Cystic fibrosis and physiological responses to exercise

Expert Review of Respiratory Medicine

Volumn 8, Issue 6, 2014, Pages 751-762

  Williams, Craig A ^a   Saynor, Zoe L ^a   Tomlinson, Owen W ^a   Barker, Alan R ^a  

^a UNIVERSITY OF EXETER   (United Kingdom)

Author keywords

cardiopulmonary exercise testing; inspiratory muscle training; Ivacaftor; oxygen uptake kinetics; pediatrics; skeletal muscle

Indexed keywords

CARDIOPULMONARY EXERCISE TEST; CLINICAL PROTOCOL; CYSTIC FIBROSIS; EXERCISE; EXERCISE TOLERANCE; HUMAN; OXYGEN CONSUMPTION; PEDIATRICS; PHYSIOLOGICAL PROCESS; PRESCRIPTION; REVIEW; KINESIOTHERAPY; PATHOPHYSIOLOGY; PHYSIOLOGY;

CYSTIC FIBROSIS; EXERCISE; EXERCISE THERAPY; EXERCISE TOLERANCE; HUMANS; OXYGEN CONSUMPTION;

EID: 84910650267     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.2014.966693     Document Type: Review

References (101)

1. Collins FS. Cystic Fibrosis. Molecular biology and therapeutic implications. Science 1992;256:774-9
2. Orenstein DM, Higgins LW. Update on the role of exercise in cystic fibrosis. Curr Opin in Pulm Med 2005;111:519-23
3. Cystic Fibrosis Trust. UK Cystic Fibrosis registry annual data report 2012. 2013. Available from: www.cysticfibrosis.org.uk/ media/316760/Scientific%20Registry% 20Review%202012.pdf
4. Bar-Or O, Rowland TW. Pediatric Exercise Medicine. From physiologic principles to health care application. Human Kinetics; Champaign, IL, USA: 2004
5. Schniederman JE, Wilkes DL, Atenafu EG, et al. Longitudinal relationship between physical activity and lung health in patients with Cystic Fibrosis. Eur Resp J 2014;43: 817-23
6. Stevens D, Oades PJ, Armstrong N, et al. A survey of exercise testing and training in UK cystic fibrosis clinics. J Cyst Fibros 2010;9(5):302-6
7. Wasserman K, Hansen JE, Sue DY, et al. Principles of exercise testing and interpretation: pathophysiology and clinical applications. Lippincott Williams & Wilkins; MD, USA: 2005 .
8. Dodge JA, Lewis PA, Stanton M, et al. Cystic Fibrosis mortality and survival in the UK: 1947-2007. Eur Resp J 2007;29:522-6
9. Rosenthal M. Prognostication in cystic fibrosis: another futile pastime? Arch Dis Child 2013;99:2-3
10. Cystic Fibrosis Trust. Standards for clinical care of children and adolescents with cystic fibrosis in the UK. 2011. Available from: www.cysticfibrosis.org.uk/media/82070/CD-Standards-of-Care-Dec-11.pdf [Last accessed 29 January 14]
11. Armstrong DK, Cunningham S, Davies JC, Alton E. Gene therapy in cystic fibrosis. Arch Dis Child doi: 10/1136/archdischild- 2012-302158
12. ATS/ACCP Joint statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211-77
13. Barker M, Hebestreit A, Gruber W, et al. Exercise testing and training in German CF centres. Pediatr Pulmonol 2004;37(4):351-5
14. Kaplan TA, ZeBranek JD, McKey RM Jr. Use of exercise testing in the management of cystic fibrosis: short communication about a survey of cystic fibrosis referral centres. Pediatr Pulmonol 1991;10(3):205-7
15. de Jong W, Kaptein AA, van der Schans CP, et al. Quality of life in patients with cystic fibrosis. Pediatr Pulmonol 1997;23(2): 95-100
16. Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med 1992;327(25): 1785-8
17. Moorcroft AJ, Dodd ME, Webb AK. Exercise testing and prognosis in adult cystic fibrosis. Thorax 1997;52(3):291-3
18. Pianosi P, Leblanc J, Almudevar A. Peak oxygen uptake and mortality in children with cystic fibrosis. Thorax 2005;60(1):50-4
