title: Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact. Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations. The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events. Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy. GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β(2)-agonists (LABAs), such as formoterol and salmeterol. Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present. Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components. This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease.
authors: Department of Medicine, David Geffen School of Medicine at UCLA, 405 Hilgard Avenue, Los Angeles, CA 90095, USA. DTashkin@mednet.ucla.edu
authors: Donald P
authors: DP
authors: Tashkin
authors: Gary T
authors: GT
authors: Ferguson
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D019317:Evidence-Based Medicine; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists
references: N Engl J Med. 2008 Oct 9;359(15):1543-54
references: 18836213
references: Respir Res. 2012 Feb 17;13:15
references: 22340019
references: Am J Respir Crit Care Med. 2001 Sep 1;164(5):778-84
references: 11549532
references: Respir Med. 2005 May;99(5):524-8
references: 15823447
references: Pulm Pharmacol Ther. 2010 Aug;23(4):257-67
references: 20381630
references: Pharmacol Rev. 2012 Jul;64(3):450-504
references: 22611179
references: Eur Respir Rev. 2011 Sep 1;20(121):183-94
references: 21881146
references: Drugs. 2010 Dec 3;70(17):2269-80
references: 21080743
references: Chest. 2012 Jan;141(1):81-86
references: 21799028
references: J Med Econ. 2011;14(4):486-96
references: 21679019
references: Int J Pharm. 2004 Sep 28;283(1-2):1-9
references: 15363496
references: Respir Med. 2010 Jul;104(7):995-1004
references: 20303247
references: Chest. 2005 Mar;127(3):809-17
references: 15764761
references: Respir Med. 2011 Mar;105(3):435-41
references: 20880687
references: Respir Med. 2012 Mar;106(3):382-9
references: 21975275
references: Respir Med. 2008 Dec;102(12):1701-7
references: 18760583
references: Eur Respir J. 2006 Jan;27(1):188-207
references: 16387952
references: Ther Adv Respir Dis. 2007 Oct;1(1):25-33
references: 19124345
references: Respir Med. 2010 Sep;104(9):1288-96
references: 20580216
references: Respir Res. 2011 Dec 07;12:156
references: 22151296
references: Cochrane Database Syst Rev. 2011 Sep 07;(9):CD009039
references: 21901729
references: Chest. 1997 Dec;112(6):1514-21
references: 9404747
references: Respir Med. 2010 Mar;104(3):412-7
references: 19892540
references: Arch Intern Med. 1999 Jan 25;159(2):156-60
references: 9927098
references: Respir Res. 2010 Oct 29;11:149
references: 21034447
references: Eur Respir J. 2009 Sep;34(3):757-69
references: 19720811
references: Drugs. 2009 Jun 18;69(9):1205-16
references: 19537837
references: Respir Med. 2011 Jun;105(6):930-8
references: 21367593
references: Respir Med. 2009 Apr;103(4):516-24
references: 19208459
references: COPD. 2009 Feb;6(1):17-25
references: 19229704
references: Respir Med. 2008 Nov;102(11):1511-20
references: 18804362
references: J Assoc Physicians India. 1991 Sep;39(9):680-2
references: 1839993
references: Pulm Pharmacol Ther. 2004;17(1):35-9
references: 14643169
references: Clin Respir J. 2012 Oct;6(4):248-57
references: 22329914
references: Int J Chron Obstruct Pulmon Dis. 2010 Nov 24;5:401-6
references: 21191434
references: Int J Chron Obstruct Pulmon Dis. 2012;7:153-64
references: 22419863
references: Future Med Chem. 2011 Oct;3(13):1585-605
references: 21942250
references: Health Technol Assess. 2001;5(26):1-149
references: 11701099
references: Respir Med. 2010 Aug;104(8):1179-88
references: 20172704
references: N Engl J Med. 2011 Dec 15;365(24):2247-9
references: 22168640
references: Br J Pharmacol. 2011 May;163(1):4-17
references: 21232045
references: J Aerosol Med. 2005 Fall;18(3):273-82
references: 16181002
references: Am J Respir Crit Care Med. 2009 Oct 15;180(8):741-50
references: 19644045
references: Respir Med. 2010 Oct;104(10):1482-9
references: 20541381
references: Int J Clin Pract. 2012 Mar;66(3):309-17
references: 22340451
references: Mol Pharmacol. 2011 Mar;79(3):389-99
references: 21139051
references: J Asthma. 1994;31(3):193-9
references: 8195061
references: Respir Med. 2008 Apr;102(4):593-604
references: 18083019
references: Respir Care. 2005 Oct;50(10):1313-21; discussion 1321-2
references: 16185367
references: Chest. 2006 Sep;130(3):647-56
references: 16963658
references: Chest. 2006 Mar;129(3):509-17
references: 16537846
references: Respir Med. 2004 Dec;98(12):1214-21
references: 15588043
references: Future Med Chem. 2011 Oct;3(13):1703-18
references: 21942257
references: Respiration. 2008;75(1):18-25
references: 17911976
references: Chest. 2000 Nov;118(5):1294-302
references: 11083677
references: Thorax. 2010 Dec;65(12):1086-91
references: 20978028
references: Chest. 2008 Aug;134(2):255-262
references: 18403672
references: Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 1):1256-61
references: 7952549
references: Prim Care Respir J. 2012 Mar;21(1):101-8
references: 22222945
references: COPD. 2010 Oct;7(5):331-6
references: 20854047
references: Respirology. 2011 Feb;16(2):350-8
references: 21138499
references: Eur Respir J. 2004 Jun;23(6):832-40
references: 15218994
references: Expert Opin Investig Drugs. 2012 Oct;21(10):1489-501
references: 22916733
references: Respir Care. 2011 Apr;56(4):477-87
references: 21255503
references: Int J Chron Obstruct Pulmon Dis. 2008;3(4):763-70
references: 19281091
references: Lancet Respir Med. 2013 Mar;1(1):51-60
references: 24321804
references: Pulm Pharmacol. 1994 Apr;7(2):103-7
references: 7915921
references: J Pharmacol Exp Ther. 2009 Nov;331(2):740-51
references: 19710368
references: Chest. 2005 Sep;128(3):1168-78
references: 16162703
references: Eur Respir J. 2005 Aug;26(2):214-22
references: 16055868
references: N Engl J Med. 2011 Mar 24;364(12):1093-1103
references: 21428765
references: Int J Chron Obstruct Pulmon Dis. 2010 Apr 07;5:57-71
references: 20463947
references: COPD. 2010 Dec;7(6):418-27
references: 21166630
references: Curr Med Res Opin. 2010 Nov;26(11):2527-33
references: 20843166
references: Chest. 1994 May;105(5):1411-9
references: 8181328
references: Int J Chron Obstruct Pulmon Dis. 2012;7:495-502
references: 22888221
references: Respir Med. 2006 Nov;100(11):1925-32
references: 16626956
references: Chest. 1999 Apr;115(4):966-71
references: 10208193
references: Trends Pharmacol Sci. 2011 Aug;32(8):495-506
references: 21683458
references: Respir Med. 2008 Apr;102(4):479-87
references: 18258423
references: Chest. 2006 Dec;130(6):1695-703
references: 17166984
references: COPD. 2009 Oct;6(5):404-15
references: 19863370
references: Ann Intern Med. 2007 Apr 17;146(8):545-55
references: 17310045