Department of Medicine, University of North Carolina (UNC), Chapel Hill, North Carolina, USA.
Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
JCI Insight. 2018 Dec 20;3(24):122695. doi: 10.1172/jci.insight.122695.
The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes.
We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures.
Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores.
Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function.
ClinicialTrials.gov, NCT01521338.
CFF Therapeutics (GOAL11K1).
在囊性纤维化患者中，使用有效的小分子调节剂恢复囊性纤维化跨膜转导调节因子（CFTR）功能，为研究 CFTR 离子通道功能、器官水平生理学和临床结果之间的关系提供了机会。
我们对使用 ivacaftor 治疗 G551D-CFTR 突变的囊性纤维化患者进行了一项多中心、前瞻性、观察性研究。在开始治疗前（1 个月和 3 个月）以及临床结果测量的同时，进行肺黏液清除率（MCC）的测量。
在开始使用 ivacaftor 1 个月后，全肺、中央肺和外周肺 MCC 明显加速，并在 3 个月时持续。MCC 的改善与用力呼气第一秒量（FEV1）的改善相关，但与汗氯或症状评分无关。
用 ivacaftor 恢复 CFTR 活性导致 MCC 显著改善。这种生理评估提供了一种方法来描述未来的 CFTR 调节剂治疗方法，并可能有助于预测肺功能的改善。
ClinicialTrials.gov，NCT01521338。
CFF 治疗学（GOAL11K1）。
