Exercise intolerance is a key element in the pathophysiology and course of Chronic Obstructive Pulmonary Disease (COPD). As such, evaluating exercise tolerance has become an important part of the management of COPD. A wide variety of exercise-testing protocols is currently available, each protocol having its own strengths and weaknesses relative to their discriminative, methodological, and evaluative characteristics. This paper aims to review the responsiveness of several exercise-testing protocols used to evaluate the efficacy of pharmacological and nonpharmacological interventions to improve exercise tolerance in COPD. This will be done taking into account the minimally important difference, an important concept in the interpretation of the findings about responsiveness of exercise testing protocols. Among the currently available exercise-testing protocols (incremental, constant work rate, or self-paced), constant work rate exercise tests (cycle endurance test and endurance shuttle walking test) emerge as the most responsive ones for detecting and quantifying changes in exercise capacity after an intervention in COPD. 1. Introduction Chronic airflow limitation is the defining physiological feature of Chronic Obstructive Pulmonary Disease (COPD) whose main symptom is dyspnea. Exercise intolerance is another major consequence of COPD, leading to a sedentary life style and poor quality of life [1, 2]. In fact, exercise intolerance is central to the progression of the downward spiral of COPD [3]. Considering the key role of exercise intolerance in the pathophysiology and course of COPD, the evaluation of exercise tolerance should now be included in the assessment of this disease [4], especially for the evaluation of the response to pharmacological and nonpharmacological interventions [5–7]. Also, the heterogeneity in the mechanisms of exercise intolerance in COPD highlights the importance of comprehensive exercise testing, assessing all systems potentially involved [8]. Exercise testing is currently included in the follow-up of chronic diseases like COPD. Exercise testing can be used to document the severity of pulmonary disease, the functional impact of altered respiratory function and to better understand the physiopathological mechanisms involved in exercise intolerance; this refers to the discriminative characteristic of the test. Exercise testing can also be used to quantify the impact of an intervention to improve exercise tolerance [9, 10] or dyspnea [11, 12] and in the preoperative and pre rehabilitation assessments of patients, corresponding to
References
[1]
F. J. Martinez, G. Foster, J. L. Curtis et al., “Predictors of mortality in patients with emphysema and severe airflow obstruction,” American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 12, pp. 1326–1334, 2006.
[2]
T. Oga, K. Nishimura, M. Tsukino, S. Sato, and T. Hajiro, “Analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status,” American Journal of Respiratory and Critical Care Medicine, vol. 167, no. 4, pp. 544–549, 2003.
[3]
J. Reardon, R. Casaburi, M. Morgan, L. Nici, and C. Rochester, “Pulmonary rehabilitation for COPD,” Respiratory Medicine, vol. 99, no. 2, pp. S19–S27, 2005.
[4]
American Thoracic Society, “ATS/ACCP Statement on cardiopulmonary exercise testing,” American Journal of Respiratory and Critical Care Medicine, vol. 167, pp. 211–277, 2003.
[5]
S. Bernard, F. Whittom, P. Leblanc et al., “Aerobic and strength training in patients with chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 3, pp. 896–901, 1999.
[6]
J. J. W. Liesker, P. J. Wijkstra, N. H. T. Ten Hacken, G. H. Koéter, D. S. Postma, and H. A. M. Kerstjens, “A systematic review of the effects of bronchodilators on exercise capacity in patients with COPD,” Chest, vol. 121, no. 2, pp. 597–608, 2002.
[7]
V. Pepin, L. Laviolette, C. Brouillard et al., “Significance of changes in endurance shuttle walking performance,” Thorax, vol. 66, no. 2, pp. 115–120, 2011.
[8]
V. Pepin, D. Saey, L. Laviolette, and F. Maltais, “Exercise capacity in chronic obstructive pulmonary disease: mechanisms of limitation,” Journal of Chronic Obstructive Pulmonary Disease, vol. 4, no. 3, pp. 195–204, 2007.
[9]
B. Aguilaniu, “Impact of bronchodilator therapy on exercise tolerance in COPD,” International Journal of COPD, vol. 5, no. 1, pp. 57–71, 2010.
[10]
L. Laviolette, J. Bourbeau, S. Bernard et al., “Assessing the impact of pulmonary rehabilitation on functional status in COPD,” Thorax, vol. 63, no. 2, pp. 115–121, 2008.
