pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2019-29-6-725-733pulmo-1257Research ArticleОБЗОРЫREVIEWДисфункция малых дыхательных путей при бронхиальной астмеSmall respiratory passages dysfunction in bronchial asthmaКытиковаО. Ю.KytikovaO. Yu.

Кытикова Оксана Юрьевна – к. м. н., научный сотрудник лаборатории восстановительного лечения

690105, Владивосток, ул. Русская, 73Г

тел.: (423) 278-82-01

Oksana Y. Kytikova, Candidate of Medical Sciences, researcher at the Laboratory of Rehabilitation Treatment

ul. Russkaya 73G, Vladivostok, 690105, Russia

tel.: (423) 278-82-01

kytikova@yandex.ruАнтонюкМ. В.AntonyukM. V.

Антонюк Марина Владимировна – д. м. н., профессор, заведующая лабораторией восстановительного лечения; профессор школы биомедицины

690105, Владивосток, ул. Русская, 73Г; 690091, Владивосток, ул. Суханова, 8

тел.: (423) 278-82-01

Marina V. Antonyuk, Doctor of medical sciences, professor, head of the restoration treatment laboratory; professor of the School of Biomedicine 

ul. Russkaya 73G, Vladivostok, 690105, Russia; ul. Sukhanova 8, Vladivostok, 690091, Russia

tel.: (423) 2788-201

antonyukm@mail.ruГельцерБ. И.Gel'tserB. I.

Гельцер Борис Израилевич – д. м. н., профессор, член-корр. Российской академии наук, директор департамента клинической медицины

690091, Владивосток, ул. Суханова, 8

тел.: (423) 240-66-38

Boris I. Gel'tser, Doctor of Medical Sciences, Professor, Corresponding Member of Russian Academy of Sciences, Director of Clinical Medicine Department

ul. Sukhanova 8, Vladivostok, 690091, Russia

tel.: (423) 240-66-38

geltcer.bi@dvfu.ruМинееваЕ. Е.MineevaE. E.

Минеева Елена Евгеньевна – к. м. н. научный сотрудник лаборатории восстановительного лечения

690105, Владивосток, ул. Русская, 73Г

тел.: (423) 278-82-01

Elena E.Mineeva, Candidate of Medical Sciences researcher at the laboratory of rehabilitation treatment

ul. Russkaya 73G, Vladivostok, 690105, Russia

tel.: (423) 278-82-01

elmineeva@yandex.ruГвозденкоТ. А.GvozdenkoT. A.

Гвозденко Татьяна Александровна – д. м. н., профессор Российской академии наук, главный научный сотрудник лаборатории восстановительного лечения

690105, Владивосток, ул. Русская, 73Г

тел.: (423) 278-82-01

Tat'yana A.Gvozdenko, Doctor of medical sciences, professor of the Russian Academy of Sciences, chief research officer of the rehabilitation treatment laboratory

ul. Russkaya 73G, Vladivostok, 690105, Russia

tel.: (423) 278-82-01

vfdnz@mail.ruВладивостокский филиал Федерального государственного бюджетного научного учреждения «Дальневосточный научный центр физиологии и патологии дыхания» – Научно-исследовательский институт медицинской климатологии и восстановительного леченияРоссияVladivostok branch of the Federal State Budgetary Scientific Institution "Far Eastern Scientific Center of Physiology and Pathology of Breathing" – Research Institute of Medical Climatology and Rehabilitation TreatmentRussian FederationВладивостокский филиал Федерального государственного бюджетного научного учреждения «Дальневосточный научный центр физиологии и патологии дыхания» – Научно-исследовательский институт медицинской климатологии и восстановительного лечения; Федеральное государственное автономное образовательное учреждение высшего образования «Дальневосточный федеральный университет» Министерства науки и высшего образования Российской ФедерацииРоссияVladivostok branch of the Federal State Budgetary Scientific Institution "Far Eastern Scientific Center of Physiology and Pathology of Breathing" – Research Institute of Medical Climatology and Rehabilitation Treatment; Federal State Autonomous Educational Institution of Higher Education "Far Eastern Federal University" of the Ministry of Science and Higher Education of the Russian FederationRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Дальневосточный федеральный университет» Министерства науки и высшего образования Российской ФедерацииРоссияFederal State Autonomous Educational Institution of Higher Education "Far Eastern Federal University" of the Ministry of Science and Higher Education of the Russian FederationRussian Federation201927022020296725733Copyright © Кытикова О.Ю., Антонюк М.В., Гельцер Б.И., Минеева Е.Е., Гвозденко Т.А., 20202020Кытикова О.Ю., Антонюк М.В., Гельцер Б.И., Минеева Е.Е., Гвозденко Т.А.Kytikova O.Y., Antonyuk M.V., Gel'tser B.I., Mineeva E.E., Gvozdenko T.A.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/1257

