Advertisement

COPD pp 333-349 | Cite as

Pharmacologic Management of COPD

  • Joo Hun ParkEmail author
Chapter
  • 10 Downloads

Abstract

Pharmacologic therapy in COPD aimed to achieve symptomatic relief, improve quality of life, and prevent the disease progression measured by lung function decline or aggravation of emphysema. Pharmacologic agents which can effectively stop disease progression are not currently available so far, although some therapeutic trials in animal studies demonstrated promising results [1–5]. However, pharmacologic therapy can improve major symptoms and quality of life in COPD. Among many therapeutic agents, bronchodilators including β2 agonist, anticholinergic agent, inhaled corticosteroid, and phosphodiesterase 4 inhibitor (roflumilast) are deemed to be the mainstay of COPD treatment [6–9]. Bronchodilators can improve main symptoms and exercise capacity in COPD by decreasing airflow limitation and reducing dynamic pulmonary hyperinflation, although the positive outcome on mortality and decline of lung function has not been proven yet [10–12].

References

  1. 1.
    Wright JL, Zhou S, Preobrazhenska O, Marshall C, Sin DD, Laher I, et al. Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling. Am J Respir Crit Care Med. 2011;183(1):50–8. PubMed PMID: 20709821. Epub 2010/08/17. engPubMedCrossRefGoogle Scholar
  2. 2.
    Bracke KR, D’Hulst AI, Maes T, Moerloose KB, Demedts IK, Lebecque S, et al. Cigarette smoke-induced pulmonary inflammation and emphysema are attenuated in CCR6-deficient mice. J Immunol. 2006;177(7):4350–9. PubMed PMID: 16982869. Epub 2006/09/20. engPubMedCrossRefGoogle Scholar
  3. 3.
    Churg A, Zhou S, Wang X, Wang R, Wright JL. The role of interleukin-1beta in murine cigarette smoke-induced emphysema and small airway remodeling. Am J Respir Cell Mol Biol. 2009;40(4):482–90. PubMed PMID: 18931327PubMedCrossRefGoogle Scholar
  4. 4.
    Churg A, Wang R, Wang X, Onnervik PO, Thim K, Wright JL. Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs. Thorax. 2007;62(8):706–13. PubMed PMID: 17311841. Pubmed Central PMCID: 2117295PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Lee JH, Lee DS, Kim EK, Choe KH, Oh YM, Shim TS, et al. Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs. Am J Respir Crit Care Med. 2005;172(8):987–93. PubMed PMID: 16002570PubMedCrossRefGoogle Scholar
  6. 6.
    Cooper CB, Tashkin DP. Recent developments in inhaled therapy in stable chronic obstructive pulmonary disease. BMJ. 2005;330(7492):640–4. PubMed PMID: 15774995. Pubmed Central PMCID: 554913PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Man SF, McAlister FA, Anthonisen NR, Sin DD. Contemporary management of chronic obstructive pulmonary disease: clinical applications. JAMA. 2003;290(17):2313–6. PubMed PMID: 14600190PubMedCrossRefGoogle Scholar
  8. 8.
    Sin DD, McAlister FA, Man SF, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease: scientific review. JAMA. 2003;290(17):2301–12. PubMed PMID: 14600189PubMedCrossRefGoogle Scholar
  9. 9.
    Wilt TJ, Niewoehner D, MacDonald R, Kane RL. Management of stable chronic obstructive pulmonary disease: a systematic review for a clinical practice guideline. Ann Intern Med. 2007;147(9):639–53. PubMed PMID: 17975187PubMedCrossRefGoogle Scholar
  10. 10.
    Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–54. PubMed PMID: 18836213CrossRefGoogle Scholar
  11. 11.
    Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775–89. PubMed PMID: 17314337. Epub 2007/02/23. engCrossRefGoogle Scholar
  12. 12.
    Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, 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(8):545–55. PubMed PMID: 17310045PubMedCrossRefGoogle Scholar
  13. 13.
    O’Reilly J, Jones MM, Parnham J, Lovibond K, Rudolf M, Guideline DG. Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance. BMJ. 2010;340:c3134. PubMed PMID: 20581031PubMedCrossRefGoogle Scholar
  14. 14.
    Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, 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(4):347–65. PubMed PMID: 22878278PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Jenkins CR, Postma DS, Anzueto AR, Make BJ, Peterson S, Eriksson G, et al. Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease. BMC Pulm Med. 2015;15:97. PubMed PMID: 26293575. Pubmed Central PMCID: 4546184PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Qaseem A, Wilt TJ, Weinberger SE, Hanania NA, Criner G, van der Molen T, 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(3):179–91. PubMed PMID: 21810710PubMedCrossRefGoogle Scholar
  17. 17.
    Reddel HK, Bateman ED, Becker A, Boulet LP, Cruz AA, Drazen JM, et al. A summary of the new GINA strategy: a roadmap to asthma control. Eur Respir J. 2015;46:622–30. PubMed PMID: 26206872PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Kato G, Takahashi K, Tashiro H, Kurata K, Shirai H, Kimura S, et al. Beta2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells. BMC Immunol. 2014;15:39. PubMed PMID: 25359462. Pubmed Central PMCID: 4228181PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Billington CK, Ojo OO, Penn RB, Ito S. cAMP regulation of airway smooth muscle function. Pulm Pharmacol Ther. 2013;26(1):112–20. PubMed PMID: 22634112. Pubmed Central PMCID: 3574867PubMedCrossRefGoogle Scholar
  20. 20.
    Roux FJ, Grandordy B, Douglas JS. Functional and binding characteristics of long-acting beta 2-agonists in lung and heart. Am J Respir Crit Care Med. 1996;153(5):1489–95. PubMed PMID: 8630591PubMedCrossRefGoogle Scholar
  21. 21.
    Berton DC, Barbosa PB, Takara LS, Chiappa GR, Siqueira AC, Bravo DM, et al. Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD. Thorax. 2010;65(7):588–93. PubMed PMID: 20627914PubMedCrossRefGoogle Scholar
  22. 22.
    Oga T, Nishimura K, Tsukino M, Sato S, Hajiro T, Mishima M. A comparison of the effects of salbutamol and ipratropium bromide on exercise endurance in patients with COPD. Chest. 2003;123(6):1810–6. PubMed PMID: 12796154PubMedCrossRefGoogle Scholar
  23. 23.
    Grainge CL, Lau LC, Ward JA, Dulay V, Lahiff G, Wilson S, et al. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med. 2011;364(21):2006–15. PubMed PMID: 21612469PubMedCrossRefGoogle Scholar
  24. 24.
    Larsson S, Svedmyr N. Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol in asthmatics. Am Rev Respir Dis. 1977;116(5):861–9. PubMed PMID: 921062PubMedGoogle Scholar
  25. 25.
    Anderson GP, Linden A, Rabe KF. Why are long-acting beta-adrenoceptor agonists long-acting? Eur Respir J. 1994;7(3):569–78. PubMed PMID: 7912202PubMedCrossRefGoogle Scholar
  26. 26.
    Cazzola M, Centanni S, Regorda C, di Marco F, di Perna F, Carlucci P, et al. Onset of action of single doses of formoterol administered via Turbuhaler in patients with stable COPD. Pulm Pharmacol Ther. 2001;14(1):41–5. PubMed PMID: 11162418PubMedCrossRefGoogle Scholar
  27. 27.
    Cazzola M, Pasqua F, Ferri L, Biscione G, Cardaci V, Matera MG. Rapid onset of bronchodilation with formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler as compared to formoterol alone in patients with COPD. Pulm Pharmacol Ther. 2011;24(1):118–22. PubMed PMID: 20816833PubMedCrossRefGoogle Scholar
  28. 28.
    McMahon AW, Levenson MS, McEvoy BW, Mosholder AD, Murphy D. Age and risks of FDA-approved long-acting beta(2)-adrenergic receptor agonists. Pediatrics. 2011;128(5):e1147–54. PubMed PMID: 22025595PubMedCrossRefGoogle Scholar
  29. 29.
    Sears MR. The FDA-mandated trial of safety of long-acting beta-agonists in asthma: finality or futility? Thorax. 2013;68(2):195–8. PubMed PMID: 22858928PubMedCrossRefGoogle Scholar
  30. 30.
    Jaeschke R, O’Byrne PM, Mejza F, Nair P, Lesniak W, Brozek J, et al. The safety of long-acting beta-agonists among patients with asthma using inhaled corticosteroids: systematic review and metaanalysis. Am J Respir Crit Care Med. 2008;178(10):1009–16. PubMed PMID: 18776152PubMedCrossRefGoogle Scholar
  31. 31.
