Beyond Dual Bronchodilation – Triple Therapy, When and Why

References

• Calzetta L, Matera MG, Rogliani P, Cazzola M. The role of triple therapy in the management of COPD. Expert Rev Clin Pharmacol. 2020;13(8):865–874. doi:10.1080/17512433.2020.1787830
   PubMed Web of Science ®Google Scholar
• Grewe FA, Sievi NA, Bradicich M, et al. Compliance of pharmacotherapy with GOLD guidelines: a longitudinal study in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2020;15:627–635. doi:10.2147/COPD.S240444
   PubMed Web of Science ®Google Scholar
• Maniscalco M, Martucci M, Fuschillo S, de Felice A, D’Anna SE, Cazzola M. A case scenario study on adherence to COPD GOLD recommendations by general practitioners in a rural area of southern Italy: the “progetto PADRE”. Respir Med. 2020;170:105985. doi:10.1016/j.rmed.2020.105985
   PubMed Web of Science ®Google Scholar
• Brusselle G, Price D, Gruffydd-Jones K, et al. The inevitable drift to triple therapy in COPD: an analysis of prescribing pathways in the UK. Int J Chron Obstruct Pulmon Dis. 2015;10:2207–2217. doi:10.2147/COPD.S91694
   PubMed Web of Science ®Google Scholar
• Simeone JC, Luthra R, Kaila S, et al. Initiation of triple therapy maintenance treatment among patients with COPD in the US. Int J Chron Obstruct Pulmon Dis. 2016;12:73–83. doi:10.2147/COPD.S122013
   PubMed Web of Science ®Google Scholar
• Palmiotti GA, Lacedonia D, Liotino V, et al. Adherence to GOLD guidelines in real-life COPD management in the Puglia region of Italy. Int J Chron Obstruct Pulmon Dis. 2018;13:2455–2462. doi:10.2147/COPD.S157779
   PubMed Web of Science ®Google Scholar
• Di Marco F, Santus P, Terraneo S, et al. Characteristics of newly diagnosed COPD patients treated with triple inhaled therapy by general practitioners: a real world Italian study. NPJ Prim Care Respir Med. 2017;27(1):51. doi:10.1038/s41533-017-0051-9
   PubMed Web of Science ®Google Scholar
• Larsson K, Ekberg-Jansson A, Stridsman C, Hanno M, Vanfleteren LEGW. Adherence to treatment recommendations for chronic obstructive pulmonary disease - Results from the Swedish National Airway Register. Int J Chron Obstruct Pulmon Dis. 2021;16:909–918. doi:10.2147/COPD.S300299
   PubMed Web of Science ®Google Scholar
• Cazzola M, Matera MG. Triple combinations in chronic obstructive pulmonary disease - is three better than two? Expert Opin Pharmacother. 2014;15(17):2475–2478. doi:10.1517/14656566.2014.972367
   PubMed Web of Science ®Google Scholar
• Schabert V, Shah S, Holmgren U, Cabrera C. Prescribing pathways to triple therapy in patients with chronic obstructive pulmonary disease in the United States. Ther Adv Respir Dis. 2021;15:17534666211001018. doi:10.1177/17534666211001018
   Web of Science ®Google Scholar
• Monteagudo M, Barrecheguren M, Solntseva I, et al. Clinical characteristics and factors associated with triple therapy use in newly diagnosed patients with COPD. NPJ Prim Care Respir Med. 2021;31(1):16. doi:10.1038/s41533-021-00227-x
   PubMed Web of Science ®Google Scholar
• Quint JK, O’Leary C, Venerus A, et al. Prescribing pathways to triple therapy: a multi-country, retrospective observational study of adult patients with chronic obstructive pulmonary disease. Pulm Ther. 2020;6(2):333–350. doi:10.1007/s41030-020-00132-7
   PubMedGoogle Scholar
• Singh D, Agusti A, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Respir J. 2019;53(5):1900164. doi:10.1183/13993003.00164-2019
   PubMed Web of Science ®Google Scholar
• Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020;201(9):e56–e69. doi:10.1164/rccm.202003-0625ST
   PubMed Web of Science ®Google Scholar
• Bourbeau J, Bhutani M, Hernandez P, et al. Canadian Thoracic Society Clinical Practice Guideline on pharmacotherapy in patients with COPD - 2019 update of evidence. Can J Respir Crit Care Sleep Med. 2019;3(4):210–232.
