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Review

New physiological insights into dyspnea and exercise intolerance in chronic obstructive pulmonary disease patients

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Pages 651-662 | Published online: 09 Jan 2014

References

  • Pellegrino R, Viegi G, Brusasco V et al. Interpretative strategies for lung function tests. Eur. Respir. J. 26(5), 948–968 (2005).
  • Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. 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 (1993).
  • O’Donnell DE, Laveneziana P. Physiology and consequences of lung hyperinflation in COPD. Eur. Respir. Rev. 15(100), 61–67 (2006).
  • O’Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 158(5 Pt 1), 1557–1565 (1998).
  • O’Donnell DE, Travers J, Webb KA et al. Reliability of ventilatory parameters during cycle ergometry in multicentre trials in COPD. Eur. Respir. J. 34(4), 866–874 (2009).
  • Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in subjects with chronic airflow obstruction. J. Appl. Physiol. 49(3), 511–515 (1980).
  • Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in normal males. J. Appl. Physiol. 49(3), 506–510 (1980).
  • Vogiatzis I, Georgiadou O, Golemati S et al. Patterns of dynamic hyperinflation during exercise and recovery in patients with severe chronic obstructive pulmonary disease. Thorax 60(9), 723–729 (2005).
  • Deesomchok A, Webb KA, Forkert L et al. Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity. COPD 7(6), 428–437 (2010).
  • Guenette JA, Jensen D, Webb KA, Ofir D, Raghavan N, O’Donnell DE. Sex differences in exertional dyspnea in patients with mild COPD: physiological mechanisms. Respir. Physiol. Neurobiol. 177(3), 218–227 (2011).
  • Ofir D, Laveneziana P, Webb KA, Lam YM, O’Donnell DE. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 177(6), 622–629 (2008).
  • O’Donnell DE, Guenette JA, Maltais F, Webb KA. Decline of resting inspiratory capacity in COPD: the impact on breathing pattern, dyspnea, and ventilatory capacity during exercise. Chest 141(3), 753–762 (2012).
  • O’Donnell DE, Deesomchok A, Lam YM et al. Effects of BMI on static lung volumes in patients with airway obstruction. Chest 140(2), 461–468 (2011).
  • Barberà JA, Riverola A, Roca J et al. Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 149(2 Pt 1), 423–429 (1994).
  • Hogg JC, Chu F, Utokaparch S et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 350(26), 2645–2653 (2004).
  • McDonough JE, Yuan R, Suzuki M et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N. Engl. J. Med. 365(17), 1567–1575 (2011).
  • Rodríguez-Roisin R, Drakulovic M, Rodríguez DA, Roca J, Barberà JA, Wagner PD. Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity. J. Appl. Physiol. 106(6), 1902–1908 (2009).
  • Buist AS, Ross BB. Quantitative analysis of the alveolar plateau in the diagnosis of early airway obstruction. Am. Rev. Respir. Dis. 108(5), 1078–1087 (1973).
  • Tantucci C, Donati P, Nicosia F et al. Inspiratory capacity predicts mortality in patients with chronic obstructive pulmonary disease. Respir. Med. 102(4), 613–619 (2008).
  • Zaman M, Mahmood S, Altayeh A. Low inspiratory capacity to total lung capacity ratio is a risk factor for chronic obstructive pulmonary disease exacerbation. Am. J. Med. Sci. 339(5), 411–414 (2010).
  • Albuquerque AL, Nery LE, Villaça DS et al. Inspiratory fraction and exercise impairment in COPD patients GOLD stages II–III. Eur. Respir. J. 28(5), 939–944 (2006).
  • Casanova C, Cote C, de Torres JP et al. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 171(6), 591–597 (2005).
  • Laghi F, Tobin MJ. Disorders of the respiratory muscles. Am. J. Respir. Crit. Care Med. 168(1), 10–48 (2003).
  • Orozco-Levi M, Gea J, Lloreta JL et al. Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease. Eur. Respir. J. 13(2), 371–378 (1999).
