No room to breathe: The importance of lung hyperinflation in COPD

Primary Care Respiratory Journal

Volumn 22, Issue 1, 2013, Pages 101-111

  Thomas, Mike ^a   Decramer, Marc ^b   O'Donnell, Denis E ^c  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^c KINGSTON GENERAL HOSPITAL   (Canada)

Author keywords

COPD; Dyspnoea; Exacerbations; Exercise; Hyperinflation; Inspiratory capacity

Indexed keywords

ACETYLCYSTEINE; ACLIDINIUM BROMIDE; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BRONCHODILATING AGENT; BUDESONIDE PLUS FORMOTEROL; CHOLINERGIC RECEPTOR BLOCKING AGENT; CORTICOSTEROID; FLUTICASONE PROPIONATE; FLUTICASONE PROPIONATE PLUS SALMETEROL; FORMOTEROL; GLYCOPYRRONIUM BROMIDE; INDACATEROL; IPRATROPIUM BROMIDE; LONG ACTING DRUG; OXYGEN; PLACEBO; ROFLUMILAST; SALMETEROL; THEOPHYLLINE; TIOTROPIUM BROMIDE;

ARTIFICIAL VENTILATION; ASSISTED VENTILATION; ATELECTASIS; BREATHING RATE; BRONCHITIS; BRONCHODILATATION; CARDIOVASCULAR DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; COMORBIDITY; DAILY LIFE ACTIVITY; DISEASE ACTIVITY; DISEASE COURSE; DISEASE EXACERBATION; DYSPNEA; EMPHYSEMA; ENDURANCE TRAINING; EXERCISE; EXPIRATORY FLOW; FORCED EXPIRATORY VOLUME; HEALTH EDUCATION; HEART FAILURE; HUMAN; HYPERINFLATION; HYPOXIA; INSPIRATORY CAPACITY; INSPIRATORY RESERVE VOLUME; LUNG COMPLIANCE; LUNG FUNCTION; LUNG MECHANICS; LUNG PRESSURE; LUNG SURGERY; LUNG VENTILATION; MONOTHERAPY; MUSCLE WEAKNESS; NUTRITION EDUCATION; OXYGEN DESATURATION; OXYGEN THERAPY; PATHOGENESIS; PATHOPHYSIOLOGY; PHYSICAL ACTIVITY; PHYSICAL CAPACITY; PHYSICAL DECONDITIONING; POSITIVE END EXPIRATORY PRESSURE; PULMONARY REHABILITATION; QUALITY OF LIFE; RESIDUAL VOLUME; RESPIRATORY DISTRESS; REVIEW; SMOKING CESSATION; TIDAL VOLUME; TOTAL LUNG CAPACITY; TREATMENT DURATION; TREATMENT OUTCOME;

DISEASE PROGRESSION; DYSPNEA; EXERCISE; HUMANS; LUNG; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE;

EID: 84874739705     PISSN: 14714418     EISSN: 14751534     Source Type: Journal    
DOI: 10.4104/pcrj.2013.00025     Document Type: Review

References (120)

1. Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet 2007;370:741-50. http://dx.doi.org/10.1016/S0140-6736(07)61377-4
2. East of England Public Health Observatory. Modelled estimate of prevalence of COPD in England. http://www.apho.org.uk/resource/item.aspx?RID=111122 (accessed 9 July 2012).
3. Hill K, Goldstein RS, Guyatt GH, et al. Prevalence and underdiagnosis of chronic obstructive pulmonary disease among patients at risk in primary care. CMAJ 2010;182:673-8. http://dx.doi.org/10.1503/cmaj.091784
4. Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007;370:765-73. http://dx.doi.org/10.1016/S0140-6736(07)61380-4
5. Garcia-Aymerich J, Serra P, I, Mannino DM, et al. Lung function impairment, COPD hospitalisations and subsequent mortality. Thorax 2011;66:585-90. http://dx.doi.org/10.1136/thx.2010.152876
6. Jones PW. Activity limitation and quality of life in COPD. COPD 2007;4:273-8. http://dx.doi.org/10.1080/15412550701480265
7. O'Donnell DE, Webb KA. The major limitation to exercise performance in COPD is dynamic hyperinflation. J Appl Physiol 2008;105:753-5. http://dx.doi.org/10.1152/japplphysiol.90336.2008b
8. Rennard S, Decramer M, Calverley PM, et al. Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey. Eur Respir J 2002;20:799-805. http://dx.doi.org/10.1183/09031936.02.03242002
9. Ofir D, Laveneziana P, Webb KA, et al. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:622-9. http://dx.doi.org/10.1164/rccm.200707-1064OC
10. Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645-53. http://dx.doi.org/10.1056/NEJMoa032158
11. McDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med 2011;365:1567-75. http://dx.doi.org/10.1056/NEJMoa1106955
12. O'Donnell DE, Parker CM. COPD exacerbations. 3: Pathophysiology. Thorax 2006;61:354-61. http://dx.doi.org/10.1136/thx.2005.041830
13. Decramer M. Respiratory muscles in COPD: regulation of trophical status. Verh K Acad Geneeskd Belg 2001;63:577-602.
14. Decramer M. Pulmonary rehabilitation 2007: from bench to practice and back. Clin Invest Med 2008;31:E312-E318.
15. Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med 1996;153:976-80.
16. O'Donnell DE. Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006;3:180-4. http://dx.doi.org/10.1513/pats.200508-093DO
17. McKenzie DK, Butler JE, Gandevia SC. Respiratory muscle function and activation in chronic obstructive pulmonary disease. J Appl Physiol 2009;107:621-9. http://dx.doi.org/10.1152/japplphysiol.00163.2009
18. Cassart M, Pettiaux N, Gevenois PA, et al. Effect of chronic hyperinflation on diaphragm length and surface area. Am J Respir Crit Care Med 1997;156:504-08.
19. Gorman RB, McKenzie DK, Pride NB, et al. Diaphragm length during tidal breathing in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:1461-9. http://dx.doi.org/10.1164/rccm.200111-087OC
20. Similowski T, Yan S, Gauthier AP, et al. Contractile properties of the human diaphragm during chronic hyperinflation. N Engl J Med 1991;325:917-23. http://dx.doi.org/10.1056/NEJM199109263251304
21. Klimathianaki M, Vaporidi K, Georgopoulos D. Respiratory muscle dysfunction in COPD: from muscles to cell. Curr Drug Targets 2011;12:478-88. http://dx.doi.org/10.2174/138945011794751474
22. Parker CM, Voduc N, Aaron SD, et al. Physiological changes during symptom recovery from moderate exacerbations of COPD. Eur Respir J 2005;26:420-8. http://dx.doi.org/10.1183/09031936.05.00136304
23. 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 2005;172:1510-6. http://dx.doi.org/10.1164/rccm.200504-595OC
24. Celli BR, Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J 2007;29:1224-38. http://dx.doi.org/10.1183/09031936.00109906
25. Vogelmeier C, Hederer B, Glaab T, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med 2011;364:1093-103. http://dx.doi.org/10.1056/NEJMoa1008378
26. Washko GR, Fan VS, Ramsey SD, et al. The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med 2008;177:164-9. http://dx.doi.org/10.1164/rccm.200708-1194OC
27. Wedzicha JA, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med 2008;177:19-26. http://dx.doi.org/10.1164/rccm.200707-973OC
28. Coussa ML, Guerin C, Eissa NT, et al. Partitioning of work of breathing in mechanically ventilated COPD patients. J Appl Physiol 1993;75:1711-19.
