Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, Virginia 22908-0386, USA.
Respir Care. 2011 Sep;56(9):1369-86; discussion 1386-8. doi: 10.4187/respcare.01306.
Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Surfactant replacement has become routine for the prevention and treatment of infant RDS and other causes of neonatal lung injury. The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ARDS than in RDS, where simple deficiency is causative. This failure may relate to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution, or simply an inability of the drug to substantially impact the underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest that direct types of ALI (eg, aspiration, pneumonia) may be more responsive to surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal studies are needed, however, to further clarify aspects of drug composition, timing, delivery, and dosing before additional human trials are pursued, as the results of human trials to date have been inconsistent and largely disappointing. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future.
自 1959 年 Avery 和 Mead 确定表面活性剂缺乏是婴儿呼吸窘迫综合征（RDS）的潜在原因以来，我们对肺表面活性物质在呼吸生理和急性肺损伤（ALI）病理生理学中的作用的理解有了很大的进展。表面活性剂替代已成为预防和治疗婴儿 RDS 和其他新生儿肺损伤的常规方法。然而，表面活性剂在新生儿期后的肺损伤中的作用证明更加复杂。相对表面活性剂缺乏、功能障碍和抑制都导致了 ALI 和急性呼吸窘迫综合征（ARDS）中所见的紊乱生理学。因此，外源性表面活性剂虽然是一种合理的治疗方法，但在 ALI/ARDS 中的疗效不如 RDS 中那么有效，而 RDS 中简单的缺乏是致病的。这种失败可能与许多因素有关，其中包括药物表面活性剂的不足、剂量或药物输送不足、药物分布不良，或者药物根本无法对 ALI/ARDS 的潜在病理生理学产生实质性影响。动物和人体研究都表明，直接型 ALI（例如，吸入、肺炎）可能比间接性肺损伤（例如，败血症、胰腺炎）对表面活性剂治疗更敏感。然而，需要进行动物研究，以进一步阐明药物成分、时间、输送和剂量方面的问题，然后再进行额外的人体试验，因为迄今为止的人体试验结果不一致，且大多令人失望。进一步的研究，也许是更强大的药物表面活性剂的开发，为外源性表面活性剂在未来治疗 ALI/ARDS 的治疗方法中找到一席之地提供了希望。
