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Respiratory Research
Published in: Respiratory Research 1/2017

Open Access 01-12-2017 | Review

Optimizing bronchodilation in the prevention of COPD exacerbations

Authors: Marc Miravitlles, Antonio Anzueto, José R. Jardim

Published in: Respiratory Research | Issue 1/2017

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Abstract

The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA.
Literature
1.
Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370:786–6.PubMedCrossRef
2.
Vogelmeier CF, Criner GJ, Martínez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, López Varela MV, Nishimura M, Roche N, Rodríguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agustí A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Arch Bronconeumol. 2017;53:128–49.PubMedCrossRef
3.
4.
Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60:925–31.PubMedPubMedCentralCrossRef
5.
Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157:1418–22.PubMedCrossRef
6.
Miravitlles M, Ferrer M, Pont A, Zalacain R, Alvarez-Sala JL, Masa F, Verea H, Murio C, Ros F, Vidal R. Effect of exacerbations on quality of life in patients with chronic obstructive pulmonary disease: a 2 year follow up study. Thorax. 2004;59:387–95.PubMedPubMedCentralCrossRef
7.
Celli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, Jones PW, Vestbo J, Knobil K, Yates JC, Calverley PM. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med. 2008;178:332–8.PubMedCrossRef
8.
Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57:847–52.PubMedPubMedCentralCrossRef
9.
Dhamane AD, Moretz C, Zhou Y, Burslem K, Saverno K, Jain G, Renda A, Kaila S. COPD exacerbation frequency and its association with health care resource utilization and costs. Int J Chron Obstruct Pulmon Dis. 2015;10:2609–18.PubMedPubMedCentralCrossRef
10.
Miravitlles M, Murio C, Guerrero T, Gisbert R. Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest. 2002;121:1449–55.PubMedCrossRef
11.
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.PubMedPubMedCentralCrossRef
12.
Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, MacNee W, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128–38.PubMedCrossRef
13.
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J, Almagro P, Quintano JA, Trigueros JA, Cosío BG, Casanova C, Riesco JA, Simonet P, Rigau D, Soriano JB, Ancochea J. Spanish COPD guidelines (GesEPOC) 2017. Pharmacological treatment of stable chronic obstructive pulmonary disease. Arch Bronconeumol. 2017;53:324–35.
14.
National Institute for Health and Care Excellence (NICE). Chronic obstructive pulmonary disease. Management of chronic obstructive pulmonary disease in adults in primary and secondary care. NICE clinical guideline 101 (partial update). Updated June 2010. Available at: https://​www.​nice.​org.​uk/​guidance/​cg101. Accessed 5 June 2017.
15.
Montes De Oca M, Lopez Varela MV, Acuna A, Schiavi E, Rey MA, Jardim J, Casas A, Tokumoto A, Torres Duque CA, Ramirez-Venegas A, et al. ALAT-2014 Chronic Obstructive Pulmonary Disease (COPD) Clinical Practice Guidelines: questions and answers. Arch Bronconeumol. 2015;51:403–16.PubMedCrossRef
16.
O’Donnell DE, Hernandez P, Kaplan A, Aaron S, Bourbeau J, Marciniuk D, Balter M, Ford G, Gervais A, Lacasse Y, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2008 update - highlights for primary care. Can Respir J. 2008;15:1A–8A.PubMedPubMedCentralCrossRef
17.
Price D, West D, Brusselle G, Gruffydd-Jones K, Jones R, Miravitlles M, Rossi A, Hutton C, Ashton VL, Stewart R, Bichel K. Management of COPD in the UK primary-care setting: an analysis of real-life prescribing patterns. Int J Chron Obstruct Pulmon Dis. 2014;9:889–905.PubMedPubMedCentralCrossRef
18.
Vestbo J, Vogelmeier C, Small M, Higgins V. Understanding the GOLD 2011 Strategy as applied to a real-world COPD population. Respir Med. 2014;108:729–36.PubMedCrossRef
19.
Price D, Yawn B, Brusselle G, Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD. Prim Care Respir J. 2013;22:92–100.PubMedCrossRef
20.
