Aerobic fitness in children and young adults with primary ciliary dyskinesia

Astrid Madsen, Kent Green, Frederik Buchvald, Birgitte Hanel, Kim Gjerum Nielsen, Astrid Madsen, Kent Green, Frederik Buchvald, Birgitte Hanel, Kim Gjerum Nielsen

Abstract

Background: Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO2peak) in a large well-characterized cohort of PCD patients, and explored whether VO2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level.

Methods: VO2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N2 MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference.

Results: Forty-four PCD patients aged 6-29 years exhibited reduced VO2peak compared to healthy controls (P<0.001) and the national reference. VO2peak was abnormal (z-score <-1.96) in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N2 MBW were significantly abnormal, but VO2peak only correlated with FEV1 and DLCO/VA. VO2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001), exhibited by 39% of PCD patients.

Conclusion: One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle-related diseases.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow chart showing the inclusion…
Figure 1. Flow chart showing the inclusion and investigation process.
Figure 2. VO 2peak z-scores in 44…
Figure 2. VO2peak z-scores in 44 Danish PCD patients and 33 healthy control subjects according to age distribution.
Solid line indicates a z-score of 0, and dashed lines indicate z-scores ±1.96.
Figure 3. VO 2peak in PCD patients…
Figure 3. VO2peak in PCD patients with normal FEV1 and reduced FEV1 (<−1.96 z-score) compared to healthy subjects.
Dots are single participants. Red squares are median values with error bars of 95% CI.

