pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2016-26-1-65-72pulmo-674Research ArticleОБЗОРЫREVIEWПерспективы фармакотерапии хронической обструктивной болезни легких: возможности комбинированных бронходилататоров и место ингаляционных глюкокортикостероидов. Заключение Совета экспертовPerspectives of pharmacological therapy of chronic obstructive pulmonary disease: opportunities of dual bronchodilation and a role of inhaled steroids. Expert Council ConsensusАвдеевС. Н.AvdeevS. N.

д. м. н., профессор, руководитель клинического отдела ФГБУ «НИИ пульмонологии» ФМБА России; тел. / факс: (495) 465-52-64;

MD, Professor, Head of Clinical Division, Federal Pulmonology Research Institute, Federal Medical and Biological Agency of Russia; tel. / fax: (495) 465-52-64;

serg_avdeev@list.ruАйсановЗ. Р.AysanovZ. R.

д. м. н., профессор, руководитель отдела клинической физиологии и клинических исследований ФГБУ «НИИ пульмонологии» ФМБА России; тел. / факс: (495) 465-52-64;

MD, Professor, Head of Division of Clinical Physiology and Clinical Trials, Federal Institution "Pulmonology Research Institute", Federal Medical and Biological Agency of Russia; tel. / fax: (495) 465-52-64;

aisanov@mail.ruБелевскийА. С.BelevskiyA. S.

д. м. н., профессор, зав. кафедрой пульмонологии факультета усовершенствования врачей ГБОУ ВПО «Российский национальный исследовательский медицинский университет имени Н.И.Пирогова» Минздрава России; тел.: (495) 963-24-67;

MD, Professor, Head of Department of Pulmonology, Faculty of Postgraduate Physician Training, State Institution "N.I.Pirogov Russian National Research Medical University", Healthcare Ministry of Russia; tel.: (495) 963-24-67;

pulmobas@yandex.ruВизельА. А.Vizel'A. A.

д. м. н., профессор, зав. кафедрой фтизиопульмонологии ГБОУ ВПО «Казанский государственный медицинский университет» Минздрава России; тел.: (9872) 96-25-99

MD, Professor, Head of Department of Phthisiology and Pulmonology, State Institution  Kazan State Medical University, Healthcare Ministry of Russia; tel.: (9872) 96-25-99

lordara@inbox.ruИгнатоваГ. Л.IgnatovaG. L.

д. м. н., профессор, зав. кафедрой терапии ФДПО ГБОУ ВПО «Южно-Уральский государственный медицинский университет» Минздрава России, зав. городским пульмонологическим центром, главный пульмонолог Челябинска; тел.: (351) 908-20-71;

MD, Professor, Head of Department of Therapy, Faculty of Postgraduate Physician Training, State Institution “Chelyabinsk State Medical Academy”, Healthcare Ministry of Russia; Head of the City Pulmonology Center; Cheif  pulmonologist of Chelyabinsk ; tel. (351) 908-20-71

iglign@mail.ruКняжескаяН. П.KnyazheskayaN. P.

к. м. н., доцент кафедры пульмонологии факультета усовершенствования врачей ГБОУ ВПО «Российский национальный исследовательский медицинский университет имени Н.И.Пирогова» Минздрава России; тел.: (495) 963-24-67;

PhD, Associate Professor at Department of of Pulmonology, Faculty of Postgraduate Physician Training, State Institution "N.I.Pirogov Russian National Research Medical University", Healthcare Ministry of Russia; tel.: (495) 963-24-67;

kniajeskaia@mail.ruЛещенкоИ. В.LeshchenkoI. V.

