Skip to main content
Log in

A Systematic Review of Reference Values in Pediatric Cardiopulmonary Exercise Testing

Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Cardiopulmonary exercise testing (CPET) is used for the diagnosis and prognosis of cardiovascular and pulmonary conditions in children and adolescents. Several authors have published reference values for pediatric CPET, but evaluation of their validity is lacking. The aim of this study was to review pediatric CPET references values published between 1980 and 2014. We specifically assessed the adequacy of the normalization methods used to adjust for body size. Articles that proposed references values were reviewed. We abstracted information on exercise protocols, CPET measurements and normalization methods. We then evaluated the studies’ methodological quality and assessed them for potential biases. Thirty-four studies were included. We found important heterogeneity in the choice of exercise protocols and in the approach to adjustment for body size or other relevant confounding factors. Adjustment for body size was principally done using linear regression for age or weight. Assessment of potential biases (residual association, heteroscedasticity and departure from the normal distribution) was mentioned in only a minority of studies. Our study shows that contemporary pediatric reference values for CPET have been developed based on heterogeneous exercise protocols and variable normalization strategies. Furthermore, assessment of potential bias has been inconsistent and insufficiently described. High-quality reference values with adequate adjustment for confounding variables are needed in order to optimize CPET’s specificity and sensitivity to detect abnormal cardiopulmonary response to exercise.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akkerman M, van Brussel M, Bongers BC, Hulzebos EH, Helders PJ, Takken T (2010) Oxygen uptake efficiency slope in healthy children. Pediatr Exerc Sci 22(3):431–441

    PubMed  Google Scholar 

  2. Al-Hazzaa HM (2001) Development of maximal cardiorespiratory function in Saudi boys. A cross-sectional analysis. Saudi Med J 22(10):875–881

    CAS  PubMed  Google Scholar 

  3. Altman DG (1993) Construction of age-related reference centiles using absolute residuals. Stat Med 12(10):917–924

    Article  CAS  PubMed  Google Scholar 

  4. Andersen LB, Henckel P, Saltin B (1987) Maximal oxygen uptake in Danish adolescents 16–19 years of age. Eur J Appl Physiol Occup Physiol 56(1):74–82

    Article  CAS  PubMed  Google Scholar 

  5. Armstrong N, Welsman JR (2001) Peak oxygen uptake in relation to growth and maturation in 11- to 17-year-old humans. Eur J Appl Physiol 85(6):546–551

    Article  CAS  PubMed  Google Scholar 

  6. Armstrong N, Williams J, Balding J, Gentle P, Kirby B (1991) The peak oxygen uptake of British children with reference to age, sex and sexual maturity. Eur J Appl Physiol Occup Physiol 62(5):369–375

    Article  CAS  PubMed  Google Scholar 

  7. Armstrong N, Kirby BJ, McManus AM, Welsman JR (1995) Aerobic fitness of prepubescent children. Ann Hum Biol 22(5):427–441

    Article  CAS  PubMed  Google Scholar 

  8. Armstrong N, Kirby BJ, McManus AM, Welsman JR (1997) Prepubescents’ ventilatory responses to exercise with reference to sex and body size. Chest 112(6):1554–1560

    Article  CAS  PubMed  Google Scholar 

  9. ATS/ACCP Statement on cardiopulmonary exercise testing (2003). Am J Respir Crit Care Med 167(2):211–277. doi:10.1164/rccm.167.2.211167/2/211

  10. Buys R, Van De Bruaene A, De Meester P, Budts W, Vanhees L (2012) Predictors of mid-term event-free survival in adults with corrected tetralogy of Fallot. Acta Cardiol 67(4):415–421

    PubMed  Google Scholar 

  11. Chua TP, Ponikowski P, Harrington D, Anker SD, Webb-Peploe K, Clark AL, Poole-Wilson PA, Coats AJ (1997) Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol 29(7):1585–1590

    Article  CAS  PubMed  Google Scholar 

  12. Cooper DM, Weiler-Ravell D (1984) Gas exchange response to exercise in children. Am Rev Respir Dis 129(2 Pt 2):S47–S48

