medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-16-174-184medsovet-6476Research ArticleРациональная фармакотерапияRational pharmacotherapyТройная терапия в едином ингаляторе при хронической обструктивной болезни легких: клинические исследования и клиническое наблюдение (реальная практика)Triple therapy in a single inhaler for chronic obstructive pulmonary disease: clinical studies and case report (real practice)https://orcid.org/0000-0003-1851-0941СалуховВ. В.SalukhovV. V.

Салухов Владимир Владимирович, д.м.н., начальник 1-й кафедры и клиники (терапии усовершенствования врачей) имени академика Н.С. Молчанова

194044, Россия, Санкт-Петербург, ул. Академика Лебедева, д. 6

Vladimir V. Salukhov, Dr. Sci. (Med.), Head of the N.S. Molchanov 1st Therapeutic Clinic of Postgraduate Education

6, Akademik Lebedev St., St Petersburg, 194044, Russia

vlasaluk@yandex.ruhttps://orcid.org/0000-0002-8396-1936КрюковЕ. В.KryukovE. V.

Крюков Евгений Владимирович, чл.‑корр. РАН, д.м.н., профессор, начальник

194044, Россия, Санкт-Петербург, ул. Академика Лебедева, д. 6

Evgeniy V. Kryukov, Corr. Member RAS, Dr. Sci. (Med.), Professor, Chief

6, Akademik Lebedev St., St Petersburg, 194044, Russia

evgeniy.md@mail.ruhttps://orcid.org/0000-0002-6521-7986ХаритоновМ. А.KharitonovM. A.

Харитонов Михаил Анатольевич, д.м.н., профессор 1-й кафедры (терапии усовершенствования врачей) имени академика Н.С. Молчанова

194044, Россия, Санкт-Петербург, ул. Академика Лебедева, д. 6

Mikhail A. Kharitonov, Dr. Sci. (Med.), Professor of the N.S. Molchanov 1st Therapeutic Clinic of Postgraduate Education

6, Akademik Lebedev St., St Petersburg, 194044, Russia

micjul11@yandex.ruhttps://orcid.org/0000-0002-7958-7451СередаВ. П.SeredaV. P.

Середа Виталий Петрович, д.м.н., главный врач; старший преподаватель кафедры пропедевтики внутренних болезней

194044, Россия, Санкт-Петербург, ул. Академика Лебедева, д. 6

191186, Россия, Санкт-Петербург, Чебоксарский пер., д. 1/6, литер А

Vitaliy P. Sereda, Dr. Sci. (Med.), Head Physician; Senior Lecturer of the Department of Propaedeutics of Internal Diseases

6, Akademik Lebedev St., St Petersburg, 194044, Russia

letter A, 1/6, Cheboksarskiy Lane, St Petersburg, 191186, Russia

vsereda@sogaz-clinic.ruhttps://orcid.org/0000-0003-1525-3601МинаковА. А.MinakovA. A.

Минаков Алексей Александрович, адъюнкт 1-й кафедры (терапии усовершенствования врачей) имени академика Н.С. Молчанова

194044, Россия, Санкт-Петербург, ул. Академика Лебедева, д. 6

Aleksey A. Minakov, Adjunct of the N.S. Molchanov 1st Therapeutic Clinic of Postgraduate Education

6, Akademik Lebedev St., St Petersburg, 194044, Russia

minakom@mail.ruВоенно-медицинская академия имени С.М. КироваРоссияMilitary Medical Academy named after S.M. KirovRussian FederationВоенно-медицинская академия имени С.М. Кирова; Международный медицинский центр «СОГАЗ»РоссияMilitary Medical Academy named after S.M. Kirov; SOGAZ International Medical CenterRussian Federation202130102021016174184Copyright © Салухов В.В., Крюков Е.В., Харитонов М.А., Середа В.П., Минаков А.А., 20212021Салухов В.В., Крюков Е.В., Харитонов М.А., Середа В.П., Минаков А.А.Salukhov V.V., Kryukov E.V., Kharitonov M.A., Sereda V.P., Minakov A.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6476