19. Perez M, Groeneveld IF, Santana-Sosa E, et al. Aerobic fitness is associated with lower risk of hospitalization in children with cystic fibrosis. Pediatr Pulmonol 2014;49(7):641-9
20. Divangahi M, Balghi H, Danialou G, et al. Lack of CFTR in skeletal muscle predisposes to muscle wasting and diaphragm muscle pump failure in cystic fibrosis mice. PLoS Genet 2009;5(7): e1000586
21. Ionescu AA, Ionescu A-A, Payne N, et al. Subclinical right ventricular dysfunction in cystic fibrosis. Am J Respir Crit Care Med 2001;163:1212-18
22. Lands LC, Heigenhauser GJ, Jones NL. Cardiac output determination during progressive in cystic fibrosis. Chest 1992;102:1118-23
23. Arena R, Guazzi M, Myers J, et al. The relationship between minute ventilation and oxygen consumption in heart failure: comparing peak VE/VO2 and the oxygen uptake efficiency slope. Int J Cardiol 2011; 154(3):384-5
24. Kasikcioglu E, Toker A, Tanju S, et al. Oxygen uptake kinetics during exercise testing and postoperative complications in patients with lung cancer. Lung Cancer 2009;66(1):85-8
25. Bell SC, Morris NR. Exercise testing in patients with cystic fibrosis: why and which? J. Cyst. Fibrosis 2010;9(5):299-301
26. Bradley JM, Madge S, Morton AM, et al. Cystic fibrosis research in allied health and nursing professions. J Cyst Fibros 2012; 11(5):387-92
27. Saynor ZL, Barker AR, Oades PJ, Williams CA. A protocol to determine valid V?O2max in young cystic fibrosis patients. J Sci Med Sport 2013;16(6):539-44
28. Saynor ZL, Barker AR, Oades PJ, Williams CA. Reproducibility of maximal cardiopulmonary exercise testing for young cystic fibrosis patients. J Cystic Fibros Available from:
29. Godfrey S. Exercise testing in children: applications in health and disease. W.B. Saunders; Philadelphia, PA: 1974
30. Bongers B, van Brussel M, Hulzebos HJ, Takken T. Paediatric exercise testing in clinics and classrooms: a comparative review of different assessments. OA Epidemiology 2013;1(2):14
31. Barker AR, Williams CA, Jones AM, et al. Establishing maximal oxygen uptake in young people during a ramp cycle test to exhaustion. Br J Sports Med 2011;45(6): 498-503
32. Rowland TW. Does peak V?O2 reflect V?O2max in children?: evidence from supramaximal testing. Med Sci Sports Exerc 1993;25:689-93
33. Ruf K, Winkler B, Hebestreit A, et al. Risks associated with exercise testing and sports participation in cystic fibrosis. J Cyst Fibros 2010;9:339-45
34. Stringer WW. Cardiopulmonary exercise testing: current applications. Expert Rev Resp Med 2010;4(2):179-88
35. Porszasz J, Stringer WW, Casaburi R. Equipment, measurements and quality control in clinical exercise testing. In: Ward SA, Palange P, editors. Clinical Exercise Testing. European Respiratory Society Task Force Project; 2007. 1-21
36. Radtke T, Stevens D, Benden C, Williams CA. Clinical exercise testing in children and adolescents with Cystic fibrosis. Pediatr PhysTher 2009;21:275-81
37. Palange P, Ward SA, Carlsen K-H, et al. Recommendations on the use of exercise testing in clinical practice. Eur Respir J 2007;28:185-209
38. American College of Sports Medicine. ACSM's guidelines for exercise testing and prescription. Lippincott Williams & Wilkins; MD, USA: 2000
39. Albouaini K, Egred M, Alahmar A, Wright D. Cardiopulmonary exercise testing and its application. Heart 2007;93:1285-92
40. Elina R, Husain R, Lang C. Cardiopulmonary exercise testing: utility in research and patient care. JUMMEC 2003;8:9-22
