Idiopathic Pulmonary Fibrosis May Be a Disease of Recurrent, Tractional Injury to the Periphery of the Aging Lung A Unifying Hypothesis Regarding Etiology and Pathogenesis
Idiopathic Pulmonary Fibrosis May Be a Disease of Recurrent, Tractional Injury to the Periphery of the Aging Lung A Unifying Hypothesis Regarding Etiology and Pathogenesis
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DOI：
10.5858/arpa.2011-0511-oa
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发表时间：
2012-06-01
影响因子：
4.6
通讯作者：
Leslie, Kevin O.
中科院分区：
文献类型：
--
作者：
Leslie, Kevin O.
背景：特发性肺纤维化是一种发生在老年人身上的进行性、致命性肺部疾病。尽管50年来积累了关于这种疾病的数据，但在减缓功能丧失或降低患者死亡率方面进展甚微。目的：提出一种关于特发性肺纤维化病因和发病机制的新假说。设计-综述已发表的有关特发性肺纤维化患者的流行病学、临床表现、自然病史、放射学表现和病理结果的数据。结果：特发性肺纤维化患者可能在遗传上易对周围肺造成牵拉性损伤。其结果是上皮-间充质界面的反复损伤，优先发生在基底肺小叶的外缘，在那里吸气时牵拉应力高，顺应性相对较低，在呼气末肺泡有更大的塌陷倾向。一个独特的“网状损伤网络”(成纤维细胞病灶)形成，伴随着伤口修复的延长阶段(撕裂和缓慢修复)。在肺小叶周围的疤痕中可见离散的肺泡塌陷区域。这个循环重复很多年，导致进行性纤维重塑和小叶中的肺泡被被疤痕(蜂窝状肺)包围的细支气管囊取代。肺表面活性物质功能异常被认为是初始肺损伤的潜在机制。发病年龄可能与所需的环境暴露阈值(如吸烟)或对老化肺的其他共病损伤有关。结论-提出了支持这一假说的证据，并讨论了可能的机制。提出了对辅因子有贡献的潜在作用。(ARCH Pathol Lab Med.2012年；第136：591-600；DOI：10.5858/arpa.2011-0511-OA)
Context.-Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality.Objective.-To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis.Design.-Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis.Results.-Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury'' (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung.Conclusions.-Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented. (Arch Pathol Lab Med. 2012;136:591-600; doi: 10.5858/arpa.2011-0511-OA)