Determinants of exercise capacity in cystic fibrosis patients with mild-to-moderate lung disease

Jean Pastré, Anne Prévotat, Catherine Tardif, Carole Langlois, Alain Duhamel, Benoit Wallaert, Jean Pastré, Anne Prévotat, Catherine Tardif, Carole Langlois, Alain Duhamel, Benoit Wallaert

Abstract

Background: Adult patients with cystic fibrosis (CF) frequently have reduced exercise tolerance, which is multifactorial but mainly due to bronchial obstruction. The aim of this retrospective analysis was to determine the mechanisms responsible for exercise intolerance in patients with mild-to-moderate or severe disease.

Methods: Cardiopulmonary exercise testing with blood gas analysis at peak exercise was performed in 102 patients aged 28 ± 11 years: 48 patients had severe lung disease (FEV1 < 50%, group 1) and 54 had mild-to-moderate lung disease (FEV1 ≥ 50%, group 2). VO2 peak was measured and correlated with clinical, biological, and functional parameters.

Results: VO2 peak for all patients was 25 ± 9 mL/kg/min (65 ± 21% of the predicted value) and was < 84% of predicted in 82% of patients (100% of group 1, 65% of group 2). VO2 peak was correlated with body mass index, C-reactive protein, FEV1, FVC, RV, DLCO, VE/VCO2 peak, VD/VT, PaO2, PaCO2, P(A-a)O2, and breathing reserve. In multivariate analysis, FEV1 and overall hyperventilation during exercise were independent determinants of exercise capacity (R(2) = 0.67). FEV1 was the major significant predictor of VO2 peak impairment in group 1, accounting for 31% of VO2 peak alteration, whereas excessive overall hyperventilation (reduced or absent breathing reserve and VE/VCO2) accounted for 41% of VO2 alteration in group 2.

Conclusion: Exercise limitation in adult patients with CF is largely dependent on FEV1 in patients with severe lung disease and on the magnitude of the ventilatory response to exercise in patients with mild-to-moderate lung disease.

Figures

Figure 1
Figure 1
Correlation between VO2 peak and FEV1, FVC, VE/CO2 peak, BR, P(A-a)O2 peak, and VD/VT peak in CF patients. VO2 peak, FEV1, FVC, and BR are expressed as percentage of predicted values. P(A-a)O2 peak is expressed as mm Hg.