д. м. н., профессор кафедры фтизиатрии, пульмонологии и торакальной хирургии ГБОУ ВПО «Уральский государственный медицинский университет» Минздрава России, главный внештатный специалист-пульмонолог Минздрава Свердловской области и Управления здравоохранения г. Екатеринбурга, научный руководитель клиники «Медицинское объединение «Новая больница»; тел.: (912) 288-28-23;

MD, Professor, at Department of Phthisiology, Pulmonology and Thoracic Surgery, Ural State Medical University, Healthcare Ministry of Russia; Chief Pulmonologist Sverdlovsk region and Ekaterinburg, Academic Advisor of “Novaya bol'nitsa” clinical association; tel.: (912) 288-28-23

leshchenkoiv@yandex.ruОвчаренкоС. И.OvcharenkoS. I.

д. м. н., профессор кафедры факультетской терапии № 1 лечебного факультета ГБОУ ВПО «Первый московский государственный медицинский университет им. И.М.Сеченова» Минздрава России; тел.: (499) 248-45-23;

MD, Professor at Department of General Internal Medicine No.1, Medical Faculty, I.M.Sechenov First Moscow State Medical University, Healthcare Ministry of Russia; tel.: (499) 248-45-23

svetftk@mail.ruТрофимовВ. И.TrofimovV. I.

д. м. н., зав. кафедрой госпитальной терапии ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России, главный внештатный пульмонолог Северо-Западного региона; тел.: (921) 913-13-28;

MD, Professor, Head of M.V.Chernorutskiy Department of Hospital Internal Medicine, State Institution “Academician I.P.Pavlov First Saint-Petersburg State Medical University”, Healthcare Ministry of Russia; Chief Pulmonologist of the North-West Region of Russia; tel.: (921) 913-13-28;

trofvi@mail.ruШмелевЕ. И.ShmelevE. I.

д. м. н., профессор, руководитель отдела дифференциальной диагностики туберкулеза ФГБНУ «Центральный научно-исследовательский институт туберкулеза» РАН; тел.: (499) 785-90-08

MD, Professor, Head of Division of Differentiated Diagnostics of Tuberculosis, Federal Central Research Institute of Tuberculosis, Russian Medical Science Academy; tel.: (499) 785-90-08

eishmelev@mail.ruФГБУ «НИИ пульмонологии» ФМБА России: 105077, Москва, ул. 11-я Парковая, 32, корп. 4;РоссияFederal Pulmonology Research Institute, Federal Medical and Biological Agency of Russia: 32, build. 4, 11th Parkovaya str., Moscow, 105077, RussiaRussian FederationГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России: 117997, Москва, ул. Островитянова, 1;РоссияN.I.Pirogov Russian State National Research Medical University, Healthcare Ministry of Russia: 1, Ostrovityanova str., Moscow, 117997, RussiaRussian FederationГБОУ ВПО «Казанский государственный медицинский университет» Минздрава России: 420012, Казань, ул. Бутлерова, 49РоссияKazan State Medical University, Healthcare Ministry of Russia: 49, Butlerova str., Kazan', 420012, Tatarstan Republik;Russian FederationГБОУ ВПО «Южно-Уральский государственный медицинский университет» Минздрава России: 454092, Челябинск, ул. Воровского, 64РоссияSouth Ural State Medical University, Healthcare Ministry of Russia: 64, Vorovskogo str., Chelyabinsk, 454092, RussiaRussian FederationГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России: 117997, Москва, ул. Островитянова, 1РоссияN.I.Pirogov Russian State National Research Medical University, Healthcare Ministry of Russia: 1, Ostrovityanova str., Moscow, 117997, RussiaRussian FederationГБОУ ВПО «Уральский государственный медицинский университет» Минздрава России: 620028, Екатеринбург, ул. Репина, 3РоссияUral State Medical University, Healthcare Ministry of Russia: 3, Repina str., Ekaterinburg, 620028, RussiaRussian FederationГБОУ ВПО «Первый московский государственный медицинский университет им. И.М.Сеченова» Минздрава России: 119991, Москва, ул. Трубецкая, 8, стр. 2РоссияI.M.Sechenov First Moscow State Medical University, Healthcare Ministry of Russia: 8, build. 2, Trubetskaya str., Moscow, 119991, RussiaRussian FederationГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П.Павлова» Минздрава России: 197022, Санкт-Петербург, ул. Льва Толстого, 6 / 8РоссияAcademician I.P.Pavlov First Saint-Petersburg State Medical University, Healthcare Ministry of Russia: 6 / 8, L'va Tolstogo str., Saint-Petersburg, 197089, Russia;Russian FederationФГБНУ «Центральный НИИ туберкулеза» РАН: 107564, Москва, Яузская аллея, 2РоссияFederal Central Research Institute of Tuberculosis, Russian Medical Science Academy: 2, Yauzskaya walk, Moscow, 107564, RussiaRussian Federation2016190420162616572Copyright © Авдеев С.Н., Айсанов З.Р., Белевский А.С., Визель А.А., Игнатова Г.Л., Княжеская Н.П., Лещенко И.В., Овчаренко С.И., Трофимов В.И., Шмелев Е.И., 20162016Авдеев С.Н., Айсанов З.Р., Белевский А.С., Визель А.А., Игнатова Г.Л., Княжеская Н.П., Лещенко И.В., Овчаренко С.И., Трофимов В.И., Шмелев Е.И.Avdeev S.N., Aysanov Z.R., Belevskiy A.S., Vizel' A.A., Ignatova G.L., Knyazheskaya N.P., Leshchenko I.V., Ovcharenko S.I., Trofimov V.I., Shmelev E.I.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/674