    Sears MR. Safety of long-acting beta-agonists: are new data really required? Chest. 2009;136(2):604–7. PubMed PMID: 19505986PubMedCrossRefGoogle Scholar
  32. 32.
    Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev. 2010;5:CD005535. PubMed PMID: 20464739. Pubmed Central PMCID: 4169792Google Scholar
  33. 33.
    Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Molken MP, Beeh KM, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011;364(12):1093–103. PubMed PMID: 21428765PubMedCrossRefGoogle Scholar
  34. 34.
    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. PubMed PMID: 22972134Google Scholar
  35. 35.
    Vogelmeier CF, Asijee GM, Kupas K, Beeh KM. Tiotropium and salmeterol in COPD patients at risk of exacerbations: a post hoc analysis from POET-COPD((R)). Adv Ther. 2015;32(6):537–47. PubMed PMID: 26100349. Pubmed Central PMCID: 4487350PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Kim JS, Park J, Lim SY, Oh YM, Yoo KH, Park YB, et al. Comparison of clinical efficacy and safety between indacaterol and tiotropium in COPD: meta-analysis of randomized controlled trials. PLoS One. 2015;10(3):e0119948. PubMed PMID: 25799171. Pubmed Central PMCID: 4370711PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Mahler DA, Kerstjens HA, Donohue JF, Buhl R, Lawrence D, Altman P. Indacaterol vs tiotropium in COPD patients classified as GOLD a and B. Respir Med. 2015;109(8):1031–9. PubMed PMID: 26094050PubMedCrossRefGoogle Scholar
  38. 38.
    Donohue JF, Fogarty C, Lotvall J, Mahler DA, Worth H, Yorgancioglu A, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med. 2010;182(2):155–62. PubMed PMID: 20463178PubMedCrossRefGoogle Scholar
  39. 39.
    Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;9:CD006829. PubMed PMID: 22972099. Pubmed Central PMCID: 4170910Google Scholar
  40. 40.
    Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;3:CD010115. PubMed PMID: 24615270Google Scholar
  41. 41.
    Janson C, Larsson K, Lisspers KH, Stallberg B, Stratelis G, Goike H, et al. Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta2 agonist: observational matched cohort study (PATHOS). BMJ. 2013;346:f3306. PubMed PMID: 23719639. Pubmed Central PMCID: 3666306PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Vogelmeier CF, Bateman ED, Pallante J, Alagappan VK, D’Andrea P, Chen H, et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respir Med. 2013;1(1):51–60. PubMed PMID: 24321804PubMedCrossRefGoogle Scholar
  43. 43.
    Rabe KF, Timmer W, Sagkriotis A, Viel K. Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD. Chest. 2008;134(2):255–62. PubMed PMID: 18403672PubMedCrossRefGoogle Scholar
  44. 44.
    Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285–94. PubMed PMID: 25196117PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Liesker JJ, Wijkstra PJ, Ten Hacken NH, Koeter GH, Postma DS, Kerstjens HA. A systematic review of the effects of bronchodilators on exercise capacity in patients with COPD. Chest. 2002;121(2):597–608. PubMed PMID: 11834677PubMedCrossRefGoogle Scholar
  46. 46.
    Quinn D, Seale JP, Reisner C, Fischer T, Golden M, Fernandez C, et al. A randomized study of formoterol fumarate in a porous particle metered-dose inhaler in patients with moderate-to-severe COPD. Respir Med. 2014;108(9):1327–35. PubMed PMID: 25060541PubMedCrossRefGoogle Scholar
  47. 47.
    Rossi A, van der Molen T, del Olmo R, Papi A, Wehbe L, Quinn M, et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD. Eur Respir J. 2014;44(6):1548–56. PubMed PMID: 25359348PubMedCrossRefGoogle Scholar
  48. 48.
    Chowdhury BA, Seymour SM, Michele TM, Durmowicz AG, Liu D, Rosebraugh CJ. The risks and benefits of indacaterol—the FDA’s review. N Engl J Med. 2011;365(24):2247–9. PubMed PMID: 22168640PubMedCrossRefGoogle Scholar
  49. 49.
    Chapman KR, Rennard SI, Dogra A, Owen R, Lassen C, Kramer B, et al. Long-term safety and efficacy of indacaterol, a long-acting beta(2)-agonist, in subjects with COPD: a randomized, placebo-controlled study. Chest. 2011;140(1):68–75. PubMed PMID: 21349928PubMedCrossRefGoogle Scholar
  50. 50.
