Issues of triple therapy of chronic obstructive pulmonary disease. Comments to the algorithm. A resolution of expert panel, June 13, 2018, Vladivostok

Minimizing the risk of exacerbations of chronic obstructive pulmonary disease (COPD) along with symptoms control are the most important therapeutic tasks in COPD. The effective solution of this problem is still being discussed. The prevention of COPD exacerbations is of social and economic importance and should be the primary concern in the treatment of this disease. Unresolved problems in the treatment of COPD are low patient compliance to therapy and side effects of medication. According to recent guidelines, in case of persistent COPD exacerbations with patients receiving long-acting bronchodilators (LABA), the use of inhaled corticosteroids (ICS) must be considered; this reduces the incidence of moderate and severe COPD exacerbations, especially if a patient has a history of bronchial asthma or blood and/or sputum eosinophilia. Availability of LABA/LAMA and ICS/LABA fixed combinations in Russia provides two possible options to administer a free triple combination consisting of a single LAMA plus ICS/LABA or ICS plus LAMA/LAMA. According to multiple trials, the use of fixed combinations could provide twice improvement in the patient adherence to the therapy, which therefore leads to higher efficiency. The main complaint about ICS with COPD patients is an increased risk of pneumonia as well as the development of systemic adverse reactions typical for corticosteroids. However, the use of extra-fine ICS could significantly reduce the risk of pneumonia compared with fine-particle inhalators and also increases the effectiveness of therapy as the pathological process in COPD mainly involves the small airways.

exacerbations of chronic obstructive pulmonary disease, combined therapy, inhaled corticosteroids, extra-fine ICS

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease. 2018 Report. Available at: https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf

2. Aisanov Z., Avdeev S., Arkhipov V. et al. Russian guidelines for the management of COPD: algorithm of pharmacologic treatment. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 183–187. DOI: 10.2147/COPD.S153770

3. Janson С., Marks G., Buist S. et al. The impact of COPD on health status: findings from the BOLD study. Eur. Respir. J. 2013; 42 (6): 1472–1483. DOI: 10.1183/09031936.00153712.

4. Krysanov I.S. [A cost-efficacy analysis of chronic obstructive pulmonary disease in Russian Federation]. Kachestvennaya klinicheskaya praktika. 2014; (2): 51–56. Available at: https://cyberleninka.ru/article/v/analiz-stoimosti-hronicheskoy-obstruktivnoy-bolezni-lyogkih-v-rossiyskoy-federatsii (in Russian).

5. Andersson F., Borg S., Jansson S.A. et al. The costs of exacerbations in chronic obstructive pulmonary disease (COPD). Respir. Med. 2002; 96 (6): 700–708. DOI: 10.1053/rmed.2002.1334.

6. Chuchalin A.G., Avdeev S.N., Aisanov Z.R. et al. [Russian Respiratory Society. Federal Guidelines on Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease]. Pul'monologiya. 2014; (3): 15–54. DOI: 10.18093/0869-0189-2014-0-3-15-54 (in Russian).

7. Avdeev S.N., Belevskiy A.S., Ezhov A.V. et al. [Therapeutic approaches to the treatment of acute exacerbations of chronic obstructive pulmonary disease in Russian Federation: results of NIS CLOUD non-interventional study]. Pul'monologiya. 2018; 28 (4): 411–423. DOI: 10.18093/0869-0189-2018-28-4-411-423 (in Russian).

8. Matkovic Z., Miravitlles M. Chronic bronchial infection in COPD. Is there an infective phenotype? Respir. Med. 2013; 107 (1): 10–22. DOI: 10.1016/j.rmed.2012.10.024.

9. Emel'yanov A.V. [Inhaled corticosteroids in chronic obstructive pulmonary disease: what is their role for the treatment of the disease?]. Russkiy meditsinskiy zhurnal. 2017; (3): 227–231 (in Russian).

10. Stanescu D., Sanna A., Veriter C. et al. Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax. 1996; 51 (3): 267–271. DOI: 10.1136/thx.51.3.267.

11. King P.T. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clin. Transl. Med. 2015; 4 (1): 68. DOI: 10.1186/s40169-015-0068-z.

12. Price D., West D., Brusselle G. et al. Management of COPD in the UK primary-care setting: an analysis of reallife prescribing patterns. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9: 889–904. DOI:10.2147/COPD.S62750.

13. Short P.M., Williamson P.A., Elder D.H. et al. The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting β-agonist therapy in COPD. Chest. 2012; 141 (1): 81–86. DOI: 10.1378/chest.11-0038.

14. James G.D., Donaldson G.C., Wedzicha J.A., Nazareth I. Trends in management and outcomes of COPD patients in primary care, 2000–2009: a retrospective cohort study. NPJ Prim. Care Respir. Med. 2014; 24: 14015. DOI:10.1038/npjpcrm.2014.15.

15. 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 (1): 2207–2217. DOI: 10.2147/COPD.S91694.

