Objectives: Ireland has the highest rate of Cystic Fibrosis (CF) in the world. It is caused by genetic mutations, which alter the function of the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR expression plays an intrinsic role in skeletal muscle atrophy and dysfunction in CF. Orkambi is a new therapy which corrects and potentiates CFTR function in the most common genotype mutation in Ireland - phe508del. It was made available to patients in Ireland with <40% predicted FEV1, who's CF gene was homozygous for phe508del in 2016. It is hypothesised that correcting the underlying CFTR dysfunction may improve muscle function in this population. The aim of this study is to investigate changes in muscle strength and exercise tolerance in patients commencing Orkambi. No previous study had been completed examining this relationship
Methods: Subjects with CF and clinically stable disease were recruited on commencing Orkambi. Baseline characteristics of age, BMI and FEV1 were recorded. Muscle strength was assessed by measuring isokinetic strength of quadriceps muscle on Biodex®, and grip strength by hand held dynamometry. Exercise capacity was measured using the 6 Minute Walk Test. No additional exercise intervention was prescribed following testing.Testing was repeated 3 and 6 months post commencing the drug.
Results: 17 subjects were recruited, 6 subjects were lost to follow up. 6 month follow up data was available for 11 subjects. Repeat measure ANOVA was carried out on 6 Minute walk test distance, peak torque quads/body weight, quad acceleration time and grip strength. Only grip strength increased significantly (84% predicted at Day 0 to 98% predicted at 6 months). No clinically important differences were found in any of the four variables at 3 or 6 months.
Conclusion: The current study hypothesized that with the introduction of Orkambi, muscle strength would improve without additional physiotherapy intervention. Whilst no large patterns of improvements were seen, it is also important to note that there was not a decline in strength within the same period. Further study with a larger population, of more diverse levels of lung disease severity is warranted. Expected improvements in 6 Minute Walk Test distances did not occur. However, reduction in exercise capacity in CF is multifactorial. This highlights the continued importance of exercise and physical activity promotion on initiation of novel therapies in CF.
References:
McKone & Fletcher, (2015) Cystic Fibrosis Registry of Ireland Annual Report.
Gruet M, Troosters T, Verges S, (2017), Peripheral muscle abnormalities in cystic fibrosis: Etiology, clinical implications and response to therapeutic interventions. Journal of Cystic Fibrosis
Ethics: Ethical Approval for this study has been granted by St. Vincents University Hospital Ethics Board.