    Kempsford R, Norris V, Siederer S. 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. 2013;26(2):256–64. PubMed PMID: 23232038PubMedCrossRefGoogle Scholar
  51. 51.
    Hanania NA, Feldman G, Zachgo W, Shim JJ, Crim C, Sanford L, et al. The efficacy and safety of the novel long-acting beta2 agonist vilanterol in patients with COPD: a randomized placebo-controlled trial. Chest. 2012;142(1):119–27. PubMed PMID: 22241764PubMedCrossRefGoogle Scholar
  52. 52.
    Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013;1(3):210–23. PubMed PMID: 24429127PubMedCrossRefGoogle Scholar
  53. 53.
    Celli B, Crater G, Kilbride S, Mehta R, Tabberer M, Kalberg C, et al. Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: a randomized, controlled study. Chest. 2014;145(5):981–91. PubMed PMID: 24385182PubMedCrossRefGoogle Scholar
  54. 54.
    Maleki-Yazdi MR, Kaelin T, Richard N, Zvarich M, Church A. Efficacy and safety of umeclidinium/vilanterol 62.5/25 mcg and tiotropium 18 mcg in chronic obstructive pulmonary disease: results of a 24-week, randomized, controlled trial. Respir Med. 2014;108(12):1752–60. PubMed PMID: 25458157PubMedCrossRefGoogle Scholar
  55. 55.
    Joos GF, Aumann JL, Coeck C, Korducki L, Hamilton AL, Kunz C, et al. A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1 profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting beta2-agonist, in patients with chronic obstructive pulmonary disease. Respir Med. 2015;109(5):606–15. PubMed PMID: 25776199PubMedCrossRefGoogle Scholar
  56. 56.
    Koch A, Pizzichini E, Hamilton A, Hart L, Korducki L, De Salvo MC, et al. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat(R) 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. PubMed PMID: 25045258. Pubmed Central PMCID: 4094569PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Buhl R, Maltais F, Abrahams R, Bjermer L, Derom E, Ferguson G, et al. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4). Eur Respir J. 2015;45(4):969–79. PubMed PMID: 25573406. Pubmed Central PMCID: 4391658PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Singh D, Ferguson GT, Bolitschek J, Gronke L, Hallmann C, Bennett N, et al. Tiotropium + olodaterol shows clinically meaningful improvements in quality of life. Respir Med. 2015;109(10):1312–9. PubMed PMID: 26320402PubMedCrossRefGoogle Scholar
  59. 59.
    Hill NS. Fluid and electrolyte considerations in diuretic therapy for hypertensive patients with chronic obstructive pulmonary disease. Arch Intern Med. 1986;146(1):129–33. PubMed PMID: 2867747PubMedCrossRefGoogle Scholar
  60. 60.
    de Vries F, Pouwels S, Bracke M, Leufkens HG, Cooper C, Lammers JW, et al. Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2007;16(6):612–9. PubMed PMID: 16998945PubMedCrossRefGoogle Scholar
  61. 61.
    Au DH, Curtis JR, Every NR, McDonell MB, Fihn SD. Association between inhaled beta-agonists and the risk of unstable angina and myocardial infarction. Chest. 2002;121(3):846–51. PubMed PMID: 11888971PubMedCrossRefGoogle Scholar
  62. 62.
    Au DH, Lemaitre RN, Curtis JR, Smith NL, Psaty BM. The risk of myocardial infarction associated with inhaled beta-adrenoceptor agonists. Am J Respir Crit Care Med. 2000;161(3 Pt 1):827–30. PubMed PMID: 10712329PubMedCrossRefGoogle Scholar
  63. 63.
    Wilchesky M, Ernst P, Brophy JM, Platt RW, Suissa S. Bronchodilator use and the risk of arrhythmia in COPD: part 2: reassessment in the larger Quebec cohort. Chest. 2012;142(2):305–11. PubMed PMID: 22871756PubMedCrossRefGoogle Scholar
  64. 64.
    Wilchesky M, Ernst P, Brophy JM, Platt RW, Suissa S. Bronchodilator use and the risk of arrhythmia in COPD: part 1: Saskatchewan cohort study. Chest. 2012;142(2):298–304. PubMed PMID: 22871755PubMedCrossRefGoogle Scholar
  65. 65.
    Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for reversible airway disease. Cochrane Database Syst Rev. 2002;4:CD002992. PubMed PMID: 12519582Google Scholar
  66. 66.
    van Gestel YR, Hoeks SE, Sin DD, Welten GM, Schouten O, Witteveen HJ, et al. Impact of cardioselective beta-blockers on mortality in patients with chronic obstructive pulmonary disease and atherosclerosis. Am J Respir Crit Care Med. 2008;178(7):695–700. PubMed PMID: 18565952PubMedCrossRefGoogle Scholar
  67. 67.
    Ekstrom MP, Hermansson AB, Strom KE. Effects of cardiovascular drugs on mortality in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):715–20. PubMed PMID: 23328521PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Du Q, Sun Y, Ding N, Lu L, Chen Y. Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-analysis of observational studies. PLoS One. 2014;9(11):e113048. PubMed PMID: 25427000. Pubmed Central PMCID: 4245088PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Weatherall M, Wijesinghe M, Perrin K, Harwood M, Beasley R. Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy. Thorax. 2010;65(1):39–43. PubMed PMID: 20029037PubMedCrossRefGoogle Scholar
  70. 70.
    Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, et al. The use of beta-agonists and the risk of death and near death from asthma. N Engl J Med. 1992;326(8):501–6. PubMed PMID: 1346340PubMedCrossRefGoogle Scholar
  71. 71.
    Gershon AS, Campitelli MA, Croxford R, Stanbrook MB, To T, Upshur R, et al. Combination long-acting beta-agonists and inhaled corticosteroids compared with long-acting beta-agonists alone in older adults with chronic obstructive pulmonary disease. JAMA. 2014;312(11):1114–21. PubMed PMID: 25226477PubMedCrossRefGoogle Scholar
  72. 72.
    Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB. Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med. 2008;149(6):380–90. PubMed PMID: 18794557PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Rogers DF. Motor control of airway goblet cells and glands. Respir Physiol. 2001;125(1–2):129–44. PubMed PMID: 11240157PubMedCrossRefGoogle Scholar
  74. 74.
    Gross NJ. Tiotropium bromide. Chest. 2004;126(6):1946–53. PubMed PMID: 15596697PubMedCrossRefGoogle Scholar
  75. 75.
    Mak JC, Barnes PJ. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung. Am Rev Respir Dis. 1990;141(6):1559–68. PubMed PMID: 2350099PubMedCrossRefGoogle Scholar
  76. 76.
    Walch L, Brink C, Norel X. The muscarinic receptor subtypes in human blood vessels. Therapie. 2001;56(3):223–6. PubMed PMID: 11475798PubMedGoogle Scholar
  77. 77.
    Walch L, Gascard JP, Dulmet E, Brink C, Norel X. Evidence for a M(1) muscarinic receptor on the endothelium of human pulmonary veins. Br J Pharmacol. 2000;130(1):73–8. PubMed PMID: 10781000. Pubmed Central PMCID: 1572048PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Kistemaker LE, Bos ST, Mudde WM, Hylkema MN, Hiemstra PS, Wess J, et al. Muscarinic M(3) receptors contribute to allergen-induced airway remodeling in mice. Am J Respir Cell Mol Biol. 2014;50(4):690–8. PubMed PMID: 24156289PubMedCrossRefGoogle Scholar
  79. 79.
    Kistemaker LE, van Os RP, Dethmers-Ausema A, Bos IS, Hylkema MN, van den Berge M, et al. Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced neutrophilic airway inflammation in mice. Am J Physiol Lung Cell Mol Physiol. 2015;308(1):L96–103. PubMed PMID: 25381025. Pubmed Central PMCID: 4315453PubMedCrossRefGoogle Scholar
  80. 80.
    Kistemaker LE, Bos IS, Hylkema MN, Nawijn MC, Hiemstra PS, Wess J, et al. Muscarinic receptor subtype-specific effects on cigarette smoke-induced inflammation in mice. Eur Respir J. 2013;42(6):1677–88. PubMed PMID: 23397297PubMedCrossRefGoogle Scholar
  81. 81.
    Saitoh H, Masuda T, Shimura S, Fushimi T, Shirato K. Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands. Am J Physiol Lung Cell Mol Physiol. 2001;280(1):L79–87. PubMed PMID: 11133497PubMedCrossRefGoogle Scholar
  82. 82.
    Fryer AD, Stein LH, Nie Z, Curtis DE, Evans CM, Hodgson ST, et al. Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. J Clin Invest. 2006;116(1):228–36. PubMed PMID: 16374515. Pubmed Central PMCID: 1319219PubMedCrossRefGoogle Scholar
  83. 83.
