Pharmacological and non-pharmacological management of COPD; limitations and future prospects: a review of current literature

  • Anees ur RehmanEmail author
  • Mohamed Azmi Ahmad Hassali
  • Sameen Abbas
  • Irfhan Ali Bin Hyder Ali
  • Sabariah Noor Harun
  • Jaya Muneswarao
  • Rabia Hussain
Review Article



This article aimed to summarize the pharmacological and non-pharmacological management of COPD and limitations and prospects of the currently available pharmacological therapies in the management of COPD.


COPD is a complex comorbid disease that irreversibly affects the pulmonary system and is considered the fifth leading cause of death worldwide. Currently, the diagnosis, assessment and management of COPD are difficult because of its complex syndrome involving numerous pulmonary and extra-pulmonary components. It is diagnosed based on the subjective and objective findings of a chronic cough, sputum production, dyspnoea, exercise intolerance and spirometry values. The GOLD report recommends bronchodilators as the first-line treatment agents in all stages of COPD severity, commonly combined with inhaled corticosteroids (ICS), methylxanthines and antibiotics, depending upon the condition and symptoms of patients. Non-pharmacological treatments of COPD include smoking cessation, influenza and pneumococcal vaccination, pulmonary rehabilitation, LTOT and surgical lung volume reduction. The efficacy of the therapy is directly related to the patients’ inhaler use training and education. A new future in COPD medication is essential to ensure the optimal management of COPD. New alternative sources should be considered in the treatment of COPD.


New approaches such as e-technology can play an essential role in improving compliance and adherence to therapy. New therapies with better and long-lasting effects and minimized side effects need to be discovered to improve the pharmacological management of COPD.


COPD Pharmacological treatment Non-pharmacological management Immunization Review 



The authors are very grateful to the teaching faculty of the School of Pharmaceutical Science, University Sains Malaysia, especially Dr. Ahmad Noori, who gave their valuable feedback on the systematic review, and to the library staff for searching and requesting the full-text articles from the authors.


This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest among the authors.