[11]
American Thoracic Society, “Dyspnea. Mechanisms, assessment, and management: a consensus statement,” in American Journal of Respiratory and Critical Care Medicine, vol. 159, pp. 321–340, 1999.
[12]
H. Perrault, J. Baril, S. Henophy, A. Rycroft, J. Bourbeau, and F. Maltais, “Paced-walk and step tests to assess exertional dyspnea in COPD,” Journal of Chronic Obstructive Pulmonary Disease, vol. 6, no. 5, pp. 330–339, 2009.
[13]
R. Jaeschke, J. Singer, and G. H. Guyatt, “Measurement of health status: ascertaining the minimal clinically important difference,” Controlled Clinical Trials, vol. 10, no. 4, pp. 407–415, 1989.
[14]
B. Make, “How can we assess outcomes of clinical trials: The MCID Approach,” Journal of Chronic Obstructive Pulmonary Disease, vol. 4, no. 3, pp. 191–194, 2007.
[15]
G. R. Norman, J. A. Sloan, and K. W. Wyrwich, “Interpretation of changes in health-related quality of life the remarkable universality of half a standard deviation,” Medical Care, vol. 41, no. 5, pp. 582–592, 2003.
[16]
T. E. Dolmage, K. Hill, R. A. Evans, and R. S. Goldstein, “Has my patient responded? Interpreting clinical measurements such as the 6-minute-walk test,” in American Journal of Respiratory and Critical Care Medicine, vol. 184, pp. 642–646, 2011.
[17]
D. A. Redelmeier, A. M. Bayoumi, R. S. Goldstein, and G. H. Guyatt, “Interpreting small differences in functional status: the six minute walk test in chronic lung disease patients,” American Journal of Respiratory and Critical Care Medicine, vol. 155, no. 4, pp. 1278–1282, 1997.
[18]
P. O. Astrand, K. Rodahl, H. A. Dahl, and S. B. Stromme, Textbook of Work Physiology : Physiological Bases of Exercise, Human Kinetic, Champaign, Ill, USA, 4th edition, 2003.
[19]
Y. Lacasse, R. Goldstein, T. J. Lasserson, and S. Martin, “Pulmonary rehabilitation for chronic obstructive pulmonary disease,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD003793, 2006.
[20]
S. J. Butcher and R. L. Jones, “The impact of exercise training intensity on change in physiological function in patients with chronic obstructive pulmonary disease,” Sports Medicine, vol. 36, no. 4, pp. 307–325, 2006.
[21]
M. K. Beauchamp, M. Nonoyama, R. S. Goldstein et al., “Interval versus continuous training in individuals with chronic obstructive pulmonary disease- a systematic review,” Thorax, vol. 65, no. 2, pp. 157–164, 2010.
[22]
D. E. O'Donnell, T. Fluge, F. Gerken et al., “Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD,” European Respiratory Journal, vol. 23, no. 6, pp. 832–840, 2004.
[23]
T. Oga, K. Nishimura, M. Tsukino, T. Hajiro, A. Ikeda, and T. Izumi, “The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease: a comparison of three different exercise tests,” American Journal of Respiratory and Critical Care Medicine, vol. 161, no. 6, pp. 1897–1901, 2000.
[24]
J. J. W. Liesker, V. Van De Velde, M. Meysman et al., “Effects of formoterol (Oxis Turbuhaler) and ipratropium on exercise capacity in patients with COPD,” Respiratory Medicine, vol. 96, no. 8, pp. 559–566, 2002.
[25]
O. Akkoca Yildiz, Z. P. Onen, G. Demir, B. Eris Gulbay, S. Saryal, and G. Karabiyikoglu, “Is there any difference between effects of ipratropium bromide and formoterol on exercise capacity in moderate COPD patients?” Tuberkuloz ve Toraks, vol. 54, no. 2, pp. 105–113, 2006.
[26]
A. Ikeda, K. Nishimura, H. Koyama, N. Sugiura, and T. Izumi, “Oxitropium bromide improves exercise performance in patients with COPD,” Chest, vol. 106, no. 6, pp. 1740–1745, 1994.
[27]
A. Ikeda, K. Nishimura, H. Koyama, M. Tsukino, M. Mishima, and T. Izumi, “Dose response study of ipratropium bromide aerosol on maximum exercise performance in stable patients with chronic obstructive pulmonary disease,” Thorax, vol. 51, no. 1, pp. 48–53, 1996.
