pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2023-33-6-810-818pulmo-4394Research ArticleОБЗОРЫREVIEWПрименение тиотропия бромида в лечении хронической обструктивной болезни легкихTiotropium bromide in the treatment of chronic obstructive pulmonary diseasehttps://orcid.org/0000-0003-4678-3904ТитоваО. Н.TitovaO. N.

Титова Ольга Николаевна – доктор медицинских наук, профессор, директор Научно-исследовательского института пульмонологии Научно-клинического исследовательского центра.

197022, Санкт-Петербург, ул. Льва Толстого, 6–8; тел.: (812) 338-78-40

Olga N. Titova - Doctor of Medicine, Professor, Director, Research Institute of Pulmonology, Scientific and Clinical Research Center.

Ul. L`va Tolstogo 6 – 8, Saint-Petersburg, 197022; tel.: (812) 338-78-40

titova-on@mail.ruhttps://orcid.org/0000-0002-1166-9717КузубоваН. А.KuzubovaN. A.

Кузубова Наталия Анатольевна – доктор медицинских наук, заместитель директора по научной работе Научно-исследовательского института пульмонологии.

197022, Санкт-Петербург, ул. Льва Толстого, 6–8; тел.: (812) 338-66-16

Nataliya A. Kuzubova - Doctor of Medicine, Deputy Director for Research, Research Institute of Pulmonology.

Ul. L`va Tolstogo 6 – 8, Saint-Petersburg, 197022; tel.: (812) 338-66-16

kuzubova@mail.ruhttps://orcid.org/0000-0002-9270-3779КозыревА. Г.KozyrevA. G.

Козырев Андрей Геннадьевич – кандидат медицинских наук, руководитель отдела хронической обструктивной патологии легких Научно-исследовательского института пульмонологии.

197022, Санкт-Петербург, ул. Льва Толстого, 6–8; тел.: (812) 33878-89

Andrey G. Kozyrev, Candidate of Medicine, Head of the Department of Chronic Obstructive Pulmonary Pathology, Research Institute of Pulmonology.

Ul. L`va Tolstogo 6 – 8, Saint-Petersburg, 197022; tel.: (812) 338-78-89

kozyrev@bk.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Educational Institution of Higher Education “Academician I.P.Pavlov First St. Petersburg State Medical University” of the Ministry of Healthcare of Russian FederationRussian Federation202313122023336810818Copyright © Титова О.Н., Кузубова Н.А., Козырев А.Г., 20232023Титова О.Н., Кузубова Н.А., Козырев А.Г.Titova O.N., Kuzubova N.A., Kozyrev A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/4394

Длительно действующие антихолинергические препараты (ДДАХП) широко используются при лечении хронической обструктивной болезни легких (ХОБЛ).

Целью обзора явился анализ актуальных сведений об одном из ДДАХП – тиотропия бромиде. Хронологически тиотропия бромид является первым ДДАХП в клинической практике. Он применяется с помощью порошкового или аэрозольного ингалятора (Респимат). Продолжительность бронхолитического эффекта позволяет ингалировать тиотропия бромид 1 раз в день. Терапия тиотропия бромидом оказывает существенное влияние на функциональные респираторные показатели, при этом уменьшается легочная гиперинфляция, улучшаются переносимость физической нагрузки и качество жизни. В отношении профилактики обострений ХОБЛ тиотропия бромид превосходит короткодействующие бронхолитические препараты, длительно действующие β2-агонисты (ДДБА) и сопоставим с другими ДДАХП, а также комбинациями ДДБА и ингаляционных глюкокортикостероидов. Тиотропия бромид обладает благоприятным профилем безопасности. В настоящее время в Российской Федерации доступны генерические препараты тиотропия бромида, в т. ч. Респиум®. По результатам клинического исследования подтверждены неменьшие эффективность и безопасность указанного генерического препарата в сравнении с оригинальным.

Заключение. Тиотропия бромид является эффективным и безопасным средством для поддерживающей терапии ХОБЛ и снижения количества обострений заболевания. При наличии генерических версий тиотропия бромида расширяется перечень эффективных ингаляционных средств, которые могут быть назначены врачом.

