mvjrМедицинский вестник Юга РоссииMedical Herald of the South of Russia2219-80752618-7876The Rostov State Medical University10.21886/2219-8075-2026-17-3-43-50mvjr-2222Research ArticleВНУТРЕННИЕ БОЛЕЗНИINTERNAL DISEASESРоль нетоза в патогенезе заболеваний органов дыханияThe role of netosis in the pathogenesis of respiratory diseaseshttps://orcid.org/0000-0002-9107-7964ГорблянскийЮ. Ю.GorblyanskyYu. Yu.

Горблянский Юрий Юрьевич, д. м. н., проф., заведующий кафедрой профпатологии и пульмонологии

Ростов-на-Дону

Yury Y. Gorblyansky, Dr. Sci. (Med.), Professor, Head of the Department of Occupational Pathology and Pulmonology

Rostov-on-Don

gorblyansky.profpatolog@yandex.ruhttps://orcid.org/0009-0003-2144-9544АвакянцФ. А.AvakyantsF. A.

Авакянц Фаина Александровна, врач-пульмонолог, заведующий пульмонологическим отделением

Ростов-на-Дону

Faina A. Avakyants, Pulmonologist, Head of the Pulmonology Department

Rostov-on-Don

2757961@gmail.comhttps://orcid.org/0009-0006-8588-466XШапкинаМ. А.ShapkinaM. A.

Шапкина Мария Александровна, лаборант кафедры профпатологии и пульмонологии

Ростов-на-Дону

Mariia A. Shapkina, Laboratory Assistant, Department of Occupational Pathology and Pulmonology

Rostov-on-Don

shapkina.med@gmail.comhttps://orcid.org/0000-0002-1047-6278ЛукашевичМ. Г.LukashevichM. G.

Лукашевич Марина Георгиевна, к. м. н., доц., заведующий кафедрой детских болезней №3

Ростов-на-Дону

Marina G. Lukashevich, Cand. Sci. (Med.), Associate Professor, Head of the Department of Pediatric Diseases No.3

Rostov-on-Don

Mlukashevi4@yandex.ruРостовский государственный медицинский университетРоссияRostov State Medical UniversityRussian FederationОбластная клиническая больница №2РоссияRegional Clinical Hospital №2Russian Federation2026220920261734350Copyright © Горблянский Ю.Ю., Авакянц Ф.А., Шапкина М.А., Лукашевич М.Г., 20262026Горблянский Ю.Ю., Авакянц Ф.А., Шапкина М.А., Лукашевич М.Г.Gorblyansky Y.Y., Avakyants F.A., Shapkina M.A., Lukashevich M.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medicalherald.ru/jour/article/view/2222

Нейтрофильные внеклеточные ловушки (НВЛ) — сетчатые структуры из ДНК и антимикробных белков, высвобождаемые активированными нейтрофилами в процессе нетоза. Целью обзора является систематический анализ роли нетоза в патогенезе респираторных заболеваний и оценка потенциальных терапевтических стратегий. Рассмотрены механизмы нетоза (литический и витальный нетоз), двойственная функция НВЛ — от антимикробной защиты до медиатора тканевого повреждения. Особое внимание уделено нетозу при COVID-19, бронхиальной астме (в особенности нейтрофильные фенотипы), хронической обструктивной болезни легких и муковисцидозе. Обсуждаются подходы к модуляции и ингибированию нетоза: ДНКаза I, ингибиторы протеаз, ингибиторы фосфодиэстеразы 4 типа, дипептидилпептидазы-1, биологическая терапия. Анализ 55 публикаций (PubMed, e-Library) подтверждает, что нетоз — ключевое патогенетическое звено, а не только биомаркер. Это делает НВЛ перспективной мишенью для лечения, несмотря на гетерогенность заболеваний и сложность регуляции нетоза. Проанализированы результаты исследований по обнаружению, визуализации нейтрофильных внеклеточных ловушек, механизмам ловушкообразования в патогенезе заболеваний органов дыхания, моделированию на лабораторных животных патологических состояний с последующим применением таргетной терапии в отношении компонентов НВЛ.

Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA and antimicrobial proteins released by activated neutrophils during NETosis. This review aims to systematically analyze the role of NETosis in the pathogenesis of respiratory diseases and evaluate potential therapeutic strategies. We discuss the mechanisms of NETosis (lytic and vital), the dual function of NETs — ranging from antimicrobial defense to mediating tissue damage — as well as current detection. Particular emphasis is placed on the role of NETosis in COVID-19, bronchial asthma (specifically neutrophilic phenotypes), chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Therapeutic approaches targeting the modulation and inhibition of NETosis are discussed, including DNase I, protease inhibitors, phosphodiesterase-4 (PDE4) inhibitors, dipeptidyl peptidase-1 (DPP-1) inhibitors, and biological therapies. Analysis of 55 publications retrieved from PubMed and eLibrary confirms that NETosis is a central pathogenetic mechanism rather than solely a biomarker. This positions NETs as a promising therapeutic target, despite disease heterogeneity and the complexity of NETosis regulation. The review also summarizes research findings on NET detection and visualization, mechanisms of NET formation in respiratory pathology, animal modeling of disease states, and the subsequent application of targeted therapies directed against NET components.

обзорнетознейтрофильные внеклеточные ловушки (НВЛ)нейтрофилыреспираторные заболеваниятаргетная терапияreviewNETosisneutrophil extracellular traps (NETs)neutrophilsrespiratory diseasestargeted therapyReferencesДолгушин И.И., Андреева Ю.С., Савочкина А.Ю., Рыжкова А.И., Маркова В.А., Васильева Н.А. Нейтрофильные ловушки: методы определения, биологическая роль. Медицинская наука и образование Урала. 2009;10(3):10-11.Dolgushin I.I., Andreeva J.S., Savochkina A.J., Ryzhkova A.I., Markova V.A., Vasileva N.A. Neutrophils traps: definition methods, a biological role. Medical science and education of Ural. 2009;10(3):10-11. (In Russ.) eLIBRARY ID: 22796194 EDN: TEWBUXДолгушин И.И., Шишкова Ю.С., Савочкина А.Ю. Методы обнаружения нейтрофильных ловушек. Аллергология и иммунология. 2009;10(4):458-462.Dolgushin I.I., Shishkova Yu.S., Savochkina A.Yu. Detection methods of neutrophil extracellular traps. Allergologiya i immunologiya. 2009;10(4):458-462. (In Russ.) eLIBRARY ID: 13022259 EDN: KYZCZDНикольский А.А., Шиловский И.П., Воробьева Н.В., Юмашев К.В., Пасихов Г.Б., и др. Влияние интерлейкина-37 на процесс НЕТоза у нейтрофилов человека in vitro. Иммунология. 2024;45(6):701-709.Nikolskii A.A., Shilovskiy I.P., Vorobjeva N.V., Yumashev K.V., Pasikhov G.B., et al. The effect of interleukin-37 on the process of NETosis in human neutrophils in vitro. Immunologiya. 2024;45(6):701–709. (In Russ.) https://doi.org/10.33029/1816-2134-2024-45-6-701-709Плескова С.Н., Горшкова Е.Н., Боряков А.В., Крюков Р.Н. Морфологические особенности быстрого и классического нетоза. Цитология. 2019;61(9):704-712.Pleskova S.N., Gorshkova E.N., Boryakov A.V., Kriukova R.N. Morphological features of quick and classical netosis. Tsitologiya. 2019;61(9):704-712. (In Russ.). https://doi.org/10.1134/S0041377119090098King PT, Dousha L. Neutrophil Extracellular Traps and Respiratory Disease. J Clin Med. 2024;13(8):2390. https://doi.org/10.3390/jcm13082390King PT, Dousha L. Neutrophil Extracellular Traps and Respiratory Disease. J Clin Med. 2024;13(8):2390. https://doi.org/10.3390/jcm13082390Воробьева Н.