[28]
S. Jenkins, “Which is the best exercise test to assess therapeutic intervention in COPD?” Chronic Respiratory Disease, vol. 5, no. 1, pp. 3–5, 2008.
[29]
D. Hsia, R. Casaburi, A. Pradhan, E. Torres, and J. Porszasz, “Physiological responses to linear treadmill and cycle ergometer exercise in COPD,” European Respiratory Journal, vol. 34, no. 3, pp. 605–615, 2009.
[30]
R. S. Mathur, S. M. Revill, D. D. Vara, R. Walton, and M. D. L. Morgan, “Comparison of peak oxygen consumption during cycle and treadmill exercise in severe chronic obstructive pulmonary disease,” Thorax, vol. 50, no. 8, pp. 829–833, 1995.
[31]
T. L. Griffiths, M. L. Burr, I. A. Campbell et al., “Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial,” Lancet, vol. 355, no. 9201, pp. 362–368, 2000.
[32]
S. J. Singh, D. L. Smith, M. E. Hyland, and M. D. L. Morgan, “A short outpatient pulmonary rehabilitation programme: immediate and longer term effects on exercise performance and quality of life,” Respiratory Medicine, vol. 92, no. 9, pp. 1146–1154, 1998.
[33]
S. J. Deacon, E. E. Vincent, P. L. Greenhaff et al., “Randomized controlled trial of dietary creatine as an adjunct therapy to physical training in chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 3, pp. 233–239, 2008.
[34]
S. M. Revill, M. D. L. Morgan, S. J. Singh, J. Williams, and A. E. Hardman, “The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease,” Thorax, vol. 54, no. 3, pp. 213–222, 1999.
[35]
R. Aalbers, J. Ayres, V. Backer et al., “Formoterol in patients with chronic obstructive pulmonary disease: a randomized, controlled, 3-month trial,” European Respiratory Journal, vol. 19, no. 5, pp. 936–943, 2002.
[36]
M. Wadbo, C. G. L？fdahl, K. Larsson et al., “Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study,” European Respiratory Journal, vol. 20, no. 5, pp. 1138–1146, 2002.
[37]
T. Sukisaki, H. Senjyu, K. Oishi, N. Rikitomi, and K. Ariyoshi, “Single dose of inhaled procaterol has a prolonged effect on exercise performance of patients with COPD,” Physiotherapy Theory and Practice, vol. 24, no. 4, pp. 255–263, 2008.
[38]
R. A. Stockley, N. Chopra, and L. Rice, “Addition of salmeterol to existing treatment in patients with COPD: a 12 month study,” Thorax, vol. 61, no. 2, pp. 122–128, 2006.
[39]
C. Verkindre, F. Bart, B. Aguilaniu et al., “The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease,” Respiration, vol. 73, no. 4, pp. 420–427, 2006.
[40]
M. A. Puhan, D. Chandra, Z. Mosenifar et al., “The minimal important difference of exercise tests in severe COPD,” European Respiratory Journal, vol. 37, no. 4, pp. 784–790, 2011.
[41]
E. R. Sutherland and B. J. Make, “Maximum exercise as an outcome in COPD: minimal clinically important difference,” Journal of Chronic Obstructive Pulmonary Disease, vol. 2, no. 1, pp. 137–141, 2005.
[42]
S. J. Singh, P. W. Jones, R. Evans, and M. D. L. Morgan, “Minimum clinically important improvement for the incremental shuttle walking test,” Thorax, vol. 63, no. 9, pp. 775–777, 2008.
[43]
R. Casaburi, “Factors determining constant work rate exercise tolerance in COPD and their role in dictating the minimal clinically important difference in response to interventions,” Journal of Chronic Obstructive Pulmonary Disease, vol. 2, no. 1, pp. 131–136, 2005.
[44]
M. A. Puhan, M. J. Mador, U. Held, R. Goldstein, G. H. Guyatt, and H. J. Schünemann, “Interpretation of treatment changes in 6-minute walk distance in patients with COPD,” European Respiratory Journal, vol. 32, no. 3, pp. 637–643, 2008.
[45]
C. Cambach, R. V. M. Chadwick-Straver, R. C. Wagenaar, A. R. J. Van Keimpema, and H. C. G. Kemper, “The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial,” European Respiratory Journal, vol. 10, pp. 104–113, 1997.
[46]
K. C. Ong, W. F. Chong, C. Soh, and A. Earnest, “Comparison of different exercise tests in assessing outcomes of pulmonary rehabilitation,” Respiratory Care, vol. 49, no. 12, pp. 1498–1503, 2004.