The aim of this review was to analyze current information on tiotropium bromide as one of the LAMAs. Tiotropium was chronologically the first LAMA in clinical practice. It is administered using a dry powder inhaler or an aerosol inhaler (Respimat soft mist inhaler). Due to the long bronchodilator effect, tiotropium can be inhaled once a day. The drug has a significant effect on functional respiratory parameters, reduces lung hyperinflation, improves exercise tolerance and quality of life. Tiotropium is superior to short-acting bronchodilators and long-acting β2-agonists (LABAs) and is comparable to other LAMAs, as well as combinations of LABAs and inhaled corticosteroids in the prevention of COPD exacerbations. Tiotropium bromide has a favorable safety profile. Generic tiotropium drug products, including Respium®, are currently available in the Russian Federation. A clinical trial confirmed the non-inferiority and safety of generic tiotropium drug compared to the original branded product.

Conclusion. Tiotropium is an effective and safe medication for the maintenance treatment of COPD and for reducing COPD exacerbations. The generic tiotropium drug products widen the range of effective inhaled medications available to physicians.

хроническая обструктивная болезнь легкихдлительно действующий антихолинергический препараттиотропия бромидРеспиум®chronic obstructive pulmonary diseaselong-acting muscarinic antagonisttiotropium bromideRespium®Статья подготовлена при поддержке компании ООО «ПСК Фарма» (Россия) в соответствии с действующим законодательством Российской Федерации и принципами Добросовестной практики научных публикацийThe article was prepared with the support of PSK Pharma LLC (Russia) in accordance with the current legislation of the Russian Federation and the principles of Good Clinical Practice in scientific publicationsReferencesВсемирная организация здравоохранения. Информационные бюллетени. Хроническая обструктивная болезнь легких (ХОБЛ). Доступно на: https://www.who.int/ru/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)World Health Organization. Fact sheets. [Chronic obstructive pulmonary disease (COPD)]. Available at: https://www.who.int/ru/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd) (in Russian).Adeloye D., Song P., Zhu Y. et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir. Med. 2022; 10 (5): 447–458. DOI: 10.1016/S2213-2600(21)00511-7.Adeloye D., Song P., Zhu Y. et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir. Med. 2022; 10 (5): 447–458. DOI: 10.1016/S2213-2600(21)00511-7.GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet. 2021; 397 (10292): 2337–2360. DOI: 10.1016/S0140-6736(21)01169-7.GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet. 2021; 397 (10292): 2337–2360. DOI: 10.1016/S0140-6736(21)01169-7.Lange P., Marott J.L., Vestbo J. et al. Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. Am. J. Respir. Crit. Care Med. 2012; 186 (10): 975–981. DOI: 10.1164/rccm.201207-1299OC.Lange P., Marott J.L., Vestbo J. et al. Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. Am. J. Respir. Crit. Care Med. 2012; 186 (10): 975–981. DOI: 10.1164/rccm.201207-1299OC.Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD: 2023 Report. Available at: https://goldcopd.org/2023-gold-report-2/Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD: 2023 Report. Available at: https://goldcopd.org/2023-gold-report-2/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. DOI: 10.18093/0869-0189-2023-33-5-587-594.Avdeev S.N., Leshhenko I.V., Aisanov Z.R. [New concept and algorithm for the management of patients with chronic obstructive pulmonary disease]. Pul'monologiya. 2023; 33 (5): 587–594. DOI: 10.18093/0869-0189-2023-33-5-587-594 (in Russian).Vogelmeier C., Hederer B., Glaab T. et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N. Engl. J. Med. 2011; 364 (12): 1093–1103. DOI: 10.1056/NEJMoa1008378.Vogelmeier C., Hederer B., Glaab T. et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N. Engl. J. Med. 2011; 364 (12): 1093–1103. DOI: 10.1056/NEJMoa1008378.Decramer M.L., Chapman K.R., Dahl R. 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 (7): 524–533. DOI: 10.1016/S2213-2600(13)70158-9.Decramer M.L., Chapman K.R., Dahl R. 