Bryrup Thomas, Faurholt-Jepsen Daniel, Pressler Tacjana, Henriksen Esben Herborg, Leo-Hansen Christian, Nielsen Bibi Uhre, Højte Christine, Mathiesen Inger Hee Mabuza, Katzenstein Terese L, Jeppesen Majbritt, Jensen-Fangel Søren, Olesen Hanne Vebert, Skov Marianne, Qvist Tavs, Olsen Mette Frahm
The Danish Cystic Fibrosis Cohort, Copenhagen, Aarhus, Denmark.
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
APMIS. 2024 Oct;132(10):728-733. doi: 10.1111/apm.13453. Epub 2024 Aug 2.
Sweat chloride concentration, a diagnostic feature in cystic fibrosis (CF), reflects CF transmembrane conductance regulator (CFTR) activity. CFTR modulator therapies, especially elexacaftor/tezacaftor/ivacaftor (ETI), has improved CF outcomes. We report nationwide, real-world data on sweat chloride concentration in people with CF (pwCF) with and without modulator therapies. All Danish pwCF with a minimum of one F508del allele were included. Sweat chloride measurements were stratified by genotype and modulator treatment. Differences were assessed using mixed-effects models. We included 977 sweat chloride measurements from 430 pwCF, 71% of which were F508del homozygous. Heterozygous and homozygous ETI-treated pwCF had an estimated mean sweat chloride concentration of 43 mmol/L (95% confidence interval: 39; 48) and 43 mmol/L (39; 47), respectively-48% and 59% lower than those without treatment. High variation in concentrations remained regardless of treatment status. Despite ETI treatment, 27% heterozygous and 23% homozygous pwCF had elevated concentrations (≥60 mmol/L). These real-world data confirm a substantial decrease in sweat chloride concentration during modulator treatment, especially ETI, where mean concentrations halved. However, large variation remained, including persistently high concentrations. These findings emphasize the potential of sweat chloride concentration as a treatment response biomarker and the need to explore its heterogeneity and relationship with clinical outcomes.
汗液氯化物浓度是囊性纤维化（CF）的一项诊断特征，反映了CF跨膜传导调节因子（CFTR）的活性。CFTR调节剂疗法，尤其是依列卡福/替扎卡福/依伐卡福（ETI），改善了CF的治疗效果。我们报告了全国范围内接受和未接受调节剂治疗的CF患者（pwCF）汗液氯化物浓度的真实世界数据。纳入了所有至少携带一个F508del等位基因的丹麦pwCF患者。汗液氯化物测量结果按基因型和调节剂治疗进行分层。使用混合效应模型评估差异。我们纳入了430名pwCF患者的977次汗液氯化物测量结果，其中71%为F508del纯合子。杂合子和纯合子ETI治疗的pwCF患者的估计平均汗液氯化物浓度分别为43 mmol/L（95%置信区间：39；48）和43 mmol/L（39；47），分别比未治疗者低48%和59%。无论治疗状态如何，浓度仍存在很大差异。尽管接受了ETI治疗，27%的杂合子和23%的纯合子pwCF患者的浓度仍升高（≥60 mmol/L）。这些真实世界数据证实了调节剂治疗期间，尤其是ETI治疗期间，汗液氯化物浓度大幅下降，平均浓度减半。然而，仍存在很大差异，包括持续高浓度。这些发现强调了汗液氯化物浓度作为治疗反应生物标志物的潜力，以及探索其异质性及其与临床结果关系的必要性。