Наиболее важными симптомами при хронической обструктивной болезни легких (ХОБЛ) являются одышка, кашель и продукция мокроты. По данным различных исследований, у пациентов ХОБЛ на текущей терапии клинически значимая одышка сохраняется в 50–70 % случаев. Одышка имеет важное прогностическое значение, часто коррелирует с частотой обострений и выживаемостью больных. Важные критерии эффективности проводимой терапии – снижение выраженности симптомов (в первую очередь – одышки). Инструменты измерения одышки несовершенны, понятие – субъективно, однако существующие количественные инструменты ее оценки позволяют определить степень выраженности симптомов у пациентов с ХОБЛ. Применяемые инструменты (модифицированная шкала Британского Медицинского cовета – Modified Medical Research Council; COPD Assessment Test – САТ) должны быть адаптированы к уровню оказания медицинской помощи (первичное звено, специалист и т. д.). Длительно действующие бронходилататоры являются обязательным компонентом терапии больного ХОБЛ независимо от его фенотипа. Пациенты, получающие комбинированные лекарственные средства, включающие ингаляционные глюкокортикостероиды (иГКС), должны быть фенотипированы для определения показаний для назначения ГКС. Длительная терапия иГКС показана пациентам следующих групп: с сочетанием бронхиальной астмы и ХОБЛ; с высоким риском обострений (объем форсированного выдоха за 1-ю секунду (ОФВ1) < 50 %долж. при > 2 неинфекционных обострениях в год или > 1 госпитализацией по поводу неинфекционного обострения); с эозинофилией мокроты > 3 % и / или > 300 клеток в 1 мл крови с учетом тяжести течения заболевания. При назначении иГКС необходимо учитывать риск побочных эффектов. Не следует добавлять иГКС при ОФВ1 ≥ 50 %, у пациентов с < 2 обострениями или отсутствием указаний на госпитализацию по поводу обострения ХОБЛ в течение 1 года; иГКС могут быть отменены, если они были назначены не по показаниям. У пациентов с сохраняющейся симптоматикой на фоне монотерапии длительно действующими бронходилататорами, иГКС / длительно действующими b2-агонистами или без четких показаний к назначению иГКС оптимальным выбором может послужить комбинация индакатерол / гликопирроний.