29. O'Donnell DE, Ora J, Webb KA, et al. Mechanisms of activity-related dyspnea in pulmonary diseases. Respir Physiol Neurobiol 2009;167:116-32. http://dx.doi.org/10.1016/j.resp.2009.01.010
30. Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012;185:435-52. http://dx.doi.org/10.1164/rccm.201111-2042ST
31. Laveneziana P, Webb KA, Ora J, et al. Evolution of dyspnea during exercise in chronic obstructive pulmonary disease: impact of critical volume constraints. Am J Respir Crit Care Med 2011;184:1367-73. http://dx.doi.org/10.1164/rccm.201106-1128OC
32. 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 2012;141:753-62. http://dx.doi.org/10.1378/chest.11-0787
33. Williams M, Cafarella P, Olds T, et al. The language of breathlessness differentiates between patients with COPD and age-matched adults. Chest 2008;134:489-96. http://dx.doi.org/10.1378/chest.07-2916
34. Williams M, Cafarella P, Olds T, et al. Affective descriptors of the sensation of breathlessness are more highly associated with severity of impairment than physical descriptors in people with COPD. Chest 2010;138:315-22. http://dx.doi.org/10.1378/chest.09-2498
35. Deesomchok A, Webb KA, Forkert L, et al. Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity. COPD 2010;7:428-37. http://dx.doi.org/10.3109/15412555.2010.528087
36. Garcia-Rio F, Lores V, Mediano O, et al. Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009;180:506-12. http://dx.doi.org/10.1164/rccm.200812-1873OC
37. Hannink JD, van Helvoort HA, Dekhuijzen PN, Heijdra YF. Dynamic hyperinflation during daily activities: does COPD global initiative for chronic obstructive lung disease stage matter? Chest 2010;137:1116-21. http://dx.doi.org/10.1378/chest.09-1847
38. Levine S, Kaiser L, Leferovich J, Tikunov B. Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease. N Engl J Med 1997;337:1799-806. http://dx.doi.org/10.1056/NEJM199712183372503
39. Ottenheijm CA, Heunks LM, Dekhuijzen RP. Diaphragm adaptations in patients with COPD. Respir Res 2008;9:12. http://dx.doi.org/10.1186/1465-9921-9-12
40. Pitta F, Troosters T, Spruit MA, et al. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171:972-7. http://dx.doi.org/10.1164/rccm.200407-855OC
41. Shrikrishna D, Patel M, Tanner RJ, et al. Quadriceps wasting and physical inactivity in patients with COPD. Eur Respir J 2012;40:1115-22. http://dx.doi.org/10.1183/09031936.00170111
42. Watz H, Waschki B, Boehme C, et al. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med 2008;177:743-51. http://dx.doi.org/10.1164/rccm.200707-1011OC
43. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009;33:262-72. http://dx.doi.org/10.1183/09031936.00024608
44. Decramer M, Cooper CB. Treatment of COPD: the sooner the better? Thorax 2010;65:837-41. http://dx.doi.org/10.1136/thx.2009.133355
45. Decramer M, Rennard S, Troosters T, et al. COPD as a lung disease with systemic consequences: clinical impact, mechanisms, and potential for early intervention. COPD 2008;5:235-56. http://dx.doi.org/10.1080/15412550802237531
46. Malerba M, Ragnoli B, Salameh M, et al. Sub-clinical left ventricular diastolic dysfunction in early stage of chronic obstructive pulmonary disease. J Biol Regul Homeost Agents 2011;25:443-51.
47. 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 2010;339:411-14.
48. 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 2005;171:591-7. http://dx.doi.org/10.1164/rccm.200407-867OC
49. Yuan R, Hogg JC, Pare PD, et al. Prediction of the rate of decline in FEV(1) in smokers using quantitative computed tomography. Thorax 2009;64:944-9. http://dx.doi.org/10.1136/thx.2008.112433
50. Casanova C, de Torres JP, guirre-Jaime A, et al. The progression of chronic obstructive pulmonary disease is heterogeneous: the experience of the BODE cohort. Am J Respir Crit Care Med 2011;184:1015-21. http://dx.doi.org/10.1164/rccm.201105-0831OC
51. Mohamed Hoesein FA, Zanen P, Boezen HM, et al. Lung function decline in heavy male smokers relates to baseline airflow obstruction severity. Chest 2012 Jun 21 [Epub ahead of print]. http://dx.doi.org/10.1378/chest.11-2837