Дисфункция малых дыхательных путей (ДМДП) выявляется у подавляющего большинства пациентов, страдающих бронхиальной астмой (БА). В настоящее время ДМДП признана важной патогенетической чертой БА. Целью настоящего обзора является анализ современных научных знаний о малоизученных аспектах участия малых дыхательных путей (МДП) в развитии патологического процесса при БА, а также влияния дисфункции мелких бронхов на клиническое течение, частоту обострений и контроль над заболеванием. Обсуждается важность диагностики ДМДП у больных БА для назначения оптимального и своевременного лечения. Описываются современные методы диагностики патологии МДП; рассматривается информативность их применения в аспекте сравнительного изучения.

The small respiratory passages dysfunction (SRPD) is found in the vast majority of patients with bronchial asthma (BA). The SRPD is currently recognized as the important pathogenetic feature of BA. The purpose of this review is to analyze the current scientific knowledge about the poorly studied aspects of the small respiratory passages (SRR) participation in the development of pathological process in BA, as well as the impact of small bronchial dysfunction on the clinical course, the exacerbation frequency and the disease control. The importance of SRPD diagnostics in BA patients for optimal and timely treatment is discussed. The modern methods of RPD pathology diagnostics are described; their informative use in the comparative study aspect is considered.

бронхиальная астмамалые дыхательные путиbronchial asthmasmall respiratory passagesReferencesGlobal Initiative for Asthma. Global strategy for Asthma Management and Prevention. Update 2018. Available at: https://ginasthma.orgGlobal Initiative for Asthma. Global strategy for Asthma Management and Prevention. Update 2018. Available at: https://ginasthma.orgКытикова О.Ю., Гвозденко Т.А., Антонюк М.В. Современные аспекты распространенности хронических бронхолегочных заболеваний. Бюллетень физиологии и патологии дыхания. 2017; 64: 94–100. Доступно на: https://cyberleninka.ru/article/n/sovremennye-aspekty-rasprostranennosti-hronicheskih-bronholegochnyh-zabolevaniy/viewerKytikova O.Yu., Gvozdenko T.A., Antonyuk M.V. [The modern aspects of the chronic bronchopulmonary diseases prevalence]. Byulleten' fiziologii i patologii dykhaniya. 2017; 64: 94–100. Available at: https://cyberleninka.ru/article/n/sovremennye-aspekty-rasprostranennosti-hronicheskih-bronholegochnyh-zabolevaniy/viewer (in Russian).Глобальная стратегия лечения и профилактики бронхиальной астмы (пересмотр 2014 г.). Пер. с англ. под ред. А.С.Белевского. М.: РРО; 2015.Belevsky A., ed. [Global strategy for the treatment and prevention of bronchial asthma (2014 revision)]. Translate from English. Мoscow: RRО; 2015 (in Russian).Masoli М. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004; 59 (5): 469–478. DOI: 10.1111/j.1398-9995.2004.00526.x.Masoli М. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004; 59 (5): 469–478. DOI: 10.1111/j.1398-9995.2004.00526.x.Sánchez-García S., Habernau Mena A., Quirce S. Biomarkers in inflammometry pediatric asthma: utility in daily clinical practice. Eur. Clin. Respir. J. 2017; 4 (1): 1356160. DOI: 10.1080/20018525.2017.1356160.Sánchez-García S., Habernau Mena A., Quirce S. Biomarkers in inflammometry pediatric asthma: utility in daily clinical practice. Eur. Clin. Respir. J. 2017; 4 (1): 1356160. DOI: 10.1080/20018525.2017.1356160.Asher I., Pearce N. Global burden of asthma among children. Int. J. Tuberc. Lung Dis. 2014; 18 (11): 1269–1278. DOI: 10.5588/ijtld.14.0170.Asher I., Pearce N. Global burden of asthma among children. Int. J. Tuberc. Lung Dis. 2014; 18 (11): 1269–1278. DOI: 10.5588/ijtld.14.0170.Chung K.F., Wenzel S.E., Brozek J.L. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 2014; 43 (2): 343–373. DOI: 10.1183/09031936.00202013.Chung K.F., Wenzel S.E., Brozek J.L. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 2014; 43 (2): 343–373. DOI: 10.1183/09031936.00202013.Soriano J.B., Abajobir A.A., Abate K.H. et al. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 2017; 5 (9): 691–706. DOI: 10.1016/S2213-2600(17)30293-X.Soriano J.B., Abajobir A.A., Abate K.H. et al. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 2017; 5 (9): 691–706. DOI: 10.1016/S2213-2600(17)30293-X.Zeiger R.S., Schatz M., Dalal A.A. et al. Utilization and costs of severe uncontrolled asthma in a managed-care setting. J. Allergy Clin. Immunol. Pract. 2016; 4 (1): 120–129.е3. DOI: 10.1016/j.jaip.2015.08.003.Zeiger R.S., Schatz M., Dalal A.A. et al. Utilization and costs of severe uncontrolled asthma in a managed-care setting. J. Allergy Clin. Immunol. Pract. 2016; 4 (1): 120–129.е3. DOI: 10.1016/j.jaip.2015.08.003.Vos T., Barber R.M., Bell B. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990 – 2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 386 (9995): 743–800. DOI: 10.1016/S0140-6736(15)60692-4.Vos T., Barber R.M., Bell B. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990 – 2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 386 (9995): 743–800. DOI: 10.1016/S0140-6736(15)60692-4.Agustí A., Bafadhel M., Beasley R. et al. Precision medicine in airway diseases: moving to clinical practice. Eur. Respir. J. 2017; 50 (4): 1701655. DOI: 10.1183/13993003.01655-2017.Agustí A., Bafadhel M., Beasley R. et al. Precision medicine in airway diseases: moving to clinical practice. Eur. Respir. J. 2017; 50 (4): 1701655. DOI: 10.1183/13993003.01655-2017.Traulsen L.K., Halling A., Bælum J. et al. Determinants of persistent asthma in young adults. Eur. Clin. Respir. J. 2018; 5 (1): 1478593. DOI: 10.1080/20018525.2018.1478593.Traulsen L.K., Halling A., Bælum J. et al. Determinants of persistent asthma in young adults. Eur. Clin. Respir. J. 2018; 5 (1): 1478593. DOI: 10.1080/20018525.2018.1478593.Price D., Fletcher M., van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim. Care Respir. Med. 2014; 24:14009. DOI: 10.1038/npjpcrm.2014.9.Price D., Fletcher M., van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim. Care Respir. Med. 2014; 24:14009. DOI: 10.1038/npjpcrm.2014.9.Van Schayck O.C. Global strategies for reducing the burden from asthma. Prim. Сare Respir. J. 2013; 22 (2): 239–243. DOI: 10.4104/pcrj.2013.00052.Van Schayck O.C. Global strategies for reducing the burden from asthma. Prim. Сare Respir. J. 2013; 22 (2): 239–243. DOI: 10.4104/pcrj.2013.00052.Deliu M., Yavuz T.S., Sperrin M. et al. Features of asthma which provide meaningful insights for understanding the disease heterogeneity. Clin. Exp. Allergy. 2018; 48 (1): 39–47. DOI: 10.1111/cea.13014.Deliu M., Yavuz T.S., Sperrin M. et al. Features of asthma which provide meaningful insights for understanding the disease heterogeneity. Clin. Exp. Allergy. 