    Fisher JT, Vincent SG, Gomeza J, Yamada M, Wess J. Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2 or M3 muscarinic acetylcholine receptors. FASEB J. 2004;18(6):711–3. PubMed PMID: 14977875PubMedCrossRefGoogle Scholar
  84. 84.
    Nie Z, Scott GD, Weis PD, Itakura A, Fryer AD, Jacoby DB. Role of TNF-alpha in virus-induced airway hyperresponsiveness and neuronal M(2) muscarinic receptor dysfunction. Br J Pharmacol. 2011;164(2b):444–52. PubMed PMID: 21457223. Pubmed Central PMCID: 3188913PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Coulson FR, Fryer AD. Muscarinic acetylcholine receptors and airway diseases. Pharmacol Ther. 2003;98(1):59–69. PubMed PMID: 12667888PubMedCrossRefGoogle Scholar
  86. 86.
    Barnes PJ. Muscarinic receptor subtypes in airways. Eur Respir J. 1993;6(3):328–31. PubMed PMID: 8472820PubMedGoogle Scholar
  87. 87.
    Wadbo M, Lofdahl CG, Larsson K, Skoogh BE, Tornling G, Arwestrom E, et al. Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study. Eur Respir J. 2002;20(5):1138–46. PubMed PMID: 12449166PubMedCrossRefGoogle Scholar
  88. 88.
    Cheyne L, Irvin-Sellers MJ, White J. Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013;9:CD009552. PubMed PMID: 24043433Google Scholar
  89. 89.
    Ni H, Soe Z, Moe S. Aclidinium bromide for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;9:CD010509. PubMed PMID: 25234126Google Scholar
  90. 90.
    Frith PA, Thompson PJ, Ratnavadivel R, Chang CL, Bremner P, Day P, et al. Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study-a randomised controlled trial. Thorax. 2015;70(6):519–27. PubMed PMID: 25841237. Pubmed Central PMCID: 4453631PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Rodrigo GJ, Neffen H. A systematic review of the efficacy and safety of a fixed-dose combination of umeclidinium and vilanterol for the treatment of COPD. Chest. 2015;148(2):397–407. PubMed PMID: 25798635PubMedCrossRefGoogle Scholar
  92. 92.
    Rodrigo GJ, Plaza V. Efficacy and safety of a fixed-dose combination of indacaterol and Glycopyrronium for the treatment of COPD: a systematic review. Chest. 2014;146(2):309–17. PubMed PMID: 24556877PubMedCrossRefGoogle Scholar
  93. 93.
    Gross NJ. Ipratropium bromide. N Engl J Med. 1988;319(8):486–94. PubMed PMID: 2970009PubMedCrossRefGoogle Scholar
  94. 94.
    Ziment I. Pharmacologic therapy of obstructive airway disease. Clin Chest Med. 1990;11(3):461–86. PubMed PMID: 2205440PubMedGoogle Scholar
  95. 95.
    Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The lung health study. JAMA. 1994;272(19):1497–505. PubMed PMID: 7966841PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Sin DD, Tu JV. Lack of association between ipratropium bromide and mortality in elderly patients with chronic obstructive airway disease. Thorax. 2000;55(3):194–7. PubMed PMID: 10679537. Pubmed Central PMCID: 1745709PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Tashkin DP, Ashutosh K, Bleecker ER, Britt EJ, Cugell DW, Cummiskey JM, et al. Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease. A 90-day multi-center study. Am J Med. 1986;81(5A):81–90. PubMed PMID: 2947465PubMedCrossRefGoogle Scholar
  98. 98.
    Colice GL. Nebulized bronchodilators for outpatient management of stable chronic obstructive pulmonary disease. Am J Med. 1996;100(1A):11S–8S. PubMed PMID: 8610712PubMedCrossRefGoogle Scholar
  99. 99.
    Chervinsky P. Concomitant bronchodilator therapy and ipratropium bromide. A clinical review. Am J Med. 1986;81(5A):67–73. PubMed PMID: 2947463PubMedCrossRefGoogle Scholar
  100. 100.
    Disse B, Reichl R, Speck G, Traunecker W, Ludwig Rominger KL, Hammer R. Ba 679 BR, a novel long-acting anticholinergic bronchodilator. Life Sci. 1993;52(5–6):537–44. PubMed PMID: 8441333PubMedCrossRefGoogle Scholar
  101. 101.
