Benden Christian, Schwarz Carsten
Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006, Zurich, Switzerland.
Division of Cystic Fibrosis, CF Center Westbrandenburg, Campus Potsdam, Potsdam, Germany.
Pulm Ther. 2021 Dec;7(2):377-393. doi: 10.1007/s41030-021-00170-9. Epub 2021 Aug 18.
Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian people and is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein. It is a multisystem disorder; however, CF lung disease causes most of its morbidity and mortality. Although survival for CF has improved over time due to a multifaceted symptomatic management approach, CF remains a life-limiting disease. For individuals with progressive advanced CF lung disease (ACFLD), lung transplantation is considered the ultimate treatment option if compatible with goals of care. Since 2012, newer drugs, called CFTR modulators, have gradually become available, revolutionizing CF care, as these small-molecule drugs target the underlying defect in CF that causes decreased CFTR protein synthesis, function, or stability. Because of their extremely high efficacy and overall respectable tolerability, CFTR modulator drugs have already proven to have a substantial positive impact on the lives of individuals with CF. Individuals with ACFLD have generally been excluded from initial clinical trials. Now, however, these drugs are being used in clinical practice in selected individuals with ACFLD, showing promising results, although randomized controlled trial data for CFTR modulators in this subgroup of patients are lacking. Such data need to be gathered, ideally in randomized controlled trials including patients with ACFLD. Furthermore, the efficacy and tolerability of the newer modulator therapies in individuals with ACFLD need to be monitored, and their impact on lung disease progression and the need for lung transplantation as the ultimate therapy call for an objective evaluation in larger patient cohorts. As of today, guidelines for referral and listing of lung transplant candidates with CF have not incorporated the status of the new CFTR modulator therapies in the referral and listing process. The purpose of this review article, therefore, is threefold: first, to describe the effects of new therapies, with a focus on the subgroup of individuals with ACFLD; second, to provide an update on the recent outcomes after lung transplantation for individuals with CF; and third, to discuss the referral, evaluation, and timing for lung transplantation as the ultimate therapeutic option in view of the new treatments available in CF.
囊性纤维化（CF）是白种人中最常见的常染色体隐性疾病，由编码CF跨膜传导调节因子（CFTR）蛋白的基因突变引起。它是一种多系统疾病；然而，CF肺部疾病导致了其大部分的发病和死亡。尽管由于多方面的症状管理方法，CF患者的生存率随着时间的推移有所提高，但CF仍然是一种限制生命的疾病。对于患有进行性晚期CF肺部疾病（ACFLD）的个体，如果符合护理目标，肺移植被认为是最终的治疗选择。自2012年以来，一种名为CFTR调节剂的新型药物逐渐问世，彻底改变了CF的治疗方式，因为这些小分子药物针对CF的潜在缺陷，该缺陷导致CFTR蛋白合成、功能或稳定性下降。由于其极高的疗效和总体可观的耐受性，CFTR调节剂药物已被证明对CF患者的生活产生了重大的积极影响。ACFLD患者通常被排除在初始临床试验之外。然而，现在这些药物正在被用于部分ACFLD患者的临床实践中，并显示出有希望的结果，尽管在这一亚组患者中缺乏CFTR调节剂的随机对照试验数据。需要收集这些数据，理想情况下是在包括ACFLD患者的随机对照试验中。此外，需要监测新型调节剂疗法在ACFLD个体中的疗效和耐受性，以及它们对肺部疾病进展的影响和作为最终治疗手段的肺移植需求，这需要在更大的患者队列中进行客观评估。截至目前，CF肺移植候选者的转诊和列入名单指南在转诊和列入名单过程中尚未纳入新型CFTR调节剂疗法的情况。因此，这篇综述文章的目的有三个：第一，描述新疗法的效果，重点关注ACFLD个体亚组；第二，提供CF患者肺移植后近期结果的最新情况；第三，鉴于CF中可用的新治疗方法，讨论作为最终治疗选择的肺移植的转诊、评估和时机。