2018; 48 (1): 39–47. DOI: 10.1111/cea.13014.Siroux V., Basagana X., Boudier A. et al. Identifying adult asthma phenotypes using a clustering approach. Eur. Respir. J. 2011; 38 (2): 310–317. DOI: 10.1183/09031936.00120810.Siroux V., Basagana X., Boudier A. et al. Identifying adult asthma phenotypes using a clustering approach. Eur. Respir. J. 2011; 38 (2): 310–317. DOI: 10.1183/09031936.00120810.Wenzel S.E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 2012; 18 (5): 716–725. DOI: 10.1038/nm.2678.Wenzel S.E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 2012; 18 (5): 716–725. DOI: 10.1038/nm.2678.Lötval J., Akdis C.A., Bacharier L.B. et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J. Allergy Clin. Immunol. 2011; 127 (2): 355–360. DOI: 10.1016/j.jaci.2010.11.037.Lötval J., Akdis C.A., Bacharier L.B. et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J. Allergy Clin. Immunol. 2011; 127 (2): 355–360. DOI: 10.1016/j.jaci.2010.11.037.Авдеев С.Н., Айсанов З.Р., Архипов В.В. и др. Согласованные рекомендации по обоснованию выбора терапии бронхиальной̆ астмы и хронической̆ обструктивной болезни легких с учетом фенотипа заболевания и роли малых дыхательных путей. Атмосфера. Пульмонология и аллергология. 2013; (2): 15–26.Avdeev S.N., Aysanov Z.R., Arkhipov V.V. et al. [The agreed recommendations to justify therapy choice for bronchial asthma and chronic obstructive pulmonary disease, taking into account the disease phenotype and the role of the small respiratory passages]. Atmosfera. Pul'monologiya i allergologiya. 2013; (2): 15–26. (in Russian).Lipworth B., Manoharan A., Anderson W. Unlocking the quiet zone: the small airway asthma phenotype. Lancet Respir. Med. 2014; 2 (6): 497–506. DOI: 10.1016/S2213-2600(14)70103-1.Lipworth B., Manoharan A., Anderson W. Unlocking the quiet zone: the small airway asthma phenotype. Lancet Respir. Med. 2014; 2 (6): 497–506. DOI: 10.1016/S2213-2600(14)70103-1.Haccuria A., Van Muylem A., Malinovschi A. et al. Small airways dysfunction: the link between allergic rhinitis and allergic asthma. Eur. Respir. J. 2018; 51 (2). pii: 1701749. DOI: 10.1183/13993003.01749-2017.Haccuria A., Van Muylem A., Malinovschi A. et al. Small airways dysfunction: the link between allergic rhinitis and allergic asthma. Eur. Respir. J. 2018; 51 (2). pii: 1701749. DOI: 10.1183/13993003.01749-2017.Фассахов Р.С. Большая роль малых дыхательных путей: новые возможности циклесонида в терапии бронхиальной астмы. Медицинский совет. 2017; (18): 56–60. Доступно на: https://cyberleninka.ru/article/n/bolshaya-rol-malyh-dyhatelnyh-putey-novye-vozmozhnosti-tsiklesonida-v-terapii-bronhialnoy-astmy/viewerFassakhov R.S. [Significant role of small respiratory tracts: new possibilities of cyclesonide in therapy of bronchial asthma]. 2017; (18): 56–60. Available at: https://cyberleninka.ru/article/n/bolshaya-rol-malyh-dyhatelnyh-putey-novye-vozmozhnosti-tsiklesonida-v-terapii-bronhialnoy-astmy/viewer (in Russian).van der Wiel E., ten Hacken N.H., Postma D.S., van den Berge M. Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: a systematic review. J. Allergy Clin. Immunol. 2013; 131 (3): 646–657. DOI: 10.1016/j.jaci.2012.12.1567.van der Wiel E., ten Hacken N.H., Postma D.S., van den Berge M. Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: a systematic review. J. Allergy Clin. Immunol. 2013; 131 (3): 646–657. DOI: 10.1016/j.jaci.2012.12.1567.Singhania A., Rupani H., Jayasekera N. et al. Altered epithelial gene expression in peripheral airways of severe asthma. PLoS One. 2017; 12 (1): e0168680. DOI: 10.1371/journal.pone.0168680.Singhania A., Rupani H., Jayasekera N. et al. Altered epithelial gene expression in peripheral airways of severe asthma. PLoS One. 2017; 12 (1): e0168680. DOI: 10.1371/journal.pone.0168680.Stenberg H., Diamant Z., Ankerst J. et al. Small airway involvement in the late allergic response in asthma. Clin. Exp. Allergy. 