Is Progression of Pulmonary Fibrosis due to Ventilation-induced Lung Injury?
Is Progression of Pulmonary Fibrosis due to Ventilation-induced Lung Injury?
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DOI：
10.1164/rccm.201903-0497pp
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发表时间：
2019-07-15
影响因子：
24.7
通讯作者：
Schwartz, David A.
中科院分区：
文献类型：
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作者：
Albert, Richard K.;Smith, Bradford;Schwartz, David A.
肺纤维化可能与遗传变异、职业和环境暴露、多种药物的不良反应和许多结缔组织疾病有关，也可以是特发性的。肺纤维化的亚型是根据临床表现、X线表现和/或组织学确定的。由于c-jun和b-catenin上调许多促纤维化因子的表达(1)，c-jun和b-catenin激活c-jun和b-catenin(无翼整合酶1)被认为是导致纤维化的统一分子途径，但对于是什么激活了这些途径或解释了似乎是自我维持的时空进程的损伤机制，人们知之甚少(S)。呼吸机诱导的肺损伤(VILI)通过两种不相互排斥的假定机制导致急性呼吸窘迫综合征的死亡。第一种是机械应力作用于上皮细胞，这是由于呼吸循环中塌陷的肺泡和/或小气道周期性地打开和关闭而产生的(称为“不电击伤”)。第二种是当肺泡接近其最大体积时，肺泡内与空隙塌陷区域相邻的肺泡上皮细胞由于实质上的相互依赖而产生的机械应变(称为“肺泡损伤”)。在没有由于高经肺压力而崩溃的情况下，也可能发生这种压力。由于空域塌陷可以发生在自主呼吸和机械呼吸过程中，我们将VILI定义为机械通气而不是呼吸机诱导的肺损伤。这篇观点文章的目的是总结支持VILI可以是解释自持性损伤和肺纤维化进展的统一致病过程的假设的信息(图1)。我们回顾研究表明，肺泡塌陷是肺纤维化的一种反复观察到的病理发现，因此提供了发生VILI的环境。我们总结研究表明，在肺纤维化患者中，许多与肺纤维化相关的危险因素和遗传变异，以及用于研究这种疾病的大多数模型，都与肺表面活性物质异常和/或可能导致肺表面活性物质异常的AT2(肺泡2型)细胞损伤有关，从而为崩溃的发生提供了解释。我们还估计了蜗牛创伤和
Pulmonary fibrosis can develop in association with genetic variants, occupational and environmental exposures, adverse reactions to numerous medications, and many connective tissue diseases, and it can also be idiopathic. Subclassifications of pulmonary fibrosis are identified on the basis of clinical presentations, roentgenographic manifestations, and/or histology. Wnt (Wingless/integrase 1) activation of c-Jun and b-catenin has been suggested as a unifying molecular pathway resulting in fibrosis because c-Jun and b-catenin upregulate expression of many profibrotic factors (1), but little is known about what activates these pathways or the mechanism (s) explaining what appears to be a self-sustaining temporal and spatial progression of injury. Ventilator-induced lung injury (VILI) contributes to the mortality of the acute respiratory distress syndrome by two putative mechanisms that are not mutually exclusive. The first is the mechanical stress on epithelial cells that occurs as a result of cyclical opening and closing of collapsed alveoli and/or small airways during the ventilatory cycle (termed “atelectrauma”). The second is the mechanical strain on epithelial cells in alveoli that are adjacent to areas of airspace collapse when these alveoli approach their maximum volume owing to parenchymal interdependence (termed “volutrauma”). This strain can also occur in the absence of collapse as a result of high transpulmonary pressures. Because airspace collapse can occur during spontaneous breathing as well as during mechanical ventilation, we are defining VILI as ventilation-rather than ventilator-induced lung injury.The purpose of this perspective article is to summarize information supporting the hypothesis that VILI can be a unifying pathogenic process explaining the selfperpetuating injury and progression of pulmonary fibrosis (Figure 1). We review studies demonstrating that alveolar collapse has been a repeatedly observed pathologic finding in pulmonary fibrosis, thereby providing a setting in which VILI can occur. We summarize studies showing that in patients with pulmonary fibrosis, many of the risk factors and genetic variants related to the condition, as well as most of the models used to study it, are associated with surfactant abnormalities and/or with AT2 (alveolar type 2) cell injury that could result in surfactant abnormalities, thereby providing an explanation for why collapse develops. We also estimate the mechanical strain resulting from volutrauma and