  • Supinski GS, Kelsen SG. Effect of elastase-induced emphysema on the force-generating ability of the diaphragm. J. Clin. Invest. 70(5), 978–988 (1982).
  • Levine S, Kaiser L, Leferovich J, Tikunov B. Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease. N. Engl. J. Med. 337(25), 1799–1806 (1997).
  • Mercadier JJ, Schwartz K, Schiaffino S et al. Myosin heavy chain gene expression changes in the diaphragm of patients with chronic lung hyperinflation. Am. J. Physiol. 274(4 Pt 1), L527–L534 (1998).
  • Similowski T, Yan S, Gauthier AP, Macklem PT, Bellemare F. Contractile properties of the human diaphragm during chronic hyperinflation. N. Engl. J. Med. 325(13), 917–923 (1991).
  • Mador MJ, Kufel TJ, Pineda LA, Sharma GK. Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 161(1), 118–123 (2000).
  • O’Donnell DE, Bertley JC, Chau LK, Webb KA. Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms. Am. J. Respir. Crit. Care Med. 155(1), 109–115 (1997).
  • Mead J. Respiration: pulmonary mechanics. Annu. Rev. Physiol. 35, 169–192 (1973).
  • Roussos C, Macklem PT. The respiratory muscles. N. Engl. J. Med. 307(13), 786–797 (1982).
  • Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J. Appl. Physiol. 65(4), 1488–1499 (1988).
  • O’Donnell DE, Hamilton AL, Webb KA. Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD. J. Appl. Physiol. 101(4), 1025–1035 (2006).
  • O’Donnell DE, Revill SM, Webb KA. Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 164(5), 770–777 (2001).
  • Laveneziana P, Webb KA, Ora J, Wadell K, O’Donnell DE. Evolution of dyspnea during exercise in chronic obstructive pulmonary disease: impact of critical volume constraints. Am. J. Respir. Crit. Care Med. 184(12), 1367–1373 (2011).
  • O’Donnell DE, Parker CM. COPD exacerbations. 3: pathophysiology. Thorax 61(4), 354–361 (2006).
  • Parker CM, Voduc N, Aaron SD, Webb KA, O’Donnell DE. Physiological changes during symptom recovery from moderate exacerbations of COPD. Eur. Respir. J. 26(3), 420–428 (2005).
  • Stevenson NJ, Walker PP, Costello RW, Calverley PM. Lung mechanics and dyspnea during exacerbations of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 172(12), 1510–1516 (2005).
  • Carr SJ, Goldstein RS, Brooks D. Acute exacerbations of COPD in subjects completing pulmonary rehabilitation. Chest 132(1), 127–134 (2007).
  • Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R. Physical activity and hospitalization for exacerbation of COPD. Chest 129(3), 536–544 (2006).
  • Murphy PB, Kumar A, Reilly C et al. Neural respiratory drive as a physiological biomarker to monitor change during acute exacerbations of COPD. Thorax 66(7), 602–608 (2011).
  • Barberà JA, Roca J, Ferrer A et al. Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease. Eur. Respir. J. 10(6), 1285–1291 (1997).
  • Laveneziana P, Wadell K, Webb K, O’Donnell DE. Exercise limitation in chronic obstructive pulmonary disease. Curr. Respir. Med. Rev., 4(4), 258–269 (2008).
  • Stefan MS, Bannuru RR, Lessard D, Gore JM, Lindenauer PK, Goldberg RJ. The impact of COPD on management and outcomes of patients hospitalized with acute myocardial infarction: a 10-year retrospective observational study. Chest 141(6), 1441–1448 (2012).
  • Henke KG, Sharratt M, Pegelow D, Dempsey JA. Regulation of end-expiratory lung volume during exercise. J. Appl. Physiol. 64(1), 135–146 (1988).
  • Kiers A, van der Mark TW, Woldring MG, Peset R. Determination of the functional residual capacity during exercise. Ergonomics 23(10), 955–959 (1980).
  • Lind F, Hesser CM. Breathing pattern and lung volumes during exercise. Acta Physiol. Scand. 120(1), 123–129 (1984).