Алгоритмы деэскалации базисной терапии, включая отмену ингаляционных глюкокортикостероидов (ИГКС), у пациентов с хронической обструктивной болезнью легких (ХОБЛ), а также разработка четких критериев назначения тройной терапии в клинической практике остаются предметом многочисленных исследований и дискуссий. Приведенный клинический пример ведения пациента с длительным стажем курения и тяжело протекающей ХОБЛ продемонстрировал неудачный опыт деэскалации терапии с отменой ИГКС из-за опасений по факту перенесенной пневмонии. Назначенная в соответствии с современными рекомендациями двойная бронхолитическая терапия была недостаточно эффективной в отношении профилактики обострений, а стабилизация состояния пациента наблюдалась после назначения фиксированной тройной комбинации лекарств в едином ингаляторе (ВИ/УМЕК/ФФ), который содержит вилантерол (ВИ), умеклидиния бромид (УМЕК) и ИГКС флутиказона фуроат (ФФ). Положительный вклад в обеспечение клинического успеха внесли такие факторы, как строгое выполнение пациентом врачебных предписаний, отказ от курения и выполнение рекомендаций по сохранению физической активности, соблюдение строгого режима самоизоляции в период пандемии, что снизило риски респираторных вирусных инфекций. Дополнительными клиническими предикторами эффективности ИГКС при ХОБЛ явились бронхитический тип, персистенция симптомов и рецидивирование обострений заболевания после отмены препарата, уровень эозинофилии крови. В решении вопроса о назначении или отмене тройной терапии рекомендуется учитывать данные о влиянии ИГКС на улучшение функциональных показателей и клинического течения болезни с уменьшением симптомов, снижение риска обострений, рост выживаемости пациентов и позитивный прогноз в течении ХОБЛ.

Algorithms for de-escalation of basic therapy, including the abolition of inhaled corticosteroids (ICS), in patients with chronic obstructive pulmonary disease (COPD), as well as the development of clear criteria for prescribing triple therapy in clinical practice remain the subject of numerous studies and discussions. The given case report of managing a patient with a long experience of smoking and severe COPD demonstrated an unsuccessful experience of de-escalation of therapy with the abolition of ICS due to concerns about the fact of pneumonia. The dual bronchodilator therapy prescribed in accordance with modern recommendations was insufficiently effective in preventing exacerbations, and the stabilization of the patient’s condition was observed after the appointment of a fixed triple combination of drugs in a single inhaler (VI/UMEC/FF), which contains vilanterol (VI), umeclidinium bromide (UMEC) and ICS fluticasone furoate (FF). An additional contribution to ensuring clinical success was made by such factors as strict compliance with medical prescriptions by the patient, smoking cessation and compliance with recommendations for maintaining physical activity, compliance with a strict self-isolation regime during the pandemic, which reduced the risks of respiratory viral infections. Additional clinical predictors of the effectiveness of ICS in COPD were the bronchitis type, the persistence of symptoms and the recurrence of exacerbations of the disease after discontinuation of the drug, the level of blood eosinophilia. When deciding whether to prescribe or cancel triple therapy, it is recommended to take into account the data on the effect of ICS on improving the functional parameters and clinical course of the disease with a decrease in symptoms, on reducing the risk of exacerbations, on increasing patient survival and a positive prognosis during COPD.