References

    1. (1997) Clinical exercise testing with reference to lung diseases: indications, standardization and interpretation strategies. ERS Task Force on Standardization of Clinical Exercise Testing. European Respiratory Society. Eur Respir J 10: 2662–2689.
    1. Blair SN, Kohl HW III, Paffenbarger RS Jr, Clark DG, Cooper KH, et al. (1989) Physical fitness and all-cause mortality. A prospective study of healthy men and women. JAMA 262: 2395–2401.
    1. Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF (1992) The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med 327: 1785–1788.
    1. Urquhart DS (2011) Exercise testing in cystic fibrosis: why (and how)? J R Soc Med 104 Suppl 1S6–14.
    1. Barbato A, Frischer T, Kuehni CE, Snijders D, Azevedo I, et al. (2009) Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur Respir J 34: 1264–1276.
    1. Bush A, Chodhari R, Collins N, Copeland F, Hall P, et al. (2007) Primary ciliary dyskinesia: current state of the art. Arch Dis Child 92: 1136–1140.
    1. McManus IC, Mitchison HM, Chung EM, Stubbings GF, Martin N (2003) Primary ciliary dyskinesia (Siewert's/Kartagener's syndrome): respiratory symptoms and psycho-social impact. BMC Pulm Med 3: 4–16.
    1. Pifferi M, Bush A, Di CM, Pradal U, Ragazzo V, et al. (2010) Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia. Eur Respir J 35: 787–794.
    1. Brown DE, Pittman JE, Leigh MW, Fordham L, Davis SD (2008) Early lung disease in young children with primary ciliary dyskinesia. Pediatr Pulmonol 43: 514–516.
    1. Marthin JK, Petersen N, Skovgaard LT, Nielsen KG (2010) Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med 181: 1262–1268.
    1. Green K, Buchvald FF, Marthin JK, Hanel B, Gustafsson PM, et al. (2012) Ventilation inhomogeneity in children with primary ciliary dyskinesia. Thorax 67: 49–53.
    1. Valerio G, Giallauria F, Montella S, Vaino N, Vigorito C, et al. (2012) Cardiopulmonary assessment in primary ciliary dyskinesia. Eur J Clin Invest 42: 617–622.
    1. Wells GD, Wilkes DL, Schneiderman JE, Rayner T, Elmi M, et al. (2011) Skeletal muscle metabolism in cystic fibrosis and primary ciliary dyskinesia. Pediatr Res 69: 40–45.
    1. Marthin JK, Nielsen KG (2011) Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia. Eur Respir J 37: 559–565.
    1. Godfrey S (1970) Physiological response to exercise in children with lung or heart disease. Arch Dis Child 45: 534–538.
    1. Milani RV, Lavie CJ, Mehra MR, Ventura HO (2006) Understanding the basics of cardiopulmonary exercise testing. Mayo Clin Proc 81: 1603–1611.
    1. Mahon AD, Marjerrison AD, Lee JD, Woodruff ME, Hanna LE (2010) Evaluating the prediction of maximal heart rate in children and adolescents. Res Q Exerc Sport 81: 466–471.
    1. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 167: 211–277.
    1. Andersen LB, Haraldsdottir J (1995) Coronary heart disease risk factors, physical activity, and fitness in young Danes. Med Sci Sports Exerc 27: 158–163.
    1. Pedersen BK, Andersen LB (2011) Danish Health and Medicines Authority: Physical activity in children and adolescence. Available: Haandbog.pdf. Accessed 8 February 2013.
    1. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. (2005) Standardisation of spirometry. Eur Respir J 26: 319–338.
    1. MacIntyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, et al. (2005) Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 26: 720–735.
    1. Stocks J, Quanjer PH (1995) Reference values for residual volume, functional residual capacity and total lung capacity. ATS Workshop on Lung Volume Measurements. Official Statement of The European Respiratory Society. Eur Respir J 8: 492–506.
    1. Stanojevic S, Wade A, Stocks J, Hankinson J, Coates AL, et al. (2008) Reference ranges for spirometry across all ages: a new approach. Am J Respir Crit Care Med 177: 253–260.
    1. Koopman M, Zanen P, Kruitwagen CL, van der Ent CK, Arets HG (2011) Reference values for paediatric pulmonary function testing: The Utrecht dataset. Respir Med 105: 15–23.
    1. Zapletal A, Paul T, Samanek M (1977) Significance of contemporary methods of lung function testing for the detection of airway obstruction in children and adolescents (author's transl). Z Erkr Atmungsorgane 149: 343–371.
    1. Kirkby J, Stanojevic S, Welsh L, Lum S, Badier M, et al. (2010) Reference equations for specific airway resistance in children: the Asthma UK initiative. Eur Respir J 36: 622–629.
    1. Cotes JE, Chinn DJ, Quanjer PH, Roca J, Yernault JC (1993) Standardization of the measurement of transfer factor (diffusing capacity). Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 16: 41–52.
    1. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, et al... (1993) Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 16: 5–40.
    1. Robinson PD, Goldman MD, Gustafsson PM (2009) Inert gas washout: theoretical background and clinical utility in respiratory disease. Respiration 78: 339–355.
    1. Houltz B, Green K, Lindblad A, Singer F, Robinson P, et al... (2012) Tidal N2 washout ventilation inhomogeneity in a reference population aged 7–70 years (Abstract B3797). Eur Respir J Suppl .
    1. Jones PW, Quirk FH, Baveystock CM (1991) The St George's Respiratory Questionnaire. Respir Med 85 Suppl B: 25–31.
    1. Henry B, Aussage P, Grosskopf C, Goehrs JM (2003) Development of the Cystic Fibrosis Questionnaire (CFQ) for assessing quality of life in pediatric and adult patients. Qual Life Res 12: 63–76.
    1. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP (2009) Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol 34: 447–454.
    1. Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30: 473–483.
    1. Pianosi P, Leblanc J, Almudevar A (2005) Relationship between FEV1 and peak oxygen uptake in children with cystic fibrosis. Pediatr Pulmonol 40: 324–329.
    1. Cropp GJ, Pullano TP, Cerny FJ, Nathanson IT (1982) Exercise tolerance and cardiorespiratory adjustments at peak work capacity in cystic fibrosis. Am Rev Respir Dis 126: 211–216.
    1. Karila C, de BJ, Waernessyckle S, Benoist MR, Scheinmann P (2001) Cardiopulmonary exercise testing in children: an individualized protocol for workload increase. Chest 120: 81–87.
    1. 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: 74–82.
    1. Bouchard C, Dionne FT, Simoneau JA, Boulay MR (1992) Genetics of aerobic and anaerobic performances. Exerc Sport Sci Rev 20: 27–58.
    1. Wasserman K, Hansen JE, Sue DY, and Whipp BJ (1987) Principles of Exercise Testing and Interpretation. Philadelphia, Lea and febiger.
    1. Gulmans VA, de MK, 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: 94–97.
    1. Ellerman A, Bisgaard H (1997) Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. Eur Respir J 10: 2376–2379.
    1. Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, et al. (2004) Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med 169: 459–467.
    1. Pifferi M, Bush A, Pioggia G, Caramella D, Tartarisco G, et al. (2012) Evaluation of pulmonary disease using static lung volumes in primary ciliary dyskinesia. Thorax 67: 993–999.
    1. Hellinckx J, Demedts M, De BK (1998) Primary ciliary dyskinesia: evolution of pulmonary function. Eur J Pediatr 157: 422–426.
    1. Fitting JW (2004) Transfer factor for carbon monoxide: a glance behind the scene. Swiss Med Wkly 134: 413–418.
    1. Bassett DR Jr, Howley ET (2000) Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sports Exerc 32: 70–84.
    1. Guazzi M, Reina G, Tumminello G, Guazzi MD (2004) Improvement of alveolar-capillary membrane diffusing capacity with exercise training in chronic heart failure. J Appl Physiol 97: 1866–1873.
    1. de JW, Kaptein AA, van der Schans CP, Mannes GP, van Aalderen WM, et al. (1997) Quality of life in patients with cystic fibrosis. Pediatr Pulmonol 23: 95–100.
    1. Andersen LB, Froberg K, Kristensen PL, Moller NC, Resaland GK, et al. (2010) Secular trends in physical fitness in Danish adolescents. Scand J Med Sci Sports 20: 757–763.
    1. Shephard RJ (2003) Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med 37: 197–206.
    1. Bestcilia (2013) Better Experimental Screening and Treatment for Primary Ciliary Dyskinesia. Available at:
    1. Rowland TW (1994) Effect of prolonged inactivity on aerobic fitness of children. J Sports Med Phys Fitness 34: 147–155.
    1. Resaland GK, Andersen LB, Mamen A, Anderssen SA (2011) Effects of a 2-year school-based daily physical activity intervention on cardiorespiratory fitness: the Sogndal school-intervention study. Scand J Med Sci Sports 21: 302–309.
    1. Anderssen SA, Cooper AR, Riddoch C, Sardinha LB, Harro M, et al. (2007) Low cardiorespiratory fitness is a strong predictor for clustering of cardiovascular disease risk factors in children independent of country, age and sex. Eur J Cardiovasc Prev Rehabil 14: 526–531.
    1. Olbrich H, Schmidts M, Werner C, Onoufriadis A, Loges NT, et al. (2012) Recessive HYDIN Mutations Cause Primary Ciliary Dyskinesia without Randomization of Left-Right Body Asymmetry. Am J Hum Genet 91: 672–684.

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