Case-Based Review

Management of Stable Chronic Obstructive Pulmonary Disease

Journal of Clinical Outcomes Management. 2017 June;24(6)

References

1. Segreti A, Stirpe E, Rogliani P, Cazzola M. Defining phenotypes in COPD: an aid to personalized healthcare. Mol Diagn Ther 2014;18:381–8.

2. Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med 2010;182:598–604.

3. Aubier M, Marthan R, Berger P, et al. [COPD and inflammation: statement from a French expert group: inflammation and remodelling mechanisms]. Rev Mal Respir 2010;27:1254–66.

4. Wang ZL. Evolving role of systemic inflammation in comorbidities of chronic obstructive pulmonary disease. Chin Med J (Engl) 2010;123:3467–78.

5. 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.

6. Miniño AM, Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2008. Natl Vital Stat Rep 2011;59:1–126.

7. Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global strategy for the diagnosis, management, and prevention of COPD 2017. Accessed at www.goldcopd.org.

8. Jones PW, Harding G, Berry P, et al. Development and first validation of the COPD Assessment Test. Eur Respir J 2009;34:648–54.

9. Wadbo M, Löfdahl CG, Larsson K, et al. Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study. Eur Respir J 2002;20:1138–46.

10. Ram FS, Sestini P. Regular inhaled short acting beta2 agonists for the management of stable chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. Thorax 2003;58:580–4.

11. Colice GL. Nebulized bronchodilators for outpatient management of stable chronic obstructive pulmonary disease. Am J Med 1996;100(1A):11S–8S.

12. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. COMBIVENT Inhalation Aerosol Study Group. Chest 1994;105:1411–9.

13. Friedman M, Serby CW, Menjoge SS, et al. Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD. Chest 1999;115:635–41.

14. Cook D, Guyatt G, Wong E, et al. Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:85–90.

15. Wilchesky M, Ernst P, Brophy JM, et al. Bronchodilator use and the risk of arrhythmia in COPD: part 2: reassessment in the larger Quebec cohort. Chest 2012;142:305–11.

16. Scott VL, Frazee LA. Retrospective comparison of nebulized levalbuterol and albuterol for adverse events in patients with acute airflow obstruction. Am J Ther 2003;10:341–7.

17. Wong CS, Pavord ID, Williams J, et al. Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 1990;336:1396–9.

18. Cole JM, Sheehan AH, Jordan JK. Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary disease. Ann Pharmacother 2012;46:1717–21.

19. 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.

20. Pearlman DS, Chervinsky P, LaForce C, et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med 1992;327:1420–5.

21. Takahashi T, Belvisi MG, Patel H, et al. Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. Am J Respir Crit Care Med 1994;150(6 Pt 1):1640–5.

22. Donohue JF, Fogarty C, Lötvall J, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med 2010;182:155–62.

23. Koch A, Pizzichini E, Hamilton A, et al. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis 2014;9:697–714.

24. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775–89.

25. Hanania NA, Feldman G, Zachgo W, et al. The efficacy and safety of the novel long-acting β2 agonist vilanterol in patients with COPD: a randomized placebo-controlled trial. Chest 2012;142:119–27.

26. Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543–54.

27. Decramer ML, Chapman KR, Dahl R, et al. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallel-group study. Lancet Respir Med 2013;1:524–33.

28. Jones PW, Singh D, Bateman ED, et al. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study. Eur Respir J 2012;40:830–6.

29. D’Urzo A, Ferguson GT, van Noord JA, et al. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respir Res 2011;12:156.

30. Antoniu SA. UPLIFT Study: the effects of long-term therapy with inhaled tiotropium in chronic obstructive pulmonary disease. Evaluation of: Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008;359:1543–54. Expert Opin Pharmacother 2009;10:719–22.

31. Nelson HS, Gross NJ, Levine B, et al. Cardiac safety profile of nebulized formoterol in adults with COPD: a 12-week, multicenter, randomized, double- blind, double-dummy, placebo- and active-controlled trial. Clin Ther 2007;29:2167–78.

32. Gershon A, Croxford R, Calzavara A, et al. Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease. JAMA Intern Med 2013;173:1175–85.

33. Aljaafareh A, Valle JR, Lin YL, et al. Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study. SAGE Open Med 2016;4:2050312116671337.

34. O’Connor AB. Tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2009;360:185–6.

35. Kesten S, Jara M, Wentworth C, Lanes S. Pooled clinical trial analysis of tiotropium safety. Chest 2006;130:1695–703.

36. Wise RA, Anzueto A, Cotton D, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med 2013;369:1491–501.

37. 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.