    Article  CAS  PubMed  Google Scholar 

  13. Cooper DM, Weiler-Ravell D, Whipp BJ, Wasserman K (1984) Growth-related changes in oxygen uptake and heart rate during progressive exercise in children. Pediatr Res 18(9):845–851. doi:10.1203/00006450-198409000-00008

    Article  CAS  PubMed  Google Scholar 

  14. Cooper DM, Weiler-Ravell D, Whipp BJ, Wasserman K (1984) Aerobic parameters of exercise as a function of body size during growth in children. J Appl Physiol Respir Environ Exerc Physiol 56(3):628–634

    CAS  PubMed  Google Scholar 

  15. Cooper DM, Kaplan MR, Baumgarten L, Weiler-Ravell D, Whipp BJ, Wasserman K (1987) Coupling of ventilation and CO2 production during exercise in children. Pediatr Res 21(6):568–572. doi:10.1203/00006450-198706000-00012

    Article  CAS  PubMed  Google Scholar 

  16. Dencker M, Thorsson O, Karlsson MK, Linden C, Svensson J, Wollmer P, Andersen LB (2006) Daily physical activity and its relation to aerobic fitness in children aged 8–11 years. Eur J Appl Physiol 96(5):587–592. doi:10.1007/s00421-005-0117-1

    Article  PubMed  Google Scholar 

  17. Diller GP, Dimopoulos K, Okonko D, Uebing A, Broberg CS, Babu-Narayan S, Bayne S, Poole-Wilson PA, Sutton R, Francis DP, Gatzoulis MA (2006) Heart rate response during exercise predicts survival in adults with congenital heart disease. J Am Coll Cardiol 48(6):1250–1256

    Article  PubMed  Google Scholar 

  18. Diller GP, Giardini A, Dimopoulos K, Gargiulo G, Muller J, Derrick G, Giannakoulas G, Khambadkone S, Lammers AE, Picchio FM, Gatzoulis MA, Hager A (2010) Predictors of morbidity and mortality in contemporary Fontan patients: results from a multicenter study including cardiopulmonary exercise testing in 321 patients. Eur Heart J 31(24):3073–3083. doi:10.1093/eurheartj/ehq356ehq356

    Article  PubMed  Google Scholar 

  19. Dubowy KO, Baden W, Bernitzki S, Peters B (2008) A practical and transferable new protocol for treadmill testing of children and adults. Cardiol Young 18(6):615–623. doi:10.1017/S1047951108003181S1047951108003181

    Article  PubMed  Google Scholar 

  20. Fernandes SM, Alexander ME, Graham DA, Khairy P, Clair M, Rodriguez E, Pearson DD, Landzberg MJ, Rhodes J (2011) Exercise testing identifies patients at increased risk for morbidity and mortality following Fontan surgery. Congenit Heart Dis 6(4):294–303. doi:10.1111/j.1747-0803.2011.00500.x

    Article  PubMed  Google Scholar 

  21. Flandrois R, Grandmontagne M, Mayet MH, Favier R, Frutoso J (1982) Maximal oxygen uptake in French children in relation to age, sex and physical training. J Physiol (Paris) 78(2):186–194

    CAS  Google Scholar 

  22. Francis DP, Shamim W, Davies LC, Piepoli MF, Ponikowski P, Anker SD, Coats AJ (2000) Cardiopulmonary exercise testing for prognosis in chronic heart failure: continuous and independent prognostic value from VE/VCO(2)slope and peak VO(2). Eur Heart J 21(2):154–161. doi:10.1053/euhj.1999.1863S0195668X99918638

    Article  CAS  PubMed  Google Scholar 

  23. Geithner CA, Thomis MA, Vanden Eynde B, Maes HH, Loos RJ, Peeters M, Claessens AL, Vlietinck R, Malina RM, Beunen GP (2004) Growth in peak aerobic power during adolescence. Med Sci Sports Exerc 36(9):1616–1624

    Article  PubMed  Google Scholar 

  24. Giardini A, Specchia S, Tacy TA, Coutsoumbas G, Gargiulo G, Donti A, Formigari R, Bonvicini M, Picchio FM (2007) Usefulness of cardiopulmonary exercise to predict long-term prognosis in adults with repaired tetralogy of Fallot. Am J Cardiol 99(10):1462–1467

