Triple fixed combinations therapy in patients with chronic obstructive pulmonary disease
Abstract. Modern concept of chronic obstructive pulmonary disease (COPD) treatment takes into account individual characteristics of the patient and includes methods that relieve symptoms, reduce risk of exacerbations, slow down the progression of the disease and reduce COPD mortality. Bronchodilator therapy with long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) is the recommended initial treatment regimen for COPD. In patients with COPD and eosinophilia and/or high risk of exacerbation during LAMA + LABA therapy, Russian clinical guidelines recommend starting triple therapy by inhaled corticosteroids (ICS) / LAMA / LABA. Currently, sufficient data have been accumulated on the advantages of prescribing triple fixed combinations of ICS / LAMA / LABA using a single inhaler. They include improved adherence to treatment and control over inhalation technique, reduced probability of missing the next dose of the drug, and a decrease in the total number of inhalations. The review presents clinical studies describing the experience of triple therapy of ICS / LAMA / LABA using a separate and a single delivery system.Karoli N.A., Kanaeva T.V.
Keywords
References
1. Steiropoulos P, Georgatou N, Krommidas G, Bartziokas K, Korkontzelou A, Katerelos P et al. Extrafine single inhaler triple therapy effectiveness in COPD patients previously treated with multiple-inhaler triple therapy: The TRIWIN study. Ther Adv Respir Dis. 2024;18:17534666241263439.
PMID: 39049587. PMCID: PMC11301738. https://doi.org/10.1177/17534666241263439
2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2023 Report). URL: https://goldcopd.org/wp-content/uploads/2023/03/GOLD-2023-ver-1.3-17Feb2023_WMV.pdf (date of access – 12.05.2025).
3. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442.
PMID: 17132052. PMCID: PMC1664601. https://doi.org/10.1371/journal.pmed.0030442
4. Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017;195(5) 557–82.
PMID: 28128970. https://doi.org/10.1164/rccm.201701-0218PP
5. Клинические рекомендации. Хроническая обструктивная болезнь легких. Ассоциация врачей и специалистов медицины труда, общероссийская общественная организация «Российское научное медицинское общество терапевтов», Российское респираторное общество. Рубрикатор клинических рекомендаций Минздрава России. 2024. ID: 603_3. Доступ: https://cr.minzdrav.gov.ru/preview-cr/603_3 (дата обращения – 12.05.2025). (Clinical guidelines. Chronic obstructive pulmonary disease. Association of Doctors and Occupational Medicine Specialists, Russian Scientific Medical Society of Internal Medicine, Russian Respiratory Society. Rubricator of clinical recommendations of the Russian Ministry of Health. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2024. ID: 603_3. URL: https://cr.minzdrav.gov.ru/preview-cr/603_3 (date of access – 12.05.2025) (In Russ.)).
6. Kew KM, Dias S, Cates CJ. Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: A network meta-analysis. Cochrane Database Syst Rev. 2014;2014(3):CD010844.
PMID: 24671923. PMCID: PMC10879916. https://doi.org/10.1002/14651858.cd010844.pub2
7. Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: Time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018;13:3971–81.
PMID: 30587953. PMCID: PMC6296179. https://doi.org/10.2147/COPD.S185975
8. Zhang S, Wang J, Li X, Zhang H. Comparative effectiveness and safety of triple therapy and non-triple therapy interventions for COPD: An overview of systematic reviews. Ther Adv Respir Dis. 2024;18:17534666241259634.
PMID: 38877687. PMCID: PMC11179455. https://doi.org/10.1177/17534666241259634
9. Singh D, Corradi M, Spinola M, Papi A, Usmani OS, Scuri M et al. Triple therapy in COPD: New evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide. Int J Chron Obstruct Pulmon Dis. 2017;12:2917–28.
PMID: 29062229. PMCID: PMC5638574. https://doi.org/10.2147/copd.s146822
10. Cuperus LJA, van der Palen J, Aldenkamp A, van Huisstede A, Bischoff EWMA, van Boven JFM et al.; TRICOLON study group. Adherence to single inhaler triple therapy and digital inhalers in chronic obstructive pulmonary disease: A literature review and protocol for a randomized controlled trial (TRICOLON study). BMC Pulm Med. 2024;24(1):317.
