Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR

Scott H. Donaldson, Beth L Laube, Timothy E. Corcoran, Pradeep Bhambhvani, Kirby Zeman, Agathe Ceppe, Pamela L. Zeitlin, Peter Mogayzel, Michael Boyle, Landon W. Locke, Michael M. Myerburg, Joseph M. Pilewski, Brian Flanagan, Steven M. Rowe, William D. Bennett

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. METHODS: We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. RESULTS: Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. CONCLUSIONS: Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. TRIAL REGISTRATION: ClinicialTrials.gov, NCT01521338. FUNDING: CFF Therapeutics (GOAL11K1).

Original languageEnglish (US)
JournalJCI insight
Volume3
Issue number24
DOIs
StatePublished - Dec 20 2018

Fingerprint

Mucociliary Clearance
Cystic Fibrosis
Lung
Sweat
Forced Expiratory Volume
Ion Channels
Observational Studies
ivacaftor
Chlorides
Therapeutics
Outcome Assessment (Health Care)
Prospective Studies
Mutation

Keywords

  • Chloride channels
  • Diagnostic imaging
  • Pulmonology

Cite this

Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR. / Donaldson, Scott H.; Laube, Beth L; Corcoran, Timothy E.; Bhambhvani, Pradeep; Zeman, Kirby; Ceppe, Agathe; Zeitlin, Pamela L.; Mogayzel, Peter; Boyle, Michael; Locke, Landon W.; Myerburg, Michael M.; Pilewski, Joseph M.; Flanagan, Brian; Rowe, Steven M.; Bennett, William D.

In: JCI insight, Vol. 3, No. 24, 20.12.2018.

Research output: Contribution to journalArticle

Donaldson, SH, Laube, BL, Corcoran, TE, Bhambhvani, P, Zeman, K, Ceppe, A, Zeitlin, PL, Mogayzel, P, Boyle, M, Locke, LW, Myerburg, MM, Pilewski, JM, Flanagan, B, Rowe, SM & Bennett, WD 2018, 'Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR', JCI insight, vol. 3, no. 24. https://doi.org/10.1172/jci.insight.122695
Donaldson, Scott H. ; Laube, Beth L ; Corcoran, Timothy E. ; Bhambhvani, Pradeep ; Zeman, Kirby ; Ceppe, Agathe ; Zeitlin, Pamela L. ; Mogayzel, Peter ; Boyle, Michael ; Locke, Landon W. ; Myerburg, Michael M. ; Pilewski, Joseph M. ; Flanagan, Brian ; Rowe, Steven M. ; Bennett, William D. / Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR. In: JCI insight. 2018 ; Vol. 3, No. 24.
@article{2fef429390ae40be891d670546ae82bf,
title = "Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR",
abstract = "BACKGROUND: The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. METHODS: We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. RESULTS: Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. CONCLUSIONS: Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. TRIAL REGISTRATION: ClinicialTrials.gov, NCT01521338. FUNDING: CFF Therapeutics (GOAL11K1).",
keywords = "Chloride channels, Diagnostic imaging, Pulmonology",
author = "Donaldson, {Scott H.} and Laube, {Beth L} and Corcoran, {Timothy E.} and Pradeep Bhambhvani and Kirby Zeman and Agathe Ceppe and Zeitlin, {Pamela L.} and Peter Mogayzel and Michael Boyle and Locke, {Landon W.} and Myerburg, {Michael M.} and Pilewski, {Joseph M.} and Brian Flanagan and Rowe, {Steven M.} and Bennett, {William D.}",
year = "2018",
month = "12",
day = "20",
doi = "10.1172/jci.insight.122695",
language = "English (US)",
volume = "3",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "24",

}

TY - JOUR

T1 - Effect of ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis patients with G551D-CFTR

AU - Donaldson, Scott H.

AU - Laube, Beth L

AU - Corcoran, Timothy E.

AU - Bhambhvani, Pradeep

AU - Zeman, Kirby

AU - Ceppe, Agathe

AU - Zeitlin, Pamela L.

AU - Mogayzel, Peter

AU - Boyle, Michael

AU - Locke, Landon W.

AU - Myerburg, Michael M.

AU - Pilewski, Joseph M.

AU - Flanagan, Brian

AU - Rowe, Steven M.

AU - Bennett, William D.

PY - 2018/12/20

Y1 - 2018/12/20

N2 - BACKGROUND: The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. METHODS: We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. RESULTS: Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. CONCLUSIONS: Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. TRIAL REGISTRATION: ClinicialTrials.gov, NCT01521338. FUNDING: CFF Therapeutics (GOAL11K1).

AB - BACKGROUND: The ability to restore cystic fibrosis transmembrane regulator (CFTR) function with effective small molecule modulators in patients with cystic fibrosis provides an opportunity to study relationships between CFTR ion channel function, organ level physiology, and clinical outcomes. METHODS: We performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures. RESULTS: Marked acceleration in whole lung, central lung, and peripheral lung MCC was observed 1 month after beginning ivacaftor and was sustained at 3 months. Improvements in MCC correlated with improvements in forced expiratory volume in the first second (FEV1) but not sweat chloride or symptom scores. CONCLUSIONS: Restoration of CFTR activity with ivacaftor led to significant improvements in MCC. This physiologic assessment provides a means to characterize future CFTR modulator therapies and may help to predict improvements in lung function. TRIAL REGISTRATION: ClinicialTrials.gov, NCT01521338. FUNDING: CFF Therapeutics (GOAL11K1).

KW - Chloride channels

KW - Diagnostic imaging

KW - Pulmonology

UR - http://www.scopus.com/inward/record.url?scp=85063247142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063247142&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.122695

DO - 10.1172/jci.insight.122695

M3 - Article

VL - 3

JO - JCI insight

JF - JCI insight

SN - 2379-3708

IS - 24

ER -