RT Journal Article
T1 CFTR Genotype and Maximal Exercise Capacity in Cystic Fibrosis: A Cross-sectional Study.
A1 Radtke, Thomas
A1 Hebestreit, Helge
A1 Gallati, Sabina
A1 Schneiderman, Jane E
A1 Braun, Julia
A1 Stevens, Daniel
A1 Hulzebos, Erik Hj
A1 Takken, Tim
A1 Boas, Steven R
A1 Urquhart, Don S
A1 Lands, Larry C
A1 Tejero, Sergio
A1 Sovtic, Aleksandar
A1 Dwyer, Tiffany
A1 Petrovic, Milos
A1 Harris, Ryan A
A1 Karila, Chantal
A1 Savi, Daniela
A1 Usemann, Jakob
A1 Mei-Zahav, Meir
A1 Hatziagorou, Elpis
A1 Ratjen, Felix
A1 Kriemler, Susi
A1 CFTR-Exercise study group, 
K1 cystic fibrosis transmembrane conductance regulator
K1 peak oxygen uptake
K1 lung disease
K1 cardiorespiratory fitness
AB 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. This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (V.O2peak), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. 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. 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 ± 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 V.O2peak (percent predicted) (adjusted β = −0.95; 95% CI, −4.18 to 2.29; P = 0.57) or maximum work rate (Wattmax) (adjusted β = −1.38; 95% CI, −5.04 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 = −8.24%; 95% CI, −14.53 to −2.99; P = 0.003) and lower Wattmax (adjusted β = −7.59%; 95% CI, −14.21 to −0.95; 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 V.O2peak. 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.
YR 2017
FD 2017-11-15
LK http://hdl.handle.net/10668/11802
UL http://hdl.handle.net/10668/11802
LA en
DS RISalud
RD Apr 4, 2025