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Zemanick ET, Konstan MW, VanDevanter DR, et al. Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study. J Cyst Fibros. 2021;20(6):965-971doi: 10.1016/j.jcf.2021.01.011.
Zemanick, E. T., Konstan, M. W., VanDevanter, D. R., Rowe, S. M., Clancy, J. P., Odem-Davis, K., Skalland, M., & Mayer-Hamblett, N. (2021). Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 20(6), 965-971. https://doi.org/10.1016/j.jcf.2021.01.011
Zemanick, Edith T, et al. "Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study." Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society vol. 20,6 (2021): 965-971. doi: https://doi.org/10.1016/j.jcf.2021.01.011
Zemanick ET, Konstan MW, VanDevanter DR, Rowe SM, Clancy JP, Odem-Davis K, Skalland M, Mayer-Hamblett N. Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study. J Cyst Fibros. 2021 Nov;20(6):965-971. doi: 10.1016/j.jcf.2021.01.011. Epub 2021 Feb 08. PMID: 33573995; PMCID: PMC8349375.
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J Cyst Fibros. 2021 Nov;20(6):965-971. doi: 10.1016/j.jcf.2021.01.011. Epub 2021 Feb 08.

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

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

Edith T Zemanick, Michael W Konstan, Donald R VanDevanter, Steven M Rowe, J P Clancy, Katherine Odem-Davis, Michelle Skalland, Nicole Mayer-Hamblett

Affiliations

  1. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: [email protected].
  2. Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland OH USA; Rainbow Babies and Children's Hospital, Cleveland OH USA.
  3. Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland OH USA.
  4. Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL USA.
  5. Cystic Fibrosis Foundation, Bethesda, MD USA.
  6. Seattle Children's Research Institute, Seattle, WA 98145, USA.
  7. Seattle Children's Research Institute, Seattle, WA 98145, USA; Department of Biostatistics and Pediatrics, University of Washington, Seattle, WA 98195, USA.

PMID: 33573995 PMCID: PMC8349375 DOI: 10.1016/j.jcf.2021.01.011

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Copyright © 2021. Published by Elsevier B.V.

Keywords: CFTR modulator; Ivacaftor; Lumacaftor-ivacaftor; Sweat chloride; Sweat test

Conflict of interest statement

Declaration of Competing Interest ETZ, NMH, DRV, SMR, MWK: grants or consulting CFF; DRV consults for aMoon, Arrevus, Eloxx, Enbiotix, Felix, Ionis, Matinas, Merck, Polyphor, Respirion, Savara; SMR co

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