Department of Pathology, University of Verona, Italy.
Respir Res. 2012 Jan 11;13(1):3. doi: 10.1186/1465-9921-13-3.
New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences. There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema). The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD).
最近提出了关于慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）发病机制的新观点，尽管这些致命疾病在临床表现、影像学和病理学方面存在明显差异，但它们之间存在惊人的相似之处。越来越多的证据支持一种“双重打击”发病模式，在 COPD 和 IPF 中，肺实质加速衰老的累积作用（由端粒功能障碍和/或多种遗传易感性因素决定），以及香烟烟雾诱导的氧化损伤的有害活性，能够严重损害两个肺前体细胞区室（IPF 中的肺泡上皮前体细胞、COPD/肺气肿中的间充质前体细胞）的再生潜能。参与肺组织更新的信号通路（主要是 Wnt 和 Notch）随后发生的不同程度的紊乱，最终可能导致这些疾病中肺泡实质的独特异常组织重塑和功能障碍（IPF 中的不可逆纤维化和细支气管蜂巢状改变，COPD 中的肺气肿和气道慢性炎症）。
