350
Views
0
CrossRef citations to date
0
Altmetric
Review

Fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease

ORCID Icon, ORCID Icon ORCID Icon, ORCID Icon ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 955-967 | Received 19 Jul 2017, Accepted 27 Sep 2017, Published online: 06 Oct 2017

References

  • Miravitlles M, Vogelmeier C, Roche N, et al. A review of national guidelines for management of COPD in Europe. Eur Respir J. 2016;47:625–637.
  • O’Donnell DE, Hernandez P, Kaplan A, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2008 update - highlights for primary care. Can Respir J. 2008;15(sA):1A–8A.
  • Abdool-Gaffar MS, Ambaram A, Ainslie GM, et al. Guideline for the management of chronic obstructive pulmonary disease–2011 update. S Afr Med J. 2011;101:63–73.
  • Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155:179–191.
  • Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. Bethesda, National Heart, Lung and Blood Institute, Apr 2001; NIH Publication No 2701:1-100. [update 2017; cited 2017 Sep]. http://goldcopd.org/gold-reports/
  • Kew KM, Mavergames C, Walters JA. Long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013;10:CD010177.
  • Chen WC, Huang CH, Sheu CC, et al. Long-acting beta2-agonists versus long-acting muscarinic antagonists in patients with stable COPD: a systematic review and meta-analysis of randomized controlled trials. Respirology. 2017 Jun 27;22:1313–1319. [Epub ahead of print]. DOI:10.1111/resp.13100
  • Yang IA, Clarke MS, Sim EH, et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;7:CD002991.
  • Arpinelli F, Caramori G, Magnoni MS. [Risk of pneumonia during long term regular treatment of stable COPD with inhaled glucocorticoids: a systematic review. Recenti Prog Med. 2017;108:175–182.
  • Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;3:CD010115.
  • Spencer S, Karner C, Cates CJ, et al. Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;12:CD007033.
  • Nannini LJ, Poole P, Milan SJ, et al. Combined corticosteroid and long-acting beta-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013;11:CD003794.
  • Calverley PM, Anderson JA, Celli B, et al.; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–789.
  • La Vecchia C, Fabbri LM. Prevention of death in COPD. N Engl J Med. 2007;356:2211–2212.
  • Scott DA, Woods B, Thompson JC, et al. Mortality and drug therapy in patients with chronic obstructive pulmonary disease: a network meta-analysis. BMC Pulm Med. 2015;15:145.
  • Dong YH, Lin HH, Shau WY, et al. 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;68:48–56.
  • Cyr MC, Beauchesne MF, Lemière C, et al. Effects of inhaled corticosteroids in monotherapy or combined with long-acting {beta}2-agonists on mortality among patients with chronic obstructive pulmonary disease. Ann Pharmacother. 2010;44:613–622.
  • Donohue JF, Betts KA, Du EX, et al. Comparative efficacy of long-acting β2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis. Int J Chron Obstruct Pulmon Dis. 2017;12:367–381.
  • Cazzola M, Matera MG. Fixed-dose combination inhalers. Handb Exp Pharmacol. 2017;237:117–129.
  • Horita N, Goto A, Shibata Y, et al. Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2017;2:CD012066.
  • Harlander M, Barrecheguren M, Turel M, et al. Should patients switched from D to B in the GOLD 2017 classification be discontinued from inhaled corticosteroids? COPD. 2017;14:465–468.
  • Chalmers JD, Tebboth A, Gayle A, et al. Determinants of initial inhaled corticosteroid use in patients with GOLD A/B COPD: a retrospective study of UK general practice. NPJ Prim Care Respir Med. 2017;27:43–51.
  • White P, Thornton H, Pinnock H, et al. Overtreatment of COPD with inhaled corticosteroids–implications for safety and costs: cross-sectional observational study. PLoS One. 2013;8:e75221–e75230.
  • Magnoni MS, Caminati M, Senna G, et al. Asthma under/misdiagnosis in primary care setting: an observational community-based study in Italy. Clin Mol Allergy. 2015;13:26–30.