Buhl R, Maltais F, Abrahams R, Bjermer L, Derom E, Ferguson G, Fležar M, Hébert J, McGarvey L, Pizzichini E, et al. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2–4). Eur Respir J. 2015;45:969–79.PubMedPubMedCentralCrossRef
21.
Bateman ED, Ferguson GT, Barnes N, Gallagher N, Green Y, Henley M, Banerji D. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013;42:1484–94.PubMedPubMedCentralCrossRef
22.
Donohue JF, Maleki-Yazdi MR, Kilbride S, Mehta R, Kalberg C, Church A. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mg in COPD. Respir Med. 2013;107:1538–46.PubMedCrossRef
23.
Singh D, Jones PW, Bateman ED, Korn S, Serra C, Molins E, Caracta C, Gil EG, Leselbaum A. Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study. BMC Pulm Med. 2014;14:178.PubMedPubMedCentralCrossRef
24.
Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandstöm T, Taylor AF, D’Andrea P, Arrasate C, Chen H, Banerji D. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med. 2013;1:199–209.PubMedCrossRef
25.
Vogelmeier CF, Bateman ED, Pallante J, Alagappan VK, D’Andrea P, Chen H, Banerji D. 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;1:51–60.PubMedCrossRef
26.
Donohue JF, Worsley S, Zhu CQ, Hardaker L, Church A. Improvements in lung function with umeclidinium/vilanterol versus fluticasone propionate/salmeterol in patients with moderate-to-severe COPD and infrequent exacerbations. Respir Med. 2015;109:870–81.PubMedCrossRef
27.
Vogelmeier C, Paggiaro PL, Dorca J, Sliwinski P, Mallet M, Kirsten AM, Beier J, Seoane B, Segarra RM, Leselbaum A. Efficacy and safety of aclidinium/formoterol versus salmeterol/fluticasone: a phase 3 COPD study. Eur Respir J. 2016;48:1030–9.PubMedCrossRef
28.
Zhong N, Wang C, Zhou X, Zhang N, Humphries M, Wang C, Thach C, Patalano F, Banerji D. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:1015–26.PubMedPubMedCentral
29.
Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, Thach C, Fogel R, Patalano F, Vogelmeier C. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016;374:2222–34.PubMedCrossRef
30.
Welte T, Vogelmeier C, Dahl R, Chapman KR, Rudolf M, Mehta R, D’Andrea P, Chen H, Banerji D. Once-daily QVA149 has a good safety profile in patients with COPD. Eur Respir J. 2013;42 Suppl 57:143s–44s. Abstract P757.
31.
Ferguson GT, Barnes N, Mehta R, D’Andrea P, Chen H, Banerji D. Cardio- and cerebro-vascular safety of QVA149: Results from a pooled analysis. Eur Respir J. 2013;42 Suppl 57:878s. Abstract P4139.
32.
Korn S, Kerwin E, Donohue J, Shreshta P, Leselbaum A, Lei A. Safety of aclidinium bromide/formoterol fumarate fixed-dose combination in COPD: pooled analyses of three Phase III studies. Eur Respir J. 2014;44 Suppl 58:P2416. Abstract.
33.
Buhl R, Abrahams R, Bjermer L, Derom E, Flezar M, Hebert J, Veale A, Groenke L, Hamilton A, Tetzlaff K, et al. Safety of once-daily tiotropium and olodaterol fixed-dose combination via the Respimat in chronic obstructive pulmonary disease in two 1-year studies. Eur Respir J. 2014;44 Suppl 59:P922. Abstract.
34.
Barrecheguren M, Monteagudo M, Ferrer J, Borrell E, Llor C, Esquinas C, Miravitlles M. Treatment patterns in COPD patients newly diagnosed in primary care. A population-based study. Respir Med. 2016;111:47–53.PubMedCrossRef
35.
Au DH, Bryson CL, Chien JW, Sun H, Udris EM, Evans LE, Bradley KA. The effects of smoking cessation on the risk of chronic obstructive pulmonary disease exacerbations. J Gen Intern Med. 2009;24:457–63.PubMedPubMedCentralCrossRef
36.
37.
Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE, Lung Health Study Research G. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005;142:233–9.PubMedCrossRef
38.
Vozoris NT, Stanbrook MB. Smoking prevalence, behaviours, and cessation among individuals with COPD or asthma. Respir Med. 2011;105:477–84.PubMedCrossRef
39.
Scanlon PD, Connett JE, Waller LA, Altose MD, Bailey WC, Buist AS, Tashkin DP. Lung Health Study Research G. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease. The Lung Health Study. Am J Respir Crit Care Med. 2000;161:381–90.PubMedCrossRef
40.
Poole PJ, Chacko E, Wood-Baker RW, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006:CD002733.
41.
Wongsurakiat P, Lertakyamanee J, Maranetra KN, Jongriratanakul S, Sangkaew S. Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients. J Med Assoc Thai. 2003;86:497–508.PubMed
42.
Nichol KL, Margolis KL, Wuorenma J, Von Sternberg T. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med. 1994;331:778–84.PubMedCrossRef
43.
Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, Bresee JS, Cox NJ. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2009;58:1–52.PubMed
44.
Huang CL, Nguyen PA, Kuo PL, Iqbal U, Hsu YH, Jian WS. Influenza vaccination and reduction in risk of ischemic heart disease among chronic obstructive pulmonary elderly. Comput Methods Programs Biomed. 2013;111:507–11.PubMedCrossRef
45.
Santus P, Radovanovic D, Balzano G, Pecchiari M, Raccanelli R, Sarno N, Di Marco F, Jones PW, Carone M. Improvements in lung diffusion capacity following pulmonary rehabilitation in COPD with and without ventilation inhomogeneity. Respiration. 2016;92:295–307.
46.
McCarthy B, Casey D, Devane D, Murphy K, Murphy E, Lacasse Y. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;2:CD003793.
47.
Puhan MA, Gimeno-Santos E, Scharplatz M, Troosters T, Walters EH, Steurer J. Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;CD005305.
48.
van Ranst D, Stoop WA, Meijer JW, Otten HJ, van de Port IG. Reduction of exacerbation frequency in patients with COPD after participation in a comprehensive pulmonary rehabilitation program. Int J Chron Obstruct Pulmon Dis. 2014;9:1059–67.PubMedPubMedCentralCrossRef
49.
Washko GR, Fan VS, Ramsey SD, Mohsenifar Z, Martinez F, Make BJ, Sciurba FC, Criner GJ, Minai O, Decamp MM, et al. The effect of lung volume reduction surgery on chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;177:164–69.PubMedCrossRef
50.
Zanoria SJ, ZuWallack R. Directly measured physical activity as a predictor of hospitalizations in patients with chronic obstructive pulmonary disease. Chron Respir Dis. 2013;10:207–13.PubMedCrossRef
51.
Esteban C, Arostegui I, Aburto M, Moraza J, Quintana JM, Aizpiri S, Basualdo LV, Capelastegui A. Influence of changes in physical activity on frequency of hospitalization in chronic obstructive pulmonary disease. Respirology. 2014;19:330–8.PubMedCrossRef
52.
Chawla H, Bulathsinghala C, Tejada JP, Wakefield D, ZuWallack R. Physical activity as a predictor of thirty-day hospital readmission after a discharge for a clinical exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014;11:1203–9.PubMedCrossRef
53.
Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Mölken MP, Beeh KM, Rabe KF, Fabbri LM. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011;364:1093–103.PubMedCrossRef
54.
Wedzicha JA, Calverley PM, Seemungal TA. Hagan G, Ansari Z, Stockley RA, INSPIRE investigators. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177:19–26.PubMedCrossRef
55.
56.
Eglen RM, Hegde SS, Watson N. Muscarinic receptor subtypes and smooth muscle function. Pharmacol Rev. 1996;48:531–65.PubMed
57.
O’Donnell DE, Fluge T, Gerken F, Hamilton A, Webb K, Aguilaniu B, Make B, Magnussen H. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23:832–40.PubMedCrossRef
58.