The most important symptoms of chronic obstructive pulmonary disease are dyspnea, cough and sputum production. According to results of several studies, 50% – 70% of COPD patients under regular therapy continue to experience dyspnea. Dyspnea has a great prognostic importance, it often correlates to exacerbation rate and the patients’ survival. Symptom reduction is one of the key outcomes of therapy of COPD. Measuring tools for assessment dyspnea are imperfect as dyspnea is a subjective feature. Nevertheless, available quantitative tools allow assessment symptom severity in COPD patients. Such tools (modified Medical Research Council scale and COPD Assessment Test – САТ) should be adopted to a medical care level (primary, secondary or tertiary care). Long-acting bronchodilators are the essential component of treatment COPD independently on COPD phenotype. COPD phenotype should be diagnosed before administration of combined drugs containing inhaled steroids (ICS). Long-term therapy with ICS is appropriate for the following groups of patients: overlap COPD and asthma phenotype; high risk of exacerbations (FEV1 < 50% pred., > 2 non-infectious exacerbations or > 1 hospitalization related to non-infectious exacerbation during the previous year); patients with sputum eosinophilia > 3% and / or blood eosinophilia > 300 cells × ml-1 with consideration of the disease severity. A physician should consider a risk of adverse events of ICS. ICS should not be administered to COPD patients with FEV1 > 50% pred. or having < 2 acute exacerbations or no one hospitalization related to acute exacerbation of COPD during the previous year. ICS could be withdrawn if their administration did not match these criteria. Patients with persistent symptoms under monotherapy with long-acting bronchodilators, ICS / long-acting b2-agonists and who do not match the criteria for treatment with ICS should be treated with indacaterol / glycopyrronium combination.

