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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U2 - 10.1513/AnnalsATS.201707-570OC
DO - 10.1513/AnnalsATS.201707-570OC
M3 - Article
C2 - 29140739
AN - SCOPUS:85045317669
VL - 15
SP - 209
EP - 216
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
SN - 2325-6621
IS - 2
ER -