Beeh KM, Burgel PR, Franssen FM, Lopez-Campos JL, Loukides S, Hurst JR, Fležar M, Ulrik CS, Di Marco F, Stolz D, et al. How do dual long-acting bronchodilators prevent exacerbations of chronic obstructive pulmonary disease? Am J Respir Crit Care Med. 2016: doi: 10.​1164/​rccm.​201609-201794CI.
59.
Meyer T, Reitmeir P, Brand P, Herpich C, Sommerer K, Schulze A, Scheuch G, Newman S. Effects of formoterol and tiotropium bromide on mucus clearance in patients with COPD. Respir Med. 2011;105:900–6.PubMedCrossRef
60.
D’Urzo AD, Rennard SI, Kerwin EM, Mergel V, Leslbaum AR, Caracta CF. Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study. Respir Res. 2014;15:123.PubMedPubMedCentralCrossRef
61.
Santus P, Buccellati C, Centanni S, Fumagalli F, Busatto P, Blasi F, Sala A. Bronchodilators modulate inflammation in chronic obstructive pulmonary disease subjects. Pharmacol Res. 2012;66:343–48.PubMedCrossRef
62.
Casaburi R, Mahler DA, Jones PW, Wanner A, San PG, ZuWallack RL, Menjoge SS, Serby CW, Witek Jr T. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19:217–24.PubMedCrossRef
63.
Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax. 2003;58:399–404.PubMedPubMedCentralCrossRef
64.
Niewoehner DE, Rice K, Cote C, Paulson D, Cooper Jr JA, Korducki L, Cassino C, Kesten S. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med. 2005;143:317–26.PubMedCrossRef
65.
Dusser D, Bravo ML, Iacono P. The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur Respir J. 2006;27:547–55.PubMedCrossRef
66.
Powrie DJ, Wilkinson TM, Donaldson GC, Jones P, Scrine K, Viel K, Kesten S, Wedzicha JA. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur Respir J. 2007;30:472–78.PubMedCrossRef
67.
Tonnel AB, Perez T, Grosbois JM, Verkindre C, Bravo ML, Brun M. Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD. Int J Chron Obstruct Pulmon Dis. 2008;3:301–10.PubMedPubMedCentralCrossRef
68.
Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543–54.PubMedCrossRef
69.
Bateman E, Singh D, Smith D, Disse B, Towse L, Massey D, Blatchford J, Pavia D, Hodder R. Efficacy and safety of tiotropium Respimat SMI in COPD in two 1-year randomized studies. Int J Chron Obstruct Pulmon Dis. 2010;5:197–208.PubMedPubMedCentral
70.
Bateman ED, Tashkin D, Siafakas N, Dahl R, Towse L, Massey D, Pavia D, Zhong NS. A one-year trial of tiotropium Respimat plus usual therapy in COPD patients. Respir Med. 2010;104:1460–72.PubMedCrossRef
71.
D’Urzo A, Ferguson GT, van Noord JA, Hirata K, Martin C, Horton R, Lu Y, Banerji D, Overend T. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respir Res. 2011;12:156.PubMedPubMedCentralCrossRef
72.
Kerwin E, Hébert J, Gallagher N, Martin C, Overend T, Alagappan VK, Lu Y, Banerji D. Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study. Eur Respir J. 2012;40:1106–14.PubMedPubMedCentralCrossRef
73.
Kerwin EM, D’Urzo AD, Gelb AF, Lakkis H, Garcia GE, Caracta CF. Efficacy and safety of a 12-week treatment with twice-daily aclidinium bromide in COPD patients (ACCORD COPD I). COPD. 2012;9:90–101.PubMedCrossRef
74.
Jones PW, Singh D, Bateman ED, Agusti A, Lamarca R, de Miquel G, Segarra R, Caracta C, Garcia GE. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study. Eur Respir J. 2012;40:830–6.PubMedCrossRef
75.
Celli B, Crater G, Kilbride S, Mehta R, Tabberer M, Kalberg CJ, Church A. Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: a randomized, controlled study. Chest. 2014;145:981–91.PubMedCrossRef
76.
77.