В. Участие нерецепторных тирозинкиназ Src-семейства в образовании нейтрофильных внеклеточных ловушек. Вестник Московского университета. Серия 16. Биология. 2023;78(1):11-16.Vorobjeva N.V. Participation of non-receptor Src family tyrosine kinases in the formation of neutrophil extracellular traps. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2023;78(1):11-16. (In Russ.) https://doi.org/10.55959/MSU0137-0952-16-78-1-2Xuan N, Zhao J, Kang Z, Cui W, Tian BP. Neutrophil extracellular traps and their implications in airway inflammatory diseases. Front Med (Lausanne). 2024;10:1331000. https://doi.org/10.3389/fmed.2023.1331000Xuan N, Zhao J, Kang Z, Cui W, Tian BP. Neutrophil extracellular traps and their implications in airway inflammatory diseases. Front Med (Lausanne). 2024;10:1331000. https://doi.org/10.3389/fmed.2023.1331000Poto R, Shamji M, Marone G, Durham SR, Scadding GW, Varricchi G. Neutrophil Extracellular Traps in Asthma: Friends or Foes? Cells. 2022;11(21):3521. https://doi.org/10.3390/cells11213521Poto R, Shamji M, Marone G, Durham SR, Scadding GW, Varricchi G. Neutrophil Extracellular Traps in Asthma: Friends or Foes? Cells. 2022;11(21):3521. https://doi.org/10.3390/cells11213521Андрюков Б.Г., Сомова Л.М., Дробот Е.И., Матосова Е.В. Защитные стратегии нейтрофильных гранулоцитов от патогенных бактерий. Здоровье. Медицинская экология. Наука. 2017;(1):4-18.Andryukov B.G., Somova L.M., Drobot E.I., Matosova E.V. Defensive strategy of neutrophilic granulocytes against pathogenic bacteria. Health. Medical ecology. Science. 2017;(1):4-18. (In Russ.) https://doi.org/10.5281/zenodo.345606Шустова С.А., Мирошкина Т.А. Защитные механизмы легких. Российский медико-биологический вестник имени академика И.П. Павлова. 2020;28(4):567-577.Shustova S.A., Miroshkina T.A. Protective mechanisms of lungs. I.P. Pavlov Russian Medical Biological Herald. 2020;28(4):567-577. (In Russ.) https://doi.org/10.23888/PAVLOVJ2020284567-577Коротина О.Л., Генералов И.И. Нейтрофильные внеклеточные ловушки: механизмы образования, функции. Иммунопатология, аллергология, инфектология. 2012;(4):23-32.Korotina O.L., Generalov I.I. Neutrophil extracellular traps: mechanisms of formation, functions. Immunopathology, allergology, infectology. 2012;(4):23-32. (In Russ.) eLIBRARY ID: 21179382 EDN: RVMEMDKeir HR, Richardson H, Fillmore C, Shoemark A, Lazaar AL, et al. CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin. ERJ Open Res. 2020;6(4):00583-2020. https://doi.org/10.1183/23120541.00583-2020Keir HR, Richardson H, Fillmore C, Shoemark A, Lazaar AL, et al. CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin. ERJ Open Res. 2020;6(4):00583-2020. https://doi.org/10.1183/23120541.00583-2020Jo A, Kim DW. Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications. Int J Mol Sci. 2023;24(5):5034. https://doi.org/10.3390/ijms24055034Jo A, Kim DW. Neutrophil Extracellular Traps in Airway Diseases: Pathological Roles and Therapeutic Implications. Int J Mol Sci. 2023;24(5):5034. https://doi.org/10.3390/ijms24055034Zhao J, Zhen N, Zhou Q, Lou J, Cui W, et al. NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury. Int J Mol Sci. 2023;24(6):5125. https://doi.org/10.3390/ijms24065125Zhao J, Zhen N, Zhou Q, Lou J, Cui W, et al. NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury. Int J Mol Sci. 2023;24(6):5125. https://doi.org/10.3390/ijms24065125Karnaushkina