PMID: 38965541. PMCID: PMC11225120. https://doi.org/10.1186/s12890-024-03044-3
11. Miravitlles M, Acharya S, Aggarwal B, Fernandes FLA, Dreyse J, Jardim JR et al. Clinical concepts for triple therapy use in patients with COPD: A Delphi consensus. Int J Chron Obstruct Pulmon Dis. 2023;18:1853–66.
PMID: 37662490. PMCID: PMC10474219. https://doi.org/10.2147/copd.s424128
12. 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):143–52.
PMID: 32856967. https://doi.org/10.1080/17476348.2020.1816830
13. Cazzola M, Rogliani P, Laitano R, Calzetta L, Matera MG. Beyond dual bronchodilation – triple therapy, when and why. Int J Chron Obstruct Pulmon. Dis. 2022;17:165–80.
PMID: 35068929. PMCID: PMC8766250. https://doi.org/10.2147/copd.s345263
14. Yu AP, Guerin A, de Leon DP, Ramakrishnan K, Wu EQ, Mocarski M et al. Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: Multiple versus single long-acting maintenance inhalers. J Med Econ. 2011;14(4):486–96.
PMID: 21679019. https://doi.org/10.3111/13696998.2011.594123
15. Авдеев С.Н., Лещенко И.В., Айсанов З.Р. Новая концепция и алгоритм ведения пациентов с хронической обструктивной болезнью легких. Пульмонология. 2023;33(5):587–594. (Avdeev SN, Leshchenko IV, Aysanov ZR. New concept and algorithm for the management of patients with chronic obstructive pulmonary disease. Pulmonologiya = Pulmonology. 2023;33(5):587–594 (In Russ.)).
EDN: XWOLJE. https://doi.org/10.18093/0869-0189-2023-33-5-587-594
16. Singh D, Brooks J, Hagan G, Cahn A, O’Connor BJ. Superiority of “triple” therapy with salmeterol / fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax. 2008;63(7):592–98.
PMID: 18245142. https://doi.org/10.1136/thx.2007.087213
17. Jung KS, Park HY, Park SY, Kim SK, Kim Y-K, Shim J-J et al.; Korean Academy of Tuberculosis and Respiratory Diseases study group; Korea Chronic Obstructive Pulmonary Disease study group. Comparison of tiotropium plus fluticasone propionate / salmeterol with tiotropium in COPD: A randomized controlled study. Respir Med. 2012;106(3):382–89.
PMID: 21975275. https://doi.org/10.1016/j.rmed.2011.09.004
18. Siler TM, Kerwin E, Singletary K, Brooks J, Church A. Efficacy and safety of umeclidinium added to fluticasone propionate / salmeterol in patients with COPD: Results of two randomized, double-blind studies. COPD. 2016;13(1):1–10.
PMID: 26451734. PMCID: PMC4778542. https://doi.org/10.3109/15412555.2015.1034256
19. Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R et al.; Canadian Thoracic Society / Canadian Respiratory Clinical Research Consortium. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: A randomized trial. Ann Intern Med. 2007;146(8):545–55.
PMID: 17310045. https://doi.org/10.7326/0003-4819-146-8-200704170-00152
20. Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, Kessler R. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180(8):741–50.
PMID: 19644045. https://doi.org/10.1164/rccm.200904-0492OC
21. Wedzicha JA, Singh D, Vestbo J, Paggiaro PL, Jones PW, Bonnet-Gonod F et al.; FORWARD Investigators. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014;108(8):1153–62.
PMID: 24953015. https://doi.org/10.1016/j.rmed.2014.05.013
22. Salvi S, Balki A, Krishnamurthy S, Panchal S, Patil S, Kodgule R et al. Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: A double-blind, randomised controlled trial. ERJ Open Res. 2021;7(3):00255-2021.
PMID: 34322547. PMCID: PMC8311133. https://doi.org/10.1183/23120541.00255-2021
23. Zhang S, Wang J, Li X, Zhang H. Comparative effectiveness and safety of triple therapy and non-triple therapy interventions for COPD: An overview of systematic reviews. Ther Adv Respir Dis. 2024;18:17534666241259634.
PMID: 38877687. PMCID: PMC11179455. https://doi.org/10.1177/17534666241259634
24. van Gefen WH, Tan DJ, Walters JA, Walters EH. Inhaled corticosteroids with combination inhaled long-acting beta2-agonists and long-acting muscarinic antagonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2023;12(12):CD011600.