Dahl R, Chung KF, Buhl R, Magnussen H, Nonikov V, Jack D, Bleasdale P, Owen R, Higgins M, Kramer B. Efficacy of a new once-daily long-acting inhaled b2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax. 2010;65:473–9.
78.
Chapman KR, Rennard SI, Dogra A, Owen R, Lassen C, Kramer B, INDORSE study investigators. Long-term safety and efficacy of indacaterol, a long-acting β2-agonist, in subjects with COPD: a randomized, placebo-controlled study. Chest. 2011;140:68–75.
79.
Donohue J, Fogarty C, Lötvall J, Mahler DA, Worth H, Yorgancioglu A, Iqbal A, Swales J, Owen R, Higgins M, Kramer B; INHANCE Study Investigators, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med. 2010;182:155–62.
80.
Decramer ML, Chapman KR, Dahl R, Frith P, Devouassoux G, Fritscher C, Cameron R, Shoaib M, Lawrence D, Young D, 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.PubMedCrossRef
81.
Cazzola M, Molimard M. The scientific rationale for combining long-acting β-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther. 2010;23:257–67.
82.
83.
Bateman ED, Chapman KR, Singh D, D’Urzo AD, Molins E, Leselbaum A, Gil EG. Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT). Respir Res. 2015;16:92.PubMedPubMedCentralCrossRef
84.
Leidy NK, Wilcox TK, Jones PW, Murray L, Winnette R, Howard K, Petrillo J, Powers J, Sethi S. Development of the EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO) measure. Value Health. 2010;13:965–75.PubMedCrossRef
85.
Decramer M, Anzueto A, Kerwin E, Kaelin T, Richard N, Crater G, Tabberer M, Harris S, Church A. 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;2:472–86.
86.
87.
Calverley PM, Anderson JA. Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J, investigators T. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–89.PubMedCrossRef
88.
Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, 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;1:210–23.PubMedCrossRef
89.
Martinez FJ, Vestbo J, Anderson JA, Brook RD, Celli BR, Cowans NJ, Crim C, Dransfield M, Kilbride S, Yates J, et al. Effect of fluticasone furoate and vilanterol on exacerbations of COPD in patients with moderate airflow obstruction. Am J Respir Crit Care Med. 2017;195:881–8.PubMedCrossRef
90.
Banerji D, Fedele M, Chen H. Once-daily dual bronchodilation with QVA149 reduces COPD exacerbations: results from the IGNITE program. Chest. 2014;145(3_Meeting abstracts):403A. Abstract.CrossRef
91.
Vogelmeier C, Zhong N, Humphries MJ, Mezzi K, Fogel R, Bader G, Patalano F, Banerji D. Indacaterol/glycopyrronium in symptomatic patients with COPD (GOLD B and GOLD D) versus salmeterol/fluticasone: ILLUMINATE/LANTERN pooled analysis. Int J Chron Obstruct Pulmon Dis. 2016;11:3189–97.PubMedPubMedCentralCrossRef
92.
Singh D, Worsley S, Zhu CQ, Hardaker L, Church A. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulm Med. 2015;15:91.PubMedPubMedCentralCrossRef
93.
Singh D, Papi A, Corradi M, Pavlisova I, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016;388:963–73.
94.
Vestbo J, Papi A, Corradi M, Blazhko V, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Singh D. 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. 2017;389:1919–29.
95.
Pascoe SJ, Lipson DA, Locantore N, Barnacle H, Brealey N, Mohindra R, Dransfield MT, Pavord I, Barnes N. A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol. Eur Respir J. 2016;48:320–30.PubMedCrossRef
96.
Poole P, Black PN, Cates CJ. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;8:CD001287.
97.
Criner GJ, Bourbeau J, Diekemper RL, Ouellette DR, Goodridge D, Hernandez P, Curren K, Balter MS, Bhutani M, Camp PG, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015;147:894–942.PubMedCrossRef
98.
Pela R, Calcagni AM, Subiaco S, Isidori P, Tubaldi A, Sanguinetti CM. N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD. Respiration. 1999;66:495–500.PubMedCrossRef
99.
