CFTR genotype and maximal exercise capacity in cystic fibrosis a cross-sectional study

Thomas Radtke, Helge Hebestreit, Sabina Gallati, Jane E. Schneiderman, Julia Braun, Daniel Stevens, Erik H.J. Hulzebos, Tim Takken, Steven R. Boas, Don S. Urquhart, Larry C. Lands, Sergio Tejero, Aleksandar Sovtic, Tiffany Dwyer, Milos Petrovic, Ryan A. Harris, Chantal Karila, Daniela Savi, Jakob Usemann, Meir Mei-ZahavElpis Hatziagorou, Felix Ratjen, Susi Kriemler

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Rationale: Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. Objectives: This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (VO 2peak ), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. Methods: In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I-V. Results: The final analysis included 726 patients (45% females; age range, 8-61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V O2peak , 77.3 6 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I-III and either VO 2peak (percent predicted) (adjusted b = 20.95; 95% CI, 24.18 to 2.29; P = 0.57) or maximum work rate (Watt max ) (adjusted β = 21.38; 95% CI, 25.04 to 2.27; P = 0.46) compared with classes IV-V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V O2peak (β = 28.24%; 95% CI, 214.53 to 22.99; P = 0.003) and lower Watt max (adjusted β = 27.59%; 95% CI, 214.21 to 20.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for relevant confounders, lung function and body mass index were associated with VO 2peak . Conclusions: CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.

Original languageEnglish (US)
Pages (from-to)209-216
Number of pages8
JournalAnnals of the American Thoracic Society
Volume15
Issue number2
DOIs
StatePublished - Feb 2018

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Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Cross-Sectional Studies
Genotype
Exercise
Mutation
Exercise Test
Forced Expiratory Volume
North America
Muscle Cells
Linear Models
Skeletal Muscle
Body Mass Index

Keywords

  • Cardiorespiratory fitness
  • Cystic fibrosis transmembrane conductance regulator
  • Lung disease
  • Peak oxygen uptake

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Radtke, T., Hebestreit, H., Gallati, S., Schneiderman, J. E., Braun, J., Stevens, D., ... Kriemler, S. (2018). CFTR genotype and maximal exercise capacity in cystic fibrosis a cross-sectional study. Annals of the American Thoracic Society, 15(2), 209-216. https://doi.org/10.1513/AnnalsATS.201707-570OC

CFTR genotype and maximal exercise capacity in cystic fibrosis a cross-sectional study. / Radtke, Thomas; Hebestreit, Helge; Gallati, Sabina; Schneiderman, Jane E.; Braun, Julia; Stevens, Daniel; Hulzebos, Erik H.J.; Takken, Tim; Boas, Steven R.; Urquhart, Don S.; Lands, Larry C.; Tejero, Sergio; Sovtic, Aleksandar; Dwyer, Tiffany; Petrovic, Milos; Harris, Ryan A.; Karila, Chantal; Savi, Daniela; Usemann, Jakob; Mei-Zahav, Meir; Hatziagorou, Elpis; Ratjen, Felix; Kriemler, Susi.

In: Annals of the American Thoracic Society, Vol. 15, No. 2, 02.2018, p. 209-216.

