Ingbar D H, Matthay R A
Pulmonary Section, Yale University School of Medicine, New Haven, Connecticut.
Crit Care Clin. 1986 Jul;2(3):629-65.
The high in-hospital mortality of ARDS has not diminished over the past 10 years, despite improvements in supportive intensive care. Much of the mortality arises from infections, particularly sepsis and pneumonia, and from organ failure, especially kidney failure. The rapid advances in understanding the interlocking pathophysiologic mechanisms of ARDS have not yet been translated into therapeutic trials of new methods for diminishing the injury or for stimulating normal repair. In part, this is because it is difficult to predict which high-risk patients will develop ARDS and then intervene early in the injury process. Patients in whom the risk for ARDS is extremely high have a very high mortality even without ARDS, thereby making efficacy of an early or prophylactic therapy quite difficult to prove. In spite of severe pathologic abnormalities, including fibrosis, early in the course of ARDS, most survivors return to almost normal pulmonary function. The few cases that have been studied with serial biopsies demonstrate resolution of fibrosis. This amazing recovery poses many fascinating questions about how the lung repairs itself. Given the heterogeneous causes of ARDS and the large number of structural, cellular, and biochemical abnormalities described, one can postulate that any one of numerous factors is important in normal repair. Most promising of these are the degree of basement membrane damage, the control of type II cell proliferation and differentiation, the control of collagen synthesis, the anatomic localization of fibrosis, and the control of collagenase action. These interactions of epithelial and mesenchymal tissues probably recreate the process of lung development in the injured adult lung. At a clinical level, the role of oxygen toxicity remains a significant issue. Oxygen acting as an oxidant may be partially responsible for the small airways disease seen in approximately one quarter to one third of survivors. The mortality data stress the need for better ways of preventing and diagnosing lung infections. Better definition of the clinical factors that put survivors at risk for persistent loss of lung function is also needed, and could define a subgroup in which trials of agents designed to improve repair would be most worthwhile. More information about the long-term pathologic course, though difficult to obtain, would also be very important. Perhaps some registry of ARDS survivors would permit closer follow-up and make available more late autopsy pathology when these people die of other causes. The rapid time course of ARDS provides an ideal testing ground for agents designed to either decrease lung injury or stimulate repair.(ABSTRACT TRUNCATED AT 400 WORDS)
尽管支持性重症监护有所改善，但在过去10年中，急性呼吸窘迫综合征（ARDS）的院内高死亡率并未降低。大部分死亡源于感染，尤其是脓毒症和肺炎，以及器官衰竭，特别是肾衰竭。在理解ARDS相互关联的病理生理机制方面取得的快速进展尚未转化为减少损伤或刺激正常修复的新方法的治疗试验。部分原因是难以预测哪些高危患者会发生ARDS，然后在损伤过程早期进行干预。ARDS风险极高的患者即使没有ARDS死亡率也非常高，因此早期或预防性治疗的疗效很难得到证实。尽管在ARDS病程早期存在包括纤维化在内的严重病理异常，但大多数幸存者的肺功能几乎恢复正常。少数接受系列活检研究的病例显示纤维化得到缓解。这种惊人的恢复引发了许多关于肺如何自我修复的有趣问题。鉴于ARDS病因的异质性以及所描述的大量结构、细胞和生化异常，人们可以推测众多因素中的任何一个在正常修复中都很重要。其中最有希望的因素包括基底膜损伤程度、II型细胞增殖和分化的控制、胶原蛋白合成的控制、纤维化的解剖定位以及胶原酶作用的控制。上皮组织和间充质组织的这些相互作用可能在受损的成年肺中重现肺发育过程。在临床层面，氧毒性的作用仍然是一个重要问题。作为氧化剂的氧气可能部分导致约四分之一至三分之一幸存者出现小气道疾病。死亡率数据强调需要更好的预防和诊断肺部感染的方法。还需要更明确地界定使幸存者面临持续肺功能丧失风险的临床因素，这可以确定一个亚组，在该亚组中进行旨在改善修复的药物试验将最有价值。关于长期病理过程的更多信息虽然难以获得，但也非常重要。也许ARDS幸存者登记册将允许进行更密切的随访，并在这些人死于其他原因时提供更多晚期尸检病理学信息。ARDS的快速病程为旨在减少肺损伤或刺激修复的药物提供了理想的试验场。（摘要截断于400字）