  • Llordés M, Jaén A, Almagro P, et al. Prevalence, risk factors and diagnostic accuracy of COPD among smokers in primary Care. COPD. 2015;12:404–412.
  • Miravitlles M, Andreu I, Romero Y, et al. Difficulties in differential diagnosis of COPD and asthma in primary care. Br J Gen Pract. 2012;62:e68–e75.
  • Al-Kassimi FA, Abba AA, Al-Hajjaj MS, et al. Asthma masquerading as chronic obstructive pulmonary disease: a study of smokers fulfilling the GOLD definition of chronic obstructive pulmonary disease. Respiration. 2011;82:19–27.
  • Marsh SE, Travers J, Weatherall M, et al. Proportional classifications of COPD phenotypes. Thorax. 2008;63:761–767.
  • Magnussen H, Disse B, Rodriguez-Roisin R, et al.; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371:1285–1294.
  • Rossi A, Guerriero M, Corrado A, OPTIMO/AIPO Study Group. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir Res. 2014;15:77–88.
  • Calzetta L, Matera MG, Braido F, et al. Withdrawal of inhaled corticosteroids in COPD: a meta-analysis. Pulm Pharmacol Ther. 2017;45:148–158.
  • Wedzicha JA, Banerji D, Chapman KR, et al.; FLAME Investigators. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016;374:2222–2234.
  • Zhong N, Wang C, Zhou X, et al.; LANTERN Investigators. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:1015–1026.
  • Kunz LI, Ten Hacken NH, Lapperre TS, et al.; GLUCOLD Study Group. Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids. Eur Respir J. 2017;49:pii: 1600839. Print 2017 Jan. DOI:10.1183/13993003.00839-2016
  • Kunz LIZ, Postma DS, Klooster K, et al.; GLUCOLD Study Group. Relapse in FEV1 decline after steroid withdrawal in COPD. Chest. 2015;148:389–396.
  • Agustí A, Dekhuijzen PR. Maximal bronchodilation: a therapeutic target in COPD? Lancet Respir Med. 2017;5:540–542.
  • Vestbo J, Woodcock A. Clinical trial research in focus: time to reflect on the design of exacerbation trials in COPD. Lancet Respir Med. 2017;5:466–468.
  • Mirza S, Benzo R. Chronic obstructive pulmonary disease phenotypes: implications for care. Mayo Clin Proc. 2017;92:1104–1112.
  • Caramori G, Chung KF, Adcock IM. Profile of fluticasone furoate/vilanterol dry powder inhaler combination therapy as a potential treatment for COPD. Int J Chron Obstruct Pulmon Dis. 2014;9:249–256.
  • Adcock IM, Mumby S. Glucocorticoids. Handb Exp Pharmacol. 2016;2017(237):171–196.
  • Barnes PJ. Glucocorticosteroids. Handb Exp Pharmacol. 2017;237:93–115.
  • Ramamoorthy S, Cidlowski JA. Corticosteroids: mechanisms of action in health and disease. Rheum Dis Clin North Am. 2016;42:15–31.
  • Salter M, Biggadike K, Matthews JL, et al. Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease. Am J Physiol Lung Cell Mol Physiol. 2007;293:L660–667.
  • Biggadike K, Bledsoe RK, Hassell AM, et al. X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain. J Med Chem. 2008;51:3349–3352.
  • Valotis A, Högger P. Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate. Respir Res. 2007;8:54.
  • Rossios C, To Y, To M, et al. Long-acting fluticasone furoate has a superior pharmacological profile to fluticasone propionate in human respiratory cells. Eur J Pharmacol. 2011;670:244–251.
  • Allen A, Bal J, Cheesbrough A, et al. Pharmacokinetics and pharmacodynamics of intravenous and inhaled fluticasone furoate in healthy Caucasian and East Asian subjects. Br J Clin Pharmacol. 2014;77:808–820.
  • Cazzola M, Page CP, Calzetta L, et al. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012;64:450–504.
  • Cazzola M, Page CP, Rogliani P, et al. β2-agonist therapy in lung disease. Am J Respir Crit Care Med. 2013;187:690–696.