2017; 47 (12): 1555–1565. DOI: 10.1111/cea.13036.Stenberg H., Diamant Z., Ankerst J. et al. Small airway involvement in the late allergic response in asthma. Clin. Exp. Allergy. 2017; 47 (12): 1555–1565. DOI: 10.1111/cea.13036.Knihtilä H., Kotaniemi-Syrjänen A., Pelkonen A.S. et al. Small airway function in children with mild to moderate asthmatic symptoms. Ann. Allergy Asthma Immunol. 2018; 121 (4): 451–457. DOI: 10.1016/j.anai.2018.07.026.Knihtilä H., Kotaniemi-Syrjänen A., Pelkonen A.S. et al. Small airway function in children with mild to moderate asthmatic symptoms. Ann. Allergy Asthma Immunol. 2018; 121 (4): 451–457. DOI: 10.1016/j.anai.2018.07.026.Contoli M., Kraft M., Hamid Q. et al. Do small airway abnormalities characterize asthma phenotypes? In search of proof. Clin. Exp. Allergy. 2012; 42 (8): 1150–1160. DOI: 10.1111/j.1365-2222.2012.03963.x.Contoli M., Kraft M., Hamid Q. et al. Do small airway abnormalities characterize asthma phenotypes? In search of proof. Clin. Exp. Allergy. 2012; 42 (8): 1150–1160. DOI: 10.1111/j.1365-2222.2012.03963.x.Carvalho T.C., Peters J.I., Williams R.O. Influence of particle size on regional lung deposition – what evidence is there? Int. J. Pharm. 2011; 406 (1–2): 1–10. DOI: 10.1016/j.ijpharm.2010.12.040.Carvalho T.C., Peters J.I., Williams R.O. Influence of particle size on regional lung deposition – what evidence is there? Int. J. Pharm. 2011; 406 (1–2): 1–10. DOI: 10.1016/j.ijpharm.2010.12.040.Ivancsó I., Böcskei R., Müller V. et al. Extrafine inhaled corticosteroid therapy in the control of asthma. J. Asthma Allergy. 2013; 6: 69–80. DOI: 10.2147/JAA.S25415.Ivancsó I., Böcskei R., Müller V. et al. Extrafine inhaled corticosteroid therapy in the control of asthma. J. Asthma Allergy. 2013; 6: 69–80. DOI: 10.2147/JAA.S25415.Verbanck S. Physiological measurement of the small airways. Respiration. 2012; 84: 177–188. DOI: 10.1159/000341742.Verbanck S. Physiological measurement of the small airways. Respiration. 2012; 84: 177–188. DOI: 10.1159/000341742.Jarjour N.N., Erzurum S.C., Bleecker E.R. et al. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. Am. J. Respir. Crit. Care Med. 2012; 185 (4): 356–362. DOI: 10.1164/rccm.201107-1317PP.Jarjour N.N., Erzurum S.C., Bleecker E.R. et al. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. Am. J. Respir. Crit. Care Med. 2012; 185 (4): 356–362. DOI: 10.1164/rccm.201107-1317PP.Desiraju K., Agrawal A. Impulse oscillometry: the state-of-art for lung function testing. Lung India. 2016; 33 (4): 410–416. DOI: 10.4103/0970-2113.184875.Desiraju K., Agrawal A. Impulse oscillometry: the state-of-art for lung function testing. Lung India. 2016; 33 (4): 410–416. DOI: 10.4103/0970-2113.184875.Zysman-Colman Z., Lands L.C. Whole body plethysmography: practical considerations. Paediatr. Respir. Rev. 2016; 19: 39–41. DOI: 10.1016/j.prrv.2015.11.008.Zysman-Colman Z., Lands L.C. Whole body plethysmography: practical considerations. Paediatr. Respir. Rev. 2016; 19: 39–41. DOI: 10.1016/j.prrv.2015.11.008.Sarmand N., Gompelmann D. [Interventional bronchoscopy: What is possible and what makes sense?]. Dtsch Med. Wochenschr. 2018; 143 (15): 1097–1102. DOI: 10.1055/a-0551-2626 (in German).Sarmand N., Gompelmann D. [Interventional bronchoscopy: What is possible and what makes sense?]. Dtsch Med. Wochenschr. 