clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2026-104-4-256-263clinmed-1453Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESРемоделирование дыхательных путей при бронхиальной астме: патогенетические аспекты и трудности диагностикиAirway remodeling in bronchial asthma: pathogenetic aspects and diagnostic difficultiesМинееваЕ. Е.MineevaE. E.

Минеева Елена Евгеньевна – канд. мед. наук, научный сотрудник лаборатории восстановительного лечения

Владивосток

Elena E. Mineeva – Candidate of Medical Sciences, Researcher at the Rehabilitation Treatment Laboratory

Vladivostok

elmineeva@yandex.ruhttps://orcid.org/0000-0002-2492-3198АнтонюкМ. В.AntonyukM. V.

Антонюк Марина Владимировна – д-р мед. наук, профессор, заведующая лабораторией восстановительного лечения

Владивосток

Marina V. Antonyuk – Doctor of Medical Sciences, Professor, Head of the Rehabilitation Treatment Laboratory

Vladivostok

https://orcid.org/0000-0002-6413-9840ГвозденкоТ. А.GvozdenkoT. A.

Гвозденко Татьяна Александровна – д-р мед. наук, профессор РАН, главный научный сотрудник лаборатории восстановительного лечения

Владивосток

Tatiana A. Gvozdenko – Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Chief Researcher of the Rehabilitation Treatment Laboratory

Vladivostok

Владивостокский филиал Федерального государственного бюджетного научного учреждения «Дальневосточный научный центр физиологии и патологии дыхания» — Научно-исследовательский институт медицинской климатологии и восстановительного леченияРоссияVladivostok Branch of Far Eastern Scientific Centre of Physiology and Pathology of Respiration — Institute of Medical Climatology and Rehabilitation TreatmentRussian Federation2026200620261044256263Copyright © Минеева Е.Е., Антонюк М.В., Гвозденко Т.А., 20262026Минеева Е.Е., Антонюк М.В., Гвозденко Т.А.Mineeva E.E., Antonyuk M.V., 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://www.clinmedjournal.com/jour/article/view/1453

Основной причиной тяжелого и плохо поддающегося коррекции течения бронхиальной астмы является ремоделирование дыхательных путей. Цель обзора: обобщить основные патогенетические механизмы ремоделирования дыхательных путей при бронхиальной астме и представить диагностические возможности различных методов. Результаты. Представлены основные закономерности развития и прогрессирования морфофункциональной перестройки дыхательных путей при бронхиальной астме. Показано участие иммунных клеток и роль ангиогенеза в ремоделировании дыхательных путей. Рассмотрены инструментальные и лабораторные методы диагностики. Диагностика ремоделирования дыхательных путей сталкивается с рядом трудностей. В настоящее время не существует доступных неинвазивных методов оценки ремоделирования дыхательных путей с высокой чувствительностью и специфичностью. Отсутствие информативных доступных биомаркеров ремоделирования дыхательных путей ограничивает клинические исследования этого процесса. Понимание патогенентических механизмов, своевременная диагностика и лечение ремоделирования дыхательных путей являются многообещающей стратегией предотвращения возникновения и прогрессирования астмы. Заключение. Описанные и систематизированные в обзоре патогенетические механизмы и современные методы диагностики ремоделирования дыхательных путей при бронхиальной астме призваны помочь в поиске новых терапевтических мишеней для прогнозирования и лечения заболевания.

The main reason for the severe and difficult to correct course of asthma is the remodeling of the respiratory tract. The purpose of the review is to summarize the main pathogenetic mechanisms of airway remodeling in asthma and to present the diagnostic capabilities of various methods. Results. The main patterns of development and progression of morphofunctional restructuring of the respiratory tract in asthma are presented. The involvement of immune cells and the role of angiogenesis in the remodeling of the respiratory tract are shown. Instrumental and laboratory diagnostic methods are considered. The diagnosis of airway remodeling faces a number of difficulties. Currently, there are no available non-invasive methods for assessing airway remodeling with high sensitivity and specificity. The lack of informative biomarkers available for airway remodeling limits clinical studies of this process. Understanding the pathogenetic mechanisms, timely diagnosis and treatment of airway remodeling is a promising strategy for preventing the onset and progression of asthma. Conclusion. The pathogenetic mechanisms and modern diagnostic methods of airway remodeling in asthma described and systematized in the review are intended to help in the search for new therapeutic targets for the prediction and treatment of the disease.

