medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-10-101-107medsovet-5727Research ArticleАЛЛЕРГОЛОГИЯ И ИММУНОЛОГИЯALLERGOLOGY AND IMMUNOLOGYТерапия и контроль бронхиальной астмы у детей и подростковTherapy and control of bronchial asthma in children and adolescentshttps://orcid.org/0000-0001-7676-3213СуровенкоТ. Н.SurovenkoT. N.

Суровенко Татьяна Николаевна, д.м.н., профессор Института педиатрии

690002, Владивосток, проспект Острякова, д. 2

Tatiana N. Surovenko, Dr. of Sci. (Med.), professor of the Institute of Pediatrics

2, Ostryakova Ave, Vladivostok, 690002

Tatiana.Surovenko@gmail.comhttps://orcid.org/0000-0002-4908-6146ГлушковаЕ. Ф.GlushkovaE. F.

Глушкова Евгения Федоровна, врач аллерголог-иммунолог поликлинического отделения

115522, Москва, Каширское ш., д. 24

Evgeniya F. Glushkova, allergist/immunologist of the Outpatient Department

24, Kashirskoe Shosse, Moscow, 115522

glushkovaef@gmail.comТихоокеанский государственный медицинский университетРоссияPacific State Medical UniversityRussian FederationИнститут иммунологииРоссияInstitute of ImmunologyRussian Federation202029072020010101107Copyright © Суровенко Т.Н., Глушкова Е.Ф., 20202020Суровенко Т.Н., Глушкова Е.Ф.Surovenko T.N., Glushkova E.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5727

По данным из разных регионов и источников, бронхиальной астмой в мире страдает до 22% населения. Это около 358 млн человек. При этом точных цифр распространенности этого заболевания получить не удается. Несмотря на множество проводимых исследований этого заболевания, разработанных вариантов лечения, астма так и не стала полностью контролируемым заболеванием. Проблема контроля и лечение заболевания, комплаентности пациентов остро волнует современных клиницистов. Ежегодно глобальная инициатива по лечению и профилактике бронхиальной астмы GINA выпускает новые документы и вносит изменения в лечение и диагностику этого хронического бронхолегочного заболевания. Детская же астма стала не только самым распространенным хроническим заболеванием, но и самой частой причиной госпитализации детей.Статья представляет собой обзор результатов международных рандомизированных клинических исследований и мнений экспертов относительно лечения неконтролируемой бронхиальной астмы у детей и подростков. Описаны результаты метаанализов 2017–2020 гг. относительно использования тиотропия у детей и подростков. Раскрыто использование схем базисной терапии, включающей применение тиотропия бромида в соответствии с рекомендациями Российского респираторного общества и GINA.Также авторами представлен клинический случай трудноконтролируемой бронхиальной астмы у ребенка 12 лет. Подробно описано использование тиотропия бромида у данного больного и продемонстрирована эффективность этого препарата.

Up to 22% of the population in the world suffer from bronchial asthma according to the data from different regions and sources. This is about 358 million people. At the same time, accurate figures for the prevalence of this disease cannot be obtained. Despite the many ongoing studies of this disease, developed treatment options, asthma hasn’t become a fully controlled disease. The problem of control and treatment of the disease as well as patient compliance is of great concern to modern clinicians. Every year GINA releases new documents and makes changes in the treatment and diagnosis of this chronic bronchopulmonary disease. Children’s asthma has become not only the most common chronic disease, but also the most common cause of children hospitalization.This article provides an overview of the international randomized clinical trials results and expert opinions regarding the treatment of uncontrolled bronchial asthma in children and adolescents. The results of 2017–2020 meta-analyzes regarding the use of tiotropium in children and adolescents are described. The use of basic therapy schemes is disclosed, including the use of tiotropium bromide in accordance with the recommendations of the Russian Respiratory Society and GINA.The authors also presented a clinical case of difficultly controlled bronchial asthma in a child of 12 years old. The use of tiotropium bromide in this patient is described in detail and the effectiveness of this drug is demonstrated.