хроническая обструктивная болезнь легких (ХОБЛ)диагностикалечениедвойная бронходилатацияингаляционные стероидытройная терапияchronic obstructive pulmonary disease (COPD)diagnosistreatmentdouble bronchodilationinhaled corticosteroidstriple therapyReferencesHumenberger 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. https://doi.org/10.1186/s12890-018-0724-3.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. https://doi.org/10.1186/s12890-018-0724-3.George M. Adherence in Asthma and COPD: New Strategies for an Old Problem. Respir Care. 2018;63(6):818–831. https://doi.org/10.4187/respcare.05905.George M. Adherence in Asthma and COPD: New Strategies for an Old Problem. Respir Care. 2018;63(6):818–831. https://doi.org/10.4187/respcare.05905.DiMatteo M.R. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42(3):200–209. https://doi.org/10.1097/01.mlr.0000114908.90348.f9.DiMatteo M.R. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42(3):200–209. https://doi.org/10.1097/01.mlr.0000114908.90348.f9.Rootmensen G.N., van Keimpema A.R., Jansen H.M., de Haan R.J. Predictors of incorrect inhalation technique in patients with asthma or COPD: a study using a validated videotaped scoring method. J Aerosol Med Pulm Drug Deliv. 2010;23(5):323–328. https://doi.org/10.1089/jamp.2009.0785.Rootmensen G.N., van Keimpema A.R., Jansen H.M., de Haan R.J. Predictors of incorrect inhalation technique in patients with asthma or COPD: a study using a validated videotaped scoring method. J Aerosol Med Pulm Drug Deliv. 2010;23(5):323–328. https://doi.org/10.1089/jamp.2009.0785.Barbara S., Kritikos V., Bosnic-Anticevich S. Inhaler technique: does age matter? A systematic review. Eur Respir Rev. 2017;26(146):170055. https://doi.org/10.1183/16000617.0055-2017.Barbara S., Kritikos V., Bosnic-Anticevich S. Inhaler technique: does age matter? A systematic review. Eur Respir Rev. 2017;26(146):170055. https://doi.org/10.1183/16000617.0055-2017.Van Boven J.F., Chavannes N.H., van der Molen T., Rutten-van Mölken M.P., Postma M.J., Vegter S. Clinical and economic impact of non-adherence in COPD: a systematic review. Respir Med. 2014;108(1):103–113. https://doi.org/10.1016/j.rmed.2013.08.044.Van Boven J.F., Chavannes N.H., van der Molen T., Rutten-van Mölken M.P., Postma M.J., Vegter S. Clinical and economic impact of non-adherence in COPD: a systematic review. Respir Med. 2014;108(1):103–113. https://doi.org/10.1016/j.rmed.2013.08.044.Toy E.L., Beaulieu N.U., McHale J.M., Welland T.R., Plauschinat C.A., Swensen A., Duh M.S. Treatment of COPD: relationships between daily dosing frequency, adherence, resource use, and costs. Respir Med. 2011;105(3):435–441. https://doi.org/10.1016/j.rmed.2010.09.006.Toy E.L., Beaulieu N.U., McHale J.M., Welland T.R., Plauschinat C.A., Swensen A., Duh M.S. Treatment of COPD: relationships between daily dosing frequency, adherence, resource use, and costs. Respir Med. 2011;105(3):435–441. https://doi.org/10.1016/j.rmed.2010.09.006.Lipson D.A., Barnhart F., Brealey N., Brooks J., Criner G.J., Day N.C. et al. OnceDaily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671–1680. https://doi.org/10.1056/NEJMoa1713901.Lipson D.A., Barnhart F., Brealey N., Brooks J., Criner G.J., Day N.C. et al. OnceDaily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671–1680. https://doi.org/10.1056/NEJMoa1713901.Lipson D.A., Barnacle H., Birk R., Brealey N., Locantore N., Lomas D.A. et al. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017;196(4):438–446. https://doi.org/10.1164/rccm.201703-0449OC.Lipson D.A., Barnacle H., Birk R., Brealey N., Locantore N., Lomas D.A. et al. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017;196(4):438–446. https://doi.org/10.1164/rccm.201703-0449OC.Чучалин А.Г., Авдеев С.