MA, Guryev AS, Mironov KO, Dunaeva EA, Korchagin VI, et al. Associations of Toll-like Receptor Gene Polymorphisms with NETosis Activity as Prognostic Criteria for the Severity of Pneumonia. Sovrem Tekhnologii Med. 2021;13(3):47-53. https://doi.org/10.17691/stm2021.13.3.06Karnaushkina MA, Guryev AS, Mironov KO, Dunaeva EA, Korchagin VI, et al. Associations of Toll-like Receptor Gene Polymorphisms with NETosis Activity as Prognostic Criteria for the Severity of Pneumonia. Sovrem Tekhnologii Med. 2021;13(3):47-53. https://doi.org/10.17691/stm2021.13.3.06Плескова С.Н., Михеева Э.Р., Разумкова Е.В., Горностаева Е.Е. Влияние наночастиц магнетита и бактерий на активность НАДФН-оксидазы и миелопероксидазы нейтрофильных гранулоцитов крови человека. Цитология. 2017;59(12):867-873.Pleskova S.N., Mikheeva E.R., Razumkova E.V., Gornostayeva E.E. The influence of the magnetite nanoparticles and the bacteria on the NADPH-oxidase and myeloperoxidase activity of human blood neutrophil granulocytes. Tsitologiya. 2017;59(12):867-873. (In Russ.) eLIBRARY ID: 30719829 EDN: ZWGHIVГенералов С.И., Ищенко О.В., Сушкова С.А., Генералов И.И. Оценка ловушкообразования нейтрофилами с использованием гексаазотированного фуксина и определение абзимной активности иммуноглобулинов классов А и М у пациентов с бронхиальной астмой и ХОБЛ. Иммунопатология, аллергология, инфектология. 2021;(4):34-41.Generalov S.I., Ishchenko O.V., Sushkova S.A., Generalov I.I. Detection of neutrophil extracellular traps formation using the hexaazotated fuchsin and determination of the immunoglobulin classes A and M abzyme activity in patients with bronchial asthma and COPD. Immunopathology, allergology, infectology. 2021;(4):34-41. (In Russ.) https://doi.org/10.14427/jipai.2021.4.34Генералов С.И., Ищенко О.В., Коневалова Н.Ю., Фролова А.В., Жерулик С.В., и др. Метод определения нейтрофилов и нейтрофильных внеклеточных ловушек в биологических жидкостях с помощью двойного окрашивания. Иммунопатология, аллергология, инфектология. 2020;(3):21-29.Generalov S.I., Ishchenko O.V., Konevalova N.Y., Frolova A.V., Zherulik S.V., et al. Detection of neutrophils and neutrophil extracellular traps in biological fluids by double staining assay. Immunopathology, allergology, infectology. 2020;(3):21-29. (In Russ.) https://doi.org/10.14427/jipai.2020.3.21Zhang R, Sun C, Han Y, Huang L, Sheng H, et al. Neutrophil autophagy and NETosis in COVID-19: perspectives. Autophagy. 2023;19(3):758-767. https://doi.org/10.1080/15548627.2022.2099206Zhang R, Sun C, Han Y, Huang L, Sheng H, et al. Neutrophil autophagy and NETosis in COVID-19: perspectives. Autophagy. 2023;19(3):758-767. https://doi.org/10.1080/15548627.2022.2099206Dowey R, Cole J, Thompson AAR, Hull RC, Huang C, et al. Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin. ERJ Open Res. 2022;8(2):00596-2021. https://doi.org/10.1183/23120541.00596-2021Dowey R, Cole J, Thompson AAR, Hull RC, Huang C, et al. Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the protein kinase C inhibitor ruboxistaurin. ERJ Open Res. 2022;8(2):00596-2021. https://doi.org/10.1183/23120541.00596-2021Scozzi D, Liao F, Krupnick AS, Kreisel D, Gelman AE. The role of neutrophil extracellular traps in acute lung injury. Front Immunol. 2022;13:953195. https://doi.org/10.3389/fimmu.2022.953195Scozzi D, Liao F, Krupnick AS, Kreisel D, Gelman AE. The role of neutrophil extracellular traps in acute lung injury. Front Immunol. 