  • Younes M, Kivinen G. Respiratory mechanics and breathing pattern during and following maximal exercise. J. Appl. Physiol. 57(6), 1773–1782 (1984).
  • Anthonisen NR, Danson J, Robertson PC, Ross WR. Airway closure as a function of age. Respir. Physiol. 8(1), 58–65 (1969).
  • D’Errico A, Scarani P, Colosimo E, Spina M, Grigioni WF, Mancini AM. Changes in the alveolar connective tissue of the ageing lung. An immunohistochemical study. Virchows Arch. A. Pathol. Anat. Histopathol. 415(2), 137–144 (1989).
  • Frank NR, Mead J, Ferris BG Jr. The mechanical behavior of the lungs in healthy elderly persons. J. Clin. Invest. 36(12), 1680–1687 (1957).
  • Gibson GJ, Pride NB, O’Cain C, Quagliato R. Sex and age differences in pulmonary mechanics in normal nonsmoking subjects. J. Appl. Physiol. 41(1), 20–25 (1976).
  • Knudson RJ, Clark DF, Kennedy TC, Knudson DE. Effect of aging alone on mechanical properties of the normal adult human lung. J. Appl. Physiol. 43(6), 1054–1062 (1977).
  • Johnson BD, Reddan WG, Pegelow DF, Seow KC, Dempsey JA. Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am. Rev. Respir. Dis. 143(5 Pt 1), 960–967 (1991).
  • Johnson BD, Reddan WG, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in a fit aging population. Am. Rev. Respir. Dis. 143(5 Pt 1), 968–977 (1991).
  • Ofir D, Laveneziana P, Webb KA, Lam YM, O’Donnell DE. Sex differences in the perceived intensity of breathlessness during exercise with advancing age. J. Appl. Physiol. 104(6), 1583–1593 (2008).
  • Diaz O, Villafranca C, Ghezzo H et al. Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest. Eur. Respir. J. 16(2), 269–275 (2000).
  • Marin JM, Carrizo SJ, Gascon M, Sanchez A, Gallego B, Celli BR. Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 163(6), 1395–1399 (2001).
  • Puente-Maestu L, García de Pedro J, Martínez-Abad Y, Ruíz de Oña JM, Llorente D, Cubillo JM. Dyspnea, ventilatory pattern, and changes in dynamic hyperinflation related to the intensity of constant work rate exercise in COPD. Chest 128(2), 651–656 (2005).
  • Laveneziana P, Parker CM, O’Donnell DE. Ventilatory constraints and dyspnea during exercise in chronic obstructive pulmonary disease. Appl. Physiol. Nutr. Metab. 32(6), 1225–1238 (2007).
  • O’Donnell DE, Bredenbröker D, Brose M, Webb KA. Physiological effects of roflumilast at rest and during exercise in COPD. Eur. Respir. J. 39(5), 1104–1112 (2012).
  • O’Donnell DE, Casaburi R, Vincken W et al.; INABLE 1 study group. Effect of indacaterol on exercise endurance and lung hyperinflation in COPD. Respir. Med. 105(7), 1030–1036 (2011).
  • Paoletti P, De Filippis F, Fraioli F et al. Cardiopulmonary exercise testing (CPET) in pulmonary emphysema. Respir. Physiol. Neurobiol. 179(2–3), 167–173 (2011).
  • Guenette JA, Webb KA, O’Donnell DE. Does dynamic hyperinflation contribute to dyspnoea during exercise in patients with COPD? Eur. Respir. J. 40(2), 322–329 (2012).
  • O’Donnell DE, D’Arsigny C, Fitzpatrick M, Webb KA. Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation. Am. J. Respir. Crit. Care Med. 166(5), 663–668 (2002).
  • Barbera JA, Roca J, Ramirez J, Wagner PD, Ussetti P, Rodriguez-Roisin R. Gas exchange during exercise in mild chronic obstructive pulmonary disease. Correlation with lung structure. Am. Rev. Respir. Dis. 144(3 Pt 1), 520–525 (1991).