Н., Айсанов З.Р., Белевский А.С., Лещенко И.В., Овчаренко С.И. и др. Хроническая обструктивная болезнь легких: клинические рекомендации. М.; 2018. 76 с. Режим доступа: https://spulmo.ru/upload/federal_klinicheskie_rekomendaciy_hobl.pdf.Chuchalin A.G., Avdeev S.N., Aisanov Z.R., Belevsky A.S., Leshchenko I.V., Ovcharenko S.I. et al. Chronic obstructive pulmonary disease: clinical recommendations. Moscow; 2018. 76 p. (In Russ.) Available at: https://spulmo.ru/upload/federal_klinicheskie_rekomendaciy_hobl.pdf.Magnussen H., Disse B., Rodriguez-Roisin R., Kirsten A., Watz H., Tetzlaff K. et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285–1294. https://doi.org/10.1056/NEJMoa1407154.Magnussen H., Disse B., Rodriguez-Roisin R., Kirsten A., Watz H., Tetzlaff K. et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285–1294. https://doi.org/10.1056/NEJMoa1407154.Izquierdo J.L., Cosio B.G. The dose of inhaled corticosteroids in patients with COPD: when less is better. Int J Chron Obstruct Pulmon Dis. 2018;13:3539–3547. https://doi.org/10.2147/COPD.S175047.Izquierdo J.L., Cosio B.G. The dose of inhaled corticosteroids in patients with COPD: when less is better. Int J Chron Obstruct Pulmon Dis. 2018;13:3539–3547. https://doi.org/10.2147/COPD.S175047.Chapman K.R., Hurst J.R., Frent S.M., Larbig M., Fogel R., Guerin T. et al. LongTerm Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial. Am J Respir Crit Care Med. 2018;198(3):329–339. https://doi.org/10.1164/rccm.201803-0405OC.Chapman K.R., Hurst J.R., Frent S.M., Larbig M., Fogel R., Guerin T. et al. LongTerm Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial. Am J Respir Crit Care Med. 2018;198(3):329–339. https://doi.org/10.1164/rccm.201803-0405OC.Calzetta L., Matera M.G., Braido F., Contoli M., Corsico A., Di Marco F. et al. Withdrawal of inhaled corticosteroids in COPD: A meta-analysis. Pulm Pharmacol Ther. 2017;45:148–158. https://doi.org/10.1016/j.pupt.2017.06.002.Calzetta L., Matera M.G., Braido F., Contoli M., Corsico A., Di Marco F. et al. Withdrawal of inhaled corticosteroids in COPD: A meta-analysis. Pulm Pharmacol Ther. 2017;45:148–158. https://doi.org/10.1016/j.pupt.2017.06.002.Magnussen H., Lucas S., Lapperre T., Quint J.K., Dandurand R.J., Roche N. et al. Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study. Respir Res. 2021;22(1):25. https://doi.org/10.1186/s12931-021-01615-0.Magnussen H., Lucas S., Lapperre T., Quint J.K., Dandurand R.J., Roche N. et al. Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study. Respir Res. 2021;22(1):25. https://doi.org/10.1186/s12931-021-01615-0.Van den Bemt L., van den Nieuwenhof L., Rutjes A., van der Meer V., Stege G., Wensing M. et al. Pragmatic trial on inhaled corticosteroid withdrawal in patients with COPD in general practice. NPJ Prim Care Respir Med. 2020;30(1):43. https://doi.org/10.1038/s41533-020-00198-5.Van den Bemt L., van den Nieuwenhof L., Rutjes A., van der Meer V., Stege G., Wensing M. et al. Pragmatic trial on inhaled corticosteroid withdrawal in patients with COPD in general practice. NPJ Prim Care Respir Med. 2020;30(1):43. https://doi.org/10.1038/s41533-020-00198-5.Williams N.P., Coombs N., Johnson M.J., Josephs L.K., Rigge L.A., Staples K.J. et al. Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: a population database study using linked health care records. Int J Chron Obstruct Pulmon Dis. 2017;12:313–322. https://doi.org/10.2147/COPD.S121389.Williams N.P., Coombs N., Johnson M.J., Josephs L.K., Rigge L.A., Staples K.J. et al. Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: a population database study using linked health care records. Int J Chron Obstruct Pulmon Dis. 2017;12:313–322. https://doi.org/10.2147/COPD.S121389.Donaldson G.C., Seemungal T.A., Bhowmik A., Wedzicha J.A. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57(10):847–852. https://doi.org/10.1136/thorax.57.10.847.Donaldson G.C., Seemungal T.A., Bhowmik A., Wedzicha J.A. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57(10):847–852. https://doi.org/10.1136/thorax.57.10.847.Kanner R.E., Anthonisen N.R., Connett J.E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med. 2001;164(3):358–364. https://doi.org/10.1164/ajrccm.164.3.2010017.Kanner R.E., Anthonisen N.R., Connett J.E. Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med. 2001;164(3):358–364. https://doi.org/10.1164/ajrccm.164.3.2010017.Dransfield M.T., Crim C., Criner G.J., Day N.C., Halpin D.M.G., Han M.K. et al. Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT. Ann Am Thorac Soc. 2021;18(5):788–798. https://doi.org/10.1513/AnnalsATS.202002-096OC.Dransfield M.T., Crim C., Criner G.J., Day N.C., Halpin D.M.G., Han M.K. et al. Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT. Ann Am Thorac Soc. 2021;18(5):788–798. https://doi.org/10.1513/AnnalsATS.202002-096OC.Yawn B.P., Li Y., Tian H., Zhang J., Arcona S., Kahler K.H. Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis. Int J Chron Obstruct Pulmon Dis. 2013;8:295–304. https://doi.org/10.2147/COPD.S42366.Yawn B.P., Li Y., Tian H., Zhang J., Arcona S., Kahler K.H. Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis. Int J Chron Obstruct Pulmon Dis. 2013;8:295–304. https://doi.org/10.2147/COPD.S42366.Sabroe I., Postma D., Heijink I., Dockrell D.H. The yin and the yang of immunosuppression with inhaled corticosteroids. Thorax. 2013;68(12):1085–1087. https://doi.org/10.1136/thoraxjnl-2013-203773.Sabroe I., Postma D., Heijink I., Dockrell D.H. The yin and the yang of immunosuppression with inhaled corticosteroids. Thorax. 2013;68(12):1085–1087. https://doi.org/10.1136/thoraxjnl-2013-203773.Rodrigo G.J., Castro-Rodriguez J.A., Plaza V. Safety and efficacy of combined long-acting beta-agonists and inhaled corticosteroids vs long-acting beta-agonists monotherapy for stable COPD: a systematic review. Chest. 2009;136(4):1029–1038. https://doi.org/10.1378/chest.09-0821.Rodrigo G.J., Castro-Rodriguez J.A., Plaza V. Safety and efficacy of combined long-acting beta-agonists and inhaled corticosteroids vs long-acting beta-agonists monotherapy for stable COPD: a systematic review. Chest. 2009;136(4):1029–1038. https://doi.org/10.1378/chest.09-0821.Singh S., Loke Y.K. Risk of pneumonia associated with long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease: a critical review and update. Curr Opin Pulm Med. 2010;16(2):118–122. https://doi.org/10.1097/MCP.0b013e328334c085.Singh S., Loke Y.K. Risk of pneumonia associated with long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease: a critical review and update. Curr Opin Pulm Med. 2010;16(2):118–122. https://doi.org/10.1097/MCP.0b013e328334c085.Beasley R., Harper J., Bird G., Maijers I., Weatherall M., Pavord I.D. Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology. Am J Respir Crit Care Med. 2019;199(12):1471–1477. https://doi.org/10.1164/rccm.201810-1868CI.Beasley R., Harper J., Bird G., Maijers I., Weatherall M., Pavord I.D. Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology. Am J Respir Crit Care Med. 2019;199(12):1471–1477. https://doi.org/10.1164/rccm.201810-1868CI.Brassard P., Suissa S., Kezouh A., Ernst P. Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases. Am J Respir Crit Care Med. 2011;183(5):675–678. https://doi.org/10.1164/rccm.201007-1099OC.Brassard P., Suissa S., Kezouh A., Ernst P. Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases. Am J Respir Crit Care Med. 2011;183(5):675–678. https://doi.org/10.1164/rccm.201007-1099OC.

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