2022;13:953195. https://doi.org/10.3389/fimmu.2022.953195Moore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis. Crit Care Med. 2006;34(5 Suppl):S114-7. https://doi.org/10.1097/01.CCM.0000214312.20718.3EMoore SB. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis. Crit Care Med. 2006;34(5 Suppl):S114-7. https://doi.org/10.1097/01.CCM.0000214312.20718.3ECaudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012;122(7):2661-2671. https://doi.org/10.1172/JCI61303Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012;122(7):2661-2671. https://doi.org/10.1172/JCI61303Zhou X, Jin J, Lv T, Song Y. A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury. Int J Mol Sci. 2024;25(3):1464. https://doi.org/10.3390/ijms25031464Zhou X, Jin J, Lv T, Song Y. A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury. Int J Mol Sci. 2024;25(3):1464. https://doi.org/10.3390/ijms25031464Yang Z, Li X, Wei L, Bao L, Hu H, et al. Involucrasin B suppresses airway inflammation in obese asthma by inhibiting the TLR4-NF-κB-NLRP3 pathway. Phytomedicine. 2024;132:155850. https://doi.org/10.1016/j.phymed.2024.155850Yang Z, Li X, Wei L, Bao L, Hu H, et al. Involucrasin B suppresses airway inflammation in obese asthma by inhibiting the TLR4-NF-κB-NLRP3 pathway. Phytomedicine. 2024;132:155850. https://doi.org/10.1016/j.phymed.2024.155850Li Y, Yang T, Jiang B. Neutrophil and neutrophil extracellular trap involvement in neutrophilic asthma: A review. Medicine (Baltimore). 2024;103(34):e39342. https://doi.org/10.1097/MD.0000000000039342Li Y, Yang T, Jiang B. Neutrophil and neutrophil extracellular trap involvement in neutrophilic asthma: A review. Medicine (Baltimore). 2024;103(34):e39342. https://doi.org/10.1097/MD.0000000000039342Старостин Д.О., Долгих В.Т., Кузовлев А.Н. Нейтрофилы как важнейшие факторы неспецифической резистентности организма. Клиническая патофизиология. 2023;29(1):28-45.Starostin D.O., Dolgikh V.T., Kuzovlev A.N. Neutrophils as important factors of non-specific resistance of the organism. Klinicheskaya patofiziologiya. 2023;29(1):28-45. (In Russ.) eLIBRARY ID: 53831938 EDN: QACJTSLiu J, Tao P, Su B, Zheng L, Lin Y, et al. Interleukin-33 modulates NET formation via an autophagy-dependent manner to promote neutrophilic inflammation in cigarette smoke-exposure asthma. J Hazard Mater. 2025;487:137257. https://doi.org/10.1016/j.jhazmat.2025.137257Liu J, Tao P, Su B, Zheng L, Lin Y, et al. Interleukin-33 modulates NET formation via an autophagy-dependent manner to promote neutrophilic inflammation in cigarette smoke-exposure asthma. J Hazard Mater. 2025;487:137257. https://doi.org/10.1016/j.jhazmat.2025.137257Tao P, Su B, Mao X, Lin Y, Zheng L, et al. Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis. Redox Biol. 2025;82:103594. https://doi.org/10.1016/j.redox.2025.103594Tao P, Su B, Mao X, Lin Y, Zheng L, et al. Interleukin-35 inhibits NETs to ameliorate Th17/Treg immune imbalance during the exacerbation of cigarette smoke exposed-asthma via gp130/STAT3/ferroptosis axis. Redox Biol. 2025;82:103594. https://doi.org/10.1016/j.redox.2025.103594Uddin M, Watz H, Malmgren A, Pedersen F. NETopathic Inflammation in Chronic Obstructive Pulmonary Disease and Severe Asthma. Front Immunol. 2019;10:47. https://doi.org/10.3389/fimmu.2019.00047Uddin M, Watz H, Malmgren A, Pedersen F. NETopathic Inflammation in Chronic Obstructive Pulmonary Disease and Severe Asthma. Front Immunol. 