Wurfel Mark M, Raghu Ganesh
Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle 98195-6522, USA.
Semin Respir Crit Care Med. 2002 Apr;23(2):177-87. doi: 10.1055/s-2002-25306.
Pulmonary fibrosis is a devastating disease that occurs in association with environmental exposures, several inherited diseases, collagen vascular disease, as well as in an idiopathic form. Epithelial cell damage, excessive fibroblast proliferation, upregulation of extracellular matrix production, and attenuated matrix degradation are shared pathophysiological features of these different forms of pulmonary fibrosis. Several observations suggest that genetic predisposition plays an important role in the pathophysiology of pulmonary fibrosis. There is significant inter-individual variation in the degree of pulmonary fibrosis resulting from exposure to similar levels of an inhaled fibrogenic agent. There are several inherited diseases with known genetic mutations that have high rates of pulmonary fibrosis. Idiopathic pulmonary fibrosis can occur in multiple first-degree relatives, including those separated at an early age. Finally, recent studies have identified polymorphisms within genes for cytokines, histocompatability antigens, and extracellular matrix components that are associated with the development of pulmonary fibrosis. Identification of putative pulmonary fibrosis gene/s (PF gene/s) may result in novel diagnostic and therapeutic interventions for those at risk for development of pulmonary fibrosis.
肺纤维化是一种严重的疾病，与环境暴露、多种遗传性疾病、胶原血管病以及特发性形式相关。上皮细胞损伤、成纤维细胞过度增殖、细胞外基质产生上调以及基质降解减弱是这些不同形式肺纤维化共同的病理生理特征。多项观察表明，遗传易感性在肺纤维化的病理生理过程中起重要作用。暴露于相似水平的吸入性致纤维化因子后，肺纤维化程度存在显著的个体间差异。有几种已知基因突变的遗传性疾病，其肺纤维化发生率很高。特发性肺纤维化可发生在多个一级亲属中，包括那些早年就分开的亲属。最后，最近的研究已经确定了细胞因子、组织相容性抗原和细胞外基质成分基因内的多态性，这些多态性与肺纤维化的发生有关。确定推定的肺纤维化基因（PF基因）可能会为有肺纤维化发生风险的人群带来新的诊断和治疗干预措施。