References

    1. Marcotte JE, Grisdale RK, Levison H, Coates AL, Canny GJ. Multiple factors limit exercise capacity in cystic fibrosis. Pediatr Pulmonol. 1986;2:274–281. doi: 10.1002/ppul.1950020505.
    1. Boucher GP, Lands LC, Hay JA, Hornby L. Activity levels and the relationship to lung function and nutritional status in children with cystic fibrosis. Am J Phys Med Rehabil. 1997;76:311–315. doi: 10.1097/00002060-199707000-00010.
    1. Lands LC, Heigenhauser GJ, Jones NL. Analysis of factors limiting maximal exercise performance in cystic fibrosis. Clin Sci. 1992;83:391–397.
    1. Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med. 1992;327:1785–1788. doi: 10.1056/NEJM199212173272504.
    1. Moorcroft AJ, Dodd ME, Webb AK. Exercise testing and prognosis in adult cystic fibrosis. Thorax. 1997;52:291–293. doi: 10.1136/thx.52.3.291.
    1. Pianosi P, Leblanc J, Almudevar A. Peak oxygen uptake and mortality in children with cystic fibrosis. Thorax. 2005;60:50–54. doi: 10.1136/thx.2003.008102.
    1. Van de Weert-van Leeuwen PB, Slieker MG, Hulzebos HJ, Kruitwagen CLJJ, van der Ent CK, Arets HGM. Chronic infection and inflammation affect exercise capacity in cystic fibrosis. Eur Respir J. 2012;39:893–898. doi: 10.1183/09031936.00086211.
    1. Bilton D, Dodd ME, Abbot JV, Webb AK. The benefits of exercise combined with physiotherapy in the treatment of adults with cystic fibrosis. Respir Med. 1992;86:507–511. doi: 10.1016/S0954-6111(96)80012-6.
    1. Almajed A, Lands LC. The evolution of exercise capacity and its limiting factors in Cystic Fibrosis. Paediatr Respir Rev. 2012;13:195–199. doi: 10.1016/j.prrv.2012.01.001.
    1. Troosters T, Langer D, Vrijsen B, Segers J, Wouters K, Janssens W, Gosselink R, Decramer M, Dupont L. Skeletal muscle weakness, exercise tolerance and physical activity in adults with cystic fibrosis. Eur Respir J. 2009;33:99–106. doi: 10.1183/09031936.00091607.
    1. Selvadurai HC, Allen J, Sachinwalla T, Macauley J, Blimkie CJ, Van Asperen PP. Muscle function and resting energy expenditure in female athletes with cystic fibrosis. Am J Respir Crit Care Med. 2003;168:1476–1480. doi: 10.1164/rccm.200303-363OC.
    1. Cerny FJ, Pullano TP, Cropp GJ. Cardiorespiratory adaptations to exercise in cystic fibrosis. Am Rev Respir Dis. 1982;126:217–220.
    1. Shah AR, Gozal D, Keens TG. Determinants of aerobic and anaerobic exercise performance in cystic fibrosis. Am J Respir Crit Care Med. 1998;157:1145–1150. doi: 10.1164/ajrccm.157.4.9705023.
    1. Lebecque P, Lapierre JG, Lamarre A, Coates AL. Diffusion capacity and oxygen desaturation effects on exercise in patients with cystic fibrosis. Chest. 1987;91:693–697. doi: 10.1378/chest.91.5.693.
    1. Bradley S, Solin P, Wilson J, Johns D, Walters EH, Naughton MT. Hypoxemia and hypercapnia during exercise and sleep in patients with cystic fibrosis. Chest. 1999;116:647–654. doi: 10.1378/chest.116.3.647.
    1. McKone EF, Barry SC, Fitzgerald MX, Gallagher CG. Role of arterial hypoxemia and pulmonary mechanics in exercise limitation in adults with cystic fibrosis. J Appl Physiol. 2005;99:1012–1018. doi: 10.1152/japplphysiol.00475.2004.
    1. Marcus CL, Bader D, Stabile MW, Wang CI, Osher AB, Keens TG. Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease. Chest. 1992;101:52–57. doi: 10.1378/chest.101.1.52.
    1. ATS/ACCP. Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167:211–277.
    1. Stevens D, Oades PJ, Armstrong N, Williams CA. A survey of exercise testing and training in UK cystic fibrosis clinics. J Cyst Fibros. 2010;9:302–306. doi: 10.1016/j.jcf.2010.03.004.
    1. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of spirometry. Eur Respir J. 2005;26:319–338. doi: 10.1183/09031936.05.00034805.
    1. Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CPM, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26:720–735. doi: 10.1183/09031936.05.00034905.
