pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2019-29-3-365-374pulmo-1181Research ArticleКЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯCLINICAL PHARMACOLOGYВопросы тройной терапии в лечении хронической обструктивной болезни легких. Комментарии к алгоритму. Резолюция Совета экспертов от 13.06.18 (Владивосток)Issues of triple therapy of chronic obstructive pulmonary disease. Comments to the algorithm. A resolution of expert panel, June 13, 2018, VladivostokАвдеевС. Н.AvdeevS. N.

д. м. н., член-корр. Российской академии наук, профессор, заведующий кафедрой пульмонологии,

119991, Москва, ул. Трубецкая, 8, стр. 2

Doctor of Medicine, Professor, Corresponding Member of Russian Academy of Sciences, Head of Department of Pulmonology,

 

serg_avdeev@list.ruНевзороваВ. А.NevzorovaV. A.

д. м. н., профессор, директор института терапии и инструментальной диагностики,

690002, Владивосток, пр-т Острякова, 2

Doctor of Medicine, Professor, Director of Institute of Therapy and Instrumental Diagnostics,

pr. Ostryakova 2, Vladivostok, 690002

nevzorova@inbox.ruКуделяЛ. М.KudelyaL. M.

руководитель Областного пульмонологического центра, 630087, Новосибирск, ул. Немировича-Данченко, 130;

д. м. н, профессор кафедры внутренних болезней, 630091, Новосибирск, Красный проспект, 52

Head of Regional Pulmonological Center, ul. Nemirovicha-Danchenko 130, Novosibirsk, 630087;

Doctor of Medicine, Professor, Department of Internal Medicine, Krasnyy prospect 52, Novosibirsk, 630091

oxy80@mail.ruКондрашоваН. М.KondrashovaN. M.

к. м. н., доцент института терапии и инструментальной диагностики,

690002, Владивосток, пр-т Острякова, 2

Candidate of Medicine, Associate Professor,

pr. Ostryakova 2, Vladivostok, 690002

nmk5@mail.ruСухановаГ. И.SukhanovaG. I.

д. м. н., профессор института терапии и инструментальной диагностики,

690002, Владивосток, пр-т Острякова, 2

Doctor of Medicine, Professor, Institute of Therapy and Instrumental Diagnostics,

pr. Ostryakova 2, Vladivostok, 690002

Naumo1969@yandex.ruКиняйкинМ. Ф.KinyaykinM. F.

к. м. н., доцент института терапии и инструментальной диагностики,

690002, Владивосток, пр-т Острякова, 2

Candidate of Medicine, Associate Professor, Institute of Therapy and Instrumental Diagnostics,

pr. Ostryakova 2, Vladivostok, 690002

589014@bk.ruНаумоваИ. В.NaumovaI. V.

к. м. н., доцент института терапии и инструментальной диагностики,

690002, Владивосток, пр-т Острякова, 2

Candidate of Medicine, Associate Professor, Institute of Therapy and Instrumental Diagnostics,

pr. Ostryakova 2, Vladivostok, 690002

Naumo1969@yandex.ruШкуратовА. Г.ShkuratovA. G.

к. м. н., доцент,

690002, Владивосток, пр-т Острякова, 2

Candidate of Medicine, Associate Professor,

pr. Ostryakova 2, Vladivostok, 690002

doctor-a.g@mail.ruФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М.Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M.Sechenov First Moscow State Medical University (Sechenov University), Healthcare Ministry of Russia: ul. Trubetskaya 8, build. 2, Moscow, 119991Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Тихоокеанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияPacific State Medical University, Healthcare Ministry of RussiaRussian FederationГосударственное бюджетное учреждение здравоохранения Новосибирской области «Государственная Новосибирская областная клиническая больница»; Федеральное государственное бюджетное образовательное учреждение высшего образования «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk Regional Teaching Hospital; Novosibirsk State Medical University, Healthcare Ministry of RussiaRussian Federation201917082019293365374Copyright © Авдеев С.Н., Невзорова В.А., Куделя Л.М., Кондрашова Н.М., Суханова Г.И., Киняйкин М.Ф., Наумова И.В., Шкуратов А.Г., 20192019Авдеев С.Н., Невзорова В.А., Куделя Л.М., Кондрашова Н.М., Суханова Г.И., Киняйкин М.Ф., Наумова И.В., Шкуратов А.Г.Avdeev S.N., Nevzorova V.A., Kudelya L.M., Kondrashova N.M., Sukhanova G.I., Kinyaykin M.F., Naumova I.V., Shkuratov 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/1181