  • Barnes PJ. Distribution of receptor targets in the lung. Proc Am Thorac Soc. 2004;1:345–351.
  • Caramori G, Adcock IM, Chung KF. Drugs for airway diseases. In: editors, Nijkamp FP, Parnham MJ. Principles of immunopharmacology. 4th ed. London: Springer Verlag; Forth coming.
  • Bang I, Choi HJ. Structural features of β2 adrenergic receptor: crystal structures and beyond. Mol Cells. 2015;38:105–111.
  • Chung KF, Caramori G, Adcock IM. Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future. Eur J Clin Pharmacol. 2009;65:853–871.
  • Zieba BJ, Artamonov MV, Jin L, et al. The cAMP-responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down-regulation of RhoA activity. J Biol Chem. 2011;286:16681–16692.
  • Morgan SJ, Deshpande DA, Tiegs BC, et al. β-Agonist-mediated relaxation of airway smooth muscle is protein kinase A-dependent. J Biol Chem. 2014;289:23065–23074.
  • Raju SV, Solomon GM, Dransfield MT, et al. Acquired cystic fibrosis transmembrane conductance regulator dysfunction in chronic bronchitis and other diseases of mucus clearance. Clin Chest Med. 2016;37:147–158.
  • Johnson M, Rennard S. Alternative mechanisms for long-acting beta(2)-adrenergic agonists in COPD. Chest. 2001;120:258–270.
  • Haque R, Hakim A, Moodley T, et al. Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD. J Allergy Clin Immunol. 2013;132:1166–1173.
  • Roth M, Johnson PR, Rüdiger JJ, et al. Interaction between glucocorticoids and beta2 agonists on bronchial airway smooth muscle cells through synchronised cellular signalling. Lancet. 2002;360:1293–1299.
  • Pera T, Penn RB. Bronchoprotection and bronchorelaxation in asthma: new targets, and new ways to target the old ones. Pharmacol Ther. 2016;164:82–96.
  • Walker JK, DeFea KA. Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma. Curr Opin Pharmacol. 2014;16:142–147.
  • Procopiou PA, Barrett VJ, Bevan NJ, et al. Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating metabolic inactivation: an antedrug approach. J Med Chem. 2010;53:4522–4530.
  • Slack RJ, Barrett VJ, Morrison VS, et al. In vitro pharmacological characterization of vilanterol, a novel long-acting β2-adrenoceptor agonist with 24-hour duration of action. J Pharmacol Exp Ther. 2013;344:218–230.
  • Aparici M, Gavaldà A, Ramos I, et al. In vitro and in vivo preclinical profile of abediterol (LAS100977), an inhaled long-acting β2-adrenoceptor agonist, compared with indacaterol, olodaterol and vilanterol. Eur J Pharmacol. 2016;770:61–69.
  • Hanania NA, Sharafkhaneh A, Barber R, et al. Beta-agonist intrinsic efficacy: measurement and clinical significance. Am J Respir Crit Care Med. 2002;165:1353–1358.
  • 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;26:256–264.
  • Sterling R, Lim J, Frith L, et al. Efficacy and optimal dosing interval of the long-acting beta agonist, vilanterol, in persistent asthma: a randomised trial. Respir Med. 2012;106:1110–1115.
  • Condreay L, Huang L, Harris E, et al. Genetic effects on treatment response of umeclidinium/vilanterol in chronic obstructive pulmonary disease. Respir Med. 2016;114:123–126.
  • Calzetta L, Rinaldi B, Cazzola M, et al. Pharmacodynamic and pharmacokinetic assessment of fluticasone furoate + vilanterol for the treatment of asthma. Expert Opin Drug Metab Toxicol. 2016;12:813–822.
  • Kumar R, Kumar D, Parakh A. Fluticasone furoate: a new intranasal corticosteroid. J Postgrad Med. 2012;58:79–83.
  • Kempsford R, Allen A, Bal J, et al. The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects. Br J Clin Pharmacol. 2013;75:1478–1487.
  • Allen A, Bareille PJ, Rousell VM. Fluticasone furoate, a novel inhaled corticosteroid, demonstrates prolonged lung absorption kinetics in man compared with inhaled fluticasone propionate. Clin Pharmacokinet. 2013;52:37–42.