    1. Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26:511–522. doi: 10.1183/09031936.05.00035005.
    1. Aguilaniu B, Richard R, Costes F, Bart F, Martinat Y, Stach B, Aguilaniu B, Richard R, Costes F, Bart F, Martinat Y, Stach B, Denjean A. Scientific Council of the French Lung Society. [Cardiopulmonary exercise testing] Rev Mal Respir. 2007;24:2S111–2S160.
    1. Wallaert B, Talleu C, Wemeau-Stervinou L, Duhamel A, Robin S, Aguilaniu B. Reduction of maximal oxygen uptake in sarcoidosis: relationship with disease severity. Respiration. 2011;82:501–508. doi: 10.1159/000330050.
    1. Sorbini CA, Grassi V, Solinas E, Muiesan G. Arterial oxygen tension in relation to age in healthy subjects. Respiration. 1968;25:3–13. doi: 10.1159/000192549.
    1. Hansen JE, Sue DY, Wasserman K. Predicted values for clinical exercise testing. Am Rev Respir Dis. 1984;129:S49–S55.
    1. Sauerbrei W. The Use of Resampling Methods to Simplify Regression Models in Medical Statistics. Journal of the Royal Statistical Society: Series C (Applied Statistics) 1999;48:313–329. doi: 10.1111/1467-9876.00155.
    1. Vaincre La Mucoviscidose. . 2011 Rapport annuel. 2012.
    1. Leroy S, Perez T, Neviere R, Aguilaniu B, Wallaert B. Determinants of dyspnea and alveolar hypoventilation during exercise in cystic fibrosis: impact of inspiratory muscle endurance. J Cyst Fibros. 2011;10:159–165. doi: 10.1016/j.jcf.2010.12.006.
    1. Godfrey S, Mearns M. Pulmonary function and response to exercise in cystic fibrosis. Arch Dis Child. 1971;46:144–151. doi: 10.1136/adc.46.246.144.
    1. Gulmans VA, de Meer K, Brackel HJ, Helders PJ. Maximal work capacity in relation to nutritional status in children with cystic fibrosis. Eur Respir J. 1997;10:2014–2017. doi: 10.1183/09031936.97.10092014.
    1. Nguyen S, Leroy S, Cracowski C, Perez T, Valette M, Neviere R, Aguilaniu B, Wallaert B. Prognostic value of clinical exercise testing in adult patients with cystic fibrosis. Rev Mal Respir. 2010;27:219–225. doi: 10.1016/j.rmr.2010.01.009.
    1. Van de Weert-van Leeuwen PB, Arets HGM, van der Ent CK, Beekman JM. Infection, inflammation and exercise in cystic fibrosis. Respir Res. 2013;14:32. doi: 10.1186/1465-9921-14-32.
    1. Van Heeckeren AM, Tscheikuna J, Walenga RW, Konstan MW, Davis PB, Erokwu B, Haxhiu MA, Ferkol TW. Effect of Pseudomonas infection on weight loss, lung mechanics, and cytokines in mice. Am J Respir Crit Care Med. 2000;161:271–279. doi: 10.1164/ajrccm.161.1.9903019.
    1. Klijn PHC, van der Net J, Kimpen JL, Helders PJM, van der Ent CK. Longitudinal determinants of peak aerobic performance in children with cystic fibrosis. Chest. 2003;124:2215–2219. doi: 10.1378/chest.124.6.2215.
    1. Tantisira KG, Systrom DM, Ginns LC. An elevated breathing reserve index at the lactate threshold is a predictor of mortality in patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med. 2002;165:1629–1633. doi: 10.1164/rccm.2105090.
    1. Medoff BD, Oelberg DA, Kanarek DJ, Systrom DM. Breathing reserve at the lactate threshold to differentiate a pulmonary mechanical from cardiovascular limit to exercise. Chest. 1998;113:913–918. doi: 10.1378/chest.113.4.913.
    1. McNicholl DM, Megarry J, McGarvey LP, Riley MS, Heaney LG. The utility of cardiopulmonary exercise testing in difficult asthma. Chest. 2011;139:1117–1123. doi: 10.1378/chest.10-2321.
    1. Dempsey JA. Challenges for future research in exercise physiology as applied to the respiratory system. Exerc Sport Sci Rev. 2006;34:92–98. doi: 10.1249/00003677-200607000-00002.
    1. Péronnet F, Aguilaniu B. Lactic acid buffering, nonmetabolic CO2 and exercise hyperventilation: a critical reappraisal. Respir Physiol Neurobiol. 2006;150:4–18. doi: 10.1016/j.resp.2005.04.005.
    1. Lewis DA, Sietsema KE, Casaburi R, Sue DY. Inaccuracy of noninvasive estimates of VD/VT in clinical exercise testing. Chest. 1994;106:1476–1480. doi: 10.1378/chest.106.5.1476.

Source: PubMed

3
Subscribe