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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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


FundersFunder number
21University Children’s Hospital Basel
Alfred Hospital
Cystic Fibrosis Center
Mother and Child Health Institute of Serbia
Royal Hospital for Sick Children
Sapienza University of Rome
School of Medicine, University of Belgrade, Belgrade, Serbia
University of Berne
University of Sevilla
University of Zurich
Fulbright Foundation in Greece
Feinberg School of Medicine
McGill University
Augusta University
University of Sydney
Dalhousie University
University of Toronto
Tel Aviv University
Université Paris Descartes
Hospital for Sick Children
Aristotle University of Thessaloniki


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


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