Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA; Division of Pediatric Pulmonary Medicine, National Jewish Health, Denver, CO, USA; Division of Pulmonary Sciences and Critical Care Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.
Department of Respiratory Medicine, Queensland Children's Hospital, Brisbane, QLD, Australia; Children's Health and Environment Program, Child Health Research Centre, University of Queensland, Brisbane, QLD, Australia.
Lancet. 2023 Sep 30;402(10408):1171-1184. doi: 10.1016/S0140-6736(23)01609-4. Epub 2023 Sep 9.
Following discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 and subsequent elucidation of the varied CFTR protein abnormalities that result, a new era of cystic fibrosis management has emerged-one in which scientific principles translated from the bench to the bedside have enabled us to potentially treat the basic defect in the majority of children and adults with cystic fibrosis, with a resultant burgeoning adult cystic fibrosis population. However, the long-term effects of these therapies on the multiple manifestations of cystic fibrosis are still under investigation. Understanding the effects of modulators in populations excluded from clinical trials is also crucial. Furthermore, establishing appropriate disease measures to assess efficacy in the youngest potential trial participants and in those whose post-modulator lung function is in the typical range for people without chronic lung disease is essential for continued drug development. Finally, recognising that a health outcome gap has been created for some people and widened for others who are not eligible for, cannot tolerate, or do not have access to modulators is important.
1989 年发现囊性纤维化跨膜电导调节因子（CFTR）基因后，随后阐明了导致囊性纤维化的各种 CFTR 蛋白异常，一个囊性纤维化管理的新时代出现了——从实验室到临床转化的科学原理使我们有可能治疗大多数儿童和成人囊性纤维化的基本缺陷，由此产生了日益壮大的成年囊性纤维化人群。然而，这些疗法对囊性纤维化多种表现的长期影响仍在研究中。了解在临床试验之外的人群中调节剂的影响也至关重要。此外，建立适当的疾病措施来评估在最小的潜在试验参与者和那些调节剂后肺功能处于无慢性肺部疾病人群典型范围内的人的疗效对于药物的持续开发是至关重要的。最后，认识到对于一些人来说，健康结果的差距已经出现，而对于那些不符合条件、不能耐受或无法获得调节剂的人来说，差距已经扩大，这一点很重要。