  • Allen A, Davis A, Hardes K, et al. Influence of renal and hepatic impairment on the pharmacokinetic and pharmacodynamic properties and tolerability of fluticasone furoate and vilanterol in combination. Clin Ther. 2012;34:2316–2332.
  • Harrell AW, Siederer SK, Bal J, et al. Metabolism and disposition of vilanterol, a long-acting β(2)-adrenoceptor agonist for inhalation use in humans. Drug Metab Dispos. 2013;41:89–100.
  • Mehta R, Kelleher D, Preece A, et al. Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study. Int J Chron Obstruct Pulmon Dis. 2013;8:159–167.
  • Mehta R, Hardes K, Brealey N, et al. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study. Int J Chron Obstruct Pulmon Dis. 2014;10:15–23.
  • Chen X, Zheng X, Jiang J, et al. Pharmacodynamics and pharmacokinetics of fluticasone furoate/vilanterol in healthy Chinese subjects. Pharmacotherapy. 2015;35:586–599.
  • Siederer S, Allen A, Yang S. Population pharmacokinetics of inhaled fluticasone furoate and vilanterol in subjects with chronic obstructive pulmonary disease. Eur J Drug Metab Pharmacokinet. 2016;41:743–758.
  • Boscia JA, Pudi KK, Zvarich MT, et al. Effect of once-daily fluticasone furoate/vilanterol on 24-hour pulmonary function in patients with chronic obstructive pulmonary disease: a randomized, three-way, incomplete block, crossover study. Clin Ther. 2012;34:1655–1666.
  • Lötvall J, Bakke PS, Bjermer L, et al. Efficacy and safety of 4 weeks’ treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial. BMJ Open. 2012;2:e000370.
  • Kerwin EM, Scott-Wilson C, Sanford L, et al. A randomised trial of fluticasone furoate/vilanterol (50/25 μg; 100/25 μg) on lung function in COPD. Respir Med. 2013;107:560–569.
  • Martinez FJ, Boscia J, Feldman G, et al. Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: a randomised trial. Respir Med. 2013;107:550–559.
  • Agustí A, de Teresa L, De Backer W, et al. A comparison of the efficacy and safety of once-daily fluticasone furoate/vilanterol with twice-daily fluticasone propionate/salmeterol in moderate to very severe COPD. Eur Respir J. 2014;43:763–772.
  • Bollmeier SG, Prosser TR. Combination of fluticasone furoate and vilanterol for the treatment of chronic obstructive pulmonary disease. Ann Pharmacother. 2014;48:250–257.
  • Zheng J, de Guia T, Wang-Jairaj J, et al. Efficacy and safety of fluticasone furoate/vilanterol (50/25 mcg; 100/25 mcg; 200/25 mcg) in Asian patients with chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Curr Med Res Opin. 2015;31:1191–1200.
  • Dransfield MT, Bourbeau J, Jones PW, 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;1:210–222.
  • Stone IS, Barnes NC, James WY, et al. Lung deflation and cardiovascular structure and function in chronic obstructive pulmonary disease. A randomized controlled trial. Am J Respir Crit Care Med. 2016;193:717–726.
  • Maltais F, Singh S, Donald AC, et al. Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials. Ther Adv Respir Dis. 2014;8:169–181.
  • Chapman KR, Bergeron C, Bhutani M, et al. Do we know the minimal clinically important difference (MCID) for COPD exacerbations? COPD. 2013;10:243–249.
  • Pascoe S, Locantore N, Dransfield MT, et al. 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;3:435–442.
  • Vestbo J, Anderson J, Brook RD, et al. The study to understand mortality and morbidity in COPD (SUMMIT) study protocol. Eur Respir J. 2013;41:1017–1022.
  • Vestbo J, Anderson JA, Brook RD, et al.,; SUMMIT Investigators. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. 2016;387:1817–1826.
  • Martinez FJ, Vestbo J, Anderson JA, et al.; SUMMIT Investigators. Effect of fluticasone furoate and vilanterol on exacerbations of COPD in patients with moderate airflow obstruction. Am J Respir Crit Care Med. 2017;195:881–888.
