
University of Western Ontario, Division of Respirology, London Health Sciences Centre, University Hospital, 339 Windermere Road, London, Ontario, N6A 5A5, Canada.
Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77. doi: 10.1517/14728214.12.3.461.
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening form of respiratory failure that affects a heterogeneous population of critically ill patients. Although overall mortality appears to be decreasing in recent years due to improvements in supportive care, there are presently no proven, effective pharmacological therapies to treat ARDS and prevent its associated complications. The most common cause of death in ARDS is not hypoxemia or pulmonary failure, but rather multiple organ dysfunction syndrome (MODS), suggesting that improving survival in patients with ARDS may be linked to decreasing the incidence or severity of MODS. The key to developing novel treatments depends, in part, on identifying and understanding the mechanisms by which ARDS leads to MODS, although the heterogeneity and complexity of this disorder certainly poses a challenge to investigators. Novel therapies in development for treatment of ALI/ARDS include exogenous surfactant, therapies aimed at modulating neutrophil activity, such as prostaglandin and complement inhibitors, and treatments targeting earlier resolution of ARDS, such as beta-agonists and granulocyte macrophage colony-stimulating factor. From a clinical perspective, identifying subpopulations of patients most likely to benefit from a particular therapy and recognising the appropriate stage of illness in which to initiate treatment could potentially lead to better outcomes in the short term.
急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是一种危及生命的呼吸衰竭形式,影响着危重症患者这一异质性群体。尽管近年来由于支持治疗的改善,总体死亡率似乎在下降,但目前尚无经证实的有效药物疗法来治疗ARDS并预防其相关并发症。ARDS最常见的死亡原因不是低氧血症或肺衰竭,而是多器官功能障碍综合征(MODS),这表明提高ARDS患者的生存率可能与降低MODS的发生率或严重程度有关。开发新疗法的关键部分在于识别和理解ARDS导致MODS的机制,尽管这种疾病的异质性和复杂性无疑给研究人员带来了挑战。正在研发的用于治疗ALI/ARDS的新疗法包括外源性表面活性剂、旨在调节中性粒细胞活性的疗法,如前列腺素和补体抑制剂,以及旨在更早解决ARDS的治疗方法,如β-激动剂和粒细胞巨噬细胞集落刺激因子。从临床角度来看,识别最有可能从特定疗法中获益的患者亚群,并确定开始治疗的合适疾病阶段,可能会在短期内带来更好的治疗效果。