  • Dantzker DR, D’Alonzo GE. The effect of exercise on pulmonary gas exchange in patients with severe chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 134(6), 1135–1139 (1986).
  • O’Donnell DE, Webb KA. Breathlessness in patients with severe chronic airflow limitation. Physiologic correlations. Chest 102(3), 824–831 (1992).
  • Wagner PD, Dantzker DR, Dueck R, Clausen JL, West JB. Ventilation-perfusion inequality in chronic obstructive pulmonary disease. J. Clin. Invest. 59(2), 203–216 (1977).
  • Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am. Rev. Respir. Dis. 143(1), 9–18 (1991).
  • Bye PT, Esau SA, Levy RD et al. Ventilatory muscle function during exercise in air and oxygen in patients with chronic air-flow limitation. Am. Rev. Respir. Dis. 132(2), 236–240 (1985).
  • Sinderby C, Spahija J, Beck J et al. Diaphragm activation during exercise in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 163(7), 1637–1641 (2001).
  • Polkey MI, Kyroussis D, Keilty SE et al. Exhaustive treadmill exercise does not reduce twitch transdiaphragmatic pressure in patients with COPD. Am. J. Respir. Crit. Care Med. 152(3), 959–964 (1995).
  • Laveneziana P, Palange P, Ora J, Martolini D, O’Donnell DE. Bronchodilator effect on ventilatory, pulmonary gas exchange, and heart rate kinetics during high-intensity exercise in COPD. Eur. J. Appl. Physiol. 107(6), 633–643 (2009).
  • Laveneziana P, Valli G, Onorati P, Paoletti P, Ferrazza AM, Palange P. Effect of heliox on heart rate kinetics and dynamic hyperinflation during high-intensity exercise in COPD. Eur. J. Appl. Physiol. 111(2), 225–234 (2011).
  • Travers J, Laveneziana P, Webb KA, Kesten S, O’Donnell DE. Effect of tiotropium bromide on the cardiovascular response to exercise in COPD. Respir. Med. 101(9), 2017–2024 (2007).
  • Chiappa GR, Borghi-Silva A, Ferreira LF et al. Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics. J. Appl. Physiol. 104(5), 1341–1350 (2008).
  • Montes de Oca M, Rassulo J, Celli BR. Respiratory muscle and cardiopulmonary function during exercise in very severe COPD. Am. J. Respir. Crit. Care Med. 154(5), 1284–1289 (1996).
  • Saito S, Miyamoto K, Nishimura M et al. Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD. Chest 115(2), 376–382 (1999).
  • Vassaux C, Torre-Bouscoulet L, Zeineldine S et al. Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD. Eur. Respir. J. 32(5), 1275–1282 (2008).
  • Potter WA, Olafsson S, Hyatt RE. Ventilatory mechanics and expiratory flow limitation during exercise in patients with obstructive lung disease. J. Clin. Invest. 50(4), 910–919 (1971).
  • Parshall MB, Schwartzstein RM, Adams L et al.; American Thoracic Society Committee on Dyspnea. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am. J. Respir. Crit. Care Med. 185(4), 435–452 (2012).
  • O’Donnell DE, Banzett RB, Carrieri-Kohlman V et al. Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. Proc. Am. Thorac. Soc. 4(2), 145–168 (2007).
  • Evans KC, Banzett RB, Adams L, McKay L, Frackowiak RS, Corfield DR. BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air hunger. J. Neurophysiol. 88(3), 1500–1511 (2002).
  • O’Donnell DE, Hong HH, Webb KA. Respiratory sensation during chest wall restriction and dead space loading in exercising men. J. Appl. Physiol. 88(5), 1859–1869 (2000).
  • Celli B, ZuWallack R, Wang S, Kesten S. Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest 124(5), 1743–1748 (2003).
  • Maltais F, Hamilton A, Marciniuk D et al. Improvements in symptom-limited exercise performance over 8 h with once-daily tiotropium in patients with COPD. Chest 128(3), 1168–1178 (2005).