   Web of Science ®Google Scholar
• Calzetta L, Matera MG, Cazzola M. Pharmacological interaction between LABAs and LAMAs in the airways: optimizing synergy. Eur J Pharmacol. 2015;761:168–173. doi:10.1016/j.ejphar.2015.05.020
   PubMed Web of Science ®Google Scholar
• Matera MG, Page CP, Calzetta L, Rogliani P, Cazzola M. Pharmacology and Therapeutics of Bronchodilators Revisited. Pharmacol Rev. 2020;72(1):218–252. doi:10.1124/pr.119.018150
   PubMed Web of Science ®Google Scholar
• Rogliani P, Matera MG, Facciolo F, Page C, Cazzola M, Calzetta L. Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide: synergy of triple combination therapy on human airway smooth muscle ex vivo. Br J Pharmacol. 2020;177(5):1150–1163. doi:10.1111/bph.14909
   PubMed Web of Science ®Google Scholar
• Rogliani P, Ritondo LB, Zerillo B, Matera MG, Calzetta L. Drug interaction and chronic obstructive respiratory disorders. Curr Res Pharmacol Drug Discov. 2021;2:100009. doi:10.1016/j.crphar.2020.100009
   PubMedGoogle Scholar
• Rogliani P, Ora J, Girolami A, et al. Ceiling effect of beclomethasone/formoterol/glycopyrronium triple fixed-dose combination in COPD: a translational bench-to-bedside study. Pulm Pharmacol Ther. 2021;69:102050.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Zhu J, Liu Y, et al. Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis. BMJ. 2018;363:k4388. doi:10.1136/bmj.k4388
   PubMed Web of Science ®Google Scholar
• Cazzola M, Rogliani P, Calzetta L, Matera MG. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis. Eur Respir J. 2018;52(6):1801586. doi:10.1183/13993003.01586-2018
   PubMed Web of Science ®Google Scholar
• Lai CC, Chen CH, Lin CYH, Wang CY, Wang YH. The effects of single inhaler triple therapy vs single inhaler dual therapy or separate triple therapy for the management of chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials. Int J Chron Obstruct Pulmon Dis. 2019;14:1539–1548. doi:10.2147/COPD.S200846
   PubMed Web of Science ®Google Scholar
• Calzetta L, Cazzola M, Matera MG, Rogliani P. Adding a LAMA to ICS/LABA therapy: a meta-analysis of triple combination therapy in COPD. Chest. 2019;155(4):758–770. doi:10.1016/j.chest.2018.12.016
   PubMed Web of Science ®Google Scholar
• Mammen MJ, Lloyd DR, Kumar S, et al. Triple therapy versus dual or monotherapy with long-acting bronchodilators for chronic obstructive pulmonary disease. A systematic review and meta-analysis. Ann Am Thorac Soc. 2020;17(10):1308–1318. doi:10.1513/AnnalsATS.202001-023OC
   PubMed Web of Science ®Google Scholar
• Koarai A, Yamada M, Ichikawa T, Fujino N, Kawayama T, Sugiura H. Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis. Respir Res. 2021;22(1):183. doi:10.1186/s12931-021-01777-x
   PubMed Web of Science ®Google Scholar
• Long H, Xu H, Janssens JP, Guo Y. Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials. Respir Res. 2021;22(1):209. doi:10.1186/s12931-021-01794-w
   PubMed Web of Science ®Google Scholar
• Cazzola M, Calzetta L, Rogliani P, Matera MG. Triple therapy versus dual bronchodilation and inhaled corticosteroids/long-acting β-agonists in COPD: accumulating evidence from network meta-analyses. Pulm Ther. 2019;5(2):117–126. doi:10.1007/s41030-019-00102-8
   PubMedGoogle Scholar
• Calzetta L, Ritondo BL, de Marco P, Cazzola M, Rogliani P. Evaluating triple ICS/LABA/LAMA therapies for COPD patients: a network meta-analysis of ETHOS, KRONOS, IMPACT, and TRILOGY studies. Expert Rev Respir Med. 2021;15(1):143–152. doi:10.1080/17476348.2020.1816830
   PubMed Web of Science ®Google Scholar
• Daley-Yates PT. Inhaled corticosteroids: potency, dose equivalence and therapeutic index. Br J Clin Pharmacol. 2015;80(3):372–380. doi:10.1111/bcp.12637
   PubMed Web of Science ®Google Scholar
• Matera MG, Rinaldi B, Calzetta L, Rogliani P, Cazzola M. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids for asthma treatment. Pulm Pharmacol Ther. 2019;58:101828. doi:10.1016/j.pupt.2019.101828
   PubMed Web of Science ®Google Scholar
• Cazzola M, Page CP, Rogliani P, Matera MG. β2-agonist therapy in lung disease. Am J Respir Crit Care Med. 2013;187(7):690–696. doi:10.1164/rccm.201209-1739PP
   PubMed Web of Science ®Google Scholar
• Cazzola M, Matera MG. Bronchodilators for airway disease. In: Janes SM, editor. Encyclopedia of Respiratory Medicine. Vol. 2. Elsevier, Academic Press; 2022:712–728.