    Barnes PJ, Belvisi MG, Mak JC, Haddad EB, O’Connor B. Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci. 1995;56(11–12):853–9.PubMedCrossRefGoogle Scholar
  102. 102.
    van Noord JA, Smeets JJ, Custers FL, Korducki L, Cornelissen PJ. Pharmacodynamic steady state of tiotropium in patients with chronic obstructive pulmonary disease. Eur Respir J. 2002;19(4):639–44. PubMed PMID: 11998992PubMedCrossRefGoogle Scholar
  103. 103.
    Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA, 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(1):19–26.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, 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(8):741–50.PubMedCrossRefGoogle Scholar
  105. 105.
    Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;7:CD009285.Google Scholar
  106. 106.
    Donohue JF, Niewoehner D, Brooks J, O’Dell D, Church A. Safety and tolerability of once-daily umeclidinium/vilanterol 125/25 mcg and umeclidinium 125 mcg in patients with chronic obstructive pulmonary disease: results from a 52-week, randomized, double-blind, placebo-controlled study. Respir Res. 2014;15:78. PubMed PMID: 25015176. Pubmed Central PMCID: 4113670PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Decramer M, Maltais F, Feldman G, Brooks J, Harris S, Mehta R, et al. Bronchodilation of umeclidinium, a new long-acting muscarinic antagonist, in COPD patients. Respir Physiol Neurobiol. 2013;185(2):393–9. PubMed PMID: 23026438PubMedCrossRefGoogle Scholar
  108. 108.
    Decramer M, Anzueto A, Kerwin E, Kaelin T, Richard N, Crater G, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med. 2014;2(6):472–86. PubMed PMID: 24835833PubMedCrossRefGoogle Scholar
  109. 109.
    Jones PW, Singh D, Bateman ED, Agusti A, Lamarca R, de Miquel G, et al. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study. Eur Respir J. 2012;40(4):830–6. PubMed PMID: 22441743PubMedCrossRefGoogle Scholar
  110. 110.
    Singh S, Loke YK, Enright P, Furberg CD. Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications. Thorax. 2013;68(1):114–6. PubMed PMID: 22764216PubMedCrossRefGoogle Scholar
  111. 111.
    Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2008;300(12):1439–50. PubMed PMID: 18812535PubMedCrossRefGoogle Scholar
  112. 112.
    Singh S, Loke YK, Enright PL, Furberg CD. Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials. BMJ. 2011;342:d3215. PubMed PMID: 21672999. Pubmed Central PMCID: 3114950PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Karner C, Chong J, Poole P. Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;7:CD009285. PubMed PMID: 22786525Google Scholar
  114. 114.
    Verhamme KM, Sturkenboom MC, Brusselle GG. Use of tiotropium Respimat versus HandiHaler and mortality in patients with COPD. Eur Respir J. 2014;43(6):1818–9. PubMed PMID: 24881063PubMedCrossRefGoogle Scholar
  115. 115.
    Dong YH, Lin HH, Shau WY, Wu YC, Chang CH, Lai MS. Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials. Thorax. 2013;68(1):48–56. PubMed PMID: 23042705PubMedCrossRefGoogle Scholar
  116. 116.
    Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369(16):1491–501. PubMed PMID: 23992515PubMedCrossRefGoogle Scholar
  117. 117.
    Barnes PJ. Cyclic nucleotides and phosphodiesterases and airway function. Eur Respir J. 1995;8(3):457–62. PubMed PMID: 7789494PubMedCrossRefGoogle Scholar
  118. 118.
    Aubier M. Effect of theophylline on diaphragmatic muscle function. Chest. 1987;92(1 Suppl):27S–31S. PubMed PMID: 3297524PubMedCrossRefGoogle Scholar
  119. 119.
    Ram FS, Jones PW, Castro AA, De Brito JA, Atallah AN, Lacasse Y, et al. Oral theophylline for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2002;4:CD003902. PubMed PMID: 12519617Google Scholar
  120. 120.
    Ram FS, Jardin JR, Atallah A, Castro AA, Mazzini R, Goldstein R, et al. Efficacy of theophylline in people with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. Respir Med. 2005;99(2):135–44. PubMed PMID: 15715180PubMedCrossRefGoogle Scholar
  121. 121.
    Esau SA. The effect of theophylline on hypoxic, hypercapnic hamster diaphragm muscle in vitro. Am Rev Respir Dis. 1991;143(5 Pt 1):954–9. PubMed PMID: 2024850PubMedCrossRefGoogle Scholar
  122. 122.