  • Newton MF, O’Donnell DE, Forkert L. Response of lung volumes to inhaled salbutamol in a large population of patients with severe hyperinflation. Chest 121(4), 1042–1050 (2002).
  • O’Donnell DE, Flüge T, Gerken F et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur. Respir. J. 23(6), 832–840 (2004).
  • O’Donnell DE, Forkert L, Webb KA. Evaluation of bronchodilator responses in patients with ‘irreversible’ emphysema. Eur. Respir. J. 18(6), 914–920 (2001).
  • O’Donnell DE, Lam M, Webb KA. Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 160(2), 542–549 (1999).
  • Tantucci C, Duguet A, Similowski T, Zelter M, Derenne JP, Milic-Emili J. Effect of salbutamol on dynamic hyperinflation in chronic obstructive pulmonary disease patients. Eur. Respir. J. 12(4), 799–804 (1998).
  • Boni E, Corda L, Franchini D et al. Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest. Thorax 57(6), 528–532 (2002).
  • van Noord JA, Aumann JL, Janssens E et al. Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD. Chest 129(3), 509–517 (2006).
  • Tashkin DP, Littner M, Andrews CP, Tomlinson L, Rinehart M, Denis-Mize K. Concomitant treatment with nebulized formoterol and tiotropium in subjects with COPD: a placebo-controlled trial. Respir. Med. 102(4), 479–487 (2008).
  • Guenette JA, Raghavan N, Harris-McAllister V, Preston ME, Webb KA, O’Donnell DE. Effect of adjunct fluticasone propionate on airway physiology during rest and exercise in COPD. Respir. Med. 105(12), 1836–1845 (2011).
  • Worth H, Förster K, Eriksson G, Nihlén U, Peterson S, Magnussen H. Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD. Respir. Med. 104(10), 1450–1459 (2010).
  • O’Donnell DE, Sciurba F, Celli B et al. Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest 130(3), 647–656 (2006).
  • Singh D, Brooks J, Hagan G, Cahn A, O’Connor BJ. Superiority of ‘triple’ therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 63(7), 592–598 (2008).
  • Welte T, Miravitlles M, Hernandez P et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 180(8), 741–750 (2009).
  • O’Donnell DE, Voduc N, Fitzpatrick M, Webb KA. Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease. Eur. Respir. J. 24(1), 86–94 (2004).
  • Peters MM, Webb KA, O’Donnell DE. Combined physiological effects of bronchodilators and hyperoxia on exertional dyspnoea in normoxic COPD. Thorax 61(7), 559–567 (2006).
  • O’Donnell DE, Laveneziana P, Ora J, Webb KA, Lam YM, Ofir D. Evaluation of acute bronchodilator reversibility in patients with symptoms of GOLD stage I COPD. Thorax 64(3), 216–223 (2009).
  • Gelb AF, Hogg JC, Müller NL et al. Contribution of emphysema and small airways in COPD. Chest 109(2), 353–359 (1996).
  • Kuwano K, Matsuba K, Ikeda T et al. The diagnosis of mild emphysema. Correlation of computed tomography and pathology scores. Am. Rev. Respir. Dis. 141(1), 169–178 (1990).
  • Yuan R, Hogg JC, Paré PD et al. Prediction of the rate of decline in FEV(1) in smokers using quantitative computed tomography. Thorax 64(11), 944–949 (2009).
  • Hyatt RE. Expiratory flow limitation. J. Appl. Physiol. 55(1 Pt 1), 1–7 (1983).
  • Dawson SV, Elliott EA. Wave-speed limitation on expiratory flow-a unifying concept. J. Appl. Physiol. 43(3), 498–515 (1977).
  • Pride NB, Macklem PT. Lung mechanics in disease. In: Handbook of Physiology, Part 2: The Respiratory System. Fishman AP (Ed.). American Physiological Society, Bethesda, MD, USA, 659–692 (1986).
  • Vinegar A, Sinnett EE, Leith DE. Dynamic mechanisms determine functional residual capacity in mice, Mus musculus. J. Appl. Physiol. 46(5), 867–871 (1979).

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