2019;10:47. https://doi.org/10.3389/fimmu.2019.00047Chen YR, Xiang XD, Sun F, Xiao BW, Yan MY, et al. Simvastatin Reduces NETosis to Attenuate Severe Asthma by Inhibiting PAD4 Expression. Oxid Med Cell Longev. 2023;2023:1493684. https://doi.org/10.1155/2023/1493684Chen YR, Xiang XD, Sun F, Xiao BW, Yan MY, et al. Simvastatin Reduces NETosis to Attenuate Severe Asthma by Inhibiting PAD4 Expression. Oxid Med Cell Longev. 2023;2023:1493684. https://doi.org/10.1155/2023/1493684Peng B, Yan MY, Chen YR, Sun F, Xiang XD, Liu D. The methyl-CpG binding domain 2 regulates peptidylarginine deiminase 4 expression and promotes neutrophil extracellular trap formation via the Janus kinase 2 signaling pathway in experimental severe asthma. Ann Med. 2025;57(1):2458207. https://doi.org/10.1080/07853890.2025.2458207Peng B, Yan MY, Chen YR, Sun F, Xiang XD, Liu D. The methyl-CpG binding domain 2 regulates peptidylarginine deiminase 4 expression and promotes neutrophil extracellular trap formation via the Janus kinase 2 signaling pathway in experimental severe asthma. Ann Med. 2025;57(1):2458207. https://doi.org/10.1080/07853890.2025.2458207Chen F, Yu M, Zhong Y, Wang L, Huang H. Characteristics and Role of Neutrophil Extracellular Traps in Asthma. Inflammation. 2022;45(1):6-13. https://doi.org/10.1007/s10753-021-01526-8Chen F, Yu M, Zhong Y, Wang L, Huang H. Characteristics and Role of Neutrophil Extracellular Traps in Asthma. Inflammation. 2022;45(1):6-13. https://doi.org/10.1007/s10753-021-01526-8Lange P, Ahmed E, Lahmar ZM, Martinez FJ, Bourdin A. Natural history and mechanisms of COPD. Respirology. 2021;26(4):298-321. https://doi.org/10.1111/resp.14007Lange P, Ahmed E, Lahmar ZM, Martinez FJ, Bourdin A. Natural history and mechanisms of COPD. Respirology. 2021;26(4):298-321. https://doi.org/10.1111/resp.14007Block H, Zarbock A. A Fragile Balance: Does Neutrophil Extracellular Trap Formation Drive Pulmonary Disease Progression? Cells. 2021;10(8):1932. https://doi.org/10.3390/cells10081932Block H, Zarbock A. A Fragile Balance: Does Neutrophil Extracellular Trap Formation Drive Pulmonary Disease Progression? Cells. 2021;10(8):1932. https://doi.org/10.3390/cells10081932Liao SX, Wang YW, Sun PP, Xu Y, Wang TH. Prospects of neutrophilic implications against pathobiology of chronic obstructive pulmonary disease: Pharmacological insights and technological advances. Int Immunopharmacol. 2025;144:113634. https://doi.org/10.1016/j.intimp.2024.113634Liao SX, Wang YW, Sun PP, Xu Y, Wang TH. Prospects of neutrophilic implications against pathobiology of chronic obstructive pulmonary disease: Pharmacological insights and technological advances. Int Immunopharmacol. 2025;144:113634. https://doi.org/10.1016/j.intimp.2024.113634Buttery SC, Zysman M, Vikjord SAA, Hopkinson NS, Jenkins C, Vanfleteren LEGW. Contemporary perspectives in COPD: Patient burden, the role of gender and trajectories of multimorbidity. Respirology. 2021;26(5):419-441. https://doi.org/10.1111/resp.14032Buttery SC, Zysman M, Vikjord SAA, Hopkinson NS, Jenkins C, Vanfleteren LEGW. Contemporary perspectives in COPD: Patient burden, the role of gender and trajectories of multimorbidity. Respirology. 2021;26(5):419-441. https://doi.org/10.1111/resp.14032Федосеев Г.Б., Трофимов Б.И., Рогачева Н.Н., Разумовская Т.С. Роль нейтрофилов и бактериальной инфекции респираторного тракта у больных бронхиальной астмой и хронической обструктивной болезнью легких. Российский аллергологический журнал. 