хроническая обструктивная болезнь легкихдлительно действующие бронходилататорыингаляционные глюкокортикостероидыкомбинированная терапияодышкаchronic obstructive pulmonary diseaselong-acting bronchodilatorsinhaled corticosteroidscombined therapydyspneaReferencesGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. Last updated 2016. www.goldcopd.org/Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report. Last updated 2016. www.goldcopd.org/Barnes P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 2014; 35: 71–86.Barnes P.J. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 2014; 35: 71–86.O'Donnell D.E., Mahler D.A. Effect of bronchodilators and inhaled corticosteroids on dyspnea in COPD. In: Mahler D.A., O'Donnell D.E., eds. Dyspnea: mechanisms, measurement and management. New York: Marcel Dekker; 2005: 283–299.O'Donnell D.E., Mahler D.A. Effect of bronchodilators and inhaled corticosteroids on dyspnea in COPD. In: Mahler D.A., O'Donnell D.E., eds. Dyspnea: mechanisms, measurement and management. New York: Marcel Dekker; 2005: 283–299.Miravitlles M., Worth H., Soler Catalu#ña J.J. et al. Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study. Respir. Res. 2014; 15: 122.Miravitlles M., Worth H., Soler Catalu#ña J.J. et al. Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study. Respir. Res. 2014; 15: 122.Small M., Broomfield S., Pollard R., Fermer S. P208 impact of morning symptoms experienced by COPD patients on exacerbation risk, rescue inhaler usage and normal daily activities. Thorax. 2012; 67: A155.Small M., Broomfield S., Pollard R., Fermer S. P208 impact of morning symptoms experienced by COPD patients on exacerbation risk, rescue inhaler usage and normal daily activities. Thorax. 2012; 67: A155.Leidy N.K., Sexton C., Jones P.W. et al. Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary. Thorax. 2014; 69: 443–449.Leidy N.K., Sexton C., Jones P.W. et al. Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary. Thorax. 2014; 69: 443–449.van der Molen T., Willemse B.W., Schokker S. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual. Life Outcom. 2003; 1: 13.van der Molen T., Willemse B.W., Schokker S. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual. Life Outcom. 2003; 1: 13.Kon S., Canavan J., Jones S. et al. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir. Med. 2014; 2: 195–203.Kon S., Canavan J., Jones S. et al. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir. Med. 2014; 2: 195–203.Mahler D.A., Ward J., Waterman L.A. et al. Patient-reported dyspnea in COPD reliability and association with stage of disease. Chest. 2009; 136: 1473–1479.Mahler D.A., Ward J., Waterman L.A. et al. Patient-reported dyspnea in COPD reliability and association with stage of disease. Chest. 2009; 136: 1473–1479.Sutherland E.R., Cherniack R.M. Management of chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350: 2689–2697.Sutherland E.R., Cherniack R.M. Management of chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350: 2689–2697.Kessler R., Partridge M.R., Miravitlles M. et al. Symptom variability in patients with severe COPD: a pan-European cross-sectional study. Eur. Respir. J. 2011; 37: 264–272.Kessler R., Partridge M.R., Miravitlles M. et al. Symptom variability in patients with severe COPD: a pan-European cross-sectional study. Eur. Respir. J. 2011; 37: 264–272.Hartman J.E., Boezen H.M., de Greef M.H.G. et al. Consequences of physical inactivity in chronic obstructive pulmonary disease. Exp. Rev. Respir. Med. 2010; 4: 735–745.Hartman J.E., Boezen H.M., de Greef M.H.G. et al. Consequences of physical inactivity in chronic obstructive pulmonary disease. Exp. Rev. Respir. Med. 2010; 4: 735–745.Hurst J.R., Vestbo J., Anzueto A. et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N. Engl. J. Med. 2010; 363: 1128–1138.Hurst J.R., Vestbo J., Anzueto A. et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N. Engl. J. Med. 2010; 363: 1128–1138.Nishimura K., Izumi T., Tsukino M., Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest. 2002; 121: 1434–1340.Nishimura K., Izumi T., Tsukino M., Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest. 2002; 121: 1434–1340.Fletcher C.M., Elmes P.C., Wood C.H. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br. Med. J. 1959; 1: 257–266.Fletcher C.M., Elmes P.C., Wood C.H. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br. Med. J. 1959; 1: 257–266.Mahler D., Weinberg D., Wells C., Feinstein A. The measurement of dyspnea: contents, interobserver agreement and physiologic correlates of two new clinical indexes. Chest. 