In the lungs, defective CFTR associated with cystic fibrosis (CF) represents the nidus for abnormal mucus clearance in the airways and consequently a progressive lung disease. Defective CFTR-mediated Cl⁻ secretion results in altered mucus properties, including concentration, viscoelasticity, and the ratio of the two mucins, MUC5B and MUC5AC. In the past decades, therapies targeting the CF mucus defect, directly or indirectly, have been developed; nevertheless, better treatments to prevent the disease progression are still needed. This review summarizes the existing knowledge on the defective mucus in CF disease and highlights it as a barrier to the development of future inhaled genetic therapies. The use of new mucus-targeting treatments is also discussed, focusing on their potential role to halt the progress of CF lung disease.

在肺部，与囊性纤维化 (CF) 相关的 CFTR 缺陷代表气道粘液清除异常的病灶，进而导致进行性肺部疾病。CFTR 介导的 Cl ^-分泌缺陷会导致粘液特性改变，包括浓度、粘弹性以及两种粘蛋白 MUC5B 和 MUC5AC 的比例。在过去的几十年里，直接或间接针对 CF 粘液缺陷的疗法已经被开发出来。尽管如此，仍然需要更好的治疗方法来预防疾病进展。这篇综述总结了关于 CF 疾病粘液缺陷的现有知识，并强调它是未来吸入基因疗法发展的障碍。还讨论了新的粘液靶向治疗的使用，重点关注它们在阻止 CF 肺部疾病进展方面的潜在作用。