  1. Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, Nair H, Gasevic D, Sridhar D, Campbell H (2015) Global and regional estimates of COPD prevalence: Systematic review and meta–analysis. J Glob Health 5(2)Google Scholar
  2. Agusti A, Celli B (2011) Avoiding confusion in COPD: from risk factors to phenotypes to measures of disease characterisation. 749–751Google Scholar
  3. Akwe J, Steinbach S, Murphy JJ (2016) A review of the non pharmacologic management of chronic obstructive pulmonary disease. Am J Pulmonary Respiratory Med 1:11–27Google Scholar
  4. Albert RK et al (2016) A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med 375:1617–1627CrossRefGoogle Scholar
  5. Appleton S, Jones T, Poole P, Lasserson TJ, Adams R, Smith B, Muhammed J (2006) Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst RevGoogle Scholar
  6. Beasley R, Patel M, Perrin K, O’Driscoll BR (2011) High-concentration oxygen therapy in COPD. Lancet 378:969–970CrossRefGoogle Scholar
  7. Bonini M, Usmani OS (2015) The importance of inhaler devices in the treatment of COPD. COPD Res Pract 1:9Google Scholar
  8. Bourbeau J, Bhutani M, Hernandez P, Marciniuk DD, Aaron SD, Balter M, Beauchesne MF, D'Urzo A, Goldstein R, Kaplan A, Maltais F (2017) CTS position statement: Pharmacotherapy in patients with COPD—An update. Taylor & Francis, p 222–241Google Scholar
  9. Carpenter DM, Roberts CA, Sage AJ, George J, Horne R (2017) A review of electronic devices to assess inhaler technique. Curr Allergy Asthma Rep 17:17. CrossRefGoogle Scholar
  10. Corhay J-L, Dang DN, Van Cauwenberge H, Louis R (2014) Pulmonary rehabilitation and COPD: providing patients a good environment for optimizing therapy. Int J Chronic Obstruct Pulmonary Dis 9:27Google Scholar
  11. DiSantostefano RL, Li H, Hinds D, Galkin DV, Rubin DB (2014) Risk of pneumonia with inhaled corticosteroid/long-acting β2 agonist therapy in chronic obstructive pulmonary disease: a cluster analysis. Int J Chronic Obstruct Pulmonary Dis 9:457CrossRefGoogle Scholar
  12. Farne HA, Cates CJ (2015) 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: Cd008989.
  13. Ford ES (2015) Trends in mortality from COPD among adults in the United States. Chest 148:962–970CrossRefGoogle Scholar
  14. Geake JB, Dabscheck EJ, Wood-Baker R, Cates CJ (2015) Indacaterol, a once-daily beta2-agonist, versus twice-daily beta2-agonists or placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2015:1–82Google Scholar
  15. Gershon AS et al (2014) Combination long-acting β-agonists and inhaled corticosteroids compared with long-acting β-agonists alone in older adults with chronic obstructive pulmonary disease. JAMA 312:1114–1121CrossRefGoogle Scholar
  16. Golpe R, Suárez-Valor M, Martín-Robles I, Sanjuán-López P, Cano-Jiménez E, Castro-Añón O, de Llano LAP (2018) Mortality in COPD patients according to clinical phenotypes. Int J Chronic Obstruct Pulmonary Dis 13:1433CrossRefGoogle Scholar
  17. Gross NJ, Barnes PJ (2017) New therapies for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 195:159–166CrossRefGoogle Scholar
  18. Han MK, Postma D, Mannino DM, Giardino ND, Buist S, Curtis JL, Martinez FJ (2007) Gender and chronic obstructive pulmonary disease: why it matters. Am J Respir Crit Care Med 176:1179–1184CrossRefGoogle Scholar
  19. Han J, Dai L, Zhong N (2013) Indacaterol on dyspnea in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized placebo-controlled trials. BMC Pulmonary Med 13:26CrossRefGoogle Scholar
  20. Hay J et al (1992) Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease. Eur Respir J 5:659–664Google Scholar
  21. Herath SC, Poole P (2014) Prophylactic antibiotic therapy for chronic obstructive pulmonary disease. JAMA 311(21):2225–2226CrossRefGoogle Scholar
  22. Himes BE, Weitzman ER (2016) Innovations in health information technologies for chronic pulmonary diseases. Respir Res 17(1):38CrossRefGoogle Scholar
  23. Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T (2014) Antidepressants for smoking cessation. Cochrane Database Syst RevGoogle Scholar
  24. Janson C et al (2018) Identifying the associated risks of pneumonia in COPD patients: ARCTIC an observational study. Respir Res 19:172CrossRefGoogle Scholar
  25. Júnior DSB, de Andrade AD, Teixeira AS, Cavalcanti CA, Morais AB, Marinho PE (2015) Whole-body vibration improves functional capacity and quality of life in patients with severe chronic obstructive pulmonary disease (COPD): a pilot study. Int J Chronic Obstruct Pulmonary Dis 10:125Google Scholar
