Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study.
Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study.
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DOI：
10.1016/j.jcf.2021.01.011
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Mayer-Hamblett N
中科院分区：
文献类型：
--
作者：
Zemanick ET;Konstan MW;VanDevanter DR;Rowe SM;Clancy JP;Odem-Davis K;Skalland M;Mayer-Hamblett N
CFTR调节的汗液氯化物变化特征及其与临床结局的相关性（CFTR-SC）研究是一项大型流行病学研究，旨在确定使用市售CFTR调节剂的囊性纤维化（CF）患者的汗液氯化物反应与临床结局之间的关系。研究可行性的一个挑战是在调节剂启动之前捕获汗液氯化物测量值。我们测试了历史汗液氯化物接近当代前调节剂值的假设，以估计CFTR调节剂诱导的变化，允许单次访问研究设计。GOAL和前景是对开始ivacaftor或lumacaftor-ivacaftor的个体进行的多中心前瞻性研究。在入组时，测量调节剂前汗液氯化物并记录历史结果。在1、3和6个月时测量调节剂后汗液氯化物。对于该分析，估计了历史汗液氯化物和调节前汗液氯化物之间的差异。CFTR调节剂诱导的汗液氯化物平均变化使用历史和预调节汗液氯化物进行比较。配对的历史和调节前汗液氯化物（n=406名参与者）显示，平均17.2年内的平均变化为−1.0 mmol/L（95% CI：−2.71，0.66）。使用历史值或预调节剂值计算对依伐卡托或鲁玛卡托-依伐卡托的汗液响应导致调节剂响应的类似估计。基于这些结果，设计了单次调节剂后汗液氯化物测量的EST-SC研究。历史汗液氯化物值为开始接受调节剂治疗的患者提供了调节剂治疗前汗液氯化物的可靠估计值。该研究预计将采集大约5,000个汗液氯化物值，从而在CFTR调节剂时代对CF人群的汗液氯化物提供前所未有的了解。
The Characterizing CFTR modulated changes in Sweat Chloride and their Association with Clinical Outcomes (CHEC-SC) study is a large epidemiologic study designed to determine the relationship between sweat chloride response and clinical outcomes in people with cystic fibrosis (CF) on commercially approved CFTR modulators. A challenge to study feasibility was capturing sweat chloride measurements before modulator initiation. We tested the hypothesis that historic sweat chloride approximated contemporary pre-modulator values to estimate CFTR modulator-induced changes, allowing a single-visit study design. GOAL and PROSPECT were multi-center prospective studies of individuals initiating ivacaftor or lumacaftor-ivacaftor. At enrollment, pre-modulator sweat chloride was measured and historic results recorded. Post-modulator sweat chloride was measured at 1, 3 and 6 months. For this analysis, differences between historic and pre-modulator sweat chloride were estimated. CFTR modulator-induced sweat chloride mean changes were compared using historic and pre-modulator sweat chloride. Paired historic and pre-modulator sweat chloride (n=406 participants) revealed a non-significant mean change of −1.0 mmol/L (95% CI: −2.71, 0.66) over an average of 17.2 years. Calculating sweat response to ivacaftor or lumacaftor-ivacaftor using historic or pre-modulator values resulted in similar estimates of modulator response. Based on these results, the CHEC-SC study was designed with a single, post-modulator sweat chloride measurement. Historic sweat chloride values provide a reliable estimate of pre-modulator sweat chloride for people starting on modulator therapy. The CHEC-SC Study anticipates capturing approximately 5,000 sweat chloride values, providing an unprecedented understanding of sweat chloride across the CF population in the era of CFTR modulators.
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发表时间：
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影响因子：
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