бронхиальная астмаремоделирование дыхательных путейпатогенетические механизмыдиагностикаasthmarespiratory tract remodelingpathogenetic mechanismsdiagnosticsReferencesБыстрицкая Е.В., Биличенко Т.Н. Заболеваемость, инвалидность и смертность от болезней органов дыхания в Российской Федерации (2015–2019). Пульмонология. 2021;31(5):551–61.Bystritskaya E.V., Bilichenko T.N. Incidence, Disability, and Mortality from Respiratory Diseases in the Russian Federation (2015–2019). Pulmonologiya. 2021;31(5):551–61. (In Russ.). DOI: 10.18093/0869-0189-2021-31-5-551-561Авдеев С.Н., Ненашева Н.М., Жуденков К.В., Петраковская В.А., Изюмова Г.В. Распространенность, заболеваемость, фенотипы и другие характеристики тяжелой бронхиальной астмы в Российской Федерации. Пульмонология. 2018;28(3):341–58.Avdeev S.N., Nenasheva N.M., Zhudenkov K.V., Petrakovskaya V.A., Izyumova G.V. Prevalence, morbidity, phenotypes and other characteristics of severe bronchial asthma in Russian Federation. Pulmonologiya. 2018;28(3):341–58. (In Russ.). DOI: 10.18093/0869-0189-2018-28-3-341-358Boulet L.P. Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Curr. Opin. Pulm. Med. 2018;24(1):56–62. DOI: 10.1097/MCP.0000000000000441Boulet L.P. Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Curr. Opin. Pulm. Med. 2018;24(1):56–62. DOI: 10.1097/MCP.0000000000000441Fehrenbach H., Wagner C., Wegmann M. Airway remodeling in asthma: what really matters. Cell and Tissue Research. 2017;367:551–569 DOI: 10.1007/s00441-016-2566-8Fehrenbach H., Wagner C., Wegmann M. Airway remodeling in asthma: what really matters. Cell and Tissue Research. 2017;367:551–569 DOI: 10.1007/s00441-016-2566-8Потапова Н.Л., Гаймоленко И.Н. Биомаркеры ремоделирования дыхательных путей при бронхиальной астме. Доктор.ру. 2020;19(11):27–31.Potapova N.L., Gaymolenko I.N. Biomarkers of airway remodeling in bronchial asthma. Doktor.ru. 2020;19(11):27–31. (In Russ.). DOI: 10.31550/1727-2378-2020-19-11-27-31Savin I.A., Zenkova M.A., Sen’kova A.V. Bronchial Asthma, Airway Remodeling and Lung Fibrosis as Successive Steps of One Process. Int. J. Mol. Sci. 2023;24(22):16042. DOI: 10.3390/ijms242216042.Savin I.A., Zenkova M.A., Sen’kova A.V. Bronchial Asthma, Airway Remodeling and Lung Fibrosis as Successive Steps of One Process. Int. J. Mol. Sci. 2023;24(22):16042. DOI: 10.3390/ijms242216042.Wieczfinska J., Pawliczak R. Anti-fibrotic effect of ciglitazone in HRV-induced airway remodelling cell model. J. Cell. Mol. Med. 2023;27:1867–1879.Wieczfinska J., Pawliczak R. Anti-fibrotic effect of ciglitazone in HRV-induced airway remodelling cell model. J. Cell. Mol. Med. 2023;27:1867–1879.Rimkunas A., Januskevicius A., Vasyle E., Palacionyte J., Janulaityte I., Miliauskas S., Malakauskas K. Blood inflammatory-like and lung resident-like eosinophils affect migration of airway smooth muscle cells and their ECM-related proliferation in asthma. Int. J. Mol. Sci. 2023;24:3469.Rimkunas A., Januskevicius A., Vasyle E., Palacionyte J., Janulaityte I., Miliauskas S., Malakauskas K. Blood inflammatory-like and lung resident-like eosinophils affect migration of airway smooth muscle cells and their ECM-related proliferation in asthma. Int. J. Mol. Sci. 2023;24:3469.Abohalaka R. Bronchial Epithelial and Airway Smooth Muscle Cell Interactions in Health and Disease. Heliyon. 2023;9:e19976Abohalaka R. Bronchial Epithelial and Airway Smooth Muscle Cell Interactions in Health and Disease. Heliyon. 2023;9:e19976Paw M., Wnuk D., Madeja Z., Michalik M. PPARδ Agonist GW501516 suppresses the TGF-β-induced profibrotic response of human bronchial fibroblasts from asthmatic patients. Int. J. Mol. Sci. 2023;24:7721.Paw M., Wnuk D., Madeja Z., Michalik M. PPARδ Agonist GW501516 suppresses the TGF-β-induced profibrotic response of human bronchial fibroblasts from asthmatic patients. Int. J. Mol. Sci. 2023;24:7721.Крапошина А.Ю., Собко Е.А., Демко И.В., Кацер А.