PMID: 38054551. PMCID: PMC10698842. https://doi.org/10.1002/14651858.cd011600.pub3
25. Zhang S, Wang J, Li X, Zhang H. Comparative effectiveness and safety of triple therapy and non-triple therapy interventions for COPD: An overview of systematic reviews. Ther Adv Respir Dis. 2024;18:17534666241259634.
PMID: 38877687. PMCID: PMC11179455. https://doi.org/10.1177/17534666241259634
26. Papaioannou AI, Loukides S, Vassilakopoulos T, Tzanakis N, Kostikas K, Hillas G; Triple Therapy for COPD Delphi Expert Panel. A Delphi consensus project to capture Greek experts’ opinion on the position of triple therapies in COPD: Why, when and to whom. Int J Chron Obstruct Pulmon Dis. 2025;20:457–71.
PMID: 40041472. PMCID: PMC11878287. https://doi.org/10.2147/COPD.S481337
27. Bengtson LGS, DePietro M, McPheeters J, Fox KM. Real-world outcomes in patients with chronic obstructive pulmonary disease initiating long-acting mono bronchodilator therapy. Ther Adv Respir Dis. 2018;12:1753466618772750.
PMID: 29737943. PMCID: PMC5961922. https://doi.org/10.1177/1753466618772750
28. Labaki WW, Martinez FJ, Han MK. Insights into chronic obstructive pulmonary disease epidemiology, phenotypes and outcomes from SPIROMICS. BRN Rev. 2019;5(4):233–48.
https://doi.org/10.23866/brnrev:2018-0014
29. Quint JK, O’Leary C, Venerus A, Myland M, Holmgren U, Varghese P 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):333–50.
PMID: 33064273. PMCID: PMC7672143. https://doi.org/10.1007/s41030-020-00132-7
30. Bogart M, Stanford RH, Laliberté F, Germain G, Wu JW, Duh MS. Medication adherence and persistence in chronic obstructive pulmonary disease patients receiving triple therapy in a USA commercially insured population. Int J Chron Obstruct Pulmon Dis. 2019;14:343–52.
PMID: 30863037. PMCID: PMC6388782. https://doi.org/10.2147/copd.s184653
31. Sanchis J, Gich I, Pedersen S; Aerosol Drug Management Improvement Team (ADMIT). Systematic review of errors in inhaler use: Has patient technique improved over time? Chest. 2016;150(2):394–406.
PMID: 27060726. https://doi.org/10.1016/j.chest.2016.03.041
32. Dhar R, Talwar D, Salvi S, Muralimohan BV, Panchal S, Patil S et al. Use of single-inhaler triple therapy in the management of obstructive airway disease: Indian medical experts’ review. ERJ Open Res. 2022;8(1):00556-2021.
PMID: 35350278. PMCID: PMC8958219. https://doi.org/10.1183/23120541.00556-2021
33. Humenberger M, Horner A, Labek A, Kaiser B, Frechinger R, Brock C et al. Adherence to inhaled therapy and its impact on chronic obstructive pulmonary disease (COPD). BMC Pulm Med. 2018;18(1):163.
PMID: 30340565. PMCID: PMC6194635. https://doi.org/10.1186/s12890-018-0724-3
34. George M. Adherence in asthma and COPD: New strategies for an old problem. Respir Care. 2018;63(6):818–31.
PMID: 29794213. https://doi.org/10.4187/respcare.05905
35. Calzetta L, Matera MG, Braido F, Contoli M, Corsico A, Di Marco F et al. Withdrawal of inhaled corticosteroids in COPD: A meta-analysis. Pulm Pharmacol Ther. 2017;45:148–58.
PMID: 28606478. https://doi.org/10.1016/j.pupt.2017.06.002
36. Langham S, Lewis J, Pooley N, Embleton N, Langham J, Han MK, Chalmers JD. Single-inhaler triple therapy in patients with chronic obstructive pulmonary disease: A systematic review. Respir Res. 2019;20(1):242.
PMID: 31684965. PMCID: PMC6829989. https://doi.org/10.1186/s12931-019-1213-9
37. Halpin DMG, Worsley S, Ismaila AS, Beeh K-M, Midwinter D, Kocks JWH et al. INTREPID: Single- versus multiple-inhaler triple therapy for COPD in usual clinical practice. ERJ Open Res. 2021;7(2):00950-2020.