Важнейшей задачей терапии хронической обструктивной болезни легких (ХОБЛ), наряду с контролем над симптомами, является уменьшение риска обострений. Эффективное решение данной задачи до сих пор обсуждается. Предотвращение обострений ХОБЛ имеет социальную и экономическую значимость и должно являться первостепенной задачей при лечении данного заболевания. Нере - шенными проблемами в лечении ХОБЛ являются низкая приверженность пациентов терапии и побочное действие лекарственных средств. Согласно актуальным клиническим рекомендациям, при сохранении обострений ХОБЛ у пациентов, принимающих комбинированную терапию длительно действующими бронходилататорами, следует рассматривать возможность использования ингаляционных глюкокортикоcтероидов (иГКС), при приеме которых снижается частота среднетяжелых и тяжелых обострений ХОБЛ, особенно при наличии бронхиальной астмы в анамнезе или эозинофилии крови или мокроты. Наличие на российском рынке фиксированных комбинаций длительно действующих β2-агонистов (ДДБА) / длительно действующих М-холинолитических препаратов (ДДАХП) и иГКС / ДДБА позволяет использовать 2 возможные опции для формирования свободной тройной комбинации – добавление к фиксированной комбинации иГКС / ДДБА монопрепарата ДДАХП и монопрепарата иГКС – к фиксированной комбинации ДДБА / ДДАХП. По данным многочисленных исследований, использование фиксированных комбинаций позволяет улучшить приверженность пациентов терапии приблизительно в 2 раза, что, в свою очередь, приводит к улучшению эффективности терапии. Основными претензиями к иГКС-содержащим препаратам при лечении больных ХОБЛ являются увеличение риска пневмоний, а также развитие системных нежелательных реакций, характерных для приема ГКС. Однако при использовании экстрамелкодисперсных лекарственных препаратов не только значимо снижается риск развития пневмонии по сравнению с препаратами, генерирующими более крупные частицы, но и увеличивается эффективность терапии, поскольку малые дыхательные пути являются основным местом развития патогенетического процесса при ХОБЛ.

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.

обострение хронической обструктивной болезни легкихкомбинированная терапия хронической обструктивной болезни легкихингаляционные глюкокортикоcтероиды в терапии хронической обструктивной болезни легкихэкстрамелкодисперсные ингаляционные глюкокортикостероидыexacerbations of chronic obstructive pulmonary diseasecombined therapyinhaled corticosteroidsextra-fine ICSПубликация осуществлена при финансовой поддержке компании «Кьези Фармасьютикалс». Мнение автора может не совпадать с позицией компании. Компания «Кьези Фармасьютикалс» не несет ответственности за возможные нарушения авторских прав и иных прав третьих лиц в результате публикации и распространения данной информации.This publication is supported by Chiesi Pharmaceuticals. The author's opinion could differ from the position of the company. Chiesi Pharmaceuticals is not responsible for any possible pyracy and other violations of stakeholders' rights and right of other third parties resulted from this publication and the information spread.ReferencesGlobal 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.pdfGlobal 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.pdfAisanov 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.S153770Aisanov 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.S153770Janson 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.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.Крысанов И.С. Анализ стоимости хронической об - структивной болезни легких в Российской Федерации. Качественная клиническая практика. 2014; (2): 51–56. Доступно на: https://cyberleninka.ru/article/v/analizstoimosti-hronicheskoy-obstruktivnoy-bolezni-lyogkih-vrossiyskoy-federatsiiKrysanov 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).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.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.Чучалин А.Г., Авдеев С.Н., Айсанов З.Р. и др. Рос - сийское респираторное общество. Федеральные клинические рекомендации по диагностике и лечению хронической обструктивной болезни легких. Пульмо - нология. 2014; (3): 15–54. DOI: 10.18093/0869-0189-2014-0-3-15-54.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).Авдеев С.Н., Белевский А.С., Ежов А.В. и др. Тера - певтическая тактика и подходы к лечению пациентов с обострениями хронической обструктивной болезни легких в Российской Федерации: итоговые результаты наблюдательного многоцентрового неинтервенционного исследования NIS CLOUD. Пульмонология. 2018; 28 (4): 411–423. DOI: 10.18093/0869-0189-2018-28-4-411- 423.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).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.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.Емельянов А.В. Ингаляционные глюкокортикоиды при хронической обструктивной болезни легких: каково их место в лечении этого заболевания? Русский медицинский журнал. 2017; (3): 227–231.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).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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.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.pdfGlobal Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2018. Available at: https://ginasthma.org/wp-content/uploads/2019/01/2018-GINA.pdfPascoe 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.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.Singh D., Corradi M., Spinola M. et al. Extrafine beclo - metasone 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.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.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.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.Vedel-Krogh S., Nielsen S.F., Lange P. et al. Blood eosi - nophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen General Population study. Am. J. Respir. Crit. Care Med. 2016; 193 (9): 965–974.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.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.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.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.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.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.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.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.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.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.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.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.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.Wedzicha J.A., Banerji D., Chapman K.R. et al. Inda - caterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD. N. Engl. J. Med. 2016; 374 (23): 2222–2234. DOI: 10.1056/NEJMoa1516385.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.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.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.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.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.Cosio B.G., Soriano J.B., Lоpez-Campos J.L. et al. Defin - ing the Asthma–COPD Overlap Syndrome in a COPD Cohort. Chest. 2016; 149 (1): 45–52. DOI: 10.1378/chest.15-1055.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.

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