Б., Казмерчук О.В., Абрамов Ю.И. Современные представления о бронхиальной астме с фиксированной обструкцией. Терапевтический архив. 2021;93(3):337–342.Kraposhina A.Yu., Sobko E.A., Demko I.V., Kacer A.B., Kazmerchuk O.V., Abramov Yu.I. Modern concepts of bronchial asthma with fixed obstruction. Terapevticheskii Arkhiv. 2021;93(3):337–342. (In Russ.). DOI: 10.26442/00403660.2021.03.200661Haddad A., Gaudet M., Plesa M. et al. Neutrophils from severe asthmatic patients induce epithelial to mesenchymal transition in healthy bronchial epithelial cells. Respir. Res. 2019;20(1):234. DOI: 10.1186/s12931-019-1186-8Haddad A., Gaudet M., Plesa M. et al. Neutrophils from severe asthmatic patients induce epithelial to mesenchymal transition in healthy bronchial epithelial cells. Respir. Res. 2019;20(1):234. DOI: 10.1186/s12931-019-1186-8Кароли Н.А., Сажнова С.И. Бронхиальная астма с фиксированной обструкцией дыхательных путей: проблема и способы ее решения. Терапия. 2024;9:118–129.Karoli N.A., Sazhnova S.I. Bronchial asthma with fixed airway obstruction: the problem and ways to solve it. Terapiya. 2024;9:118–129. (In Russ.). DOI: 10.18565/therapy.2024.9.118-129Hough K.P., Curtiss M.L., Blain T.J., Liu R.-M., Trevor J., Deshane J.S., Thannickal V.J. Airway Remodeling in Asthma. Front. Med. 2020;7:191. doi: 10.3389/fmed.2020.00191Hough K.P., Curtiss M.L., Blain T.J., Liu R.-M., Trevor J., Deshane J.S., Thannickal V.J. Airway Remodeling in Asthma. Front. Med. 2020;7:191. doi: 10.3389/fmed.2020.00191Tatler A.L. Asthmatic airway remodeling: long overlooked but too important to ignore. Ann. Transl. Med. 2023;11(2):29. DOI: 10.21037/atm-22-5733Tatler A.L. Asthmatic airway remodeling: long overlooked but too important to ignore. Ann. Transl. Med. 2023;11(2):29. DOI: 10.21037/atm-22-5733Tai A., Tran H., Roberts M., Clarke N., Wilson J., Robertson C.F. The association between childhood asthma and adult chronic obstructive pulmonary disease. Thorax. 2014;69(9):805–810. DOI: 10.1136/thoraxjnl-2013-204815Tai A., Tran H., Roberts M., Clarke N., Wilson J., Robertson C.F. The association between childhood asthma and adult chronic obstructive pulmonary disease. Thorax. 2014;69(9):805–810. DOI: 10.1136/thoraxjnl-2013-204815Joubert P., Hamid Q. Role of airway smooth muscle in airway remodeling. J. Allergy Clin. Immunol. 2005;116(3):713–6. DOI: 10.1016/j.jaci.2005.05.042Joubert P., Hamid Q. Role of airway smooth muscle in airway remodeling. J. Allergy Clin. Immunol. 2005;116(3):713–6. DOI: 10.1016/j.jaci.2005.05.042Wilson S.J., Rigden H.M., Ward J.A., Laviolette M., Jarjour NN., Djukanović R. The relationship between eosinophilia and airway remodelling in mild asthma. Clin. Exp. Allergy. 2013;43(12):1342–50. DOI: 10.1111/cea.12156Wilson S.J., Rigden H.M., Ward J.A., Laviolette M., Jarjour NN., Djukanović R. The relationship between eosinophilia and airway remodelling in mild asthma. Clin. Exp. Allergy. 2013;43(12):1342–50. DOI: 10.1111/cea.12156Bourdin A., Neveu D., Vachier I., Paganin F., Godard P., Chanez P. Specificity of basement membrane thickening in severe asthma. J. Allergy Clin. Immunol. 2007;119(6):1367–74. DOI: 10.1016/j.jaci.2007.01.055Bourdin A., Neveu D., Vachier I., Paganin F., Godard P., Chanez P. Specificity of basement membrane thickening in severe asthma. J. Allergy Clin. Immunol. 2007;119(6):1367–74. DOI: 10.1016/j.jaci.2007.01.055Saglani S., Payne DN., Zhu J., Wang Z., Nicholson AG., Bush A., Jeffery PK. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am. J. Respir. Crit. Care Med. 2007;176(9):858–64. DOI: 10.1164/rccm.200702-212OCSaglani S., Payne DN., Zhu J., Wang Z., Nicholson AG., Bush A., Jeffery PK. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am. J. Respir. Crit. Care Med. 2007;176(9):858–64. DOI: 10.1164/rccm.200702-212OCPayne D.N., Rogers A.V., Adelroth E., Bandi V., Guntupalli K.K., Bush A., Jeffery P.K. Early thickening of the reticular basement membrane in children with difficult asthma. Am. J. Respir. Crit. Care Med. 2003;167(1):78–82. DOI: 10.1164/rccm.200205-414OCPayne D.N., Rogers A.V., Adelroth E., Bandi V., Guntupalli K.K., Bush A., Jeffery P.K. Early thickening of the reticular basement membrane in children with difficult asthma. Am. J. Respir. Crit. Care Med. 2003;167(1):78–82. DOI: 10.1164/rccm.200205-414OCBossley C.J., Fleming L., Gupta A., Regamey N., Frith J., Oates T., Saglani S. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. Journal of Allergy and Clinical Immunology. 2012;129(4):974–982.e13. DOI:10.1016/j.jaci.2012.01.059Bossley C.J., Fleming L., Gupta A., Regamey N., Frith J., Oates T., Saglani S. Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. Journal of Allergy and Clinical Immunology. 2012;129(4):974–982.e13. DOI:10.1016/j.jaci.2012.01.059Miranda C., Busacker A., Balzar S., Trudeau J., & Wenzel S.E. Distinguishing severe asthma phenotypes. Role of age at onset and eosinophilic inflammation. Journal of Allergy and Clinical Immunology. 2004;113(1):101–108. DOI:10.1016/j.jaci.2003.10.041Miranda C., Busacker A., Balzar S., Trudeau J., & Wenzel S.E. Distinguishing severe asthma phenotypes. Role of age at onset and eosinophilic infl ammation. Journal of Allergy and Clinical Immunology. 2004;113(1):101–108. DOI:10.1016/j.jaci.2003.10.041Grainge C.L., Lau L.C.K., Ward J.A., Dulay V., LahiffG., Wilson S., Howarth P.H. Effect of bronchoconstriction on airway remodeling in asthma. New England Journal of Medicine. 2011;364(21):2006–2015. DOI:10.1056/nejmoa1014350Grainge C.L., Lau L.C.K., Ward J.A., Dulay V., Lahiff G., Wilson S., Howarth P.H. Effect of bronchoconstriction on airway remodeling in asthma. New England Journal of Medicine. 2011;364(21):2006–2015. DOI:10.1056/nejmoa1014350Heijink I.H., Nawijn M.C., Hackett T.L. Airway epithelial barrier function regulates the pathogenesis of allergic asthma. Clin. Exp. Allergy. 2014;44:620–30.Heijink I.H., Nawijn M.C., Hackett T.L. Airway epithelial barrier function regulates the pathogenesis of allergic asthma. Clin. Exp. Allergy. 2014;44:620–30.White S.R. Apoptosis and the airway epithelium. J. Allergy (Cairo). 2011;2011:948406. DOI: 10.1155/2011/948406White S.R. Apoptosis and the airway epithelium. J. Allergy (Cairo). 2011;2011:948406. DOI: 10.1155/2011/948406Torrego A., Hew M., Oates T., Sukkar M., Fan Chung K. Expression and activation of TGF-beta isoforms in acute allergen-induced remodelling in asthma. Thorax. 2007;62(4):307–13. DOI: 10.1136/thx.2006.063487Torrego A., Hew M., Oates T., Sukkar M., Fan Chung K. Expression and activation of TGF-beta isoforms in acute allergen-induced remodelling in asthma. Thorax. 2007;62(4):307–13. DOI: 10.1136/thx.2006.063487Zhang S., Smartt H., Holgate S.T., Roche W.R. Growth factors secreted by bronchial epithelial cells control myofibroblast proliferation: an in vitro co-culture model of airway remodeling in asthma. Lab. Invest. 1999;79(4):395–405.Zhang S., Smartt H., Holgate S.T., Roche W.R. Growth factors secreted by bronchial epithelial cells control myofi broblast proliferation: an in vitro co-culture model of airway remodeling in asthma. Lab. Invest. 1999;79(4):395–405.Hough K.P., Curtiss M.L., Blain T.J., Liu R.M., Trevor J., Deshane J.S., Thannickal V.J. Airway Remodeling in Asthma. Front Med. (Lausanne). 2020;7:191. DOI: 10.3389/fmed.2020.00191Hough K.P., Curtiss M.L., Blain T.J., Liu R.M., Trevor J., Deshane J.S., Thannickal V.J. Airway Remodeling in Asthma. Front Med. (Lausanne). 2020;7:191. DOI: 10.3389/fmed.2020.00191Hsieh A., Assadinia N., Hackett T.L. Airway remodeling heterogeneity in asthma and its relationship to disease outcomes. Front. Physiol. 2023;14:1113100.Hsieh A., Assadinia N., Hackett T.L. Airway remodeling heterogeneity in asthma and its relationship to disease outcomes. Front. Physiol. 