Boucher R C
Cystic Fibrosis/Pulmonary Research and Treatment Center, 7011 Thurston-Bowles Building, CB# 7248, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Eur Respir J. 2004 Jan;23(1):146-58. doi: 10.1183/09031936.03.00057003.
Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal innate airway defence and how absent function of the cystic fibrosis transmembrane regulator protein (CFTR) adversely perturbs this activity. Recent data have linked the abnormal ion transport properties of CF airway epithelia to depleted airway surface liquid (ASL) volume, reflecting the combined defects of accelerated Na+ transport and the failure to secrete Cl-. Depletion of a specific compartment of the ASL, i.e. the periciliary liquid (PCL), appears to abrogate both cilia-dependent and cough clearance. Subsequent to PCL depletion, mucus adheres to airway surfaces and persistent mucin secretion generates the formation of "thickened" mucus plaques and plugs, which become the nidus for bacterial infection. The paucity of liquid in these plaques/plugs, and the hypoxia in this environment, appear to promote biofilm bacterial infection. Therapeutic agents that restore airway surface liquid volume, i.e. blockers of Na+ transport, initiators of Cl- transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis.
尽管在阐明囊性纤维化（CF）的遗传和分子基础方面已取得了令人瞩目的进展，但CF肺部疾病的发病机制仍不清楚。阐明CF肺部疾病的发病机制既需要完整描述正常的先天性气道防御，也需要了解囊性纤维化跨膜调节蛋白（CFTR）功能缺失如何对该活动产生不利干扰。最近的数据将CF气道上皮细胞异常的离子转运特性与气道表面液体（ASL）量减少联系起来，这反映了Na+转运加速和Cl-分泌失败的综合缺陷。ASL的一个特定隔室即纤毛周围液体（PCL）的减少似乎消除了依赖纤毛的清除和咳嗽清除。PCL减少后，黏液附着在气道表面，持续的黏蛋白分泌导致“增厚”的黏液斑块和栓子形成，这些成为细菌感染的病灶。这些斑块/栓子中液体的缺乏以及这种环境中的缺氧似乎促进了生物膜细菌感染。本文综述了恢复气道表面液体量的治疗药物，即Na+转运阻滞剂、Cl-转运启动剂和渗透剂，以及在囊性纤维化患者中安全使用液体恢复剂可能需要的策略。
