Doctor of Medicine Undergraduate Program, Faculty of Medicine, and.
Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Ann Am Thorac Soc. 2020 Feb;17(2):147-154. doi: 10.1513/AnnalsATS.201909-671CME.
The effects of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators on lung function, pulmonary exacerbations, and quality of life have been well documented. However, CF is a multiorgan disease, and therefore an evidence base is emerging on the systemic effects of CFTR modulators beyond the pulmonary system. This is of great clinical importance, as many of these studies provide proof of concept that CFTR modulators might be used one day to prevent or treat extrapulmonary manifestations stemming from CFTR dysfunction. In this concise review of the literature, we summarize the results of key publications that have evaluated the effects of CFTR modulators on weight and growth, pancreatic function, the gastrointestinal and hepatobiliary systems, sinus disease, bone disease, exercise tolerance, fertility, mental health, and immunity. Although many of these studies have reported beneficial extrapulmonary effects related to the use of ivacaftor (IVA) in patients with CF with at least one gating mutation, most of the evidence is low or very low quality, given the limited number of patients evaluated and the lack of control groups. Based on an even smaller number of studies evaluating the extrapulmonary effects of lumacaftor-IVA, the benefits are less clear. Although limited, these studies may provide the basis for future clinical trials to evaluate CFTR modulators on the extrapulmonary manifestations of CF.
囊性纤维化跨膜电导调节因子（CFTR）调节剂对肺功能、肺部恶化和生活质量的影响已有充分的记录。然而，囊性纤维化是一种多器官疾病，因此，CFTR 调节剂对肺部以外系统的全身影响的证据正在不断涌现。这具有重要的临床意义，因为许多这些研究提供了概念验证，即有朝一日 CFTR 调节剂可能被用于预防或治疗源自 CFTR 功能障碍的肺部以外表现。在对文献的简要回顾中，我们总结了评估 CFTR 调节剂对体重和生长、胰腺功能、胃肠道和肝胆系统、窦病、骨病、运动耐量、生育能力、心理健康和免疫的关键出版物的结果。尽管这些研究中的许多都报告了与使用至少一种门控突变的 CF 患者中的 ivacaftor（IVA）相关的有益的肺部以外的影响，但鉴于评估的患者数量有限且缺乏对照组，大多数证据质量较低或非常低。基于评估 lumacaftor-IVA 的肺部以外影响的研究数量更少，其益处不太明确。尽管数量有限，但这些研究可能为未来的临床试验提供基础，以评估 CFTR 调节剂对 CF 的肺部以外表现的影响。