PMID: 34109236. PMCID: PMC8181617. https://doi.org/10.1183/23120541.00950-2020
38. Ferguson GT, Rabe KF, Martinez FJ, Fabbri LM, Wang C, Ichinose M 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):747–58.
PMID: 30232048. https://doi.org/10.1016/s2213-2600(18)30327-8
39. Alcazar-Navarrete B, Jamart L, Sanchez-Covisa J, Juarez M, Graefenhain R, Sicras-Mainar A. Clinical characteristics, treatment persistence, and outcomes among patients with COPD treated with single- or multiple-inhaler triple therapy: A retrospective analysis in Spain. Chest. 2022;162(5):1017–29.
PMID: 35787391. https://doi.org/10.1016/j.chest.2022.06.033
40. Strange C, Tkacz J, Schinkel J, Lewing B, Agatep B, Swisher S et al. Exacerbations and real-world outcomes after single-inhaler triple therapy of budesonide / glycopyrrolate / formoterol fumarate, among patients with COPD: Results from the EROS (US) study. Int J Chron Obstruct Pulmon Dis. 2024;19:1799–1800.
https://doi.org/10.2147/copd.s484253
41. Pelaia C, Procopio G, Rotundo FL, Deodato MR, Bannera AF, Tropea FG et al. Real-life therapeutic effects of beclomethasone dipropionate / formoterol fumarate / glycopyrronium combined triple therapy in patients with chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2023;17:17534666231155778.
PMID: 36846944. PMCID: PMC9972048. https://doi.org/10.1177/17534666231155778
42. Park H, Lee HJ, Lee HW, Park TY, Heo EY, Kim DK, Lee J-K. Diagnosis and evaluation of small airway disease and COPD using impulse oscillometry. Sci Rep. 2024;14(1):28030.
PMID: 39543228. PMCID: PMC11564534. https://doi.org/10.1038/s41598-024-79818-w
43. Higham A, Booth S, Dungwa J, Singh D. Histopathology of the small airways: Similarities and differences between ageing and COPD. Pulmonology. 2025;31(1):2430032.
PMID: 39883495. https://doi.org/10.1080/25310429.2024.2430032
44. Lazarinis N, Fouka E, Linden A, Bossios A. Small airways disease in chronic obstructive pulmonary disease. Expert Rev Respir Med. 2024;18(7):539–52.
PMID: 39046133. https://doi.org/10.1080/17476348.2024.2380070
45. Yee N, Markovic D, Buhr RG, Fortis S, Arjomandi M, Couper D et al. Significance of FEV3/FEV6 in recognition of early airway disease in smokers at risk of development of COPD: Analysis of the SPIROMICS cohort. Chest. 2022;161(4):949–59.
PMID: 34767825. PMCID: PMC9005864. https://doi.org/10.1016/j.chest.2021.10.046
46. Santofimio VQ, Knox-Brown B, Potts J, Bartlett-Pestell S, Feary J, Amaral AS. Small airways obstruction and mortality: Findings from the UK biobank. Chest. 2024;166(4):712–20.
PMID: 38797279. PMCID: PMC11492227. https://doi.org/10.1016/j.chest.2024.04.016
47. Verleden SE, Hendriks JMH, Snoeckx A, Mai C, Mentens Y, Callebaut W et al. Small airway disease in pre-chronic obstructive pulmonary disease with emphysema: A cross-sectional study. Am J Respir Crit Care Med. 2024;209(6):683–92.
PMID: 38055196. https://doi.org/10.1164/rccm.202301-0132OC
48. Huang S, Wu F, Deng Z, Peng J, Dai C, Lu L et al. Comparing spirometry, impulse oscillometry with computed tomography for assessing small airway dysfunction in subjects with and without chronic obstructive pulmonary disease. BMC Pulm Med. 2025;25(1):45.
PMID: 39875840. PMCID: PMC11773755. https://doi.org/10.1186/s12890-025-03507-1
49. Tzani P, Crisafulli E, Nicolini G, Aiello M, Chetta A, Clini EM, Olivieri D. Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients. Int J Chron Obstruct Pulmon Dis. 2011;6:503–9.
PMID: 22069361. PMCID: PMC3206766. https://doi.org/10.2147/COPD.S23746
50. Kupczyk M, Kuna P. Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide as a combination therapy for chronic obstructive pulmonary disease. Expert Rev Respir Med. 2019;13(1):5–11.