2018; 143 (15): 1097–1102. DOI: 10.1055/a-0551-2626 (in German).Spahn J.D., Malka J., Szefler S.J. Current application of exhaled nitric oxide in clinical practice. J. Allergy Clin. Immunol. 2016; 138 (5): 1296–1298. DOI: 10.1016/j.jaci.2016.09.002.Spahn J.D., Malka J., Szefler S.J. Current application of exhaled nitric oxide in clinical practice. J. Allergy Clin. Immunol. 2016; 138 (5): 1296–1298. DOI: 10.1016/j.jaci.2016.09.002.Fuso L., Macis G., Condoluci C. et al. Impulse oscillometry and nitrogen washout test in the assessment of small airway dysfunction in asthma: Correlation with quantitative computed tomography. J. Asthma. 2018; 56 (3): 323–331. DOI: 10.1080/02770903.2018.1452032.Fuso L., Macis G., Condoluci C. et al. Impulse oscillometry and nitrogen washout test in the assessment of small airway dysfunction in asthma: Correlation with quantitative computed tomography. J. Asthma. 2018; 56 (3): 323–331. DOI: 10.1080/02770903.2018.1452032.Robinson P.D., Latzin P., Verbanck S. et al. Consensus statement for inert gas washout measurement using multiple- and single breath tests. Eur. Respir. J. 2013; 41 (3): 507–522. DOI: 10.1183/09031936.00069712.Robinson P.D., Latzin P., Verbanck S. et al. Consensus statement for inert gas washout measurement using multiple- and single-breath tests. Eur. Respir. J. 2013; 41 (3): 507–522. DOI: 10.1183/09031936.00069712.Kjellberg S., Viklund E., Robinson P.D. et al. Utility of single versus multiple breath washout in adult asthma. Clin. Physiol. Funct. Imaging. 2018; 38 (6). DOI: 10.1111/cpf.12503.Kjellberg S., Viklund E., Robinson P.D. et al. Utility of single versus multiple breath washout in adult asthma. Clin. Physiol. Funct. Imaging. 2018; 38 (6). DOI: 10.1111/cpf.12503.Yang Z., Jin H., Kim J.H. Attenuation profile matching: An accurate and scan parameter-robust measurement method for small airway dimensions in low-dose CT scans. Med. Phys. 2018; 45 (9). DOI: 10.1002/mp.13074.Yang Z., Jin H., Kim J.H. Attenuation profile matching: An accurate and scan parameter-robust measurement method for small airway dimensions in low-dose CT scans. Med. Phys. 2018; 45 (9). DOI: 10.1002/mp.13074.Saetta M., Di Stefano A., Rosina C. et al. Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma. Am. Rev. Respir. Dis. 1991; 143 (1): 138–143. DOI: 10.1164/ajrccm/143.1.138.Saetta M., Di Stefano A., Rosina C. et al. Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma. Am. Rev. Respir. Dis. 1991; 143 (1): 138–143. DOI: 10.1164/ajrccm/143.1.138.Balzar S. Wenzel S.E., Chu H.W. Transbronchial biopsy as a tool to evaluate small airways in asthma. Eur. Respir. J. 2002; 20 (2): 254–259. DOI: 10.1183/09031936.02.00261102.Balzar S. Wenzel S.E., Chu H.W. Transbronchial biopsy as a tool to evaluate small airways in asthma. Eur. Respir. J. 2002; 20 (2): 254–259. DOI: 10.1183/09031936.02.00261102.Anderson W.J., Zajda E., Lipworth B.J. Are we overlooking persistent small airways dysfunction in community-managed asthma? Ann. Allergy Asthma Immunol. 2012; 109 (3): 185–189.е2. DOI: 10.1016/j.anai.2012.06.022.Anderson W.J., Zajda E., Lipworth B.J. Are we overlooking persistent small airways dysfunction in community-managed asthma? Ann. Allergy Asthma Immunol. 2012; 109 (3): 185–189.е2. DOI: 10.1016/j.anai.2012.06.022.Carr T.F., Altisheh R., Zitt M. Small airways disease and severe asthma. World Allergy Organ. J. 2017; 10 (1): 20. DOI: 10.1186/s40413-017-0153-4.Carr T.F., Altisheh R., Zitt M. Small airways disease and severe asthma. World Allergy Organ. J. 2017; 10 (1): 20. DOI: 10.1186/s40413-017-0153-4.Kim S., Nam J.K., Cho S.H. et al. Severe asthma phenotypes classified by site of airway involvement and remodeling via chest CT scan. J. Investig Allergol. Clin. Immunol. 