2011;(2):34-43.Fedoseev G.B., Trofimov V.I., Rogacheva N.N., Razumovskaya N.S. Neutrophils and respiratory tract bacterial infections in patients with bronchial asthma and COPD. Russian journal of allergy. 2011;(2):34-43. (In Russ.) eLIBRARY ID: 16835788 EDN: OEKWDBSchioppa T, Nguyen HO, Salvi V, Maugeri N, Facchinetti F, et al. The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils. Int J Mol Sci. 2022;23(9):4982. https://doi.org/10.3390/ijms23094982Schioppa T, Nguyen HO, Salvi V, Maugeri N, Facchinetti F, et al. The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils. Int J Mol Sci. 2022;23(9):4982. https://doi.org/10.3390/ijms23094982Карзакова Л.М., Алексеева Е.П., Кудряшов С.И., Журавлева Н.В., Ухтерова Н.Д., Андреева Н.П. Роль иммунологических факторов в неблагоприятном исходе хронической обструктивной болезни легких. Вестник современной клинической медицины. 2022;15(1):52–61.Karzakova L.M., Alekseeva E.P., Kudryashov S.I., Zhuravleva N.V., Ukhterova N.D., Andreeva N.P. The role of immunological factors in the unfavorable outcome of chronic obstructive pulmonary disease. The Bulletin of Contemporary Clinical Medicine. 2022;15(1):52–61. (In Russ.) https://doi.org/10.20969/VSKM.2022.15(1).52-61Lin Z, Liu S, Zhang K, Feng T, Luo Y, et al. Molecular mechanisms and therapeutic targets of acute exacerbations of chronic obstructive pulmonary disease with Pseudomonas aeruginosa infection. Respir Res. 2025;26(1):115. https://doi.org/10.1186/s12931-025-03185-xLin Z, Liu S, Zhang K, Feng T, Luo Y, et al. Molecular mechanisms and therapeutic targets of acute exacerbations of chronic obstructive pulmonary disease with Pseudomonas aeruginosa infection. Respir Res. 2025;26(1):115. https://doi.org/10.1186/s12931-025-03185-xLin Z, Jiang Y, Liu H, Yang J, Yang B, et al. Airway microbiota and immunity associated with chronic obstructive pulmonary disease severity. J Transl Med. 2025;23(1):962. https://doi.org/10.1186/s12967-025-06986-2Lin Z, Jiang Y, Liu H, Yang J, Yang B, et al. Airway microbiota and immunity associated with chronic obstructive pulmonary disease severity. J Transl Med. 2025;23(1):962. https://doi.org/10.1186/s12967-025-06986-2Khan MA, Ali ZS, Sweezey N, Grasemann H, Palaniyar N. Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) Formation, and NET Degradation. Genes (Basel). 2019;10(3):183. https://doi.org/10.3390/genes10030183Khan MA, Ali ZS, Sweezey N, Grasemann H, Palaniyar N. Progression of Cystic Fibrosis Lung Disease from Childhood to Adulthood: Neutrophils, Neutrophil Extracellular Trap (NET) Formation, and NET Degradation. Genes (Basel). 2019;10(3):183. https://doi.org/10.3390/genes10030183Law SM, Hardisty G, Gillan JL, Robinson NJ, Davidson DJ, et al. Neutrophil extracellular traps are associated with airways inflammation and increased severity of lung disease in cystic fibrosis. ERJ Open Res. 2024;10(6):00312-2024. https://doi.org/10.1183/23120541.00312-2024Law SM, Hardisty G, Gillan JL, Robinson NJ, Davidson DJ, et al. Neutrophil extracellular traps are associated with airways inflammation and increased severity of lung disease in cystic fibrosis. ERJ Open Res. 2024;10(6):00312-2024. https://doi.org/10.1183/23120541.00312-2024Harwood KH, McQuade RM, Jarnicki A, Schneider-Futschik EK. Anti-Inflammatory Influences of Cystic Fibrosis Transmembrane Conductance Regulator Drugs on Lung Inflammation in Cystic Fibrosis. Int J Mol Sci. 2021;22(14):7606. https://doi.org/10.3390/ijms22147606Harwood KH, McQuade RM, Jarnicki A, Schneider-Futschik EK. Anti-Inflammatory Influences of Cystic Fibrosis Transmembrane Conductance Regulator Drugs on Lung Inflammation in Cystic Fibrosis. Int J Mol Sci. 2021;22(14):7606. https://doi.org/10.3390/ijms22147606Яшин С.