[47]
D. E. O'Donnell, M. McGuire, L. Samis, and K. A. Webb, “General exercise training improves ventilatory and peripheral muscle strength and endurance in chronic airflow limitation,” American Journal of Respiratory and Critical Care Medicine, vol. 157, no. 5, pp. 1489–1497, 1998.
[48]
J. Porszasz, M. Emtner, S. Goto, A. Somfay, B. J. Whipp, and R. Casaburi, “Exercise training decreases ventilatory requirements and exercise-induced hyperinflation at submaximal intensities in patients with COPD,” Chest, vol. 128, no. 4, pp. 2025–2034, 2005.
[49]
D. E. O'Donnell, N. Voduc, M. Fitzpatrick, and K. A. Webb, “Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease,” European Respiratory Journal, vol. 24, no. 1, pp. 86–94, 2004.
[50]
F. Maltais, A. Hamilton, D. Marciniuk et al., “Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD,” Chest, vol. 128, no. 3, pp. 1168–1178, 2005.
[51]
D. E. O'Donnell, F. Sciurba, B. Celli et al., “Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD,” Chest, vol. 130, no. 3, pp. 647–656, 2006.
[52]
F. Maltais, B. Celli, R. Casaburi et al., “Aclidinium bromide improves exercise endurance and lung hyperinflation in patients with moderate to severe COPD,” Respiratory Medicine, vol. 105, no. 4, pp. 580–587, 2011.
[53]
D. E. O'Donnell, R. Casaburi, W. Vincken et al., “Effect of indacaterol on exercise endurance and lung hyperinflation in COPD,” Respiratory Medicine, vol. 105, no. 7, pp. 1030–1036, 2011.
[54]
T. Oga, K. Nishimura, M. Tsukino, S. Sato, T. Hajiro, and M. Mishima, “A comparison of the effects of salbutamol and ipratropium bromide on exercise endurance in patients with COPD,” Chest, vol. 123, no. 6, pp. 1810–1816, 2003.
[55]
J. A. Neder, J. P. Fuld, T. Overend et al., “Effects of formoterol on exercise tolerance in severely disabled patients with COPD,” Respiratory Medicine, vol. 101, no. 10, pp. 2056–2064, 2007.
[56]
J. Travers, P. Laveneziana, K. A. Webb, S. Kesten, and D. E. O'Donnell, “Effect of tiotropium bromide on the cardiovascular response to exercise in COPD,” Respiratory Medicine, vol. 101, no. 9, pp. 2017–2024, 2007.
[57]
W. D. C. Man, N. Mustfa, D. Nikoletou et al., “Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD,” Thorax, vol. 59, no. 6, pp. 471–476, 2004.
[58]
A. Aliverti, K. Rodger, R. L. Dellacà et al., “Effect of salbutamol on lung function and chest wall volumes at rest and during exercise in COPD,” Thorax, vol. 60, no. 11, pp. 916–924, 2005.
[59]
M. M. Peters, K. A. Webb, and D. E. O'Donnell, “Combined physiological effects of bronchodilators and hyperoxia on exertional dyspnoea in normoxic COPD,” Thorax, vol. 61, no. 7, pp. 559–567, 2006.
[60]
B. J. Whipp and S. A. Ward, “Quantifying intervention-related improvements in exercise tolerance,” European Respiratory Journal, vol. 33, no. 6, pp. 1254–1260, 2009.
[61]
T. E. Dolmage, R. A. Evans, K. Hill, M. Blouin, D. Brooks, and R. S. Goldstein, “The effect of pulmonary rehabilitation on critical walk speed in patients with COPD: a comparison with self-paced walks,” Chest, vol. 141, pp. 413–419, 2012.
[62]
T. Eaton, P. Young, K. Nicol, and J. Kolbe, “The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients,” Chronic Respiratory Disease, vol. 3, no. 1, pp. 3–9, 2006.
[63]
C. Brouillard, V. Pepin, J. Milot, Y. Lacasse, and F. Maltais, “Endurance shuttle walking test: responsiveness to salmeterol in COPD,” European Respiratory Journal, vol. 31, no. 3, pp. 579–584, 2008.
[64]
M. E. Bédard, C. Brouillard, V. Pepin et al., “Tiotropium improves walking endurance in COPD,” European Respiratory Journal, vol. 39, pp. 265–271, 2012.