41. Whipp BJ, Davis JA, Torres F, Wasserman K. A test to determine parameters of aerobic function during exercise. J Appl Physiol 1981;50:217-21
42. Sexauer WP, Chang HK, Fiel SB. Utility of the breathing reserve index at the anaerobic threshold in determining ventilatory-limited exercise in adults with cystic fibrosis. Chest 2003;124(4):1469-75
43. Akkerman M, van Brussel M, Hulzebos HJ, et al. The oxygen uptake efficiency slope: what do we know? J Cardiopulm Rehabil Prev 2010;30(6):357-73
44. Bongers BC, Hulzebos EHJ, Arets BGM, Takken T. Validity of the oxygen uptake efficiency slope in children with cystic fibrosis and mild-to-moderate airflow obstruction. Pediatr Exerc Sci 2012;24: 129-41
45. Takken T, Terlingen HC, Helders PJM, et al. Cardiopulmonary fitness and muscle strength in patients with osteogensis imperfecta type I. J Pediatr 2004;145: 813-18
46. Wasserman K. The anaerobic threshold measurement to evaluate exercise performance. Am Rev Respir Dis 1984;126: S35-40
47. Casaburi R, Patessio A, Ioli F, et al. Reductions in lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 1991;143(1):9-18
48. Stevens D, Oades PJ, Armstrong N, Williams CA. Exercise metabolism during moderate-intensity exercise in children with cystic fibrosis following heavy-intensity exercise. Appl Physiol Nutr Metab 2011; 36(6):920-7
49. Rosenthal M, Narang I, Edwards L, Bush A. Non-invasive assessment of exercise performance in children with cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis: is there a CF specific muscle defect? Ped Pulmonol 2009;44:222-30
50. Kent L, O'Neill B, Davidson G, et al. Cycle ergometer tests in children with cystic fibrosis: reliability and feasibility. Pediatr Pulmonol 2012;47(12):1226-34
51. Bongers BC, Hulzebos HJ, van Brussel M, Takken T. Pediatric norms for cardiopulmonary exercise testing. Uitgeverij, BoxPress; Hoertogenbosch: 2012. p. 1-11
52. McKone EF, Barry SC, Fitzgerald MX, Gallagher CG. Reproducibility of maximal exercise ergometer testing in patients with cystic fibrosis. Chest 1999;116(2):363-8
53. Wells GD, Wilkes DL, Schneiderman JE, et al. Skeletal muscle metabolism in cystic fibrosis and primary ciliary dyskinesia. Pediatr Res 2011;69(1):40-5
54. Rosenthal M, Narang I, Edwards L, Bush A. Non-invasive assessment of exercise performance in children with cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis: is there a CF specific muscle defect? Ped Pulmonol 2009;44:222-30
55. Rand S, Prasad SA. Exercise as part of a cystic fibrosis therapeutic routine. Expert Rev Respir Med 2012;6(3):341-52
56. Hebestreit H, Hebestreit A, Trusen A, Hughson RL. Oxygen uptake kinetics are slowed in cystic fibrosis. Med Sci Sports Exerc 2005;37(1):10-17
57. Benson LN, Newth CJ, DeSouza M, et al. Radionucline assessment of right and left ventricular function during bicycle exercise in young patients with cystic fibrosis. Am Rev Respir Dis 1984;130:987-92
58. Saynor ZL, Barker AR, Oades P, Williams CA. Impaired aerobic function in young Cystic Fibrosis patients during ramp exercise. Med Sci Sports Exerc 2014. [Epub ahead of print]
59. Rossiter HB. Exercise: kinetic considerations for gas exchange. Compr Physiol 2011;1(1): 203-44
60. Armstrong N, Barker AR. Oxygen uptake kinetics in children and adolescents: a review. Pediatr Exerc Sci 2009;21(2): 130-47