2023;14:1113100.Joglekar M.M., Nizamoglu M., Fan Y.W., Nemani S.S.P., Weckmann M., Pouwels S.D., Heijink I.H., Melgert B.N., Pillay J., Burgess J.K. Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases. Front. Pharmacol. 2022;13:995051.Joglekar M.M., Nizamoglu M., Fan Y.W., Nemani S.S.P., Weckmann M., Pouwels S.D., Heijink I.H., Melgert B.N., Pillay J., Burgess J.K. Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases. Front. Pharmacol. 2022;13:995051.Mostaço-Guidolin L.B.B., Osei E.T.T., Ullah J., Hajimohammadi S., Fouadi M., Li X., Li V., Shaheen F., Yang C.X.X., Chu F. et al. Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma. Am. J. Respir. Crit. Care Med. 2019;200:431–443.Mostaço-Guidolin L.B.B., Osei E.T.T., Ullah J., Hajimohammadi S., Fouadi M., Li X., Li V., Shaheen F., Yang C.X.X., Chu F. et al. Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma. Am. J. Respir. Crit. Care Med. 2019;200:431–443.Chakir J., Shannon J., Molet S., Fukakusa M., Elias J., Laviolette M., Boulet L.P., Hamid Q. Airway remodeling-associated mediators in moderate to severe asthma: Effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. J. Allergy Clin. Immunol. 2003;111:1293–1298.Chakir J., Shannon J., Molet S., Fukakusa M., Elias J., Laviolette M., Boulet L.P., Hamid Q. Airway remodeling-associated mediators in moderate to severe asthma: Eff ect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. J. Allergy Clin. Immunol. 2003;111:1293–1298.Al-Muhsen S., Johnson J.R., Hamid Q. Remodeling in asthma. J. Allergy Clin. Immunol. 2011;128:451–462.Al-Muhsen S., Johnson J.R., Hamid Q. Remodeling in asthma. J. Allergy Clin. Immunol. 2011;128:451–462.Firszt R., Francisco D., Church T.D., Thomas J.M., Ingram J.L., Kraft M. Interleukin-13 induces collagen type-1 expression through matrix metallo-proteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma. Eur. Respir. J. 2014;43:464.Firszt R., Francisco D., Church T.D., Thomas J.M., Ingram J.L., Kraft M. Interleukin-13 induces collagen type-1 expression through matrix metallo-proteinase-2 and transforming growth factor-β1 in airway fi broblasts in asthma. Eur. Respir. J. 2014;43:464.Thiam F., Yazeedi S.A., Feng K., Phogat S., Demirsoy E., Brussow J., Abokor F.A., Osei E.T. Understanding fibroblast-immune cell interactions via co-culture models and their role in asthma pathogenesis. Front. Immunol. 2023;14:1128023.Thiam F., Yazeedi S.A., Feng K., Phogat S., Demirsoy E., Brussow J., Abokor F.A., Osei E.T. Understanding fi broblast-immune cell interactions via co-culture models and their role in asthma pathogenesis. Front. Immunol. 2023;14:1128023.Lam M., Royce S.G., Samuel C.S., Bourke J.E. Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases. Pharmacol. Ther. 2018;187:61–70.Lam M., Royce S.G., Samuel C.S., Bourke J.E. Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases. Pharmacol. Ther. 2018;187:61–70.Singla A., Reuter S., Taube C., Peters M., Peters K. The molecular mechanisms of remodeling in asthma, COPD and IPF with a special emphasis on the complex role of Wnt5A. Inflamm. Res. 2023;72:577.Singla A., Reuter S., Taube C., Peters M., Peters K. The molecular mechanisms of remodeling in asthma, COPD and IPF with a special emphasis on the complex role of Wnt5A. Inflamm. Res. 2023;72:577.Huang Y., Qiu C. Research advances in airway remodeling in asthma: a narrative review. Ann. Transl. Med. 2022;10(18):1023. DOI: 10.21037/atm-22-2835Huang Y., Qiu C. Research advances in airway remodeling in asthma: a narrative review. Ann. Transl. Med. 2022;10(18):1023. DOI: 10.21037/atm-22-2835Wang X., Xu C., Ji J. et al. IL-4/IL-13 upregulates Sonic hedgehog expression to induce allergic airway epithelial remodeling. Am. J. Physiol. Lung Cell Mol. Physiol. 2020;318:L888–99.Wang X., Xu C., Ji J. et al. IL-4/IL-13 upregulates Sonic hedgehog expression to induce allergic airway epithelial remodeling. Am. J. Physiol. Lung Cell Mol. Physiol. 