  26. Karner C, Chong J, Poole P (2014) Tiotropium versus placebo for chronic obstructive. Cochrane Database Syst Rev 2014(7).
  27. Kempsford R, Norris V, Siederer S (2013) Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD. Pulm Pharmacol Ther 26:256–264CrossRefGoogle Scholar
  28. Kew KM, Mavergames C, Walters JA (2013) Long-acting beta 2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013(10).
  29. Kikidis D, Konstantinos V, Tzovaras D, Usmani OS (2016) The digital asthma patient: the history and future of inhaler based health monitoring devices. J Aerosol Med Pulmonary Drug Del 29:219–232CrossRefGoogle Scholar
  30. Koch A, Pizzichini E, Hamilton A, Hart L, Korducki L, De Salvo MC, Paggiaro P (2014) 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 Chronic Obstruct Pulmonary Dis 9:697CrossRefGoogle Scholar
  31. Kopsaftis Z, Wood-Baker R, Poole P (2018) Influenza vaccine for chronic obstructive pulmonary disease. Front immunol 9Google Scholar
  32. Kupczyk M, Szepiel P, Kuna P (2015) Tiotropium and its efficacy in the treatment of COPD. Adv Respir Med 83:229–237Google Scholar
  33. Latifi-Navid H, Latifi-Navid S, Mostafaiy B, Jamalkandi SA, Ahmadi A (2018) Pneumococcal disease and the effectiveness of the PPV23 vaccine in adults: a two-stage Bayesian meta-analysis of observational and RCT. Sci Rep 8Google Scholar
  34. Lee B, Lee T, Jang S, Lee Y, Choi N (2017) The effect of smoking cessation interventions in patients with COPD. Syst Rev Value Health 20:A652CrossRefGoogle Scholar
  35. Lipson DA et al (2017) FULFIL trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 196:438–446CrossRefGoogle Scholar
  36. Lipson DA et al (2018) Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med 378:1671–1680CrossRefGoogle Scholar
  37. Löfdahl C-G, Tilling B, Ekström T, Jörgensen L, Johansson G, Larsson K (2010) COPD health care in Sweden–a study in primary and secondary care. Respir Med 104:404–411CrossRefGoogle Scholar
  38. Martinez FJ, Donohue JF, Rennard SI (2011) The future of chronic obstructive pulmonary disease treatment—difficulties of and barriers to drug development. Lancet 378:1027–1037CrossRefGoogle Scholar
  39. Martinez FJ, Calverley PM, Goehring U-M, Brose M, Fabbri LM, Rabe KF (2015) Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet 385:857–866CrossRefGoogle Scholar
  40. Martinez FJ, Fabbri LM, Ferguson GT, Orevillo C, Darken P, Martin UJ, Reisner C (2017) Baseline symptom score impact on benefits of glycopyrrolate/formoterol metered dose inhaler in COPD. Chest 152:1169–1178CrossRefGoogle Scholar
  41. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Corlateanu A, Vestbo J (2017) Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis. Eur Respir Rev 26:160073CrossRefGoogle Scholar
  42. Melani AS (2015) Long-acting muscarinic antagonists. Expert Rev Clin Pharmacol 8:479–501. CrossRefGoogle Scholar
  43. Miravitlles M, Anzueto A (2015) Role of infection in exacerbations of chronic obstructive pulmonary disease. Curr Opin Pulm Med 21:278–283CrossRefGoogle Scholar
  44. Morjaria JB, Rigby A, Morice AH (2017) Inhaled corticosteroid use and the risk of pneumonia and COPD exacerbations in the UPLIFT study. Lung 195:281–288CrossRefGoogle Scholar
  45. Nair SS, Nair RS, Rasheed FA (2017) Usefulness of antibiotics in acute exacerbations of COPD. J Evol Med Dent Sci 6:2672–2676CrossRefGoogle Scholar
  46. Nannini LJ, Poole P, Milan SJ, Holmes R, Normansell R (2013) Combined corticosteroid and long-acting beta2-agonist in one inhaler versus placebo for chronic obstructive Pulmonary Disease. Cochrane Database Syst Rev (11).
  47. Ni W, Shao X, Cai X, Wei C, Cui J, Wang R, Liu Y (2015) Prophylactic use of macrolide antibiotics for the prevention of chronic obstructive pulmonary disease exacerbation: a meta-analysis. PLoS One 10:e0121257CrossRefGoogle Scholar
  48. Nici L et al (2006) American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med 173:1390–1413CrossRefGoogle Scholar
  49. Papi A et al (2018) Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet 391:1076–1084CrossRefGoogle Scholar
  50. Rabe KF, Calverley PM, Martinez FJ, Fabbri LM (2017) Effect of roflumilast in patients with severe COPD and a history of hospitalisation. Eur Respir J 50:1700158CrossRefGoogle Scholar
  51. Ram FS, Jones P, Jardim J, Castro AA, Atallah ÁN, Lacasse Y, Goldstein R, Cendon S (2002) Oral theophylline for chronic obstructive pulmonary disease. Cochrane Data Syst RevGoogle Scholar