бронхиальная астмабазисная терапия бронхиальной астмылечениетиотропия бромидклинический примерasthmabasic therapy of asthmatreatmenttiotropium bromideclinical exampleReferencesОмельяновский В.В. Социально­экономическое бремя бронхиальной астмы и хронической обструктивной болезни легких в Российской Федерации. Отчет по исследованию за 2008–2009 годы. М.; 2010. 63 c.Omelyanovskiy V.V. Socio-economic burden of bronchial asthma and chronic obstructive pulmonary disease in the Russian Federation. Report on research for 2008-2009. Moscow; 2010. 63 p. (In Russ.)Chuchalin A.G., Khaltaev N., Аntonov N., Galkin D., Manakov L., Antonini P. et al. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int J COPD. 2014;9(1):963–974. doi: 10.2147/COPD.S67283.Chuchalin A.G., Khaltaev N., Аntonov N., Galkin D., Manakov L., Antonini P. et al. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int J COPD. 2014;9(1):963–974. doi: 10.2147/COPD.S67283.Karin C., Pijnenburg M., Lodrup C. Bronchial asthma. ERS Handbook: Paediatric Respiratory Medicine. European Respiratory Review. 2015;24(136):178–186. doi: 10.1183/16000617.00003714.Karin C., Pijnenburg M., Lodrup C. Bronchial asthma. ERS Handbook: Paediatric Respiratory Medicine. European Respiratory Review. 2015;24(136):178–186. doi: 10.1183/16000617.00003714.Global Initiative for Asthma. Pocket guide for asthma management and prevention 2020. GINA website. Available at: https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf.Global Initiative for Asthma. Pocket guide for asthma management and prevention 2020. GINA website. Available at: https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf.Bousqet J., Mantzouranis E., Cruz A.A., Aït-Khaled N., Baena-Cagnani C.E., Bleeckeret E.R. et al. Uniform definition of asthma severity, control and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol. 2010;126(5):926–938. doi: 10.1016/j.jaci.2010.07.019.Bousqet J., Mantzouranis E., Cruz A.A., Aït-Khaled N., Baena-Cagnani C.E., Bleeckeret E.R. et al. Uniform definition of asthma severity, control and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol. 2010;126(5):926–938. doi: 10.1016/j.jaci.2010.07.019.Chung K.F., Wenzel S.E., Brozek J.L., Bush A., Castro M., Sterk P.J. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal. 2014;43(2):343–373. doi: 10.1183/09031936.00202013.Chung K.F., Wenzel S.E., Brozek J.L., Bush A., Castro M., Sterk P.J. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. European Respiratory Journal. 2014;43(2):343–373. doi: 10.1183/09031936.00202013.Porsbjerg C., Menzies-Gow A. Co-morbidities in severe asthma Clinical impact and management. Respirology. 2017;22(4):651–661. doi: 10.1111/resp.13026.Porsbjerg C., Menzies-Gow A. Co-morbidities in severe asthma Clinical impact and management. Respirology. 2017;22(4):651–661. doi: 10.1111/resp.13026.Partridge M.R., van der Molen T., Myrseth S.E., Busse W.W. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med. 2006;6:13. doi: 10.1186/1471-2466-6-13.Partridge M.R., van der Molen T., Myrseth S.E., Busse W.W. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med. 2006;6:13. doi: 10.1186/1471-2466-6-13.Архипов В.В., Григорьева Е.В., Гавришина Е.В. Контроль над бронхиальной астмой в России: результаты многоцентрового наблюдательного исследования НИКА. Пульмонология. 2011;(6):87–93. doi: 10.18093/08690189-2011-0-6-87-93.Arkhipov V.V., Grigoryeva E.V., Gavrishina E.V. Control of bronchial asthma in Russia: results of NIKA multi-center observational study. Russian Pulmonology Journal = Pulmonologiya. 2011;(6):87–93. (In Russ.) doi: 10.18093/0869-0189-2011-0-6-87-93.Djukanovic R., Wilson J.W., Britten K.M., Wilson S.J., Walls A.F., Roche W.R. et al. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992;145(3):669–674. doi: 10.1164/ajrccm/145.3.669.Djukanovic R., Wilson J.W., Britten K.M., Wilson S.J., Walls A.F., Roche W.R. et al. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992;145(3):669–674. doi: 10.1164/ajrccm/145.3.669.Авдеев С.Н., Айсанов З.Р., Архипов В.В., Белевский А.С., Визель А.А., Демко И.В. и др. Принципы выбора терапии для больных легкой астмой. Согласованные рекомендации РААКИ и РРО. Российский аллергологический журнал. 