Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study

•Sweat chloride elevation is a key criterion to diagnose cystic fibrosis.•CFTR modulators decrease sweat chloride and improve outcomes in many people with CF.•CHEC-SC is a large study designed to measure sweat chloride response to modulators.•Historic sweat chloride values estimate contemporary pre-...

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Bibliographic Details
Published in:Journal of cystic fibrosis 2021-11, Vol.20 (6), p.965-971
Main Authors: Zemanick, Edith T., Konstan, Michael W., VanDevanter, Donald R., Rowe, Steven M., Clancy, JP, Odem-Davis, Katherine, Skalland, Michelle, Mayer-Hamblett, Nicole
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aminophenols
Aminopyridines
Benzodioxoles
CFTR modulator
Child
Chloride Channel Agonists - therapeutic use
Chlorides - metabolism
Cystic Fibrosis - diagnosis
Cystic Fibrosis Transmembrane Conductance Regulator - drug effects
Drug Combinations
Female
Humans
Ivacaftor
Lumacaftor-ivacaftor
Male
Middle Aged
Prospective Studies
Quinolones
Sweat - chemistry
Sweat chloride
Sweat test
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Summary:•Sweat chloride elevation is a key criterion to diagnose cystic fibrosis.•CFTR modulators decrease sweat chloride and improve outcomes in many people with CF.•CHEC-SC is a large study designed to measure sweat chloride response to modulators.•Historic sweat chloride values estimate contemporary pre-modulator values without systematic bias.•Thus, a single measurement is adequate to capture sweat changes in a large population. 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.
ISSN:1569-1993
1873-5010
DOI:10.1016/j.jcf.2021.01.011