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 (7): 524–533. DOI: 10.1016/S2213-2600(13)70158-9.Panning C.A., DeBisschop M. Tiotropium: an inhaled, long-acting anticholinergic drug for chronic obstructive pulmonary disease. Pharmacotherapy. 2003; 23 (2): 183–189. DOI: 10.1592/phco.23.2.183.32082.Panning C.A., DeBisschop M. Tiotropium: an inhaled, long-acting anticholinergic drug for chronic obstructive pulmonary disease. Pharmacotherapy. 2003; 23 (2): 183–189. DOI: 10.1592/phco.23.2.183.32082.van Noord J.A., Bantje T.A., Eland M.E. et al. A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group. Thorax. 2000; 55 (4): 289–294. DOI: 10.1136/thorax.55.4.289.van Noord J.A., Bantje T.A., Eland M.E. et al. A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group. Thorax. 2000; 55 (4): 289–294. DOI: 10.1136/thorax.55.4.289.Littner M.R., Ilowite J.S., Tashkin D.P. et al. Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2000; 161 (4, Pt 1): 1136–1142. DOI: 10.1164/ajrccm.161.4.9903044.Littner M.R., Ilowite J.S., Tashkin D.P. et al. Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2000; 161 (4, Pt 1): 1136–1142. DOI: 10.1164/ajrccm.161.4.9903044.Niewoehner D.E., Lapidus R., Cote C. et al. Therapeutic conversion of the combination of ipratropium and albuterol to tiotropium in patients with chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther. 2009; 22 (6): 587–592. DOI: 10.1016/j.pupt.2009.08.006.Niewoehner D.E., Lapidus R., Cote C. et al. Therapeutic conversion of the combination of ipratropium and albuterol to tiotropium in patients with chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther. 2009; 22 (6): 587–592. DOI: 10.1016/j.pupt.2009.08.006.Cooper C.B. The connection between chronic obstructive pulmonary disease symptoms and hyperinflation and its impact on exercise and function. Am. J. Med. 2006; 119 (10, Suppl. 1): 21–31. DOI: 10.1016/j.amjmed.2006.08.004.Cooper C.B. The connection between chronic obstructive pulmonary disease symptoms and hyperinflation and its impact on exercise and function. Am. J. Med. 2006; 119 (10, Suppl. 1): 21–31. DOI: 10.1016/j.amjmed.2006.08.004.O'Donnell D.E., Flüge T., Gerken F. et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur. Respir. J. 2004; 23 (6): 832–840. DOI: 10.1183/09031936.04.00116004.O'Donnell D.E., Flüge T., Gerken F. et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur. Respir. J. 2004; 23 (6): 832–840. DOI: 10.1183/09031936.04.00116004.Verkindre C., Bart F., Aguilaniu B. et al. The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease. Respiration. 2006; 73 (4): 420–427. DOI: 10.1159/000089655.Verkindre C., Bart F., Aguilaniu B. et al. The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease. Respiration. 2006; 73 (4): 420–427. DOI: 10.1159/000089655.Fležar M., Jahnz-Różyk K., Enache G. et al. SOSPES: SPIRIVA® observational study measuring SGRQ score in routine medical practice in Central and Eastern Europe. Int. J. Chron. Obstruct. Pulmon. Dis. 2013; 8: 483–492. DOI: 10.2147/COPD.S45640.Fležar M., Jahnz-Różyk K., Enache G. et al. SOSPES: SPIRIVA® observational study measuring SGRQ score in routine medical practice in Central and Eastern Europe. Int. J. Chron. Obstruct. Pulmon. Dis. 2013; 8: 483–492. DOI: 10.2147/COPD.S45640.Jahnz-Różyk K., Szepiel P. Early impact of treatment with tiotropium, long-acting anticholinergic preparation, in patients with COPD – real-life experience from an observational study. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 613–623. DOI: 10.2147/COPD.S77144.Jahnz-Różyk K., Szepiel P. Early impact of treatment with tiotropium, long-acting anticholinergic preparation, in patients with COPD – real-life experience from an observational study. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 613–623. DOI: 10.2147/COPD.S77144.Wallace A.E., Kaila S., Bayer V. et al. Health care resource utilization and exacerbation rates in patients with COPD stratified by disease severity in a commercially insured population. J. Manag. Care Spec. Pharm. 