  • Vestbo J, Leather D, Diar Bakerly N, et al.; Salford Lung Study Investigators. Effectiveness of fluticasone furoate-vilanterol for COPD in clinical practice. N Engl J Med. 2016;375:1253–1260. Please also read the comments on N. Engl. J. Med. 2016;375:2605-2607 and Dal-Ré R. Could phase 3 medicine trials be tagged as pragmatic? A case study: The Salford COPD trial. J. Eval. Clin. Pract. 2017 Jul 7. doi: 10.1111/jep.12796. [Epub ahead of print].
  • Covelli H, Pek B, Schenkenberger I, et al. Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk. Int J Chron Obstruct Pulmon Dis. 2015;11:1–12.
  • Stynes G, Svedsater H, Wex J, et al. Once-daily fluticasone furoate/vilanterol 100/25 mcg versus twice daily combination therapies in COPD - mixed treatment comparisons of clinical efficacy. Respir Res. 2015;16:25.
  • Siler TM, Kerwin E, Sousa AR, et al. Efficacy and safety of umeclidinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: results of two randomized studies. Respir Med. 2015;109:1155–1163.
  • Pascoe SJ, Lipson DA, Locantore N, et al. A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol. Eur Respir J. 2016;48:320–330.
  • https://www.gsk.com/en-gb/media/press-releases/gsk-and-innoviva-report-positive-headline-results-from-impact-study-showing-single-inhaler-triple-therapy-trelegy-ellipta-reduced-copd-exacerbations/
  • Hamilton M, Leggett R, Pang C, et al. In vitro dosing performance of the ELLIPTA® dry powder inhaler using asthma and COPD patient inhalation profiles replicated with the electronic lung (eLung™). J Aerosol Med Pulm Drug Deliv. 2015;28:498–506.
  • Kelleher DL, Mehta RS, Jean-Francois BM, et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of umeclidinium and vilanterol alone and in combination: a randomized crossover trial. PLoS One. 2012;7:e50716.
  • Mehta R, Green M, Patel B, et al. Concentration-QT analysis of the randomized, placebo- and moxifloxacin-controlled thorough QT study of umeclidinium monotherapy and umeclidinium/vilanterol combination in healthy subjects. J Pharmacokinet Pharmacodyn. 2016;43:153–164.
  • Nakahara N, Wakamatsu A, Kempsford R, et al. The safety, pharmacokinetics and pharmacodynamics of a combination of fluticasone furoate and vilanterol in healthy Japanese subjects. Int J Clin Pharmacol Ther. 2013;51:660–671.
  • Hussar DA, Ahmad A. Vilanterol trifenatate/fluticasone furoate, lomitapide mesylate, and mipomersen sodium. J Am Pharm Assoc (2003). 2013;53:662–670.
  • Rodrigo GJ, Neffen H. A systematic review with meta-analysis of fluticasone furoate/vilanterol combination for the treatment of stable COPD. Pulm Pharmacol Ther. 2017;42:1–6.
  • Pavord ID, Lettis S, Anzueto A, et al. Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis. Lancet Respir Med. 2016;4:731–741.
  • Mayoralas S, Huerta A, Parrondo J, et al. Monte-Carlo simulation to estimate the health care costs avoided with fluticasone furoate/vilanterol due to exacerbation rate reduction in spanish COPD patients. Value Health. 2014;17:A603. (abstract).
  • Fromer L, Goodwin E, Walsh J. Customizing inhaled therapy to meet the needs of COPD patients. Postgrad Med. 2010;122:83–93.
  • Lipson DA, Barnacle H, Birk R, et al. FULFIL trial: once-daily triple therapy in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;196:438–446.
  • Marwick JA, Caramori G, Mazzoni F, et al. A role for phosphoinositol 3-kinase delta in the impairment of glucocorticoid responsiveness in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2010;125:1146–1153.
  • Watz H, Mistry SJ, Lazaar AL, IPC101939 investigators. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD. Pulm Pharmacol Ther. 2013;26:588–595.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.