  52. Safka KA, McIvor RA (2015) Non-pharmacological management of chronic obstructive pulmonary disease. Ulster Med J 84:13Google Scholar
  53. Sahin H, Varol Y, Naz I, Aksel N, Tuksavul F, Ozsoz A (2018) The effect of pulmonary rehabilitation on COPD exacerbation frequency per year. Clin Respir J 12:165–174CrossRefGoogle Scholar
  54. Salvi S (2014) Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease. Clin Chest Med 35:17–27CrossRefGoogle Scholar
  55. Sehatzadeh S (2012) Influenza and pneumococcal vaccinations for patients with chronic obstructive pulmonary disease (COPD): an evidence-based review. Ontario Health Technol Asses Ser 12:1Google Scholar
  56. Singh D et al (2015) Tiotropium+ olodaterol shows clinically meaningful improvements in quality of life. Respir Med 109:1312–1319CrossRefGoogle Scholar
  57. Singh D et al (2016) The bronchodilator effects of extrafine glycopyrronium added to combination treatment with beclometasone dipropionate plus formoterol in COPD: a randomised crossover study (the TRIDENT study). Respir Med 114:84–90CrossRefGoogle Scholar
  58. Spruit MA et al (2013) An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 188:e13–e64CrossRefGoogle Scholar
  59. Spruit MA, Pitta F, McAuley E, ZuWallack RL, Nici L (2015) Pulmonary rehabilitation and physical activity in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 192:924–933CrossRefGoogle Scholar
  60. Tashkin DP (2010) Long-acting anticholinergic use in chronic obstructive pulmonary disease: efficacy and safety. Curr Opin Pulm Med 16:97–105CrossRefGoogle Scholar
  61. The Global Initiative for Chronic Obstructive Lung Disease [GOLD] Accessed 10 Sept 2018
  62. ur Rehman A, Naeem F, Abbas S, Ashfaq F, Hassali MAA (2018) Utilization of short message service (SMS) in non-pharmacological management of hypertension. A pilot study in an URBAN public hospital of Multan. Pakistan. J Public Health:1–7Google Scholar
  63. Uzun S et al (2014) Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2:361–368CrossRefGoogle Scholar
  64. Varkey JB, Varkey AB, Varkey B (2009) Prophylactic vaccinations in chronic obstructive pulmonary disease: current status. Curr Opin Pulm Med 15:90–99CrossRefGoogle Scholar
  65. Vestbo J et al (2016a) Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet 387:1817–1826CrossRefGoogle Scholar
  66. Vestbo J et al (2016b) Effectiveness of fluticasone furoate–vilanterol for COPD in clinical practice. N Engl J Med 375:1253–1260CrossRefGoogle Scholar
  67. Vestbo J et al (2017) Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet 389:1919–1929CrossRefGoogle Scholar
  68. Vogelmeier CF et al (2017) Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 195:557–582CrossRefGoogle Scholar
  69. Walters JA, Tang JNQ, Poole P, Wood-Baker R (2017) Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. The Cochrane Library; doi: 10.1002/14651858.Google Scholar
  70. Wedzicha JA et al (2016) Indacaterol–glycopyrronium versus salmeterol–fluticasone for COPD. N Engl J Med 374:2222–2234CrossRefGoogle Scholar
  71. Woodhead M et al (2011) Guidelines for the management of adult lower respiratory tract infections-full version. Clin Microbiol Infect 17:E1–E59CrossRefGoogle Scholar
  72. Wu J, Sin DD (2011) Improved patient outcome with smoking cessation: when is it too late? Int J Chronic Obstruct Pulmonary Dis 6:259Google Scholar
  73. Yamada M, Ichinose M (2015) Cutting edge of COPD therapy: current pharmacological therapy and future direction COPD. Res Pract 1:5Google Scholar
  74. Yang IA, Clarke MS, Sim EH, Fong KM (2012) Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev (7).
  75. Yusen RD et al (2018) The long-term oxygen treatment trial for chronic obstructive pulmonary disease: rationale, design, and lessons learned. Ann Am Thoracic Soc 15:89–101CrossRefGoogle Scholar
  76. ZuWallack RL, Mahler DA, Reilly D, Church N, Emmett A, Rickard K, Knobil K (2001) Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest 119:1661–1670CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Pharmaceutical SciencesUniversity Sains MalaysiaMindenMalaysia
  2. 2.Faculty of PharmacyBahauddin Zakariya UniversityMultanPakistan
  3. 3.Department of PharmacyQuaid e Azam UniversityIslamabadPakistan
  4. 4.Respiratory DepartmentHospital Pulau Pinang, Penang, Ministry of Health MalaysiaGeorge TownMalaysia
  5. 5.Pharmacy DepartmentHospital Kulim, Kedah, Ministry of Health MalaysiaKulimMalaysia

Personalised recommendations