Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
J Cyst Fibros. 2022 Jan;21(1):96-103. doi: 10.1016/j.jcf.2021.07.003. Epub 2021 Jul 19.
People with cystic fibrosis (CF) heterozygous for F508del-CFTR and a minimal function CFTR mutation (F/MF) that results in no CFTR protein or results in CFTR protein that is not responsive to tezacaftor, ivacaftor, and tezacaftor/ivacaftor in vitro comprise a sizeable percentage of the US CF population. This retrospective, cross-sectional, observational study aimed to characterize CF burden in this subpopulation.
People ≥2 years of age in the US CF Foundation Patient Registry with a CF diagnosis, F/MF genotype, and ≥1 encounters in 2017 were included. Descriptive analyses assessed lung function, nutritional parameters, microbiology, hospitalization and pulmonary exacerbation rates, and CF-related complications. Results were stratified by age group; select characteristics were summarized by percent predicted FEV (ppFEV) and ethnicity.
5348 people met inclusion criteria. Rates of positive bacterial cultures, pulmonary exacerbations, and hospitalizations were generally higher in older age groups. Prevalence of prescribed symptomatic CF therapies was substantial and also generally higher in older age groups. ppFEV was lower in older age groups. A greater percentage of adolescents and adults reported complications, including cirrhosis, osteoporosis, osteopenia, and sinus disease, than younger age groups. Increased prevalence of cultured Pseudomonas aeruginosa and prescribed chronic therapy was seen with decreasing ppFEV. In each age group, ppFEV was slightly higher in the non-Hispanic cohort than in the Hispanic cohort.
People with F/MF genotypes have substantial disease burden that worsened in older age groups consistent with the progressive nature of CF, indicating need for additional treatment options in this subpopulation.
携带有 F508del-CFTR 突变和最小功能 CFTR 突变（F/MF）的囊性纤维化（CF）杂合子的患者，这些突变导致无 CFTR 蛋白或体外对 tezacaftor、ivacaftor 和 tezacaftor/ivacaftor 无反应的 CFTR 蛋白，占美国 CF 人群的相当大比例。这项回顾性、横断面、观察性研究旨在描述这一亚人群的 CF 负担。
在美国 CF 基金会患者登记处，纳入年龄≥2 岁、CF 诊断、F/MF 基因型和 2017 年≥1 次就诊的患者。描述性分析评估了肺功能、营养参数、微生物学、住院和肺部恶化率以及 CF 相关并发症。结果按年龄组分层；按 ppFEV（预计 FEV）和种族对选定特征进行了总结。
符合纳入标准的患者共 5348 人。随着年龄的增长，阳性细菌培养、肺部恶化和住院的发生率通常更高。规定的对症 CF 治疗的患病率也相当高，并且随着年龄的增长而更高。年龄较大的年龄组的 ppFEV 较低。与年龄较小的年龄组相比，更多的青少年和成年人报告了并发症，包括肝硬化、骨质疏松症、骨量减少和窦疾病。随着 ppFEV 的降低，培养的铜绿假单胞菌和规定的慢性治疗的患病率增加。在每个年龄组中，非西班牙裔患者的 ppFEV 略高于西班牙裔患者。
F/MF 基因型患者的疾病负担很大，随着年龄的增长而恶化，这与 CF 的进行性性质一致，表明该亚人群需要额外的治疗选择。