2019; 25 (2): 205–217. DOI: 10.18553/jmcp.2019.25.2.205.Wallace A.E., Kaila S., Bayer V. et al. Health care resource utilization and exacerbation rates in patients with COPD stratified by disease severity in a commercially insured population. J. Manag. Care Spec. Pharm. 2019; 25 (2): 205–217. DOI: 10.18553/jmcp.2019.25.2.205.Niewoehner D.E., Rice K., Cote C. et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann. Intern. Med. 2005; 143 (5): 317–326. DOI: 10.7326/0003-4819-143-5-200509060-00007.Niewoehner D.E., Rice K., Cote C. et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann. Intern. Med. 2005; 143 (5): 317–326. DOI: 10.7326/0003-4819-143-5-200509060-00007.Barr R.G., Bourbeau J., Camargo C.A., Ram F.S.F. Tiotropium for stable chronic obstructive pulmonary disease: a meta-analysis. Thorax. 2006; 61 (10): 854–862. DOI: 10.1136/thx.2006.063271.Barr R.G., Bourbeau J., Camargo C.A., Ram F.S.F. Tiotropium for stable chronic obstructive pulmonary disease: a meta-analysis. Thorax. 2006; 61 (10): 854–862. DOI: 10.1136/thx.2006.063271.Dusser D., Bravo M.L., Iacono P. The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur. Respir. J. 2006; 27 (3): 547–555. DOI: 10.1183/09031936.06.00062705.Dusser D., Bravo M.L., Iacono P. The effect of tiotropium on exacerbations and airflow in patients with COPD. Eur. Respir. J. 2006; 27 (3): 547–555. DOI: 10.1183/09031936.06.00062705.Halpin D.M., Vogelmeier C., Pieper M.P. et al. Effect of tiotropium on COPD exacerbations: a systematic review. Respir. Med. 2016; 114: 1–8. DOI: 10.1016/j.rmed.2016.02.012.Halpin D.M., Vogelmeier C., Pieper M.P. et al. Effect of tiotropium on COPD exacerbations: a systematic review. Respir. Med. 2016; 114: 1–8. DOI: 10.1016/j.rmed.2016.02.012.Calzetta L., Coppola A., Ritondo B.L. et al. The impact of muscarinic receptor antagonists on airway inflammation: a systematic review. Int. J. Chron. Obstruct. Pulmon. Dis. 2021; 16: 257–279. DOI: 10.2147/COPD.S285867.Calzetta L., Coppola A., Ritondo B.L. et al. The impact of muscarinic receptor antagonists on airway inflammation: a systematic review. Int. J. Chron. Obstruct. Pulmon. Dis. 2021; 16: 257–279. DOI: 10.2147/COPD.S285867.Wedzicha J.A., Calverley P.M., Seemungal T.A. et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am. J. Respir. Crit. Care Med. 2008; 177 (1): 19–26. DOI: 10.1164/rccm.200707-973OC.Wedzicha J.A., Calverley P.M., Seemungal T.A. et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am. J. Respir. Crit. Care Med. 2008; 177 (1): 19–26. DOI: 10.1164/rccm.200707-973OC.Cheyne L., Irvin-Sellers M.J., White J. Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2015; 2015 (9): CD009552. DOI: 10.1002/14651858.CD009552.pub3.Cheyne L., Irvin-Sellers M.J., White J. Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2015; 2015 (9): CD009552. DOI: 10.1002/14651858.CD009552.pub3.Griffin J., Lee S., Caiado M. et al. Comparison of tiotropium bromide and combined ipratropium/salbutamol for the treatment of COPD: a UK General Practice Research Database 12-month follow-up study. Prim. Care Respir. J. 2008; 17 (2): 104–110. DOI: 10.3132/pcrj.2008.00024.Griffin J., Lee S., Caiado M. et al. Comparison of tiotropium bromide and combined ipratropium/salbutamol for the treatment of COPD: a UK General Practice Research Database 12-month follow-up study. Prim. Care Respir. J. 2008; 17 (2): 104–110. DOI: 10.3132/pcrj.2008.00024.Chapman K.R., Beeh K.M., Beier J. et al. A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study. BMC Pulm. Med. 2014; 14: 4. DOI: 10.1186/1471-2466-14-4.Chapman K.R., Beeh K.M., Beier J. et al. A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study. BMC Pulm. Med. 2014; 14: 4. DOI: 10.1186/1471-2466-14-4.Wedzicha J.A., Decramer M., Ficker J.H. et al. 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 (3): 199–209. DOI: 10.1016/S2213-2600(13)70052-3.Wedzicha J.A., Decramer M., Ficker J.H. et al. 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 (3): 199–209. DOI: 10.1016/S2213-2600(13)70052-3.Beier J., Kirsten A.M., Mróz R. et al. Efficacy and safety of aclidinium bromide compared with placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease: results from a 6-week, randomized, controlled phase IIIb study. COPD. 2013; 10 (4): 511–522. DOI: 10.3109/15412555.2013.814626.Beier J., Kirsten A.M., Mróz R. et al. Efficacy and safety of aclidinium bromide compared with placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease: results from a 6-week, randomized, controlled phase IIIb study. COPD. 2013; 10 (4): 511–522. DOI: 10.3109/15412555.2013.814626.