Zheng JP, Wen FQ, Bai CX, Wan HY, Kang J, Chen P, Yao WZ, Ma LJ, Li X, Raiteri L, 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.PubMedCrossRef
100.
Decramer M, Rutten-van Molken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, van Schayck CP, Olivieri D, Del Donno M, De Backer W, 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;365:1552–60.PubMedCrossRef
101.
Cazzola M, Calzetta L, Page C, Jardim J, Chuchalin AG, Rogliani P, Gabriella MM. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015;24:451–61.PubMedCrossRef
102.
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;146:611–23.PubMedCrossRef
103.
Moretti M, Bottrighi P, Dallari R, Da Porto R, Dolcetti A, Grandi P, Garuti G, Guffanti E, Roversi P, De Gugliemo M, et al. The effect of long-term treatment with erdosteine on chronic obstructive pulmonary disease: the EQUALIFE Study. Drugs Exp Clin Res. 2004;30:143–52.PubMed
104.
Moretti M, Fagnani S. Erdosteine reduces inflammation and time to first exacerbation postdischarge in hospitalized patients with AECOPD. Int J Chron Obstruct Pulmon Dis. 2015;10:2319–25.PubMedPubMedCentralCrossRef
105.
Allegra L, Cordaro CI, Grassi C. Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo-controlled trial. Respiration. 1996;63:174–80.PubMedCrossRef
106.
Zheng JP, Kang J, Huang SG, Chen P, Yao WZ, Yang L, Bai CX, Wang CZ, Wang C, Chen BY, et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study. Lancet. 2008;371:2013–18.PubMedCrossRef
107.
Luo J, Wang K, Liu D, Liang BM, Liu CT. Can roflumilast, a phosphodiesterase-4 inhibitor, improve clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease? A meta-analysis Respir Res. 2016;17:18.PubMedCrossRef
108.
Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet. 2015;385:857–66.PubMedCrossRef
109.
Martinez FJ, Rabe KF, Sethi S, Pizzichini E, McIvor A, Anzueto A, Alagappan VK, Siddiqui S, Rekeda L, Miller CJ, et al. Effect of roflumilast and inhaled corticosteroid/long-acting β2-agonist on chronic obstructive pulmonary disease exacerbations (RE2SPOND). A randomized clinical trial. Am J Respir Crit Care Med. 2016;194:559–67.
110.
111.
Uzun S, Djamin RS, Kluytmans JA, Mulder PG, van’t Veer NE, Ermens AA, Pelle AJ, Hoogsteden HC, Aerts JG, van der Eerden MM. 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.PubMedCrossRef
112.
Albert RK, Connett J, Bailey WC, Casaburi R, Cooper Jr JA, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689–98.PubMedPubMedCentralCrossRef
113.
He ZY, Ou LM, Zhang JQ, Bai J, Liu GN, Li MH, Deng JM, MacNee W, Zhong XN. Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease. Respiration. 2010;80:445–52.PubMedCrossRef
114.
Seemungal TA, Wilkinson TM, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178:1139–47.PubMedCrossRef
115.
Alcázar Navarrete B, Casanova C, Miravitlles M, de Lucas P, Riesco JA, Rodríguez González-Moro JM, Working Group “Consensus document on the appropriate use of inhaled corticosteroids in C. “Correct use of inhaled corticosteroids in chronic obstructive pulmonary disease”: a consensus document. Arch Bronconeumol. 2015;51:193–8.
116.
Suissa S, Ernst P, Vandemheen KL, Aaron SD. Methodological issues in therapeutic trials of COPD. Eur Respir J. 2008;31:927–33.PubMedCrossRef
117.
Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med. 2015;3:435–42.PubMedCrossRef
118.
Pavord ID, Lettis S, Locantore N, Pascoe S, Jones PW, Wedzicha JA, Barnes NC. Blood eosinophils and inhaled corticosteroid/long-acting β2 agonist efficacy in COPD. Thorax. 2016;71:118–25.
119.
Watz H, Tetzlaff K, Wouters EF, Kirsten A, Magnussen H, Rodriguez-Roisin R, Vogelmeier C, Fabbri LM, Chanez P, Dahl R, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial. Lancet Respir Med. 2016;4:390–8.PubMedCrossRef
120.