2018; 28 (5): 312–320. DOI: 10.18176/jiaci.0265.Kim S., Nam J.K., Cho S.H. et al. Severe asthma phenotypes classified by site of airway involvement and remodeling via chest CT scan. J. Investig Allergol. Clin. Immunol. 2018; 28 (5): 312–320. DOI: 10.18176/jiaci.0265.Georas S.N. All plugged up – noninvasive mucus score to assess airway dysfunction in asthma. J. Clin. Invest. 2018; 128 (3): 906–909. DOI: 10.1172/JCI99726.Georas S.N. All plugged up – noninvasive mucus score to assess airway dysfunction in asthma. J. Clin. Invest. 2018; 128 (3): 906–909. DOI: 10.1172/JCI99726.Perez T., Chanez P., Dusser D., Devillier P. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. Respir. Med. 2013; 107 (11): 1667–1674. DOI: 10.1016/j.rmed.2013.08.009.Perez T., Chanez P., Dusser D., Devillier P. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. Respir. Med. 2013; 107 (11): 1667–1674. DOI: 10.1016/j.rmed.2013.08.009.Usmani O.S., Singh D., Spinola M. et al. The prevalence of small airways disease in adult asthma: a systematic literature review. Respir. Med. 2016; 116: 19–27. DOI: 10.1016/j.rmed.2016.05.006.Usmani O.S., Singh D., Spinola M. et al. The prevalence of small airways disease in adult asthma: a systematic literature review. Respir. Med. 2016; 116: 19–27. DOI: 10.1016/j.rmed.2016.05.006.Bacharier L.B., Strunk R.C., Mauger D. et al. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am. J. Respir. Crit. Care Med. 2004; 170 (4): 426–432.Bacharier L.B., Strunk R.C., Mauger D. et al. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am. J. Respir. Crit. Care Med. 2004; 170 (4): 426–432.Rao D.R., Gaffin J.M., Baxi S.N. et al. The utility of forced expiratory flow between 25% and 75% of vital capacity in predicting childhood asthma morbidity and severity. J. Asthma, 2012; 49 (6): 586–592. DOI: 10.3109/02770903.2012.690481.Rao D.R., Gaffin J.M., Baxi S.N. et al. The utility of forced expiratory flow between 25% and 75% of vital capacity in predicting childhood asthma morbidity and severity. J. Asthma, 2012; 49 (6): 586–592. DOI: 10.3109/02770903.2012.690481.Shi Y., Aledia A.S., Galant S.P., George S.C. Peripheral airway impairment measured by oscillometry predicts loss of asthma control in children. J. Allergy Clin. Immunol. 2013; 131 (3): 718–723. DOI: 10.1016/j.jaci.2012.09.022.Shi Y., Aledia A.S., Galant S.P., George S.C. Peripheral airway impairment measured by oscillometry predicts loss of asthma control in children. J. Allergy Clin. Immunol. 2013; 131 (3): 718–723. DOI: 10.1016/j.jaci.2012.09.022.Li M.J., Chang C., Wang X.H. et al. [Correlation of CT small airway measurement with clinical and inflammation factors in asthma patients]. Zhonghua Yi Xue Za Zhi. 2018; 98 (27): 2184–2188. DOI: 10.3760/cma.j.issn.0376-2491.2018.27.012 (in Chinese).Li M.J., Chang C., Wang X.H. et al. [Correlation of CT small airway measurement with clinical and inflammation factors in asthma patients]. Zhonghua Yi Xue Za Zhi. 2018; 98 (27): 2184–2188. DOI: 10.3760/cma.j.issn.0376-2491.2018.27.012 (in Chinese).Alfieri V., Aiello M., Pisi R. et al. Small airway dysfunction is associated to excessive bronchoconstriction in asthmatic patients. Respir. Res. 2014; 15: 86. DOI: 10.1186/s12931-014-0086-1.Alfieri V., Aiello M., Pisi R. et al. Small airway dysfunction is associated to excessive bronchoconstriction in asthmatic patients. Respir. Res. 2014; 15: 86. DOI: 10.1186/s12931-014-0086-1.Cottini M., Lombardi C., Micheletto C. Small airway dysfunction and bronchial asthma control: the state of the art. Asthma Res. Pract. 