2020;318:L888–99.Pan YL., Zhu YT., Li M.X. Research progress of airway remodeling in bronchial asthma. Int. J. Respir. 2014;23:26–27.Pan YL., Zhu YT., Li M.X. Research progress of airway remodeling in bronchial asthma. Int. J. Respir. 2014;23:26–27.Pałgan K., Bartuzi Z. Angiogenesis in bronchial asthma. Int. J. Immunopathol. Pharmacol. 2015;28:415–20.Pałgan K., Bartuzi Z. Angiogenesis in bronchial asthma. Int. J. Immunopathol. Pharmacol. 2015;28:415–20.Guida G., Riccio A.M. Immune induction of airway remodeling. Semin. Immunol. 2019;46:101346. DOI: 10.1016/j.smim.2019.101346Guida G., Riccio A.M. Immune induction of airway remodeling. Semin. Immunol. 2019;46:101346. DOI: 10.1016/j.smim.2019.101346Choy D.F., Hart K.M., Borthwick L.A., Shikotra A., Nagarkar D.R., Siddiqui S., Jia G., Ohri C.M., Doran E., Vannella K.M., Butler C.A., Hargadon B., Sciurba J.C., Gieseck R.L., Thompson R.W., White S., Abbas A.R., Jackman J., Wu L.C., Egen J.G., Heaney L.G., Ramalingam T.R., Arron J.R., Wynn T.A., Bradding P. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci. Transl. Med. 2015;7(301):301ra129. DOI: 10.1126/scitranslmed.aab3142Choy D.F., Hart K.M., Borthwick L.A., Shikotra A., Nagarkar D.R., Siddiqui S., Jia G., Ohri C.M., Doran E., Vannella K.M., Butler C.A., Hargadon B., Sciurba J.C., Gieseck R.L., Thompson R.W., White S., Abbas A.R., Jackman J., Wu L.C., Egen J.G., Heaney L.G., Ramalingam T.R., Arron J.R., Wynn T.A., Bradding P. TH2 and TH17 infl ammatory pathways are reciprocally regulated in asthma. Sci. Transl. Med. 2015;7(301):301ra129. DOI: 10.1126/scitranslmed.aab3142Oeser K., Schwartz C., Voehringer D. Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths. Mucosal Immunol. 2015;8(3):672–82. DOI: 10.1038/mi.2014.101Oeser K., Schwartz C., Voehringer D. Conditional IL-4/IL-13-defi - cient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths. Mucosal Immunol. 2015;8(3):672–82. DOI: 10.1038/mi.2014.101Balhara J., Gounni AS. The alveolar macrophages in asthma: a double-edged sword. Mucosal Immunol. 2012;5(6):605–9. DOI: 10.1038/mi.2012.74Balhara J., Gounni AS. The alveolar macrophages in asthma: a double-edged sword. Mucosal Immunol. 2012;5(6):605–9. DOI: 10.1038/mi.2012.74Januskevicius A., Vaitkiene S., Gosens R., Janulaityte I., Hoppenot D., Sakalauskas R., Malakauskas K. Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma. BMC Pulm. Med. 2016;16(1):94. DOI: 10.1186/s12890-016-0254-9Januskevicius A., Vaitkiene S., Gosens R., Janulaityte I., Hoppenot D., Sakalauskas R., Malakauskas K. Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma. BMC Pulm. Med. 2016;16(1):94. DOI: 10.1186/s12890-016-0254-9Kobayashi T., Kim H., Liu X., Sugiura H., Kohyama T., Fang Q., Wen F.Q., Abe S., Wang X., Atkinson J.J., Shipley J.M., Senior R.M., Rennard S.I. Matrix metalloproteinase-9 activates TGF-β and stimulatesfibroblast contraction of collagen gels. Am. J. Physiol. Lung Cell Mol. Physiol. 2014;306(11):L1006–15. DOI: 10.1152/ajplung.00015.2014Kobayashi T., Kim H., Liu X., Sugiura H., Kohyama T., Fang Q., Wen F.Q., Abe S., Wang X., Atkinson J.J., Shipley J.M., Senior R.M., Rennard S.I. Matrix metalloproteinase-9 activates TGF-β and stimulatesfi broblast contraction of collagen gels. Am. J. Physiol. Lung Cell Mol. Physiol. 2014;306(11):L1006–15. DOI: 10.1152/ajplung.00015.2014Cairns J.A., Walls A.F. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J. Immunol. 1996;156(1):275–83.Cairns J.A., Walls A.F. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J. Immunol. 1996;156(1):275–83.Compton S.J., Cairns J.A., Holgate S.T., Walls A.F. The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: tryptase induces expression of mRNA for IL-1 beta and IL-8 and stimulates the selective release of IL-8 from human umbilical vein endothelial cells. J. Immunol. 