61. Yoshida T, Yamamoto K, Udo M. Relationship between cardiac output and oxygen uptake at the onset of exercise. Eur J Appl Physiol Occup Physiol 1993;66(2): 155-60
62. Krustrup P, Jones AM, Wilkerson D, et al. Muscular and pulmonary O2 uptake kinetics during moderate- and high-intensity sub-maximal knee-extensor exercise in humans. J Physiol 2009;587(Pt 8):1843-56
63. Barker AR, Welsman JR, Fulford J, et al. Muscle phosphocreatine and pulmonary oxygen uptake kinetics in children at the onset and offset of moderate intensity exercise. Eur J Appl Physiol 2008;102(6): 727-38
64. Breese BC, Barker AR, Armstrong N, et al. The effect of baseline metabolic rate on pulmonary O(2) uptake kinetics during very heavy intensity exercise in boys and men. Respir Physiol Neurobiol 2012;180(2-3): 223-9
65. Koga S, Shiojiri T, Shibasaki M, et al. Kinetics of oxygen uptake during supine and upright heavy exercise. J Appl Physiol 1999;87(1):253-60
66. Poole DC, Ward SA, Gardner GW, Whipp BJ. Metabolic and respiratory profile of the upper limit for prolonged exercise in man. Ergonomics 1988;31(9):1265-79
67. Barker AR, Bond B, Toman C, et al. Critical power in adolescents: physiological bases and assessment using all-out exercise. Eur J Appl Physiol 2011;112(4):1359-70
68. Thin AG, Linnane SJ, McKone EF, et al. Use of the gas exchange threshold to noninvasively determine the lactate threshold in patients with cystic fibrosis. Chest 2002;121(6):1761-70
69. Braggion C, Cornacchia M, Miano A, et al. Exercise tolerance and effects of training in young patients with cystic fibrosis and mild airway obstruction. Pediatr Pulmonol 1989; 7(3):145-52
70. Kusenbach G, Wieching R, Barker M, et al. Effects of hyperoxia on oxygen uptake kinetics in cystic fibrosis patients as determined by pseudo-random binary sequence exercise. Eur J Appl Physiol Occup Physiol 1999;79(2):192-6
71. Whipp BJ, Ward SA, Lamarra N, et al. Parameters of ventilatory and gas exchange dynamics during exercise. J Appl Physiol 1982;52(6):1506-13
72. Burnley M, Doust JH, Jones AM. Time required for the restoration of normal heavy exercise VO2 kinetics following prior heavy exercise. J Appl Physiol 2006;101(5):1320-7
73. Gurd BJ, Scheurmann BW, Paterson DH, Kowalchuk JM. Prior heavy-intensity exercise speeds VO2 kinetics during moderate-intensity exercise in young adults. J Appl Physiol 2005;98(4):1371-8
74. Jones AM, Burnley M. Effect of exercise modality on VO2 kinetics, in Oxygen Uptake Kinetics in Sport, Exercise and Medicine. In: Jones AM, Poole DC, editors. Routledge; London and New York: 2005. p. 95-114
75. Almajed A, Lands LC. The evolution of exercise capacity and its limiting factors in cystic fibrosis. Paediatr Respir Rev 2012; 13(4):195-9
76. Poole DC, Barstow TJ, McDonough P, Jones AM. Control of oxygen uptake during exercise. Med Sci Sports Exerc 2008;40(3): 462-74
77. Tschakovsky ME, Hughson RL. Interaction of factors determining oxygen uptake at the onset of exercise. J Appl Physiol 1999;86(4): 1101-13
78. VO2 kinetics in different disease states, in oxygen uptake kinetics in sport, exercise and medicine. Poole DC, Kindig CA, Behnke BJet al. editors. Routledge, London and New York; 2005;p. 353-72
79. Lamhonwah AM, Bear CE, Huan LJ, et al. Cystic fibrosis transmembrane conductance regulator in human muscle: dysfunction causes abnormal metabolic recovery in exercise. Ann Neurol 2010;67(6):802-8