   Google Scholar
• Matera MG, Belardo C, Rinaldi M, Rinaldi B, Cazzola M. Emerging muscarinic receptor antagonists for the treatment of asthma. Expert Opin Emerg Drugs. 2020;25(2):123–130. doi:10.1080/14728214.2020.1758059
   PubMed Web of Science ®Google Scholar
• Rogliani P, Calzetta L, Ora J, et al. Pharmacological assessment of the onset of action of Aclidinium and glycopyrronium versus tiotropium in COPD patients and human isolated bronchi. Eur J Pharmacol. 2015;761:383–390. doi:10.1016/j.ejphar.2015.04.042
   PubMed Web of Science ®Google Scholar
• Bourdin A, Molinari N, Ferguson GT, et al. Efficacy and safety of budesonide/glycopyrronium/formoterol fumarate versus other triple combinations in COPD: a systematic literature review and network meta-analysis. Adv Ther. 2021;38(6):3089–3112. doi:10.1007/s12325-021-01703-z
   PubMed Web of Science ®Google Scholar
• Ritondo BL, Puxeddu E, Calzetta L, Cazzola M, Rogliani P. Efficacy and safety of triple combination therapy for treating chronic obstructive pulmonary disease: an expert review. Expert Opin Pharmacother. 2021;22(5):611–620. doi:10.1080/14656566.2020.1845314
   PubMed Web of Science ®Google Scholar
• Agusti A, Fabbri LM, Singh D, et al. Inhaled corticosteroids in COPD: friend or foe? Eur Respir J. 2018;52(6):1801219. doi:10.1183/13993003.01219-2018
   PubMed Web of Science ®Google Scholar
• Cazzola M, Rogliani P, Stolz D, Matera MG. Pharmacological treatment and current controversies in COPD. F1000Res. 2019;8:F1000Faculty Rev–1533. doi:10.12688/f1000research.19811.1
   Google Scholar
• Stolz D, Miravitlles M. The right treatment for the right patient with COPD: lessons from the IMPACT trial. Eur Respir J. 2020;55(5):2000881. doi:10.1183/13993003.00881-2020
   PubMed Web of Science ®Google Scholar
• Cazzola M, MacNee W, Martinez FJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J. 2008;31(2):416–469. doi:10.1183/09031936.00099306
   PubMed Web of Science ®Google Scholar
• Cazzola M, Calzetta L, Rogliani P, Matera MG. The challenges of precision medicine in COPD. Mol Diagn Ther. 2017;21(4):345–355. doi:10.1007/s40291-017-0266-z
   PubMed Web of Science ®Google Scholar
• Bafadhel M, McKenna S, Terry S, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011;184(6):662–671. doi:10.1164/rccm.201104-0597OC
   PubMed Web of Science ®Google Scholar
• Harries TH, Rowland V, Corrigan CJ, et al. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. Respir Res. 2020;21(1):3. doi:10.1186/s12931-019-1268-7
   PubMed Web of Science ®Google Scholar
• Cazzola M, Puxeddu E, Ora J, Rogliani P. Evolving concepts in chronic obstructive pulmonary disease blood-based biomarkers. Mol Diagn Ther. 2019;23(5):603–614. doi:10.1007/s40291-019-00413-1
   PubMed Web of Science ®Google Scholar
• Wilkerson EM, Johansson MW, Hebert AS, et al. The peripheral blood eosinophil proteome. J Proteome Res. 2016;15(5):1524–1533. doi:10.1021/acs.jproteome.6b00006
   PubMed Web of Science ®Google Scholar
• O’Sullivan JA, Bochner BS. Eosinophils and eosinophil-associated diseases: an update. J Allergy Clin Immunol. 2018;141(2):505–517. doi:10.1016/j.jaci.2017.09.022
   PubMed Web of Science ®Google Scholar
• Cazzola M, Rogliani P, Matera MG. Escalation and de-escalation of therapy in COPD: myths, realities and perspectives. Drugs. 2015;75(14):1575–1585. doi:10.1007/s40265-015-0450-6
   PubMed Web of Science ®Google Scholar