    Article  PubMed  Google Scholar 

  25. Giardini A, Hager A, Lammers AE, Derrick G, Muller J, Diller GP, Dimopoulos K, Odendaal D, Gargiulo G, Picchio FM, Gatzoulis MA (2009) Ventilatory efficiency and aerobic capacity predict event-free survival in adults with atrial repair for complete transposition of the great arteries. J Am Coll Cardiol 53(17):1548–1555. doi:10.1016/j.jacc.2009.02.005S0735-1097(09)00458-6

    Article  PubMed  Google Scholar 

  26. Giardini A, Odendaal D, Khambadkone S, Derrick G (2011) Physiologic decrease of ventilatory response to exercise in the second decade of life in healthy children. Am Heart J 161(6):1214–1219. doi:10.1016/j.ahj.2011.03.008S0002-8703(11)00189-X

    Article  PubMed  Google Scholar 

  27. Graves LE, Batterham AM, Foweather L, McWhannell N, Hopkins ND, Boddy LM, Gobbi R, Stratton G (2013) Scaling of peak oxygen uptake in children: a comparison of three body size index models. Med Sci Sports Exerc 45(12):2341–2345. doi:10.1249/MSS.0b013e31829bfa79

    Article  CAS  PubMed  Google Scholar 

  28. Gulmans VA, de Meer K, Binkhorst RA, Helders PJ, Saris WH (1997) Reference values for maximum work capacity in relation to body composition in healthy Dutch children. Eur Respir J 10(1):94–97

    CAS  PubMed  Google Scholar 

  29. Gursel Y, Sonel B, Gok H, Yalcin P (2004) The peak oxygen uptake of healthy Turkish children with reference to age and sex: a pilot study. Turk J Pediatr 46(1):38–43

    PubMed  Google Scholar 

  30. Hansen JE, Sue DY, Wasserman K (1984) Predicted values for clinical exercise testing. Am Rev Respir Dis 129(2 Pt 2):S49–S55

    Article  CAS  PubMed  Google Scholar 

  31. Held M, Grun M, Holl R, Hubner G, Kaiser R, Karl S, Kolb M, Schafers HJ, Wilkens H, Jany B (2014) Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary hypertension in patients with normal echocardiography. Respiration 379–387. doi:10.1159/000358565

  32. Ingle L, Sloan R, Carroll S, Goode K, Cleland JG, Clark AL (2011) Prognostic significance of different measures of the ventilation-carbon dioxide relation in patients with suspected heart failure. Eur J Heart Fail 13(5):537–542. doi:10.1093/eurjhf/hfq238hfq238

    Article  CAS  PubMed  Google Scholar 

  33. Jaussaud J, Douard H (2011) Usefulness of the lowest VE/VCO2 ratio measured during exercise in heart failure. Eur J Heart Fail 13(7):809. doi:10.1093/eurjhf/hfr065hfr065

    Article  PubMed  Google Scholar 

  34. Jones NL, Summers E, Killian KJ (1989) Influence of age and stature on exercise capacity during incremental cycle ergometry in men and women. Am Rev Respir Dis 140(5):1373–1380. doi:10.1164/ajrccm/140.5.1373

    Article  CAS  PubMed  Google Scholar 

  35. Kemper HC, Verschuur R (1981) Maximal aerobic power in 13- and 14-year-old teenagers in relation to biologic age. Int J Sports Med 2(2):97–100. doi:10.1055/s-2008-1034590

    Article  CAS  PubMed  Google Scholar 

  36. Loftin M, Sothern M, Trosclair L, O’Hanlon A, Miller J, Udall J (2001) Scaling VO(2) peak in obese and non-obese girls. Obes Res 9(5):290–296. doi:10.1038/oby.2001.36

    Article  CAS  PubMed  Google Scholar 

  37. Mandadzhieva S, Marinov B, Kostianev S, Turnovska T (2005) Anthropometric and cardiopulmonary parameters in Bulgarian and Romany children: cross-sectional study. Croat Med J 46(2):294–301

    PubMed  Google Scholar 

  38. Marinov B, Kostianev S, Turnovska T (2000) Ventilatory response to exercise and rating of perceived exertion in two pediatric age groups. Acta Physiol Pharmacol Bulg 25(3–4):93–98