[65]
F. Pitta, T. Troosters, M. A. Spruit, V. S. Probst, M. Decramer, and R. Gosselink, “Characteristics of physical activities in daily life in chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 9, pp. 972–977, 2005.
[66]
C. B. Cooper, M. Abrazado, D. Legg, and S. Kesten, “Development and implementation of treadmill exercise testing protocols in COPD,” International Journal of Chronic Obstructive Pulmonary Disease, vol. 5, pp. 375–385, 2010.
[67]
F. Sava, H. Perrault, C. Brouillard et al., “Detecting improvements in dyspnea in COPD using a three-minute constant rate shuttle walking protocol,” Journal of Chronic Obstructive Pulmonary Disease, vol. 9, pp. 395–400, 2012.
[68]
Y. Lacasse, E. Wong, G. H. Guyatt, D. King, D. J. Cook, and R. S. Goldstein, “Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease,” Lancet, vol. 348, no. 9035, pp. 1115–1119, 1996.
[69]
A. E. Holland, C. J. Hill, T. Rasekaba, A. Lee, M. T. Naughton, and C. F. McDonald, “Updating the minimal important difference for six-minute walk distance in patients with chronic obstructive pulmonary disease,” Archives of Physical Medicine and Rehabilitation, vol. 91, no. 2, pp. 221–225, 2010.
[70]
M. Satake, H. Takahashi, K. Sugawara et al., “Inhibitory effect of procaterol on exercise dynamic lung hyperinflation during the 6-min walk test in stable patients with chronic obstructive pulmonary disease,” Arzneimittel-Forschung/Drug Research, vol. 61, no. 1, pp. 8–13, 2011.
[71]
T. Shioya, M. Satake, K. Sato et al., “Long-term effect of the β2-receptor agonist procaterol on daily life performance and exercise capacity in patients with stable chronic obstructive pulmonary disease: clinical study with special reference to health-related quality of life and activities of daily living,” Arzneimittel-Forschung/Drug Research, vol. 58, no. 1, pp. 24–28, 2008.
[72]
M. Cazzola, G. L. Biscione, F. Pasqua et al., “Use of 6-min and 12-min walking test for assessing the efficacy of formoterol in COPD,” Respiratory Medicine, vol. 102, no. 10, pp. 1425–1430, 2008.
[73]
G. Boyd, A. H. Morice, J. C. Pounsford, M. Siebert, N. Peslis, and C. Crawford, “An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD),” European Respiratory Journal, vol. 10, pp. 815–821, 1997.
[74]
P. Weiner, R. Magadle, N. Berar-Yanay, A. Davidovich, and M. Weiner, “The cumulative effect of long-acting bronchodilators, exercise, and inspiratory muscle training on the perception of dyspnea patients with advanced COPD,” Chest, vol. 118, no. 3, pp. 672–678, 2000.
[75]
N. Okudan, M. G？k, H. G？kbel, and M. Süerdem, “Single dose of tiotropium improves the 6-minute walk distance in chronic obstructive pulmonary disease,” Lung, vol. 184, no. 4, pp. 201–204, 2006.
[76]
V. Pepin, J. Brodeur, Y. Lacasse et al., “Six-minute walking versus shuttle walking: responsiveness to bronchodilation in chronic obstructive pulmonary disease,” Thorax, vol. 62, no. 4, pp. 291–298, 2007.
[77]
P. L. Paggiaro, R. Dahle, I. Bakran, L. Frith, K. Hollingworth, and J. Efthimiou, “Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease,” Lancet, vol. 351, no. 9105, pp. 773–780, 1998.
[78]
G. J. Criner, F. C. Cordova, S. Furukawa et al., “Prospective randomized trial comparing bilateral lung volume reduction surgery to pulmonary rehabilitation in severe chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 160, no. 6, pp. 2018–2027, 1999.
[79]
R. M. Leach, A. C. Davidson, S. Chinn, C. H. C. Twort, I. R. Cameron, and N. T. Bateman, “Portable liquid oxygen and exercise ability in severe respiratory disability,” Thorax, vol. 47, no. 10, pp. 781–789, 1992.
[80]
American Thoracic Society, “ATS statement: guidelines for the six-minute walk test,” American Journal of Respiratory and Critical Care Medicine, vol. 166, no. 1, pp. 111–117, 2002.