1998;161(4):1939–46.Compton S.J., Cairns J.A., Holgate S.T., Walls A.F. The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: tryptase induces expression of mRNA for IL-1 beta and IL-8 and stimulates the selective release of IL-8 from human umbilical vein endothelial cells. J. Immunol. 1998;161(4):1939–46.Ventura I., Vega A., Chacón P., Chamorro C., Aroca R., Gómez E., Bellido V., Puente Y., Blanca M., Monteseirín J. Neutrophils from allergic asthmatic patients produce and release metalloproteinase-9 upon direct exposure to allergens. Allergy. 2014;69(7):898–905. DOI: 10.1111/all.12414Ventura I., Vega A., Chacón P., Chamorro C., Aroca R., Gómez E., Bellido V., Puente Y., Blanca M., Monteseirín J. Neutrophils from allergic asthmatic patients produce and release metalloproteinase-9 upon direct exposure to allergens. Allergy. 2014;69(7):898–905. DOI: 10.1111/all.12414Huang G., Wang Y., Chi H. Regulation of TH17 cell differentiation by innate immune signals. Cell Mol. Immunol. 2012;9(4):287–95. DOI: 10.1038/cmi.2012.10Huang G., Wang Y., Chi H. Regulation of TH17 cell diff erentiation by innate immune signals. Cell Mol. Immunol. 2012;9(4):287–95. DOI: 10.1038/cmi.2012.10Leyva-Castillo J.M., Yoon J., Geha R.S. IL-22 promotes allergic airway inflammation in epicutaneously sensitized mice. J. Allergy Clin. Immunol. 2019;143(2):619–630.e7. DOI: 10.1016/j.jaci.2018.05.032Leyva-Castillo J.M., Yoon J., Geha R.S. IL-22 promotes allergic airway inflammation in epicutaneously sensitized mice. J. Allergy Clin. Immunol. 2019;143(2):619–630.e7. DOI: 10.1016/j.jaci.2018.05.032Khan M.A., Assiri A.M., Broering D.C. Complement mediators: key regulators of airway tissue remodeling in asthma. J. Transl. Med. 2015;13:272. DOI: 10.1186/s12967-015-0565-2Khan M.A., Assiri A.M., Broering D.C. Complement mediators: key regulators of airway tissue remodeling in asthma. J. Transl. Med. 2015;13:272. DOI: 10.1186/s12967-015-0565-2Broekema M., Timens W., Vonk J.M., Volbeda F., Lodewijk M.E., Hylkema M.N., Ten Hacken N.H., Postma D.S. Persisting remodeling and less airway wall eosinophil activation in complete remission of asthma. Am. J. Respir. Crit. Care Med. 2011;183(3):310–6. DOI: 10.1164/rccm.201003-0494OC.Broekema M., Timens W., Vonk J.M., Volbeda F., Lodewijk M.E., Hylkema M.N., Ten Hacken N.H., Postma D.S. Persisting remodeling and less airway wall eosinophil activation in complete remission of asthma. Am. J. Respir. Crit. Care Med. 2011;183(3):310–6. DOI: 10.1164/rccm.201003-0494OC.Paw M., Wnuk D., Madeja Z., Michalik M. PPARδ Agonist GW501516 Suppresses the TGF-β-Induced profibrotic response of human bronchial fibroblasts from asthmatic patients. Int. J. Mol. Sci. 2023;24(9):7721. DOI: 10.3390/ijms24097721Paw M., Wnuk D., Madeja Z., Michalik M. PPARδ Agonist GW501516 Suppresses the TGF-β-Induced profi brotic response of human bronchial fi broblasts from asthmatic patients. Int. J. Mol. Sci. 2023;24(9):7721. DOI: 10.3390/ijms24097721Stern J., Pier J., Litonjua A.A. Asthma epidemiology and risk factors. Semin. Immunopathol. 2020;42(1):5–15. DOI: 10.1007/s00281-020-00785-1Stern J., Pier J., Litonjua A.A. Asthma epidemiology and risk factors. Semin. Immunopathol. 2020;42(1):5–15. DOI: 10.1007/s00281-020-00785-1Bergeron C., Tulic M.K., Hamid Q. Tools used to measure airway remodelling in research. Eur. Respir. J. 2007;29(3):596–604. DOI: 10.1183/09031936.00019906Bergeron C., Tulic M.K., Hamid Q. Tools used to measure airway remodelling in research. Eur. Respir. J. 2007;29(3):596–604. DOI: 10.1183/09031936.00019906James A.L., Elliot J. G., Jones R.L., Carroll M. L., Mauad T., Bai T.R., Green F.H. Airway smooth muscle hypertrophy and hyperplasia in asthma. American Journal of Respiratory and Critical Care Medicine. 2012;185(10):1058–1064. DOI:10.1164/rccm.201110-1849ocJames A.L., Elliot J. G., Jones R.L., Carroll M. L., Mauad T., Bai T.R., Green F.H. Airway smooth muscle hypertrophy and hyperplasia in asthma. American Journal of Respiratory and Critical Care Medicine. 