16. Stempel D.A., Stoloff S.W., Carranza Rosenzweig J.R. et al. Adherence to asthma controller medication regimens. Respir. Med. 2005; 99 (10): 1263–1267. DOI: 10.1016/j.rmed.2005.03.002.

17. Chrischilles E., Gilden D., Kubisiak J. et al. Delivery of ipratropium and albuterol combination therapy for chronic obstructive pulmonary disease: effectiveness of a two-inone inhaler versus separate inhalers. Am. J. Manag. Care. 2002; 8 (10): 902–911.

18. Yu A.P., Guerin A., de Leon D.P. et al. Clinical and economic outcomes of multiple versus single long-acting inhalers in COPD. Respir. Med. 2011; 105 (12): 1861–1871. DOI: 10.1016/j.rmed.2011.07.001.

19. Singh D., Papi A., Corradi M. et al. 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 (10048): 963– 973. DOI: 10.1016/S0140-6736(16)31354-X.

20. Tabberer M., Lomas D.A., Birk R. et al. Once-daily triple therapy in patients with COPD: patient-reported symptoms and quality of life. Adv. Ther. 2018; 35 (1): 56–71. DOI: 10.1007/s12325-017-0650-4.

21. Lipson D.A., 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.

22. Vestbo J., Papi A., Corradi M. et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomized controlled trial. Lancet. 2017; 389 (10082): 1919–1929. DOI: 10.1016/S0140-6736(17)30188-5.

23. 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.

24. Melani A.S., Paleari D. Maintaining control of chronic obstructive airway disease: adherence to inhaled therapy and risks and benefits of switching devices. J. Chron. Obstruct. Pulmon. Dis. 2016; 13 (2): 241–250. DOI: 10.3109/15412555.2015.1045972.

25. De Backer W., Devolder A., Poli G. et al. Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J. Aerosol. Med. Pulm. Drug Deliv. 2010; 23 (3): 137–48. DOI: 10.1089/jamp.2009.0772.

26. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2018. Available at: https://ginasthma.org/wp-content/uploads/2019/01/2018-GINA.pdf

27. Pascoe S., Locantore N., Dransfield M.T. 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 (6): 435–442. DOI: 10.1016/S2213-2600(15)00106-X.

28. Singh D., Corradi M., Spinola M. et al. Extrafine beclometasone diproprionate/formoterol fumarate: a review of its effects in chronic obstructive pulmonary disease. NPJ Prim. Care Respir. Med. 2016; 26: 16030. DOI:10.1038/npjpcrm.2016.30.

29. Hastie A.T., Martinez F.J., Curtis J.L. et al. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. Lancet Respir. Med. 2017; 5 (12): 956–967. DOI: 10.1016/S2213-2600(17)30432-0.

30. Vedel-Krogh S., Nielsen S.F., Lange P. et al. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen General Population study. Am. J. Respir. Crit. Care Med. 2016; 193 (9): 965–974.

31. Yang I.A., Fong K., Black P.N. et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2011; (1): CD002991. DOI: 10.1002/14651858.CD002991.

32. Dransfield M.T., Bourbeau J., Jones P.W. 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. 2013; 1 (3): 210–223. DOI: 10.1016/S2213-2600(13) 70040-7.

33. Lipworth B.J. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch. Intern. Med. 1999; 159 (9): 941–955. DOI: 10.1001/archinte.159.9.941.

34. Festic E., Bansal V., Gupta E., Scanlon P.D. Association of inhaled corticosteroids with incident pneumonia and mortality in COPD patients; systematic review and meta-analysis. J. COPD. 2016; 13 (3): 312–326. DOI: 10.3109/15412555.2015.1081162.

35. Sonnappa S., Martin R., Israel E. et al. Risk of pneumonia in obstructive lung disease: A real-life study comparing extra-fine and fine-particle inhaled corticosteroids. PLoS One. 2017; 12 (6): e0178112. DOI: 10.1371/journal.pone.0178112.

36. Hogg J.C., Chu F., Utokaparch S. et al. The nature of smallairway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350 (26): 2645–2653. DOI: 10.1056/NEJMoa032158.

37. Wedzicha J.A., Banerji D., Chapman K.R. et al. Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD. N. Engl. J. Med. 2016; 374 (23): 2222–2234. DOI: 10.1056/NEJMoa1516385.

38. Chalmers J.D. POINT: Should an attempt be made to withdraw inhaled corticosteroids in all patients with stable GOLD 3 (30% ≤ FEV1 < 50% predicted) COPD? Yes. Chest. 2018; 153 (4): 778–782. DOI: 10.1016/j.chest.2018.01.029.

39. Pavord I.D. COUNTERPOINT: Should an attempt be made to withdraw inhaled corticosteroids in all patients with stable GOLD 3 (30% ≤ FEV1 < 50% predicted) COPD? No. Chest. 2018; 153 (4): 782–784. DOI: 10.1016/j.chest.2018.01.030.

40. Cosio B.G., Soriano J.B., Lоpez-Campos J.L. et al. Defining the Asthma–COPD Overlap Syndrome in a COPD Cohort. Chest. 2016; 149 (1): 45–52. DOI: 10.1378/chest.15-1055.