52. Vestbo J, Edwards LD, Scanlon PD, et al. Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med 2011;365:1184-92. http://dx.doi.org/10.1056/NEJMoa1105482
53. Cazzola M, MacNee W, Martinez FJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J 2008;31:416-69. http://dx.doi.org/10.1183/09031936.00099306
54. 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 2000;16:269-75. http://dx.doi.org/10.1034/j.1399-3003.2000.16b14.x
55. 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 2003;124:1743-8. http://dx.doi.org/10.1378/chest.124.5.1743
56. O'Donnell DE, Laveneziana P. Physiology and consequences of lung hyperinflation in COPD. Eur Respir Rev 2006;15:61-7. http://dx.doi.org/10.1183/09059180.00010002
57. 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 1999;160:542-9.
58. Guenette JA, Raghavan N, Harris-McAllister V, et al. Effect of adjunct fluticasone propionate on airway physiology during rest and exercise in COPD. Respir Med 2011;105:1836-45. http://dx.doi.org/10.1016/j.rmed.2011.08.021
59. Luo YM, Hopkinson NS, Polkey MI. Tough at the top: must end-expiratory lung volume make way for end-inspiratory lung volume? Eur Respir J 2012;40:283-5. http://dx.doi.org/10.1183/09031936.00021912
60. Casaburi R, Porszasz J. Reduction of hyperinflation by pharmacologic and other interventions. Proc Am Thorac Soc 2006;3:185-9. http://dx.doi.org/10.1513/pats.200508-095DO
61. Puente-Maestu L, Stringer WW. Hyperinflation and its management in COPD. Int J Chron Obstruct Pulmon Dis 2006;1:381-400. http://dx.doi.org/10.2147/copd.2006.1.4.381
62. Peters MM, Webb KA, O'Donnell DE. Combined physiological effects of bronchodilators and hyperoxia on exertional dyspnoea in normoxic COPD. Thorax 2006;61:559-67. http://dx.doi.org/10.1136/thx.2005.053470
63. Ambrosino N, Foglio K, Balzano G, et al. Tiotropium and exercise training in COPD patients: effects on dyspnea and exercise tolerance. Int J Chron Obstruct Pulmon Dis 2008;3:771-80.
64. Casaburi R, Kukafka D, Cooper CB, et al. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD. Chest 2005;127:809-17. http://dx.doi.org/10.1378/chest.127.3.809
65. Voduc N, Tessier C, Sabri E, et al. Effects of oxygen on exercise duration in chronic obstructive pulmonary disease patients before and after pulmonary rehabilitation. Can Respir J 2010;17:e14-19.
66. Casaburi R. Activity promotion: a paradigm shift for chronic obstructive pulmonary disease therapeutics. Proc Am Thorac Soc 2011;8:334-7. http://dx.doi.org/10.1513/pats.201101-001RM
67. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. www goldcopd com (accessed 14 June 2012).
68. Bellamy D, Bouchard J, Henrichsen S, et al. International Primary Care Respiratory Group (IPCRG) guidelines: management of chronic obstructive pulmonary disease (COPD). Prim Care Respir J 2006;15:48-57. http://dx.doi.org/10.1016/j.pcrj.2005.11.003
69. Marciniuk DD, Brooks D, Butcher S, et al. Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease--practical issues: a Canadian Thoracic Society clinical practice guideline. Can Respir J 2010;17:159-68.
70. Nici L, Donner C, Wouters E, et al. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med 2006;173:1390-413. http://dx.doi.org/10.1164/rccm.200508-1211ST
71. Puhan MA, Gimeno-Santos E, Scharplatz M, et al. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2011;CD005305.
72. Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med 2011;155:179-91.
73. Ries AL, Bauldoff GS, Carlin BW, et al. Pulmonary rehabilitation: Joint ACCP/AACVPR evidence-based clinical practice guidelines. Chest 2007;131:4S-42S. http://dx.doi.org/10.1378/chest.06-2418
74. Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;CD003793.
75. O'Donnell DE, Fluge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J 2004;23:832-40. http://dx.doi.org/10.1183/09031936.04.00116004
76. Man WD, Mustfa N, Nikoletou D, et al. Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD. Thorax 2004;59:471-6. http://dx.doi.org/10.1136/thx.2003.019620
77. Duranti R, Misuri G, Gorini M, et al. Mechanical loading and control of breathing in patients with severe chronic obstructive pulmonary disease. Thorax 1995;50:127-33. http://dx.doi.org/10.1136/thx.50.2.127