1984; 85: 751–758.Mahler D., Weinberg D., Wells C., Feinstein A. The measurement of dyspnea: contents, interobserver agreement and physiologic correlates of two new clinical indexes. Chest. 1984; 85: 751–758.Oga T., Nishimura K., Tsukino M. et al. Longitudinal deteriorations in patient reported outcomes in patients with COPD. Respir. Med. 2007; 101: 146–153.Oga T., Nishimura K., Tsukino M. et al. Longitudinal deteriorations in patient reported outcomes in patients with COPD. Respir. Med. 2007; 101: 146–153.Mahler D.A., Tomlinson D., Olmstead E.M. et al. Changes in dyspnea, health status, and lung function in chronic airway disease. Am. J. Respir. Crit. Care Med. 1995; 151: 61–65.Mahler D.A., Tomlinson D., Olmstead E.M. et al. Changes in dyspnea, health status, and lung function in chronic airway disease. Am. J. Respir. Crit. Care Med. 1995; 151: 61–65.Cazzola M., Hanania N.A., MacNee W. A review of the most common patient-reported outcomes in COPD – revisiting current knowledge and estimating future challenges. Int. J. COPD. 2015; 10: 725–738.Cazzola M., Hanania N.A., MacNee W. A review of the most common patient-reported outcomes in COPD – revisiting current knowledge and estimating future challenges. Int. J. COPD. 2015; 10: 725–738.Al-Ghabeesh S., Ahmad M. Unidimentional and multidimensional breathlessness specific instruments for adult population: Literature review. J. Nat. Sci. Res. 2012; 8: 1–15.Al-Ghabeesh S., Ahmad M. Unidimentional and multidimensional breathlessness specific instruments for adult population: Literature review. J. Nat. Sci. Res. 2012; 8: 1–15.Pinto-Plata V.M., Cote C., Cabral H. et al. The 6-min walk distance: change over time and value as a predictor of survival in severe COPD. Eur. Respir. J. 2004; 23: 28–33.Pinto-Plata V.M., Cote C., Cabral H. et al. The 6-min walk distance: change over time and value as a predictor of survival in severe COPD. Eur. Respir. J. 2004; 23: 28–33.Cote C.G., Pinto-Plata V., Kasprzyk K. et al. The 6-min walk distance, peak oxygen uptake, and mortality in COPD. Chest. 2007; 132; 1778–1785.Cote C.G., Pinto-Plata V., Kasprzyk K. et al. The 6-min walk distance, peak oxygen uptake, and mortality in COPD. Chest. 2007; 132; 1778–1785.Nannini L.J., Lasserson T.J., Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochane Database Syst. Rev. 2012; 9: CD006829.Nannini L.J., Lasserson T.J., Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochane Database Syst. Rev. 2012; 9: CD006829.Celli B.R., Thomas N.E., Anderson J.A. et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am. J. Respir. Crit. Care Med. 2008; 178: 332–338.Celli B.R., Thomas N.E., Anderson J.A. et al. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am. J. Respir. Crit. Care Med. 2008; 178: 332–338.Gershon A.S., Campitelli M.A., Croxford R. et al. Combination long-acting #b-agonists and inhaled corticosteroids compared with long-acting #b-agonists alone in older adults with chronic obstructive pulmonary disease. JAMA. 2014; 312: 1114–1121.Gershon A.S., Campitelli M.A., Croxford R. et al. Combination long-acting #b-agonists and inhaled corticosteroids compared with long-acting #b-agonists alone in older adults with chronic obstructive pulmonary disease. JAMA. 2014; 312: 1114–1121.Yawn B., Kleerup E., Zhang J. et al. Inhaled corticosteroid use and GOLD severity stage among patients with chronic obstructive pulmonary disease in different regions [abstract]. Am. J. Respir. Crit. Care Med. 2012; 182: A2944.Yawn B., Kleerup E., Zhang J. et al. Inhaled corticosteroid use and GOLD severity stage among patients with chronic obstructive pulmonary disease in different regions [abstract]. Am. J. Respir. Crit. Care Med. 2012; 182: A2944.Lee J.-H., Lee Y.K., Kim E.-K. et al. Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype. Respir. Med. 2010; 104: 542–549.Lee J.-H., Lee Y.K., Kim E.-K. et al. Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype. Respir. Med. 2010; 104: 542–549.Price D., Yawn B., Brusselle G., Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD. Prim. Care Respir. J. 2013; 22: 92–100.Price D., Yawn B., Brusselle G., Rossi A. Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD. Prim. Care Respir. J. 2013; 22: 92–100.Ernst P., Saad N., Suissa S. Inhaled corticosteroids in COPD: the clinical evidence. Eur. Respir. J. 2015; 45: 525–537.Ernst P., Saad N., Suissa S. Inhaled corticosteroids in COPD: the clinical evidence. Eur. Respir. J. 2015; 45: 525–537.Yawn B.P., Li Y., Tian H. et al. Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis. Int. J. Chron. Obstruct. Pulm. Dis. 2013; 8: 295–304.Yawn B.P., Li Y., Tian H. et al. Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis. Int. J. Chron. Obstruct. Pulm. Dis. 2013; 8: 295–304.Suissa S., Patenaude V., Lapi F., Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013; 68: 1029–1036.Suissa S., Patenaude V., Lapi F., Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013; 68: 1029–1036.Kaplan A.G. Applying the wisdom of stepping down inhaled corticosteroids in patients with COPD: a proposed algorithm for clinical practice. Int. J. COPD. 2015; 10: 2535–2548.Kaplan A.G. Applying the wisdom of stepping down inhaled corticosteroids in patients with COPD: a proposed algorithm for clinical practice. Int. J. COPD. 2015; 10: 2535–2548.Rossi A., Guerriero M., Corrado A. OPTIMO/AIPO Study Group. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir. Res. 2014; 15: 77.Rossi A., Guerriero M., Corrado A. OPTIMO/AIPO Study Group. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir. Res. 2014; 15: 77.Rossi A., van der Molen T., Olmo R. et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD. Eur. Respir. J. 2014; 44: 1548–1556.Rossi A., van der Molen T., Olmo R. et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD. Eur. Respir. J. 2014; 44: 1548–1556.Nadeem N.J., Taylor S.J., Eldridge S.M. Withdrawal of inhaled corticosteroids in individuals with COPD-a systematic review and comment on trial methodology. Respir. Res. 2011; 12: 107.Nadeem N.J., Taylor S.J., Eldridge S.M. Withdrawal of inhaled corticosteroids in individuals with COPD-a systematic review and comment on trial methodology. Respir. Res. 2011; 12: 107.Magnussen H., Disse B., Rodriguez-Roisin R. et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N. Engl. J. Med. 2014; 371: 1285–1294.Magnussen H., Disse B., Rodriguez-Roisin R. et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N. Engl. J. Med. 2014; 371: 1285–1294.Qaseem A., Wilt T.J., Weinberger S.E. et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann. Intern. Med. 2011; 155: 179–191.Qaseem A., Wilt T.J., Weinberger S.E. et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann. Intern. Med. 2011; 155: 179–191.NICE. Clinical Guideline 101. Chronic obstructive pulmonary disease. Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update issued June 2010). National Institute for Health and Clinical Excellence. Available from http://www.nice.org.uk/nicemedia/live/13029/49397/49397.pdfNICE. Clinical Guideline 101. Chronic obstructive pulmonary disease. Management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update issued June 2010). National Institute for Health and Clinical Excellence. Available from http://www.nice.org.uk/nicemedia/live/13029/49397/49397.pdfO'Reilly J., Jones M.M., Parnham J. et al. Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance. Br. Med. J. 2010; 340: 3134.O'Reilly J., Jones M.M., Parnham J. et al. Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance. Br. Med. J. 2010; 340: 3134.Cazzola M., Page C.P., Calzetta L., Matera M.G. Pharmacology and therapeutics of bronchodilators. Pharmacol. Rev. 2012; 64: 450–504.Cazzola M., Page C.P., Calzetta L., Matera M.G. Pharmacology and therapeutics of bronchodilators. Pharmacol. Rev. 2012; 64: 450–504.Cazzola M., Segreti A., Matera M.G. New developments in the combination treatment of COPD: focus on umeclidinium/vilanterol. Drug. Des. Devel. Ther. 2013; 7: 1201–1208.Cazzola M., Segreti A., Matera M.G. New developments in the combination treatment of COPD: focus on umeclidinium/vilanterol. Drug. Des. Devel. Ther. 2013; 7: 1201–1208.Rodrigo G.J., Plaza V. Efficacy and safety of a fixed-dose combination of indacaterol and glycopyrronium (QVA149) for the treatment of COPD: a systematic review. Chest. 2014, 146: 309–317.Rodrigo G.J., Plaza V. Efficacy and safety of a fixed-dose combination of indacaterol and glycopyrronium (QVA149) for the treatment of COPD: a systematic review. Chest. 