38. Chong J, Karner C, Poole P. Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012(9):CD009157.

39. Gan WQ, Man SF, Sin DD. Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis. BMC Pulm Med 2005;5:3.

40. Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012(7):CD002991.

41. Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current understanding and review of the literature. Chest 2004;126:213–9.

42. Drummond MB, Dasenbrook EC, Pitz MW, et al. Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA 2008;300:2407–16.

43. Lee SY, Park HY, Kim EK, et al. Combination therapy of inhaled steroids and long-acting beta2-agonists in asthma-COPD overlap syndrome. Int J Chron Obstruct Pulmon Dis 2016;11:2797–803.

44. Postma DS, Rabe KF. The asthma-COPD overlap syndrome. N Engl J Med 2015;373:1241–9.

45. Farne HA, Cates CJ. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2015:CD008989.

46. Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med 2016;374:2222–34.

47. Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007;146:545–55.

48. 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.

49. Gallelli L, Falcone D, Cannataro R, et al. Theophylline action on primary human bronchial epithelial cells under proinflammatory stimuli and steroidal drugs: a therapeutic rationale approach. Drug Des Devel Ther 2017;11:265–72.

50. Paloucek FP, Rodvold KA. Evaluation of theophylline overdoses and toxicities. Ann Emerg Med 1988;17:135–44.

51. Ram FS, Jones PW, Castro AA, et al. Oral theophylline for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002(4):CD003902.

52. 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.

53. Devereux G, Cotton S, Barnes P, et al. Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial. Trials 2015;16:267.

54. Walters JA, Walters EH, Wood-Baker R. Oral corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005(3):CD005374.

55. Horita N, Miyazawa N, Morita S, et al. Evidence suggesting that oral corticosteroids increase mortality in stable chronic obstructive pulmonary disease. Respir Res 2014;15:37.

56. Poole P, Chong J, Cates CJ. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2015(7):CD001287.

57. Zheng JP, Wen FQ, Bai CX, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med 2014;2:187–94.

58. Seemungal TA, Wilkinson TM, Hurst JR, et al. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med 2008;178:1139–47.

59. Ries AL, Kaplan RM, Limberg TM, Prewitt LM. Effects of pulmonary rehabilitation on physiologic and psychosocial outcomes in patients with chronic obstructive pulmonary disease. Ann Intern Med 1995;122:823– 32.

60. Güell R, Casan P, Belda J, et al. Long-term effects of outpatient rehabilitation of COPD: a randomized trial. Chest 2000;117:976–83.

61. Wedzicha JA, Singh R, Mackay AJ. Acute COPD exacerbations. Clin Chest Med 2014;35:157–63.

62. Wedzicha JA, Seemungal TAR. COPD exacerbations: defining their cause and prevention. Lancet 2007;370:786–96.

63. Spencer S, Calverley PMA, Burge PS, Jones PW. Impact of preventing exacerbations on deterioration of health status in COPD. Eur Respir J 2004;23:698–702.

64. Blanchette CM, Gross NJ, Altman P. Rising costs of COPD and the potential for maintenance therapy to slow the trend. Am Health Drug Benef 2014;7:98.

65. Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest 2015;147:894–942.

66. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report. Respirology 2017;22:575–601.

67. Wedzicha JA, Brill SE, Allinson JP, Donaldson GC. Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease. BMC Med 2013;11:181.

68. Seemungal TAR, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418–22.

69. Kanner RE, Anthonisen NR, Connett JE. Lower respiratory illnesses promote FEV1 decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med 2001;164:358–64.

70. Donaldson GC, Seemungal TAR, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847–52.

71. Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006;173:1114–21.

72. Rabe KF. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharmacol 2011;163:53–67.

73. Calverley PMA, Rabe KF, Goehring U-M, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009;374:685–94.

74. Fabbri LM, Calverley PMA, Izquierdo-Alonso JL, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009;374:695–703.

75. Lee S, Hui DSC, Mahayiddin AA, et al. Roflumilast in Asian patients with COPD: a randomized placebo-controlled trial. Respirology 2011;16:1249–57.

76. Calverley PM, Martinez FJ, Fabbri LM, et al. Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? The REACT study protocol. Int J Chron Obstruct Pulmon Dis 2012;7:375–82.

77. Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013(11):CD002309.

78. Sheffner AL, Medler EM, Jacobs LW, Sarett HP. The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am Rev Respir Dis 1964;90:721–9.

79. Boman G, Bäcker U, Larsson S, et al. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 1983;64:405–15.

80. Grassi C, Morandini GC. A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis. European journal of clinical pharmacology. 1976;9:393–6.

81. Hansen NCG, Skriver A, Brorsen-Riis L, et al. Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis. Respir Med 1994;88:531–5.