2017;14(3):41–50. Режим доступа: https://rusalljournal.ru/raj/article/view/313.Avdeev S.N., Aysanov Z.R., Arkhipov V.V., Belevskiy A.S., Viesel A.A., Demko I.V. et al. Principles of selecting therapy for patients with mild asthma. Raaci and rro agreed recommendations. Rossiyskiy allergologicheskiy zhurnal = Russian Journal of Allergy. 2017;14(3):41–50. (In Russ.) Available at: http://rusalljournal.ru/sc/pdf/3-2017.pdf.Gandhi N.A., Bennett B.L., Graham N.M., Pirozzi G., Stahl N., Yancopoulos G.D. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35–50. doi: 10.1038/nrd4624.Gandhi N.A., Bennett B.L., Graham N.M., Pirozzi G., Stahl N., Yancopoulos G.D. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35–50. doi: 10.1038/nrd4624.Курбачева О.М., Галицкая М.А. Место антилейкотриеновых препаратов в противовоспалительной терапии бронхиальной астмы. Российский аллергологический журнал. 2017;14(4–5):71–78. Режим доступа: https://rusalljournal.ru/raj/article/view/298.Kurbacheva O.M., Galitskaya M.A. The place of antileukotriene medications in antiinflammatory therapy of bronchial asthma. Rossiyskiy allergologicheskiy zhurnal = Russian Journal of Allergy. 2017;14(4–5):71–79. (In Russ.) Available at: https://rusalljournal.ru/raj/article/view/298.Greenberger P.A. Lessons Learned From Clinical Trials of Asthma. Allergy Asthma Proc. 2019;40(6):410–413. doi: 10.2500/aap.2019.40.4259.Greenberger P.A. Lessons Learned From Clinical Trials of Asthma. Allergy Asthma Proc. 2019;40(6):410–413. doi: 10.2500/aap.2019.40.4259.Barnes P.J. Tiotropium bromide. Expert Opin Investig Drugs. 2001;10(4):733–740. doi: 10.1517/13543784.10.4.733.Barnes P.J. Tiotropium bromide. Expert Opin Investig Drugs. 2001;10(4):733–740. doi: 10.1517/13543784.10.4.733.Meng J.F., Li H., Luo M.J., Li H.B. Efficacy of tiotropium in treating patients with moderate-to-severe asthma: A meta-analysis and systematic review based on 14 randomized controlled trials. Medicine (Baltimore). 2019;98(33):e16637. doi: 10.1097/MD.0000000000016637.Meng J.F., Li H., Luo M.J., Li H.B. Efficacy of tiotropium in treating patients with moderate-to-severe asthma: A meta-analysis and systematic review based on 14 randomized controlled trials. Medicine (Baltimore). 2019;98(33):e16637. doi: 10.1097/MD.0000000000016637.Vogelberg C., Goldstein S., Graham L., Kaplan A., de la Hoz A., Hamelmann E. A comparison of tiotropium, long-acting β2 -agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma. Respir Res. 2020;21(1):19. doi: 10.1186/s12931-0201282-9.Vogelberg C., Goldstein S., Graham L., Kaplan A., de la Hoz A., Hamelmann E. A comparison of tiotropium, long-acting β2 -agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma. Respir Res. 2020;21(1):19. doi: 10.1186/s12931-020-1282-9.Murphy K.R., Chipps B.E. Tiotropium in children and adolescents with asthma. Ann Allergy Asthma Immunol. 2020;124(3):267–276. doi: 10.1016/j.anai.2019.11.030.Murphy K.R., Chipps B.E. Tiotropium in children and adolescents with asthma. Ann Allergy Asthma Immunol. 2020;124(3):267–276. doi: 10.1016/j.anai.2019.11.030.Radovanovic D., Santus P., Blasi F., Mantero M. Erratum to: The evidence on tiotropium bromide in asthma: from the rationale to the bedside. Multidiscip Respir Med. 2017;12:17. doi: 10.1186/s40248-017-0099-y.Radovanovic D., Santus P., Blasi F., Mantero M. Erratum to: The evidence on tiotropium bromide in asthma: from the rationale to the bedside. Multidiscip Respir Med. 2017;12:17. doi: 10.1186/s40248-017-0099-y.Ohta S., Oda N., Yokoe T., Tanaka A., Yamamoto Y., Watanabe Y. et al. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy. 2010;40(8):1266–1275. doi: 10.1111/j.1365-2222.2010.03478.x.Ohta S., Oda N., Yokoe T., Tanaka A., Yamamoto Y., Watanabe Y. et al. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy. 2010;40(8):1266–1275. doi: 10.1111/j.1365-2222.2010.03478.x.Суровенко Т.Н., Глушкова Е.Ф. Новые возможности терапии бронхиальной астмы у детей. Медицинский совет. 2018;(17):192–198. doi: 10.21518/2079-701X-2018-17-192-198.Surovenko T.N., Glushkova Е.F. New possibilities for asthma therapy in children. Meditsinskiy sovet = Medical Council. 