Титова О.Н., Кузубова Н.А., Козырев А.Г., Шумилов А.А. Бронхолитическая терапия при хронической обструктивной болезни легких: что следует учитывать в клинической практике при выборе режима дозирования? Пульмонология. 2023; 33 (1): 44–50. DOI: 10.18093/0869-0189-2023-33-1-44-50.Titova O.N., Kuzubova N.A., Kozyrev A.G., Shumilov A.А. [Bronchodilator therapy in patients with chronic obstructive pulmonary disease: what should be considered in clinical practice when choosing a dosing regimen?]. Pul'monologiya. 2023; 33 (1): 44–50. DOI: 10.18093/0869-0189-2023-33-1-44-50 (in Russian).Tashkin D.P., Celli B., Senn S. et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N. Engl. J. Med. 2008; 359 (15): 1543–1554. DOI: 10.1056/NEJMoa0805800.Tashkin D.P., Celli B., Senn S. et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N. Engl. J. Med. 2008; 359 (15): 1543–1554. DOI: 10.1056/NEJMoa0805800.Rodrigo G.J., Castro-Rodriguez J.A., Nannini L.J. et al. Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: systematic review with meta-analysis. Respir. Med. 2009; 103 (10): 1421–1429. DOI: 10.1016/j.rmed.2009.05.020.Rodrigo G.J., Castro-Rodriguez J.A., Nannini L.J. et al. Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: systematic review with meta-analysis. Respir. Med. 2009; 103 (10): 1421–1429. DOI: 10.1016/j.rmed.2009.05.020.Wise R.A., Anzueto A., Cotton D. et al. Tiotropium Respimat inhaler and the risk of death in COPD. N. Engl. J. Med. 2013; 369 (16): 1491–1501. DOI: 10.1056/NEJMoa1303342.Wise R.A., Anzueto A., Cotton D. et al. Tiotropium Respimat inhaler and the risk of death in COPD. N. Engl. J. Med. 2013; 369 (16): 1491–1501. DOI: 10.1056/NEJMoa1303342.Halpin D.M., Dahl R., Hallmann C. et al. Tiotropium HandiHaler(®) and Respimat(®) in COPD: a pooled safety analysis. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 239–259. DOI: 10.2147/COPD.S75146.Halpin D.M., Dahl R., Hallmann C. et al. Tiotropium HandiHaler(®) and Respimat(®) in COPD: a pooled safety analysis. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 239–259. DOI: 10.2147/COPD.S75146.Anzueto A., Wise R., Calverley P. et al. The Tiotropium safety and performance in Respimat® (TIOSPIR®) trial: spirometry outcomes. Respir. Res. 2015; 16 (1): 107. DOI: 10.1186/s12931-015-0269-4.Anzueto A., Wise R., Calverley P. et al. The Tiotropium safety and performance in Respimat® (TIOSPIR®) trial: spirometry outcomes. Respir. Res. 2015; 16 (1): 107. DOI: 10.1186/s12931-015-0269-4.Capstick T.G., Clifton I.J. Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma. Expert Rev. Respir. Med. 2012; 6 (1): 91–101. DOI: 10.1586/ers.11.89.Capstick T.G., Clifton I.J. Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma. Expert Rev. Respir. Med. 2012; 6 (1): 91–101. DOI: 10.1586/ers.11.89.Государственный реестр лекарственных средств. Сведения о лекарственном средстве Респиум®. Доступно на: https://grls.rosminzdrav.ru/grls.aspx?s=%D0%9B%D0%9F-006263&m=RegistrationCertificateNumberState Register of Medicines. [Information about the drug Respium®]. Available at: https://grls.rosminzdrav.ru/grls.aspx?s=%D0%9B%D0%9F-006263&m=RegistrationCertificateNumber (in Russian).The COPD Assessment Test (CAT). Available at: https://www.catestonline.org/The COPD Assessment Test (CAT). Available at: https://www.catestonline.org/Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC. Committee on the Aetiology of Chronic Bronchitis (MRC breathlessness score). Br. Med. J. 1960; 2 (5213): 1665. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2098438/?page=1Standardised questionnaire on respiratory symptoms: a statement prepared and approved by the MRC. Committee on the Aetiology of Chronic Bronchitis (MRC breathlessness score). Br. Med. J. 1960; 2 (5213): 1665. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2098438/?page=1

The authors declare that there are no conflicts of interest present.