• Vanfleteren LEGW, Ullman A, Nordenson A, Andersson A, Andelid K, Fabbri LM. Triple therapy (ICS/LABA/LAMA) in COPD: thinking out of the box. ERJ Open Res. 2019;5(1):00185–2018. doi:10.1183/23120541.00185-2018
   PubMedGoogle Scholar
• Finney L, Berry M, Singanayagam A, Elkin SL, Johnston SL, Mallia P. Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease. Lancet Respir Med. 2014;2(11):919–932. doi:10.1016/S2213-2600(14)70169-9
   PubMed Web of Science ®Google Scholar
• Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020;383(1):35–48. doi:10.1056/NEJMoa1916046
   PubMed Web of Science ®Google Scholar
• Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018;391(10125):1076–1084. doi:10.1016/S0140-6736(18)30206-X
   PubMed Web of Science ®Google Scholar
• Lipson DA, Barnacle H, Birk R, et al. FULFIL trial: once-daily triple therapy for patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;196(4):438–446. doi:10.1164/rccm.201703-0449OC
   PubMed Web of Science ®Google Scholar
• Janson C, Stratelis G, Miller-Larsson A, Harrison TW, Larsson K. Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:3055–3064. doi:10.2147/COPD.S143656
   PubMed Web of Science ®Google Scholar
• Lee JH, Park YH, Kang DR, et al. Risk of pneumonia associated with inhaled corticosteroid in patients with chronic obstructive pulmonary disease: a Korean population-based study. Int J Chron Obstruct Pulmon Dis. 2020;15:3397–3406. doi:10.2147/COPD.S286149
   PubMed Web of Science ®Google Scholar
• Crim C, Dransfield MT, Bourbeau J, et al. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD. Ann Am Thorac Soc. 2015;12(1):27–34. doi:10.1513/AnnalsATS.201409-413OC
   PubMed Web of Science ®Google Scholar
• Bourbeau J, Bafadhel M, Barnes NC, et al. Benefit/risk profile of single-inhaler triple therapy in COPD. Int J Chron Obstruct Pulmon Dis. 2021;16:499–517. doi:10.2147/COPD.S291967
   PubMed Web of Science ®Google Scholar
• Almagro P, Martinez-Camblor P, Soriano JB. Inhaled corticosteroids and pneumonia mortality in COPD patients. Eur Respir J. 2019;54(3):1901035. doi:10.1183/13993003.01035-2019
   PubMed Web of Science ®Google Scholar
• Andreas S, Taube C. Inhaled therapy reduces COPD mortality. ERJ Open Res. 2020;6(4):00634–2020. doi:10.1183/23120541.00634-2020
   PubMedGoogle Scholar
• Vestbo J, Fabbri L, Papi A, et al. Inhaled corticosteroid containing combinations and mortality in COPD. Eur Respir J. 2018;52(6):1801230. doi:10.1183/13993003.01230-2018
   PubMed Web of Science ®Google Scholar
• Halpin DMG, Criner GJ, Dransfield MT, et al. Triple versus dual combination therapy in chronic obstructive pulmonary disease in Asian countries: analysis of the IMPACT trial. Pulm Ther. 2021;7(1):101–118. doi:10.1007/s41030-020-00136-3
   PubMedGoogle Scholar
• Martinez FJ, Rabe KF, Ferguson GT, et al. Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. A randomized, double-blind, multicenter, parallel-group study. Am J Respir Crit Care Med. 2021;203(5):553–564. doi:10.1164/rccm.202006-2618OC
   PubMed Web of Science ®Google Scholar
• Rogliani P, Calzetta L. Mortality in ETHOS: a Question of “power”. Am J Respir Crit Care Med. 2021;203(7):926–927. doi:10.1164/rccm.202012-4328LE
   PubMed Web of Science ®Google Scholar
• Miravitlles M, Calverley PMA, Verhamme K, et al. A pooled analysis of mortality in patients with COPD receiving triple therapy versus dual bronchodilation (abstract). Am J Respir Crit Care Med. 2021;203:A2251.