80. Pouliou E, Nanas S, Papamichalopoulos A, et al. Prolonged oxygen kinetics during early recovery from maximal exercise in adult patients with cystic fibrosis. Chest 2001; 119(4):1073-8
81. Stevens D, Oades PJ, Armstrong N, Williams CA. Early oxygen uptake recovery following exercise testing in children with chronic chest diseases. Pediatr Pulmonol 2009;44(5):480-8
82. Bradley JM, Moran F. Physical training for cystic fibrosis. Cochrane Database Syst Rev 2008(1):CD002768
83. Sosa ES, Groeneveld IF, Gonzalez-Saiz L, et al. Intrahospital weight and aerobic training in children with Cystic Fibrosis: a randomized controlled trial. Med Sci Sports Exerc 2012;44(1):2-11
84. Kriemler S, Kieser S, Junge S, et al. Effect of supervised training on FEV1 in cystic fibrosis: a randomised control trial. J Cystic Fibrosis 2013;12:714-20
85. Moeller A, Stampfli SF, Rueckert B, et al. Effects of a short-term rehabilitation program on airway inflammation in children with cystic fibrosis. Pediatr Pulmonol 2010;45:541-51
86. Schneiderman-Walker J, Pollock SL, Corey M, et al. A randomised controlled trial of a 3-year home exercise program in cystic fibrosis. J Pediatr 2000;136(3):304-10
87. Dassios T, Katelari A, Doudounakis S, Dimitrou G. Aerobic exercise and respiratory muscle strength in patients with cystic fibrosis. Respir Med 2013;107:684-90
88. Houston BW, Mills N, Solis-Moya A. Inspiratory muscle training for cystic fibrosis. Cochrane Database Syst Rev 2013;11:CD006112
89. De Jong W, van Aalderen WMC, Kraan J, et al. Inspiratory muscle training in patients with cystic fibrosis. Respir Med 2001;35: 31-6
90. Sawyer EH, Clanton TL. Improved pulmonary function and exercise tolerance with inspiratory muscle conditioning in children with cystic fibrosis. Chest 1993; 104(5):1490-7
91. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol 2012; 590(5):1077-84
92. Gruber W, Orenstein DM, Braumann KM, Beneke R. Interval exercise training in cystic fibrosis - Effects on exercise capacity in severely affected adults. J Cystic Fibros 2014;13:86-91
93. Hulzebos HJ, Snieder H, van der Net J, et al. High-intensity interval training in an adolescent with cystic fibrosis: a physiological perspective. Physio. Theory Prac 2011;27(3):231-7
94. Ledger SJ, Owen E, Prasad SA, et al. A pilot outreach physiotherapy and dietetic quality improvement initiative reduces IV antibiotic requirements in children with moderate-severe cystic fibrosis. J Cystic Fibros 2013;12:766-72
95. Daniels TWV, Rogers GB, Stressmann FA, et al. Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis. J Cystic Fibros 2013;12:22-8
96. Pike SE, Prasad SA, Balfour-Lynn IM. Effect of intravenous antibiotics on exercise tolerance (3-Min Step Test) in cystic fibrosis. Pediatr Pulmonol 2001;32:38-43
97. Quittner AL, Buu A, Messer MA, et al. Development and validation of the Cystic Fibrosis Questionnaire in the United States: a health-related quality-of-life measure for cystic fibrosis. Chest 2005;128:2347-54
98. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. New Eng J Med 2011;365(18):1663-72
99. Hebestreit H, Sauer-Heilborn A, Fischer R, et al. Effects of Ivacaftor on severely ill patients with cystic fibrosis carrying a G551D mutation. J Cystic Fibros 2013;12: 599-603
100. Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of Ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013;187(11): 1219-25
101. Harrison MJ, Murphy DM, Plant BJ. Ivacaftor in a G551D homozygote with cystic fibrosis. New Eng J Med 2013;369: 1280-2