2014, 146: 309–317.Bateman E.D., Mahler D.A., Vogelmeier C.F. et al. Recent advances in COPD disease management with fixed-dose long-acting combination therapies. Exp. Rev. Respir. Med. 2014, 8: 357–379.Bateman E.D., Mahler D.A., Vogelmeier C.F. et al. Recent advances in COPD disease management with fixed-dose long-acting combination therapies. Exp. Rev. Respir. Med. 2014, 8: 357–379.European Medicine Agency. Ultibro Breezhaler. Available from EMA: http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/human/medicines/002679/human_med_001691.jsp (accessed October 15, 2014).European Medicine Agency. Ultibro Breezhaler. Available from EMA: http://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/human/medicines/002679/human_med_001691.jsp (accessed October 15, 2014).Health Canada. Available from Health Canada: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/regist/reg_innov_dr-end.pdf (accessed October 15, 2014).Health Canada. Available from Health Canada: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/prodpharma/applic-demande/regist/reg_innov_dr-end.pdf (accessed October 15, 2014).U.S. Food and Drug Administration. Utibron Neohaler. Available from FDA: http://www.fda.govU.S. Food and Drug Administration. Utibron Neohaler. Available from FDA: http://www.fda.govFrampton J.E. QVA149 (indacaterol/glycopyrronium fixed-dose combination): a review of its use in patients with chronic obstructive pulmonary disease. Drugs. 2014; 74: 465–488.Frampton J.E. QVA149 (indacaterol/glycopyrronium fixed-dose combination): a review of its use in patients with chronic obstructive pulmonary disease. Drugs. 2014; 74: 465–488.Dahl R., Chapman K.R., Rudolf M. et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Respir. Med. 2013, 107: 1558–1567.Dahl R., Chapman K.R., Rudolf M. et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Respir. Med. 2013, 107: 1558–1567.Bateman E.D., Ferguson G.T., Barnes N. et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur. Respir. J. 2013, 42: 1484–1494.Bateman E.D., Ferguson G.T., Barnes N. et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur. Respir. J. 2013, 42: 1484–1494.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: 199–209.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: 199–209.Banerji D., Fedele M.J., Chen H., Kim H.J. Dual bronchodilation with QVA149 reduces COPD exacerbations: results from the ignite program. Respirology. 2013, 18 (Suppl. 4): 1–81.Banerji D., Fedele M.J., Chen H., Kim H.J. Dual bronchodilation with QVA149 reduces COPD exacerbations: results from the ignite program. Respirology. 2013, 18 (Suppl. 4): 1–81.Vogelmeier C.F., Bateman E.D., Pallante J. et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel-group study. Lancet Respir. Med. 2013, 1: 51–60.Vogelmeier C.F., Bateman E.D., Pallante J. et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel-group study. Lancet Respir. Med. 2013, 1: 51–60.Zhong N., Wang C., Zhou X. et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone combination (SFC) in patients with COPD: the LANTERN study. Eur. Respir. J. 2014; 44 (Suppl. 58): P2815.Zhong N., Wang C., Zhou X. et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone combination (SFC) in patients with COPD: the LANTERN study. Eur. Respir. J. 2014; 44 (Suppl. 58): P2815.Beeh K.-M., Korn S., Beier J. et al. Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: the BRIGHT study. Respir. Med. 2014, 108: 584–592.Beeh K.-M., Korn S., Beier J. et al. Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: the BRIGHT study. Respir. Med. 2014, 108: 584–592.Mahler D.A., Decramer M., D’Urzo A. et al. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur. Respir. J. 2014, 43: 1599–1609.Mahler D.A., Decramer M., D’Urzo A. et al. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur. Respir. J. 2014, 43: 1599–1609.Dahl R., Gallagher N., Green Y. et al. QVA149 provides a rapid onset of action which is sustained throughout treatment in patients with COPD. Eur. Respir. J. 2013, 42 (Suppl. 57): 3385.Dahl R., Gallagher N., Green Y. et al. QVA149 provides a rapid onset of action which is sustained throughout treatment in patients with COPD. Eur. Respir. J. 2013, 42 (Suppl. 57): 3385.Dahl R., Jadayel D., Alagappan V.K. et al. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study. Int. J. COPD. 2013, 8: 501–508.Dahl R., Jadayel D., Alagappan V.K. et al. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study. Int. J. COPD. 2013, 8: 501–508.Beeh K.M., Beier J. The short, the long and the «ultra-long»: why duration of bronchodilator action matters in chronic obstructive pulmonary disease. Adv. Ther. 2010; 27: 150–159.Beeh K.M., Beier J. The short, the long and the «ultra-long»: why duration of bronchodilator action matters in chronic obstructive pulmonary disease. Adv. Ther. 2010; 27: 150–159.

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