Research output: Contribution to journalArticle

Radtke, T, Hebestreit, H, Gallati, S, Schneiderman, JE, Braun, J, Stevens, D, Hulzebos, EHJ, Takken, T, Boas, SR, Urquhart, DS, Lands, LC, Tejero, S, Sovtic, A, Dwyer, T, Petrovic, M, Harris, RA, Karila, C, Savi, D, Usemann, J, Mei-Zahav, M, Hatziagorou, E, Ratjen, F & Kriemler, S 2018, 'CFTR genotype and maximal exercise capacity in cystic fibrosis a cross-sectional study', Annals of the American Thoracic Society, vol. 15, no. 2, pp. 209-216. https://doi.org/10.1513/AnnalsATS.201707-570OC
Radtke, Thomas ; Hebestreit, Helge ; Gallati, Sabina ; Schneiderman, Jane E. ; Braun, Julia ; Stevens, Daniel ; Hulzebos, Erik H.J. ; Takken, Tim ; Boas, Steven R. ; Urquhart, Don S. ; Lands, Larry C. ; Tejero, Sergio ; Sovtic, Aleksandar ; Dwyer, Tiffany ; Petrovic, Milos ; Harris, Ryan A. ; Karila, Chantal ; Savi, Daniela ; Usemann, Jakob ; Mei-Zahav, Meir ; Hatziagorou, Elpis ; Ratjen, Felix ; Kriemler, Susi. / CFTR genotype and maximal exercise capacity in cystic fibrosis a cross-sectional study. In: Annals of the American Thoracic Society. 2018 ; Vol. 15, No. 2. pp. 209-216.
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abstract = "Rationale: Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. Objectives: This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (VO 2peak ), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. Methods: In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I-V. Results: The final analysis included 726 patients (45{\%} females; age range, 8-61 yr; forced expiratory volume in 1 s, 16 to 123{\%} predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V O2peak , 77.3 6 19.1{\%} predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I-III and either VO 2peak (percent predicted) (adjusted b = 20.95; 95{\%} CI, 24.18 to 2.29; P = 0.57) or maximum work rate (Watt max ) (adjusted β = 21.38; 95{\%} CI, 25.04 to 2.27; P = 0.46) compared with classes IV-V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V O2peak (β = 28.24{\%}; 95{\%} CI, 214.53 to 22.99; P = 0.003) and lower Watt max (adjusted β = 27.59{\%}; 95{\%} CI, 214.21 to 20.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for relevant confounders, lung function and body mass index were associated with VO 2peak . Conclusions: CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.",
keywords = "Cardiorespiratory fitness, Cystic fibrosis transmembrane conductance regulator, Lung disease, Peak oxygen uptake",
author = "Thomas Radtke and Helge Hebestreit and Sabina Gallati and Schneiderman, {Jane E.} and Julia Braun and Daniel Stevens and Hulzebos, {Erik H.J.} and Tim Takken and Boas, {Steven R.} and Urquhart, {Don S.} and Lands, {Larry C.} and Sergio Tejero and Aleksandar Sovtic and Tiffany Dwyer and Milos Petrovic and Harris, {Ryan A.} and Chantal Karila and Daniela Savi and Jakob Usemann and Meir Mei-Zahav and Elpis Hatziagorou and Felix Ratjen and Susi Kriemler",
year = "2018",
month = "2",
doi = "10.1513/AnnalsATS.201707-570OC",
language = "English (US)",
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pages = "209--216",
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TY - JOUR

T1 - CFTR genotype and maximal exercise capacity in cystic fibrosis a cross-sectional study

AU - Radtke, Thomas

AU - Hebestreit, Helge

AU - Gallati, Sabina

AU - Schneiderman, Jane E.

AU - Braun, Julia

AU - Stevens, Daniel

AU - Hulzebos, Erik H.J.

AU - Takken, Tim

AU - Boas, Steven R.

AU - Urquhart, Don S.

AU - Lands, Larry C.

AU - Tejero, Sergio

AU - Sovtic, Aleksandar

AU - Dwyer, Tiffany

AU - Petrovic, Milos

AU - Harris, Ryan A.

AU - Karila, Chantal

AU - Savi, Daniela

AU - Usemann, Jakob

AU - Mei-Zahav, Meir

AU - Hatziagorou, Elpis

AU - Ratjen, Felix

AU - Kriemler, Susi

PY - 2018/2

Y1 - 2018/2

N2 - Rationale: Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. Objectives: This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (VO 2peak ), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. Methods: In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I-V. Results: The final analysis included 726 patients (45% females; age range, 8-61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V O2peak , 77.3 6 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I-III and either VO 2peak (percent predicted) (adjusted b = 20.95; 95% CI, 24.18 to 2.29; P = 0.57) or maximum work rate (Watt max ) (adjusted β = 21.38; 95% CI, 25.04 to 2.27; P = 0.46) compared with classes IV-V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V O2peak (β = 28.24%; 95% CI, 214.53 to 22.99; P = 0.003) and lower Watt max (adjusted β = 27.59%; 95% CI, 214.21 to 20.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for relevant confounders, lung function and body mass index were associated with VO 2peak . Conclusions: CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.

AB - Rationale: Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. Objectives: This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (VO 2peak ), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. Methods: In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I-V. Results: The final analysis included 726 patients (45% females; age range, 8-61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V O2peak , 77.3 6 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I-III and either VO 2peak (percent predicted) (adjusted b = 20.95; 95% CI, 24.18 to 2.29; P = 0.57) or maximum work rate (Watt max ) (adjusted β = 21.38; 95% CI, 25.04 to 2.27; P = 0.46) compared with classes IV-V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V O2peak (β = 28.24%; 95% CI, 214.53 to 22.99; P = 0.003) and lower Watt max (adjusted β = 27.59%; 95% CI, 214.21 to 20.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for relevant confounders, lung function and body mass index were associated with VO 2peak . Conclusions: CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.

KW - Cardiorespiratory fitness

KW - Cystic fibrosis transmembrane conductance regulator

KW - Lung disease

KW - Peak oxygen uptake

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