PMID: 30463457. https://doi.org/10.1080/17476348.2019.1548937
51. Dunn LJ, Kerwin EM, DeAngelis K, Darken P, Gillen M, Dorinsky P. Pharmacokinetics of budesonide / glycopyrrolate / formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD. Pulm Pharmacol Ther. 2020;60:101873.
PMID: 31841699. https://doi.org/10.1016/j.pupt.2019.101873
52. Singh D, Papi A, Corradi M, Pavlišová I, Montagna I, Francisco C 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):963–73.
PMID: 27598678. https://doi.org/10.1016/S0140-6736(16)31354-X
53. Vestbo J, Papi A, Corradi M, Blazhko V, Montagna I, Francisco C et al. 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(10082):1919–29.
PMID: 28385353. https://doi.org/10.1016/S0140-6736(17)30188-5
54. Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G 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):1076–84.
PMID: 29429593. https://doi.org/10.1016/s0140-6736(18)30206-x
55. Dean J, Panainte C, Khan N, Singh D. The TRIFLOW study: A randomised, cross-over study evaluating the effects of extrafine beclometasone/formoterol/glycopyrronium on gas trapping in COPD. Respir Res. 2020;21(1):323.
PMID: 33298062. PMCID: PMC7727250. https://doi.org/10.1186/s12931-020-01589-5
56. Marth K, Renner A, Pohl W. TRICOP – a real-world effectiveness study with a single-inhaler extrafine triple therapy over 52 weeks in Austrian patients with COPD. Respir Med. 2021;182:106398.
PMID: 33901786. https://doi.org/10.1016/j.rmed.2021.106398
57. Porpodis K, Bartziokas K, Chatziapostolou P, Korkontzelou A, Katerelos P, Efstathopoulos P, Bakakos P. Extrafine single inhaler triple therapy effect on health status, lung function and adherence in COPD patients: A Panhellenic prospective non-interventional study – The TRIBUNE study. Respir Med. 2023;212:107219.
PMID: 36965590. https://doi.org/10.1016/j.rmed.2023.107219
58. Steiropoulos P, Georgatou N, Krommidas G, Bartziokas K, Korkontzelou A, Katerelos P et al. Extrafine single inhaler triple therapy effectiveness in COPD patients previously treated with multiple-inhaler triple therapy: The TRIWIN study. Ther Adv Respir Dis. 2024;18:17534666241263439.
PMID: 39049587. PMCID: PMC11301738. https://doi.org/10.1177/17534666241263439
59. Martinez FJ, Rabe KF, Ferguson GT, Wedzicha JA, Singh D, Wang C 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):553–64.
PMID: 33252985. PMCID: PMC7924571. https://doi.org/10.1164/rccm.202006-2618OC
60. Sonnappa S, Martin R, Israel E, Postma D, van Aalderen W, Burden A et al.; Respiratory Effectiveness Group, Small Airways Study Group. 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.
PMID: 28617814. PMCID: PMC5472262. https://doi.org/10.1371/journal.pone.0178112
61. Usmani OS, Scichilone N, Mignot B, Belmans D, Van Holsbeke C, De Backer J et al. Airway deposition of extrafine inhaled triple therapy in patients with COPD: A model approach based on functional respiratory imaging computer simulations. Int J Chron Obstruct Pulmon Dis. 2020;15:2433–40.
PMID: 33116458. PMCID: PMC7548261. https://doi.org/10.2147/COPD.S269001
About the Authors
Nina A. Karoli, MD, Dr. Sci. (Medicine), professor, professor of the Department of hospital therapy of the Faculty of general medicine, V.I. Razumovsky Saratov State Medical University of the Ministry of Healthcare of Russia. Address: 410012, Saratov, 112 Bolshaya Kazachya St.E-mail: nina.karoli.73@gmail.com
ORCID: http://orcid.org/0000-0002-7464-826X. Scopus ID: 6603194518. eLibrary SPIN: 6506-0261
Tatyana V. Kanaeva, MD, assistant at the Department of hospital therapy of the Faculty of general medicine, V.I. Razumovsky Saratov State Medical University of the Ministry of Healthcare of Russia. 410012, Saratov, 112 Bolshaya Kazachya St.
E-mail: tatyanakanaeva7795@gmail.com
ORCID: http://orcid.org/0000-0002-9451-9318. Scopus ID: 57349117300. eLibrary SPIN: 8032-1241