    CAS  PubMed  Google Scholar 

  39. Marinov B, Mandadzhieva S, Kostianev S (2007) Oxygen-uptake efficiency slope in healthy 7- to 18-year-old children. Pediatr Exerc Sci 19(2):159–170

    PubMed  Google Scholar 

  40. Mawad W, Drolet C, Dahdah N, Dallaire F (2013) A review and critique of the statistical methods used to generate reference values in pediatric echocardiography. J Am Soc Echocardiogr 26(1):29–37. doi:10.1016/j.echo.2012.09.021S0894-7317(12)00764-X

    Article  PubMed  Google Scholar 

  41. McManus AM, Chung Yung T, Leung MP (2004) Peak oxygen uptake in relation to age, sex, and maturation in Hong Kong Chinese children. Am J Hum Biol 16(5):602–605. doi:10.1002/ajhb.20061

    Article  PubMed  Google Scholar 

  42. McNarry MA, Welsman JR (1985) Jones AM (2011) Influence of training and maturity status on the cardiopulmonary responses to ramp incremental cycle and upper body exercise in girls. J Appl Physiol 110(2):375–381. doi:10.1152/japplphysiol.00988.2010

    Article  Google Scholar 

  43. Mercier J, Varray A, Ramonatxo M, Mercier B, Prefaut C (1991) Influence of anthropometric characteristics on changes in maximal exercise ventilation and breathing pattern during growth in boys. Eur J Appl Physiol Occup Physiol 63(3–4):235–241

    Article  CAS  PubMed  Google Scholar 

  44. Nagano Y, Baba R, Kuraishi K, Yasuda T, Ikoma M, Nishibata K, Yokota M, Nagashima M (1998) Ventilatory control during exercise in normal children. Pediatr Res 43(5):704–707. doi:10.1203/00006450-199805000-00021

    Article  CAS  PubMed  Google Scholar 

  45. Nes BM, Osthus IB, Welde B, Aspenes ST, Wisloff U (2013) Peak oxygen uptake and physical activity in 13- to 18-year-olds: the Young-HUNT study. Med Sci Sports Exerc 45(2):304–313. doi:10.1249/MSS.0b013e318271ae4d

    Article  PubMed  Google Scholar 

  46. Nevill AM, Holder RL, Baxter-Jones A, Round JM, Jones DA (1998) Modeling developmental changes in strength and aerobic power in children. J Appl Physiol 84(3):963–970

    CAS  PubMed  Google Scholar 

  47. Nevill AM, Bate S, Holder RL (2005) Modeling physiological and anthropometric variables known to vary with body size and other confounding variables. Am J Phys Anthropol Suppl 41:141–153. doi:10.1002/ajpa.20356

    Article  Google Scholar 

  48. Paap D, Takken T (2014) Reference values for cardiopulmonary exercise testing in healthy adults: a systematic review. Expert Rev Cardiovasc Ther 12(12):1439–1453. doi:10.1586/14779072.2014.985657

    Article  CAS  PubMed  Google Scholar 

  49. Paridon SM, Alpert BS, Boas SR, Cabrera ME, Caldarera LL, Daniels SR, Kimball TR, Knilans TK, Nixon PA, Rhodes J, Yetman AT (2006) Clinical stress testing in the pediatric age group: a statement from the American Heart Association Council on Cardiovascular Disease in the Young, Committee on Atherosclerosis, Hypertension, and Obesity in Youth. Circulation 113(15):1905–1920

    Article  PubMed  Google Scholar 

  50. Ponikowski P, Francis DP, Piepoli MF, Davies LC, Chua TP, Davos CH, Florea V, Banasiak W, Poole-Wilson PA, Coats AJ, Anker SD (2001) Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation 103(7):967–972

    Article  CAS  PubMed  Google Scholar 

  51. Prioux J, Ramonatxo M, Mercier J, Granier P, Mercier B, Prefaut C (1997) Changes in maximal exercise ventilation and breathing pattern in boys during growth: a mixed cross-sectional longitudinal study. Acta Physiol Scand 161(4):447–458. doi:10.1046/j.1365-201X.1997.00245.x

    Article  CAS  PubMed  Google Scholar 

  52. Reybrouck T, Weymans M, Stijns H, Knops J, van der Hauwaert L (1985) Ventilatory anaerobic threshold in healthy children. Age and sex differences. Eur J Appl Physiol Occup Physiol 54(3):278–284