[81]
T. Troosters, J. Vilaro, R. Rabinovich et al., “Physiological responses to the 6-min walk test in patients with chronic obstructive pulmonary disease,” European Respiratory Journal, vol. 20, no. 3, pp. 564–569, 2002.
[82]
B. Borel, C. Fabre, S. Saison, F. Bart, and J. M. Grosbois, “An original field evaluation test for chronic obstructive pulmonary disease population: the six-minute stepper test,” Clinical Rehabilitation, vol. 24, no. 1, pp. 82–93, 2010.
[83]
B. Rammaert, S. Leroy, B. Cavestri, B. Wallaert, and J. M. Grosbois, “Home-based pulmonary rehabilitation in idiopathic pulmonary fibrosis,” Revue des Maladies Respiratoires, vol. 28, pp. e52–e57, 2011.
[84]
R. Casaburi, “Physiologic responses to training,” Clinics in Chest Medicine, vol. 15, no. 2, pp. 215–227, 1994.
[85]
R. Casaburi and R. Zuwallack, “Pulmonary rehabilitation for management of chronic obstructive pulmonary disease,” The New England Journal of Medicine, vol. 360, no. 13, pp. 1282–1335, 2009.
[86]
R. Casaburi, A. Patessio, F. Ioli, S. Zanaboni, C. F. Donner, and K. Wasserman, “Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease,” American Review of Respiratory Disease, vol. 143, no. 1, pp. 9–18, 1991.
[87]
F. Maltais, P. Leblanc, C. Simard et al., “Skeletal muscle adaptation to endurance training in patients with chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 154, no. 2, pp. 442–447, 1996.
[88]
M. J. Mador, T. J. Kufel, L. A. Pineda et al., “Effect of pulmonary rehabilitation on quadriceps fatiguability during exercise,” American Journal of Respiratory and Critical Care Medicine, vol. 163, no. 4, pp. 930–935, 2001.
[89]
R. Casaburi, J. Porszasz, M. R. Burns, E. R. Carithers, R. S. Y. Chang, and C. B. Cooper, “Physiologic benefits of exercise training in rehabilitation of patients with severe chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 155, no. 5, pp. 1541–1551, 1997.
[90]
F. Maltais, P. Leblanc, J. Jobin et al., “Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 155, no. 2, pp. 555–561, 1997.
[91]
P. Gagnon, J. S. Bussieres, F. Ribeiro et al., “Influences of spinal anesthesia on exercise tolerance in patients with COPD,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 7, pp. 606–615, 2012.
[92]
F. Gigliotti, C. Coli, R. Bianchi et al., “Exercise training improves exertional dyspnea in patients with COPD: evidence of the role of mechanical factors,” Chest, vol. 123, no. 6, pp. 1794–1802, 2003.
[93]
D. E. O'Donnell, S. M. Revill, and K. A. Webb, “Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 164, no. 5, pp. 770–777, 2001.
[94]
D. E. O'Donnell, M. Lam, and K. A. Webb, “Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 160, no. 2, pp. 542–549, 1999.
[95]
D. E. O'Donnell, A. L. Hamilton, and K. A. Webb, “Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD,” Journal of Applied Physiology, vol. 101, no. 4, pp. 1025–1035, 2006.
[96]
D. Saey, R. Debigaré, P. LeBlanc et al., “Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease,” American Journal of Respiratory and Critical Care Medicine, vol. 168, no. 4, pp. 425–430, 2003.
[97]
D. Deschênes, V. Pepin, D. Saey, P. LeBlanc, and F. Maltais, “Locus of symptom limitation and exercise response to bronchodilation in chronic obstructive pulmonary disease,” Journal of Cardiopulmonary Rehabilitation and Prevention, vol. 28, no. 3, pp. 208–214, 2008.
[98]
A. Cockcroft, A. Beaumont, L. Adams, and A. Guz, “Arterial oxygen desaturation during treadmill and bicycle exercise in patients with chronic obstructive airways disease,” Clinical Science, vol. 68, no. 3, pp. 327–332, 1985.
[99]
P. Palange, S. Forte, P. Onorati, F. Manfredi, P. Serra, and S. Carlone, “Ventilatory and metabolic adaptations to walking and cycling in patients with COPD,” Journal of Applied Physiology, vol. 88, pp. 1715–1720, 2000.
[100]
M. Poulain, F. Durand, B. Palomba et al., “6-Minute walk testing is more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with COPD,” Chest, vol. 123, no. 5, pp. 1401–1407, 2003.
