Department of Pediatric Pulmonology and Allergology, Erasmus MC-Sophia, Rotterdam, the Netherlands.
Pediatr Pulmonol. 2010 Feb;45(2):107-17. doi: 10.1002/ppul.21154.
The aims of this article are to summarize existing knowledge regarding the pathophysiology of small airways disease in cystic fibrosis (CF), to speculate about additional mechanisms that might play a role, and to consider the available or potential options to treat it. In the first section, we review the evidence provided by pathologic, physiologic, and imaging studies suggesting that obstruction of small airways begins early in life and is progressive. In the second section we discuss how the relationships between CF transmembrane conductance regulator (CFTR), ion transport, the volume of the periciliary liquid layer and airway mucus might lead to defective mucociliary clearance in small airways. In addition, we discuss how chronic endobronchial bacterial infection and a chronic neutrophilic inflammatory response increase the viscosity of CF secretions and exacerbate the clearance problem. Next, we discuss how the mechanical properties of small airways could be altered early in the disease process and how remodeling can contribute to small airways disease. In the final section, we discuss how established therapies impact small airways disease and new directions that may lead to improvement in the treatment of small airways disease. We conclude that there are many reasons to believe that small airways play an important role in the pathophysiology of (early) CF lung disease. Therapy should be aimed to target the small airways more efficiently, especially with drugs that can correct the basic defect at an early stage of disease.
本文的目的是总结囊性纤维化（CF）中小气道疾病的病理生理学的现有知识，推测可能发挥作用的其他机制，并考虑可用于治疗该病的现有或潜在方法。在第一部分中，我们回顾了病理、生理和影像学研究提供的证据，这些证据表明小气道阻塞始于生命早期，并呈进行性发展。在第二部分，我们讨论了 CF 跨膜电导调节剂（CFTR）、离子转运、纤毛液体层体积和气道黏液之间的关系如何导致小气道中黏液纤毛清除功能障碍。此外，我们还讨论了慢性支气管内细菌感染和慢性嗜中性粒细胞炎症反应如何增加 CF 分泌物的粘性并使清除问题恶化。接下来，我们讨论了小气道的力学特性如何在疾病早期发生改变，以及重塑如何导致小气道疾病。在最后一部分，我们讨论了既定的治疗方法如何影响小气道疾病，以及可能改善小气道疾病治疗的新方向。我们得出的结论是，有很多理由相信小气道在 CF 肺部疾病的病理生理学中起着重要作用。治疗应旨在更有效地针对小气道，特别是使用可以在疾病早期纠正基本缺陷的药物。
