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
N1 - Funding Information:
1Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 2Paediatric Department, University Hospitals Würzburg, Würzburg, Germany; 3Division of Human Genetics, Department of Pediatrics, Inselspital, University of Berne, Berne, Switzerland; 4Division of Respiratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; 5Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada; 6Department of Pediatrics, Division of Respirology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 7School of Health and Human Performance, Faculty of Health, Dalhousie University, Halifax, Nova Scotia, Canada; 8Child Development & Exercise Center, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands; 9Northwestern University Feinberg School of Medicine, Chicago, Illinois; 10Department of Paediatric Respiratory and Sleep Medicine, Royal Hospital for Sick Children, Edinburgh, United Kingdom; 11Montreal Children’s Hospital – McGill University Health, Montreal, Quebec, Canada; 12Orthopaedic Surgery and Sport Medicine, University of Sevilla, Hospital Virgen del Rocío, Sevilla, Spain; 13Department of Pulmonology, Mother and Child Health Institute of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia; 14Discipline of Physiotherapy, Faculty of Health Sciences, University of Sydney, Sydney, Australia; 15Department of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, Australia; 16Departement of Pulmonology, Hietzing Hospital, Vienna, Austria; 17Georgia Prevention Institute, Augusta University, Augusta, Georgia; 18Service de pneumologie et allergologie pédiatriques, Hôpital Necker Enfants malades, Assistance Publique – Hôpitaux de Paris, Université Paris Descartes, Paris, France; 19Department of Pediatrics, Cystic Fibrosis Center, Sapienza University of Rome, Rome, Italy; 20Cystic Fibrosis Unit, Bambino Gesù Children’s Hospital, Rome, Italy; 21University Children’s Hospital Basel, Basel, Switzerland; 22Pulmonary Institute, Schneider Children’s Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and 23Paediatric Pulmonology and CF Unit, Paediatric Department, Aristotle University of Thessaloniki, Thessaloniki, Greece
Publisher Copyright:
© Copyright 2018 by the American Thoracic Society.
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 -