Siddiqui SH, Pavord I, Barnes N, Lettis S, Guasconi A, Petruzzelli S. Blood eosinophils (EOS) are a biomarker of COPD exacerbation reduction with inhaled corticosteroids (ICS): an across-trials model-based approach. Eur Respir J. 2016;48:OA1763.
121.
Calverley P, Tetzlaff K, Vogelmeier C, Fabbri L, Magnussen H, Wouters E, Mezzanotte W, Disse B, Finnigan H, Asijee GM, Hallmann C, Watz H. Evaluating blood eosinophils and exacerbation history to predict ICS response in COPD. Am J Respir Crit Care Med. 2017. doi:10.​1164/​rccm.​201612-2525LE. [Epub ahead of print].
122.
Miravitlles M, D’Urzo A, Singh D, Koblizek V. Pharmacological strategies to reduce exacerbation risk in COPD: a narrative review. Respir Res. 2016;17:112.PubMedPubMedCentralCrossRef
123.
124.
Cooper CB, Barjaktarevic I. A new algorithm for the management of COPD. Lancet Respir Med. 2015;3:266–8.PubMedCrossRef
125.
Chan CK, Maltais F, Sigouin C, Haddon JM, Ford GT. A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease. Can Respir J. 2007;14:465–72.PubMedPubMedCentralCrossRef
126.
Abrahams R, Moroni-Zentgraf P, Ramsdell J, Schmidt H, Joseph E, Karpel J. Safety and efficacy of the once-daily anticholinergic BEA2180 compared with tiotropium in patients with COPD. Respir Med. 2013;107:854–62.PubMedCrossRef
127.
Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, Balter M, O’Donnell D, McIvor A, Sharma S, 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.PubMedCrossRef
128.
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;108:1752–60.PubMedCrossRef
129.
Ohar JA, Crater GD, Emmett A, Ferro TJ, Morris AN, Raphiou I, Sriram PS, Dransfield MT. Fluticasone propionate/salmeterol 250/50 μg versus salmeterol 50 μg after chronic obstructive pulmonary disease exacerbation. Respir Res. 2014;15:105.PubMedPubMedCentralCrossRef
130.
Calverley PM, Kuna P, Monsó E, Costantini M, Petruzzelli S, Sergio F, Varoli G, Papi A, Brusasco V. Beclomethasone/formoterol in the management of COPD: a randomised controlled trial. Respir Med. 2010;104:1858–68.PubMedCrossRef
131.
Bateman ED, Vogelmeier C, Chen H, Banerji D. Comparison of COPD exacerbations with once-daily QVA149 versus twice-daily salmeterol/fluticasone combination: the ILLUMINATE study. Chest. 2014;145(3_Meeting abstracts):409A. Abstract.CrossRef
132.
Vogelmeier C, Paggiaro PL, Dorca J, Sliwinski P, Mallet M, Kirsten A-M, Seoane B, Segarra RM, Leselbaum A, Gil EG. The efficacy and safety of aclidinium/formoterol fixed-dose combination compared with salmeterol/fluticasone in patients with COPD: results from a phase III study. Am J Respir Crit Care Med. 2015;191(1):A3974. Poster P3611.
133.
Beeh KM, Derom E, Echave-Sustaeta J, Gronke L, Hamilton A, Zhai D, Bjermer L. The lung function profile of once-daily tiotropium and olodaterol via Respimat® is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler® (ENERGITO® study). Int J Chron Obstruct Pulmon Dis. 2016;11:193–205.PubMedPubMedCentralCrossRef
134.
Troosters T, Sciurba FC, Decramer M, Siafakas NM, Klioze SS, Sutradhar SC, Weisman IM, Yunis C. Tiotropium in patients with moderate COPD naive to maintenance therapy: a randomised placebo-controlled trial. NPJ Prim Care Respir Med. 2014;24:14003.
Metadata
Title
Optimizing bronchodilation in the prevention of COPD exacerbations
Authors
Marc Miravitlles
Antonio Anzueto
José R. Jardim
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2017
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-017-0601-2

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