78. Kyroussis D, Polkey MI, Hamnegard CH, et al. Respiratory muscle activity in patients with COPD walking to exhaustion with and without pressure support. Eur Respir J 2000;15:649-55. http://dx.doi.org/10.1034/j.1399-3003.2000.15d05.x
79. O'Donnell DE, Banzett RB, Carrieri-Kohlman V, et al. Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. Proc Am Thorac Soc 2007;4:145-68. http://dx.doi.org/10.1513/pats.200611-159CC
80. Eiser N, Angus K, McHale S. The role of domiciliary nebulizers in managing patients with severe COPD. Respir Med 2001;95:265-74. http://dx.doi.org/10.1053/rmed.2001.1032
81. Shioya T, Satake M, Sato K, et al. Long-term effect of the beta2-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. Arzneimittelforschung 2008;58:24-8.
82. Thomas P, Pugsley JA, Stewart JH. Theophylline and salbutamol improve pulmonary function in patients with irreversible chronic obstructive pulmonary disease. Chest 1992;101:160-5. http://dx.doi.org/10.1378/chest.101.1.160
83. Laforce C, Aumann J, de Teresa PL, et al. Sustained 24-hour efficacy of once daily indacaterol (300 mug) in patients with chronic obstructive pulmonary disease: a randomized, crossover study. Pulm Pharmacol Ther 2011;24:162-8. http://dx.doi.org/10.1016/j.pupt.2010.06.005
84. Brusasco V, Canonica GW, Dal NR, et al. Formoterol by pressurized metered-dose aerosol or dry powder on airway obstruction and lung hyperinflation in partially reversible COPD. J Aerosol Med Pulm Drug Deliv 2011;24:235-43. http://dx.doi.org/10.1089/jamp.2010.0862
85. Hanania NA, Donohue JF, Nelson H, et al. The safety and efficacy of arformoterol and formoterol in COPD. COPD 2010;7:17-31. http://dx.doi.org/10.3109/15412550903499498
86. Stockley RA, Chopra N, Rice L. Addition of salmeterol to existing treatment in patients with COPD: a 12 month study. Thorax 2006;61:122-8. http://dx.doi.org/10.1136/thx.2004.033266
87. Brashier B, Dhembare P, Jantikar A, et al. Tiotropium administered by a pressurized metered dose inhaler (pMDI) and spacer produces a similar bronchodilator response as that administered by a Rotahaler in adult subjects with stable moderate-to-severe COPD. Respir Med 2007;101:2464-71. http://dx.doi.org/10.1016/j.rmed.2007.07.006
88. Stepanian IE, Khmel'kova NG, Belin-Atarac B. [The efficacy of tiotropium bromide (Spiriva) in the treatment of patients with chronic obstructive pulmonary disease of varying severity: results of the Russian trial]. Ter Arkh 2010;82:46-51.
89. Tanabe N, Muro S, Oguma T, et al. Computed tomography assessment of pharmacological lung volume reduction induced by bronchodilators in COPD. COPD 2012;9:401-08.
90. Verkindre C, Bart F, Aguilaniu B, et al. The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease. Respiration 2006;73:420-7. http://dx.doi.org/10.1159/000089655
91. Beeh KM, Singh D, Di SL, Drollmann A. Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial. Int J Chron Obstruct Pulmon Dis 2012;7:503-13. http://dx.doi.org/10.2147/COPD.S32451
92. Fujimoto K, Kitaguchi Y, Kanda S, et al. Comparison of efficacy of long-acting bronchodilators in emphysema dominant and emphysema nondominant chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011;6:219-27. http://dx.doi.org/10.2147/COPD.S18461
93. van der Vaart H, Postma DS, Grevink R, et al. Bronchodilation improves endurance but not muscular efficiency in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011;6:229-35. http://dx.doi.org/10.2147/COPD.S17482
94. Beeh KM, Wagner F, Khindri S, Drollmann AF. Effect of indacaterol on dynamic lung hyperinflation and breathlessness in hyperinflated patients with COPD. COPD 2011;8:340-5. http://dx.doi.org/10.3109/15412555.2011.594464
95. 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 2004;24:86-94. http://dx.doi.org/10.1183/09031936.04.00072703
96. Maltais F, Celli B, Casaburi R, et al. Aclidinium bromide improves exercise endurance and lung hyperinflation in patients with moderate to severe COPD. Respir Med 2011;105:580-7. http://dx.doi.org/10.1016/j.rmed.2010.11.019
97. O'Donnell DE, Casaburi R, Vincken W, et al. Effect of indacaterol on exercise endurance and lung hyperinflation in COPD. Respir Med 2011;105:1030-6. http://dx.doi.org/10.1016/j.rmed.2011.03.014