    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(6):349–53. PubMed PMID: 6738652PubMedCrossRefGoogle Scholar
  123. 123.
    Barr RG, Rowe BH, Camargo CA Jr. Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials. BMJ. 2003;327(7416):643. PubMed PMID: 14500434. Pubmed Central PMCID: 196388PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Duffy N, Walker P, Diamantea F, Calverley PM, Davies L. Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Thorax. 2005;60(9):713–7. PubMed PMID: 15939732. Pubmed Central PMCID: 1747521PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Cosio BG, Iglesias A, Rios A, Noguera A, Sala E, Ito K, et al. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax. 2009;64(5):424–9. PubMed PMID: 19158122PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, et al. A molecular mechanism of action of theophylline: induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99(13):8921–6. PubMed PMID: 12070353. Pubmed Central PMCID: 124399PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    To Y, Ito K, Kizawa Y, Failla M, Ito M, Kusama T, et al. Targeting phosphoinositide-3-kinase-delta with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182(7):897–904. PubMed PMID: 20224070. Pubmed Central PMCID: 2970861PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Lim S, Tomita K, Caramori G, Jatakanon A, Oliver B, Keller A, et al. Low-dose theophylline reduces eosinophilic inflammation but not exhaled nitric oxide in mild asthma. Am J Respir Crit Care Med. 2001;164(2):273–6. PubMed PMID: 11463600PubMedCrossRefGoogle Scholar
  129. 129.
    Sullivan P, Bekir S, Jaffar Z, Page C, Jeffery P, Costello J. Anti-inflammatory effects of low-dose oral theophylline in atopic asthma. Lancet. 1994;343(8904):1006–8. PubMed PMID: 7909049PubMedCrossRefGoogle Scholar
  130. 130.
    Culpitt SV, de Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;165(10):1371–6. PubMed PMID: 12016098PubMedCrossRefGoogle Scholar
  131. 131.
    Kanehara M, Yokoyama A, Tomoda Y, Shiota N, Iwamoto H, Ishikawa N, et al. Anti-inflammatory effects and clinical efficacy of theophylline and tulobuterol in mild-to-moderate chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2008;21(6):874–8. PubMed PMID: 18983928PubMedCrossRefGoogle Scholar
  132. 132.
    Miller CA, Slusher LB, Vesell ES. Polymorphism of theophylline metabolism in man. J Clin Invest. 1985;75(5):1415–25. PubMed PMID: 4039734. Pubmed Central PMCID: 425478PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Talseth T, Boye NP, Kongerud J, Bredesen JE. Aging, cigarette smoking and oral theophylline requirement. Eur J Clin Pharmacol. 1981;21(1):33–7. PubMed PMID: 7333344PubMedCrossRefGoogle Scholar
  134. 134.
    Horai Y, Ishizaki T, Sasaki T, Watanabe M, Kabe J. Individualized aminophylline therapy in patients with obstructive airway disease: oral dosage prediction from an intravenous test dose. Eur J Clin Pharmacol. 1982;23(2):111–21. PubMed PMID: 7140800PubMedCrossRefGoogle Scholar
  135. 135.
    Poole P, Black PN, Cates CJ. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;8:CD001287. PubMed PMID: 22895919Google Scholar
  136. 136.
    Decramer M, Rutten-van Molken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (bronchitis randomized on NAC cost-utility study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005;365(9470):1552–60. PubMed PMID: 15866309PubMedCrossRefGoogle Scholar
  137. 137.
    Zheng JP, Wen FQ, Bai CX, Wan HY, Kang J, Chen P, 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(3):187–94. PubMed PMID: 24621680PubMedCrossRefGoogle Scholar
  138. 138.
    Tse HN, Raiteri L, Wong KY, Ng LY, Yee KS, Tseng CZ. Benefits of high-dose N-acetylcysteine to exacerbation-prone patients with COPD. Chest. 2014;146(3):611–23. PubMed PMID: 24833327PubMedCrossRefGoogle Scholar
  139. 139.
    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. PubMed PMID: 26222376Google Scholar
  140. 140.
    Kew KM, Dias S, Cates CJ. Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis. Cochrane Database Syst Rev. 2014;3:CD010844. PubMed PMID: 24671923Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Pulmonary and Critical Care MedicineAjou University School of MedicineSuwonSouth Korea

Personalised recommendations