2015; 1: 13. DOI: 10.1186/s40733-015-0013-3.Cottini M., Lombardi C., Micheletto C. Small airway dysfunction and bronchial asthma control: the state of the art. Asthma Res. Pract. 2015; 1: 13. DOI: 10.1186/s40733-015-0013-3.Takeda T., Oga T., Niimi A. et al. Relationship between small airway function and health status, dyspnea and disease control in asthma. Respiration. 2010; 80 (2): 120–126. DOI: 10.1159/000242113.Takeda T., Oga T., Niimi A. et al. Relationship between small airway function and health status, dyspnea and disease control in asthma. Respiration. 2010; 80 (2): 120–126. DOI: 10.1159/000242113.Scichilone N., Battaglia S., Taormina S. et al. Alveolar nitric oxide and asthma control in mild untreated asthma. J. Allergy Clin. Immunol. 2013; 131 (6): 1513–1517. DOI: 10.1016/j.jaci.2013.03.009.Scichilone N., Battaglia S., Taormina S. et al. Alveolar nitric oxide and asthma control in mild untreated asthma. J. Allergy Clin. Immunol. 2013; 131 (6): 1513–1517. DOI: 10.1016/j.jaci.2013.03.009.Manoharan A., Anderson W.J., Lipworth J. et al. Small airway dysfunction is associated with poorer asthma control. Eur. Respir. J. 2014; 44 (5): 1353–1355. DOI: 10.1183/09031936.00082314.Manoharan A., Anderson W.J., Lipworth J. et al. Small airway dysfunction is associated with poorer asthma control. Eur. Respir. J. 2014; 44 (5): 1353–1355. DOI: 10.1183/09031936.00082314.Ong H.X., Traini D., Loo C.Y. et al. Is the cellular uptake of respiratory aerosols delivered from different devices equivalent? Eur. J. Pharm. Biopharm. 2015; 93: 320–327. DOI: 10.1016/j.ejpb.2015.04.012.Ong H.X., Traini D., Loo C.Y. et al. Is the cellular uptake of respiratory aerosols delivered from different devices equivalent? Eur. J. Pharm. Biopharm. 2015; 93: 320–327. DOI: 10.1016/j.ejpb.2015.04.012.Leach C.L., Kuehl P.J., Chand R. et al. Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients. Ann. Allergy Asthma Immunol. 2012; 108 (3): 195–200. DOI: 10.1016/j.anai.2012.01.010.Leach C.L., Kuehl P.J., Chand R. et al. Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients. Ann. Allergy Asthma Immunol. 2012; 108 (3): 195–200. DOI: 10.1016/j.anai.2012.01.010.Price D., Thomas M., Haughney J. Et al. Real-life comparison of beclometasone dipropionate as an extrafine- or larger-particle formulation for asthma. Respir. Med. 2013; 107 (7): 987–1000. DOI: 10.1016/j.rmed.2013.03.009.Price D., Thomas M., Haughney J. Et al. Real-life comparison of beclometasone dipropionate as an extrafine- or larger-particle formulation for asthma. Respir. Med. 2013; 107 (7): 987–1000. DOI: 10.1016/j.rmed.2013.03.009.Usmani O.S. Small-airway disease in asthma: pharmacological considerations. Curr. Opin. Pulm. Med. 2015; 21 (1): 55–67. DOI: 10.1097/MCP.0000000000000115.Usmani O.S. Small-airway disease in asthma: pharmacological considerations. Curr. Opin. Pulm. Med. 2015; 21 (1): 55–67. DOI: 10.1097/MCP.0000000000000115.Hoshino M. Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma. Allergol. Int. 2010; 59 (1): 59–66. DOI: 10.2332/allergolint.09-OA-0122.Hoshino M. Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma. Allergol. Int. 2010; 59 (1): 59–66. DOI: 10.2332/allergolint.09-OA-0122.

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