98. Mahler DA, D'Urzo A, Bateman ED, et al. Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison. Thorax 2012;67:781-8. http://dx.doi.org/10.1136/thoraxjnl-2011-201140
99. Hanania NA, Boota A, Kerwin E, et al. Efficacy and safety of nebulized formoterol as add-on therapy in COPD patients receiving maintenance tiotropium bromide: results from a 6-week, randomized, placebo-controlled, clinical trial. Drugs 2009;69:1205-16. http://dx.doi.org/10.2165/00003495-200969090-00005
100. Tashkin DP, Donohue JF, Mahler DA, et al. Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD. Respir Med 2009;103:516-24. http://dx.doi.org/10.1016/j.rmed.2008.12.014
101. 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 2006;129:509-17. http://dx.doi.org/10.1378/chest.129.3.509
102. Perng DW, Wu CC, Su KC, et al. Additive benefits of tiotropium in COPD patients treated with long-acting beta agonists and corticosteroids. Respirology 2006;11:598-602. http://dx.doi.org/10.1111/j.1440-1843.2006.00889.x
103. Singh D, Brooks J, Hagan G, et al. Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 2008;63:592-8. http://dx.doi.org/10.1136/thx.2007.087213
104. 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 2009;180:741-50 http://dx.doi.org/10.1164/rccm.200904-0492OC
105. Magnussen H, Paggiaro P, Schmidt H, et al. Effect of combination treatment on lung volumes and exercise endurance time in COPD. Respir Med 2012;106:1413-20. http://dx.doi.org/10.1016/j.rmed.2012.05.011
106. O'Donnell DE, Sciurba F, Celli B, et al. Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest 2006;130:647-56. http://dx.doi.org/10.1378/chest.130.3.647
107. Worth H, Forster K, Eriksson G, et al. Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD. Respir Med 2010;104:1450-9 http://dx.doi.org/10.1016/j.rmed.2010.07.006
108. Tzani P, Crisafulli E, Nicolini G, et al. Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients. Int J Chron Obstruct Pulmon Dis 2011;6:503-09.
109. Celli BR, Tashkin DP, Rennard SI, et al. Bronchodilator responsiveness and onset of effect with budesonide/formoterol pMDI in COPD. Respir Med 2011;105:1176-88. http://dx.doi.org/10.1016/j.rmed.2011.02.020
110. Lindberg A, Szalai Z, Pullerits T, Radeczky E. Fast onset of effect of budesonide/formoterol versus salmeterol/fluticasone and salbutamol in patients with chronic obstructive pulmonary disease and reversible airway obstruction. Respirology 2007;12:732-9. http://dx.doi.org/10.1111/j.1440-1843.2007.01132.x
111. O'Donnell DE, Bredenbroker D, Brose M, Webb KA. Physiological effects of roflumilast at rest and during exercise in COPD. Eur Respir J 2012;39:1104-12. http://dx.doi.org/10.1183/09031936.00096511
112. Dreyse J, Silva F, Diaz O, et al. [Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD]. Rev Med Chil 2005;133:1211-19. http://dx.doi.org/10.4067/S0034-98872005001000010
113. Waterhouse JC, Pritchard SM, Howard P. Hyperinflation, trapped gas and theophylline in chronic obstructive pulmonary disease. Monaldi Arch Chest Dis 1993;48:126-9.
114. Murciano D, Aubier M, Lecocguic Y, Pariente R. Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease. N Engl J Med 1984;311:349-53. http://dx.doi.org/10.1056/NEJM198408093110601
115. Travers J, Laveneziana P, Webb KA, et al. Effect of tiotropium bromide on the cardiovascular response to exercise in COPD. Respir Med 2007;101:2017-24.
116. Murciano D, Auclair MH, Pariente R, Aubier M. A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease. N Engl J Med 1989;320:1521-5. http://dx.doi.org/10.1056/NEJM198906083202304
117. Stav D, Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest 2009;136:381-6. http://dx.doi.org/10.1378/chest.09-0421
118. 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 2005;128:1168-78. http://dx.doi.org/10.1378/chest.128.3.1168
119. Berton DC, Reis M, Siqueira AC, et al. Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD. Respir Med 2010;104:1288-96. http://dx.doi.org/10.1016/j.rmed.2010.05.017
120. Neder JA, Fuld JP, Overend T, et al. Effects of formoterol on exercise tolerance in severely disabled patients with COPD. Respir Med 2007;101:2056-64. http://dx.doi.org/10.1016/j.rmed.2007.06.006