Change in exercise capacity measured by Cardio-pulmonary Exercise Testing (CPET) in Danish people with cystic fibrosis after initiation of treatment with Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor


      • CFTR modulating therapy improves exercise capacity in patients with cystic fibrosis.
      • Patients with moderate lung function impairments achieved the most extensive improvements.
      • Increased muscle strength and muscle power were observed after one year.
      • Exercise capacity is a feasible and relevant outcome measure evaluating CFTR modulating treatment.



      Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA).


      We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population.


      A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant.


      Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cystic Fibrosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Elborn J.S.
        Cystic fibrosis.
        Lancet. 2016; 388: 2519-2531
        • Ronan N.J.
        • Elborn J.S.
        • Plant B.J.
        Current and emerging comorbidities in cystic fibrosis.
        Presse Med. 46. 2017 (Pt 2e125-e38)
        • Jacobsen H.L.L
        Connection to the labour market prior and after lung transplantation in Danish CF patients.
        Cystisk Fibrose. 2008; : 28-29
        • Schönenberger K.A.
        • Reber E.
        • Bally L.
        • Geiser T.
        • Lin D.
        • Stanga Z.
        Nutritional assessment in adults with cystic fibrosis.
        Nutrition (Burbank, Los Angeles County, Calif). 2019; 110518
        • Hebestreit H.
        • Kieser S.
        • Rüdiger S.
        • Schenk T.
        • Junge S.
        • Hebestreit A.
        • et al.
        Physical activity is independently related to aerobic capacity in cystic fibrosis.
        Eur Respir J. 2006; 28: 734-739
        • van de Weert-van Leeuwen P.B.
        • Arets H.G.
        • van der Ent C.K.
        • Beekman J.M.
        Infection, inflammation and exercise in cystic fibrosis.
        Respir Res. 2013; 14: 32
        • Vendrusculo F.M.
        • Heinzmann-Filho J.P.
        • da Silva J.S.
        • Perez Ruiz M.
        • Donadio M.V.F
        Peak Oxygen Uptake and Mortality in Cystic Fibrosis: systematic Review and Meta-Analysis.
        Respir Care. 2019; 64: 91-98
        • Wainwright C.E.
        • Elborn J.S.
        • Ramsey B.W.
        • Marigowda G.
        • Huang X.
        • Cipolli M.
        • et al.
        Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR.
        N Engl J Med. 2015; 373: 220-231
        • Taylor-Cousar J.L.
        • Munck A.
        • McKone E.F.
        • van der Ent C.K.
        • Moeller A.
        • Simard C.
        • et al.
        Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del.
        N Engl J Med. 2017; 377: 2013-2023
      1. Zolin A.O.A, Naerrlich L., Jung A., van Rens J. The ecfs patient registry annual data report 2018. European Cystic Fibrosis Society (ECFS); 2020.

        • Donaldson S.H.
        • Pilewski J.M.
        • Griese M.
        • Cooke J.
        • Viswanathan L.
        • Tullis E.
        • et al.
        Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.
        Am J Respir Crit Care Med. 2018; 197: 214-224
        • ATS/ACCP Statement on cardiopulmonary exercise testing
        Am J Respir Crit Care Med. 2003; 167: 211-277
        • Hebestreit H.
        • Arets H.G.
        • Aurora P.
        • Boas S.
        • Cerny F.
        • Hulzebos E.H.
        • et al.
        Statement on Exercise Testing in Cystic Fibrosis.
        Respiration. 2015; 90: 332-351
        • Wark P.A.B.
        • Cookson K.
        • Thiruchelvam T.
        • Brannan J.
        • Dorahy D.J.
        Lumacaftor/Ivacaftor improves exercise tolerance in patients with Cystic Fibrosis and severe airflow obstruction.
        BMC Pulm Med. 2019; 19: 106
        • Quon B.S.
        • Ramsook A.H.
        • Dhillon S.S.
        • Mitchell R.A.
        • Boyle K.G.
        • Wilcox P.G.
        • et al.
        Short-term effects of Lumacaftor/Ivacaftor (OrkambiTM) on exertional symptoms, exercise performance, and ventilatory responses in adults with cystic fibrosis.
        Respir Res. 2020; 21: 135
        • Ejiofor L.C.K.
        • Mathiesen I.H.M.
        • Jensen-Fangel S.
        • Olesen H.V.
        • Skov M.
        • Philipsen L.K.D.
        • et al.
        Patients with cystic fibrosis and advanced lung disease benefit from lumacaftor/ivacaftor treatment.
        Pediatr Pulmonol. 2020; 55: 3364-3370
        • Wilson J.
        • You X.
        • Ellis M.
        • Urquhart D.S.
        • Jha L.
        • Duncan M.
        • et al.
        VO(2max) as an exercise tolerance endpoint in people with cystic fibrosis: lessons from a lumacaftor/ivacaftor trial.
        J Cystic Fibrosis. 2021; 20: 499-505
        • Savi D.
        • Schiavetto S.
        • Simmonds N.J.
        • Righelli D.
        • Palange P.
        Effects of Lumacaftor/Ivacaftor on physical activity and exercise tolerance in three adults with cystic fibrosis.
        J Cystic Fibrosis. 2019; 18: 420-424
      2. European Cystic Fibrosis Society Patient Registry [Internet]. European Cystic Fibrosis Society (ECFS). 2021.

        • Pianosi P.
        • Leblanc J.
        Almudevar A. Peak oxygen uptake and mortality in children with cystic fibrosis.
        Thorax. 2005; 60: 50-54
        • Hebestreit H.
        • Hulzebos E.H.J.
        • Schneiderman J.E.
        • Karila C.
        • Boas S.R.
        • Kriemler S.
        • et al.
        Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis.
        Am J Respir Crit Care Med. 2019; 199: 987-995
        • Radtke T.
        • Hebestreit H.
        • Gallati S.
        • Schneiderman J.E.
        • Braun J.
        • Stevens D.
        • et al.
        CFTR Genotype and Maximal Exercise Capacity in Cystic Fibrosis: a Cross-sectional Study.
        Ann Am Thorac Soc. 2018; 15: 209-216
        • Pastré J.
        • Prévotat A.
        • Tardif C.
        • Langlois C.
        • Duhamel A.
        • Wallaert B.
        Determinants of exercise capacity in cystic fibrosis patients with mild-to-moderate lung disease.
        BMC Pulm Med. 2014; 14: 74
        • Cardoso J.
        • Scalco J.
        • Mucha F.
        • Caputo F.
        • Schivinski C.S.
        Relationship between peripheral muscle strength, exercise capacity and body composition in children and adolescents with cystic fibrosis.
        Physiother Theory Pract. 2021; : 1-8
        • Stallings V.A.
        • Sainath N.
        • Oberle M.
        • Bertolaso C.
        • Schall J.I.
        Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations.
        J Pediatr. 2018; 201 (e4): 229-237
        • Balady G.J.
        • Arena R.
        • Sietsema K.
        • Myers J.
        • Coke L.
        • Fletcher G.F.
        • et al.
        Clinician’s Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association.
        Circulation. 2010; 122: 191-225