2018;(17):192–199. (In Russ.) doi: 10.21518/2079-701X-2018-17-192-198.Vogelberg C., Moroni-Zentgraf P., Leonaviciute-Klimantaviciene M., Sigmund R., Hamelmann E., Engel M. et al. A randomised dose-ranging study of tiotropium Respimat® in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015;16:20. doi: 10.1186/s12931-015-0175-9.Vogelberg C., Moroni-Zentgraf P., Leonaviciute-Klimantaviciene M., Sigmund R., Hamelmann E., Engel M. et al. A randomised dose-ranging study of tiotropium Respimat® in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015;16:20. doi: 10.1186/s12931-015-0175-9.Hamelmann E., Bernstein J.A., Vandewalker M., Moroni-Zentgraf P., Verri D., Unseld A., Engel M., Boner A.L. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49(1):1601100. doi: 10.1183/13993003.01100-2016.Hamelmann E., Bernstein J.A., Vandewalker M., Moroni-Zentgraf P., Verri D., Unseld A., Engel M., Boner A.L. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49(1):1601100. doi: 10.1183/13993003.01100-2016.Hamelmann E., Szefler S.J. Efficacy and Safety of Tiotropium in Children and Adolescents. Drugs. 2018;78(3):327–338. doi: 10.1007/s40265-0180862-1.Hamelmann E., Szefler S.J. Efficacy and Safety of Tiotropium in Children and Adolescents. Drugs. 2018;78(3):327–338. doi: 10.1007/s40265-0180862-1.Vogelberg C., Szefler S.J., Vrijlandt E.J.L.E., Boner A.L., Engel M., El Azzi G. et al. Tiotropium add-on therapy has a safety profile comparable with that of placebo in children and adolescents with symptomatic asthma. Eur Respir J. 2019;53(6):1801824. doi: 10.1183/13993003.01824-2018.Vogelberg C., Szefler S.J., Vrijlandt E.J.L.E., Boner A.L., Engel M., El Azzi G. et al. Tiotropium add-on therapy has a safety profile comparable with that of placebo in children and adolescents with symptomatic asthma. Eur Respir J. 2019;53(6):1801824. doi: 10.1183/13993003.01824-2018.Vrijlandt E., El Azzi G., Vandewalker M., Rupp N., Harper T., Graham L.R. et al. Safety and efficacy of tiotropium in 1–5-year-old children with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018;6(2):127–137. doi: 10.1016/S22132600(18)30012-2.Vrijlandt E., El Azzi G., Vandewalker M., Rupp N., Harper T., Graham L.R. et al. Safety and efficacy of tiotropium in 1–5-year-old children with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018;6(2):127–137. doi: 10.1016/S2213-2600(18)30012-2.Efficacy of Intermittent Tiotropium in Early Childhood Wheezing. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03199976.Efficacy of Intermittent Tiotropium in Early Childhood Wheezing. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03199976.Kalayci O., Abdelateef H., Pozo Beltrán C.F., El-Sayed Z.A., Gómez R.M., Hossny E. et al. Challenges and choices in the pharmacological treatment of non-severe pediatric asthma: A commentary for the practicing physician. World Allergy Organ J. 2019;12(9):100054. doi: 10.1016/j.waojou.2019.100054.Kalayci O., Abdelateef H., Pozo Beltrán C.F., El-Sayed Z.A., Gómez R.M., Hossny E. et al. Challenges and choices in the pharmacological treatment of non-severe pediatric asthma: A commentary for the practicing physician. World Allergy Organ J. 2019;12(9):100054. doi: 10.1016/j.waojou.2019.100054.Ducharme F.M., Lemire C., Noya F.J. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med. 2009;360:339–353. doi: 10.1056/NEJMoa0808907.Ducharme F.M., Lemire C., Noya F.J. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med. 2009;360:339–353. doi: 10.1056/NEJMoa0808907.Szefler S.J., Phillips B.R., Martinez F.D. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115(2):233–242. doi: 10.1016/j.jaci.2004.11.014.Szefler S.J., Phillips B.R., Martinez F.D. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115(2):233–242. doi: 10.1016/j.jaci.2004.11.014.Vogelberg C., Engel M., Laki I. Tiotropium add-on therapy improves lung function in children with symptomatic moderate asthma. J Allergy Clin Immunol Pract. 2018;(6)6:2160–2162. doi: 10.1016/j.jaip.2018.04.032.Vogelberg C., Engel M., Laki I. Tiotropium add-on therapy improves lung function in children with symptomatic moderate asthma. J Allergy Clin Immunol Pract. 2018;(6)6:2160–2162. doi: 10.1016/j.jaip.2018.04.032.Hamelmann E., Bateman E.D., Vogelberg C. Tiotropium add-on therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138(2):441–450. doi: 10.1016/j.jaci.2016.01.011.Hamelmann E., Bateman E.D., Vogelberg C. Tiotropium add-on therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138(2):441–450. doi: 10.1016/j.jaci.2016.01.011.

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