    Article  CAS  PubMed  Google Scholar 

  53. Rodrigues AN, Perez AJ, Carletti L, Bissoli NS, Abreu GR (2006) Maximum oxygen uptake in adolescents as measured by cardiopulmonary exercise testing: a classification proposal. J Pediatr (Rio J) 82(6):426–430. doi:10.2223/JPED.1533

    Google Scholar 

  54. Rogowski MP, Guilkey JP, Stephens BR, Cole AS, Mahon AD (2012) The influence of maturation on the oxygen uptake efficiency slope. Pediatr Exerc Sci 24(3):347–356

    PubMed  Google Scholar 

  55. Rosenthal M, Bush A (2000) Ventilatory variables in normal children during rest and exercise. Eur Respir J 16(6):1075–1083

    Article  CAS  PubMed  Google Scholar 

  56. Rowland TW (1991) “Normalizing” maximal oxygen uptake or the search for the holy grail. Pediatric Exerc Sci 3:85–102

    Google Scholar 

  57. Royston P (1991) Constructing time-specific reference ranges. Stat Med 10(5):675–690

    Article  CAS  PubMed  Google Scholar 

  58. Royston P, Wright EM (2000) Goodness-of-fit statistics for age-specific reference intervals. Stat Med 19(21):2943–2962. doi:10.1002/1097-0258(20001115)19:21<2943:AID-SIM559>3.0.CO;2-5

    Article  CAS  PubMed  Google Scholar 

  59. Solberg HE (2004) The IFCC recommendation on estimation of reference intervals. The RefVal program. Clin Chem Lab Med 42(7):710–714. doi:10.1515/CCLM.2004.121

    Article  CAS  PubMed  Google Scholar 

  60. Sue DY, Hansen JE (1984) Normal values in adults during exercise testing. Clin Chest Med 5(1):89–98

    CAS  PubMed  Google Scholar 

  61. Ten Harkel AD, Takken T, Van Osch-Gevers M, Helbing WA (2011) Normal values for cardiopulmonary exercise testing in children. Eur J Cardiovasc Prev Rehabil 18(1):48–54. doi:10.1097/HJR.0b013e32833cca4d

    PubMed  Google Scholar 

  62. Washington RL, van Gundy JC, Cohen C, Sondheimer HM, Wolfe RR (1988) Normal aerobic and anaerobic exercise data for North American school-age children. J Pediatr 112(2):223–233

    Article  CAS  PubMed  Google Scholar 

  63. Wasserman KHJ, Sue DY, Stringer WW, Sietsema KE, Sun X-G, Whipp BJ (eds) (2012) Principles of exercise testing and interpretation: including pathophysiology and clinical applications. Lippincott Williams and Wilkins, Wolters Kluwer Health, Philadelphia

    Google Scholar 

  64. Wasserman KHJ, Sue DY, Stringer WW, Sietsema KE, Sun X-G, Whipp BJ (eds) (2012) Clinical exercise testing, in principles of exercise testing and interpretation: including pathophysiology and clinical. Wolters Kluwer Health, Philadephia

  65. Wasserman KHJ, Sue DY, Stringer WW, Sietsema KE, Sun X-G, Whipp BJ (eds) (2012) Normal values, in principles of exercise testing and interpretation: including pathophysiology and clinical applications. Wolters Kluwer Health, Philadelphia

    Google Scholar 

  66. Welsman JR, Armstrong N, Nevill AM, Winter EM, Kirby BJ (1996) Scaling peak VO2 for differences in body size. Med Sci Sports Exerc 28(2):259–265

    Article  CAS  PubMed  Google Scholar 

  67. Wensel R, Opitz CF, Anker SD, Winkler J, Hoffken G, Kleber FX, Sharma R, Hummel M, Hetzer R, Ewert R (2002) Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation 106(3):319–324

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frederic Dallaire.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Blais, S., Berbari, J., Counil, FP. et al. A Systematic Review of Reference Values in Pediatric Cardiopulmonary Exercise Testing. Pediatr Cardiol 36, 1553–1564 (2015). https://doi.org/10.1007/s00246-015-1205-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-015-1205-6

Keywords

Navigation