82. Francis RS, Spicer CC. Chemotherapy in chronic bronchitis: Influence of daily penicillin and tetracycline on exacerbations and their cost: A report to the research committee of the British Tuberculosis Association by Their Chronic Bronchitis Subcommittee. BMJ 1960;1:297–303.

83. Francis RS, May JR, Spicer CC. Chemotherapy of bronchitis. BMJ 1961;2:979.

84. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689–98.

85. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med 2014;189:1503–8.

86. Uzun S, Djamin RS, Kluytmans JAJW, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014;2:361–8.

87. Collet JP, Shapiro S, Ernst P, et al. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:1719–24.

88. Jing LI. Protective effect of a bacterial extract against acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary. Age 2004;67:0–05.

89. Braido F, Tarantini F, Ghiglione V, et al. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections. Int J Chron Obstruct Pulmon Dis 2007;2:335.

90. Bhatt SP, Wells JM, Kinney GL, et al. β-Blockers are associated with a reduction in COPD exacerbations. Thorax 2016;71:8–14.

91. Bhatt SP, Connett JE, Voelker H, et al. β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol. BMJ Open 2016;6:e012292.

92. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128–8.

93. Sasaki T, Nakayama K, Yasuda H, et al. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc 2009;57:1453–7.

94. Xiong W, Zhang Qs, Zhao W, et al. A 12-month follow-up study on the preventive effect of oral lansoprazole on acute exacerbation of chronic obstructive pulmonary disease. Int J Exper Pathol 2016;97:107–13.

95. Baumeler L, Papakonstantinou E, Milenkovic B, et al. Therapy with proton-pump inhibitors for gastroesophageal reflux disease does not reduce the risk for severe exacerbations in COPD. Respirology 2016;21:883–90.

96 Sabanathan A, Sabanathan S, Shah R, Richardson J. Lung volume reduction surgery for emphysema: a review. J Cardiovasc Surg 1998;39:237.

97. Group NETTR. Patients at high risk of death after lung-volume–reduction surgery. N Engl J Med 2001;345:1075–83.

98. Group NETTR. A randomized trial comparing lung-volume–reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059–73.

99. Decker MR, Leverson GE, Jaoude WA, Maloney JD. Lung volume reduction surgery since the National Emphysema Treatment Trial: study of Society of Thoracic Surgeons database. J Thorac Cardiovasc Surg 2014;148:2651–8.

100. Deslée G, Mal H, Dutau H, et al. Lung volume reduction coil treatment vs usual care in patients with severe emphysema: the REVOLENS randomized clinical trial. JAMA 2016;315:175–84.

101. Hartman JE, Klooster K, Gortzak K, et al. Long-term follow-up after bronchoscopic lung volume reduction treatment with coils in patients with severe emphysema. Respirology 2015;20:319–26.

102. Snell GI, Hopkins P, Westall G, et al. A feasibility and safety study of bronchoscopic thermal vapor ablation: a novel emphysema therapy. Ann Thorac Surg 2009;88:1993–8.

103. Ingenito EP, Berger RL, Henderson AC, et al. Bronchoscopic lung volume reduction using tissue engineering principles. Am J Respir Crit Care Med 2003;167:771–8.

104. Ingenito EP, Loring SH, Moy ML, et al. Comparison of physiological and radiological screening for lung volume reduction surgery. Am J Respir Crit Care Med 2001;163:1068–73.

105. Shah P, Slebos D, Cardoso P, et al. Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial. Lancet 2011;378:997–1005.

106. Sciurba FC, Ernst A, Herth FJ, et al. A randomized study of endobronchial valves for advanced emphysema. N Engl J Med 2010;363:1233–44.

107. Wan IY, Toma TP, Geddes DM, et al. Bronchoscopic lung volume reduction for end-stage emphysema: report on the first 98 patients. Chest 2006;129:518–26.

108. Gompelmann D, Eberhardt R, Schuhmann M, et al. Lung volume reduction with vapor ablation in the presence of incomplete fissures: 12-month results from the STEP-UP randomized controlled study. Respiration 2016;92:397–403.

109. Come CE, Kramer MR, Dransfield MT, et al. A randomised trial of lung sealant versus medical therapy for advanced emphysema. Eur Respir J 2015;46:651–62.

110. Group NOTT. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980;93:391–8.

111. Council M. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981;1:681–6.

112. 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.

113. Vestbo J, Hurd SS, Agustí AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013;187:347–65.

114. Group L-TOTTR. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med 2016;375:1617–27.

115. McCarthy B, Casey D, Devane D, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2015(2):CD003793.

116. Griffiths TL, Burr ML, Campbell IA, et al. Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial. Lancet 2000;355:362–8.