2012;185(10):1058–1064. DOI:10.1164/rccm.201110-1849ocJeffery P., Holgate S., Wenzel S. Endobronchial biopsy workshop. Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment. Am. J. Respir. Crit. Care Med. 2003;168(6Pt2):S1–17. DOI: 10.1164/rccm.200202-150WSJeffery P., Holgate S., Wenzel S. Endobronchial biopsy workshop. Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment. Am. J. Respir. Crit. Care Med. 2003;168(6Pt2):S1–17. DOI: 10.1164/rccm.200202-150WSStewart N.J., Smith L.J., Chan H.F., Eaden J.A., Rajaram S., Swift A.J. et al. Lung MRI with hyperpolarised gases: Current future clinical perspectives. Br. J. Radiol. 2021;94(63):20210207. DOI: 10.1259/BJR.20210207Stewart N.J., Smith L.J., Chan H.F., Eaden J.A., Rajaram S., Swift A.J. et al. Lung MRI with hyperpolarised gases: Current future clinical perspectives. Br. J. Radiol. 2021;94(63):20210207. DOI: 10.1259/BJR.20210207Kasahara K., Shiba K., Ozawa T., Okuda K., Adachi M. Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma. Thorax. 2002;57(3):242–6. DOI: 10.1136/thorax.57.3.242Kasahara K., Shiba K., Ozawa T., Okuda K., Adachi M. Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma. Thorax. 2002;57(3):242–6. DOI: 10.1136/thorax.57.3.242Goorsenberg A., Kalverda KA., Annema J., Bonta P. Advances in Optical Coherence Tomography and Confocal Laser Endomicroscopy in Pulmonary Diseases. Respiration. 2020;99(3):190–205. DOI: 10.1159/000503261.Goorsenberg A., Kalverda KA., Annema J., Bonta P. Advances in Optical Coherence Tomography and Confocal Laser Endomicroscopy in Pulmonary Diseases. Respiration. 2020;99(3):190–205. DOI: 10.1159/000503261.Kramer T., Wijsman P.C., Kalverda K.A., Bonta P.I., Annema J.T. Advances in bronchoscopic optical coherence tomography and confocal laser endomicroscopy in pulmonary diseases. Curr. Opin. Pulm. Med. 2023;29(1):11–20. DOI: 10.1097/MCP.0000000000000929Kramer T., Wijsman P.C., Kalverda K.A., Bonta P.I., Annema J.T. Advances in bronchoscopic optical coherence tomography and confocal laser endomicroscopy in pulmonary diseases. Curr. Opin. Pulm. Med. 2023;29(1):11–20. DOI: 10.1097/MCP.0000000000000929Lee J.H., Haselkorn T., Borish L., Rasouliyan L., Chipps B.E., Wenzel S.E. Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma. Chest. 2007;132(6):1882–1889. DOI: 10.1378/chest.07-0713Lee J.H., Haselkorn T., Borish L., Rasouliyan L., Chipps B.E., Wenzel S.E. Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma. Chest. 2007;132(6):1882–1889. DOI: 10.1378/chest.07-0713Bonato M., Tiné M., Bazzan E. et al. Early airway pathological changes in children: new insights into the natural history of wheezing. J. Clin. Med. 2019;8(8):1180. DOI: 10.3390/jcm8081180Bonato M., Tiné M., Bazzan E. et al. Early airway pathological changes in children: new insights into the natural history of wheezing. J. Clin. Med. 2019;8(8):1180. DOI: 10.3390/jcm8081180Feroldi F., Willemse J., Davidoiu V. et al. In vivo multifunctional optical coherence tomography at the periphery of the lungs. Biomed. Opt. Express. 2019;10(6):3070–91. DOI: 10.1364/BOE.10.003070Feroldi F., Willemse J., Davidoiu V. et al. In vivo multifunctional optical coherence tomography at the periphery of the lungs. Biomed. Opt. Express. 2019;10(6):3070–91. DOI: 10.1364/BOE.10.003070Ненашева Н.М. Значение биомаркеров в диагностике и терапии бронхиальной астмы. Практическая пульмонология. 2017;4:3–9.Nenasheva N.M. The importance of biomarkers in the diagnosis and treatment of bronchial asthma. Prakticheskaya pul’monologiya. 2017;4:3–9. (In Russ).Schleich F., Demarche S., Louis R. Biomarkers in the management of difficult asthma. Curr. Top. Med. Chem. 2016;16(14):1561–73. DOI: 10.2174/1568026616666151015093406Schleich F., Demarche S., Louis R. Biomarkers in the management of difficult asthma. Curr. Top. Med. Chem. 2016;16(14):1561–73. DOI: 10.2174/1568026616666151015093406

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