   Web of Science ®Google Scholar
• Suissa S, Dell’Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67(11):957–963. doi:10.1136/thoraxjnl-2011-201518
   PubMed Web of Science ®Google Scholar
• Calzetta L, Matera MG, Braido F, et al. Withdrawal of inhaled corticosteroids in COPD: a meta-analysis. Pulm Pharmacol Ther. 2017;45:148–158. doi:10.1016/j.pupt.2017.06.002
   PubMed Web of Science ®Google Scholar
• Chalmers JD, Laska IF, Franssen FME, et al. Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline. Eur Respir J. 2020;55(6):2000351. doi:10.1183/13993003.00351-2020
   PubMed Web of Science ®Google Scholar
• Cazzola M, Celli B. Triple therapy is also effective in real-world when used in chronic obstructive pulmonary disease patients who are frequent exacerbators. Respiration. 2021;100(2):93–95. doi:10.1159/000512728
   PubMed Web of Science ®Google Scholar
• Pelaia C, Procopio G, Deodato MR, et al. Real-life clinical and functional effects of fluticasone furoate/umeclidinium/vilanterol-combined triple therapy in patients with chronic obstructive pulmonary disease. Respiration. 2021;100(2):127–134. doi:10.1159/000512064
   PubMed Web of Science ®Google Scholar
• Voorham J, Corradi M, Papi A, et al. Comparative effectiveness of triple therapy versus dual bronchodilation in COPD. ERJ Open Res. 2019;5(3):00106–2019. doi:10.1183/23120541.00106-2019
   PubMedGoogle Scholar
• Cheng W, Duan J, Zhou A, et al. Real-world effectiveness of inhalation therapy among patients with symptomatic COPD in China: a multicenter prospective study. Front Pharmacol. 2021;12:753653. doi:10.3389/fphar.2021.753653
   PubMed Web of Science ®Google Scholar
• Suissa S, Dell-Aniello S, Ernst P. Comparative effects of LAMA-LABA-ICS vs LAMA LABA for COPD: cohort study in real-world clinical practice. Chest. 2020;157(4):846–855. doi:10.1016/j.chest.2019.11.007
   PubMed Web of Science ®Google Scholar
• Buhl R, Criée CP, Kardos P, et al. Dual bronchodilation vs triple therapy in the “real-life” COPD DACCORD study. Int J Chron Obstruct Pulmon Dis. 2018;13:2557–2568. doi:10.2147/COPD.S169958
   PubMed Web of Science ®Google Scholar
• Dalon F, Roche N, Belhassen M, et al. Dual versus triple therapy in patients hospitalized for COPD in France: a claims data study. Int J Chron Obstruct Pulmon Dis. 2019;14:1839–1854. doi:10.2147/COPD.S214061
   PubMed Web of Science ®Google Scholar
• Syed AA, Sharma GN, Shrivastav B, Mohd AN. Meta-analysis of cost-effectiveness of three-drug therapy versus two-drug therapy in chronic obstructive pulmonary disease patients. J Appl Pharm Sci. 2021;11(09):129–138.
   Google Scholar
• Gutiérrez Villegas C, Paz-Zulueta M, Herrero-Montes M, Parás-Bravo P, Madrazo Pérez M. Cost analysis of chronic obstructive pulmonary disease (COPD): a systematic review. Health Econ Rev. 2021;11(1):31. doi:10.1186/s13561-021-00329-9
   PubMed Web of Science ®Google Scholar
• Buhl R, Dreher M, Korn S, et al. A non-Interventional study of tiotropium/olodaterol versus any triple combination therapy for chronic obstructive pulmonary disease: the EVELUT® study protocol. Int J Chron Obstruct Pulmon Dis. 2020;15:2601–2608. doi:10.2147/COPD.S262746
   PubMed Web of Science ®Google Scholar
• Huang WC, Chen CY, Liao WC, et al. A real world study to assess the effectiveness of switching to once daily closed triple therapy from mono/dual combination or open triple therapy in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2021;16:1555–1568. doi:10.2147/COPD.S308911
   PubMed Web of Science ®Google Scholar
• Tashkin DP, Taube C. Triple therapy for chronic obstructive pulmonary disease management. Are our expectations fulfilled? Am J Respir Crit Care Med. 2017;196(4):402–404. doi:10.1164/rccm.201704-0760ED
   PubMed Web of Science ®Google Scholar
• Lopez-Campos JL, Carrasco-Hernandez L, Quintana-Gallego E, et al. Triple therapy for COPD: a crude analysis from a systematic review of the evidence. Ther Adv Respir Dis. 2019;13:1753466619885522. doi:10.1177/1753466619885522
   Web of Science ®Google Scholar
• Cazzola M, Matera MG. An obvious paradigm: choosing bronchodilators and inhaled corticosteroids for their pharmacologic characteristics. Chest. 2021;160(4):1157–1159. doi:10.1016/j.chest.2021.06.025
   PubMed Web of Science ®Google Scholar
• Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671–1680. doi:10.1056/NEJMoa1713901
   PubMed Web of Science ®Google Scholar
• Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respir Med. 2018;6(10):747–758. doi:10.1016/S2213-2600(18)30327-8
   PubMed Web of Science ®Google Scholar