117. Garcia-Aymerich J, Lange P, Benet M, et al. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax 2006;61:772–8.

118. Thabut G, Ravaud P, Christie JD, et al. Determinants of the survival benefit of lung transplantation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:1156–63.

119. Lahzami S, Bridevaux PO, Soccal PM, et al. Survival impact of lung transplantation for COPD. Eur Respir J 2010;36:74–80.

120. Cerón Navarro J, de Aguiar Quevedo K, Ansótegui Barrera E, et al. Functional outcomes after lung transplant in chronic obstructive pulmonary disease. Arch Bronconeumol 2015;51:109–14.

121. Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015;34:1–15.

122. Minai OA, Shah S, Mazzone P, et al. Bronchogenic carcinoma after lung transplantation: characteristics and outcomes. J Thorac Oncol 2008;3:1404–9.

123. Hajizadeh N, Goldfeld K, Crothers K. What happens to patients with COPD with long-term oxygen treatment who receive mechanical ventilation for COPD exacerbation? A 1-year retrospective follow- up study. Thorax 2015;70:294–6.

124. Siouta N, van Beek K, Preston N, et al. Towards integration of palliative care in patients with chronic heart failure and chronic obstructive pulmonary disease: a systematic literature review of European guidelines and pathways. BMC Palliat Care 2016;15:18.

125. Celli BR, MacNee W; ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23:932–46.

126. Szekendi MK, Vaughn J, Lal A, et al. The prevalence of inpatients at thirty-three U.S. hospitals appropriate for and receiving referral to palliative care. J Palliat Med 2016;19:360–72.

127. Rush B, Hertz P, Bond A, et al. Use of palliative care in patients with end-stage COPD and receiving home oxygen: national trends and barriers to care in the United States. Chest 2017;151:41–6.

Our patient has evidence of air trapping and emphysema based on a high residual volume. A CT scan of the chest can determine the nature of the emphysema (heterogeneous versus homogenous) and based on these findings, further determination of the best strategy for lung volume reduction can be made.

Is there a role for long-term oxygen therapy?

Long-term oxygen therapy (LTOT) used for > 15 hours a day is thought to reduce mortality among patients with chronic obstructive pulmonary disease (COPD) and severe resting hypoxemia [110–113].More recent studies have failed to show similar beneficial effects of LTOT. A recent study examined the effects of LTOT in randomized fashion and determined that supplemental oxygen for patients with stable COPD and resting or exercise-induced moderate desaturation did not affect the time to death or first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, the rate of all hospitalizations, the rate of all COPD exacerbations, or changes in measures of quality of life, depression, anxiety, or functional status [114].

Our patient is currently on long-term oxygen therapy and in spite of some uncertainty as to its benefit, it is prudent to order oxygen therapy until further clarification is available.

What is the role of pulmonary rehabilitation?

Pulmonary rehabilitation is an established treatment for patients with chronic lung disease [115]. Benefits include improvement in exercise tolerance, symptoms, and quality of life, with a reduction in the use of health care resources [116].A Spanish population-based cohort study that looked at the influence of regular physical activity on COPD showed that patients who reported low, moderate, or high physical activity had a lower risk of COPD admissions and all-cause mortality than patients with very low physical activity after adjusting for all confounders [117].

As previously mentioned, patients in GOLD categories B, C, and D should be offered pulmonary rehabilitation as part of their treatment [7]. The ideal patient is one who is not too sick to undergo rehabilitation and is motivated to his or her quality of life.

What is the current scope of lung transplantation in the management of severe COPD?

There is a indisputable role for lung transplantation in end-stage COPD. However, lung transplantation does not benefit all COPD patients. There is a subset of patients for whom the treatment provides a survival benefit. It has been reported that 79% of patients with an FEV1 < 16% predicted will survive at least 1 year additional after transplant, but only 11% of patients with an FEV1 > 25% will do so [118]. The pre-transplant BODE (body mass index, airflow obstruction/FEV1, dyspnea, and exercise capacity) index score is used to identify the patients who will benefit from lung transplantation [119,120]. International guidelines for the selection of lung transplant candidates identify the following patient characteristics [121]:

The disease is progressive, despite maximal treatment including medication, pulmonary rehabilitation, and oxygen therapy
The patient is not a candidate for endoscopic or surgical LVRS
BODE index of 5 to 6
The partial pressure of carbon dioxide is greater than 50 mm Hg or 6.6kPa and/or partial pressure of oxygen is less than 60 mm Hg or 8kPa
FEV1 of 25% predicted