С., Юнусова Ю.Р., Исакова Н.В., Сердобольская Ю.В. Кистозный фиброз (муковисцидоз). Современные проблемы науки и образования. 2022;(5):141.Yashin S.S., Yunusova Y.R., Isakova N.V., Serdobolskaya Y.V. Cystic fibrosis. Modern problems of science and education. 2022;(5):141. (In Russ.) https://doi.org/10.17513/spno.32008Keir HR, Shoemark A, Dicker AJ, Perea L, Pollock J, et al. Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study. Lancet Respir Med. 2021;9(8):873-884. https://doi.org/10.1016/S2213-2600(20)30504-XKeir HR, Shoemark A, Dicker AJ, Perea L, Pollock J, et al. Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study. Lancet Respir Med. 2021;9(8):873-884. https://doi.org/10.1016/S2213-2600(20)30504-XКаширская Н.Ю., Красовский С.А., Черняк А.В., Шерман В.Д., Воронкова А.Ю., и др. Динамика продолжительности жизни больных муковисцидозом, проживающих в Москве, и ее связь с получаемой терапией: ретроспективный анализ за 1993–2013 гг. Вопросы современной педиатрии. 2015;14(4):503-508.Kashirskaya N.Yu., Krasovsky S.A., Chernyak A.V., Sherman V.D., Voronkova A.Yu., et al. Trends in Life Expectancy of Cystic Fibrosis Patients in Moscow and their Connection with the Treatment Received: Retrospective Analysis for 1993–2013. Current Pediatrics. 2015;14(4):503-508. (In Russ.) https://doi.org/10.15690/vsp.v14.i4.1390Махмутова В.Р., Гембицкая Т.Е., Черменский А.Г., Титова О.Н., Кузубова Н.А. Мониторинг инфицирования и резистентности Achromobacter xylosoxidans у взрослых пациентов с муковисцидозом. РМЖ. Медицинское обозрение. 2021;5(7):462-467.Makhmutova V.R., Gembitskaya T.E., Chermensky A.G., Titova O.N., Kuzubova N.A. Achromobacter xylosoxidans infection and resistance monitoring in adult cystic fibrosis patients. Russian Medical Inquiry. 2021;5(7):462–467 (in Russ.). https://doi.org/10.32364/2587-6821-2021-5-7-462-467Колбин А.С., Гомон Ю.М., Карпов О.И., Балыкина Ю.Е., Проскурин М.А. Муковисцидоз как социально-экономическая проблема. Качественная клиническая практика. 2020;(5):38-49.Kolbin A.S., Gomon Yu.M., Karpov O.I., Balykina Yu.E., Proskurin M.A. Cystic fibrosis as a social-economic burden. Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice. 2020;(5):38-49. (In Russ.) https://doi.org/10.37489/2588-0519-2020-5-38-49Morán G, Uberti B, Quiroga J. Role of Cellular Metabolism in the Formation of Neutrophil Extracellular Traps in Airway Diseases. Front Immunol. 2022;13:850416. https://doi.org/10.3389/fimmu.2022.850416Morán G, Uberti B, Quiroga J. Role of Cellular Metabolism in the Formation of Neutrophil Extracellular Traps in Airway Diseases. Front Immunol. 2022;13:850416. https://doi.org/10.3389/fimmu.2022.850416Keir HR, Chalmers JD. Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy. Eur Respir Rev. 2022;31(163):210241. https://doi.org/10.1183/16000617.0241-2021Keir HR, Chalmers JD. Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy. Eur Respir Rev. 2022;31(163):210241. https://doi.org/10.1183/16000617.0241-2021Totani L, Amore C, Piccoli A, Dell'Elba G, Di Santo A, et al. Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis. Front Pharmacol. 2021;12:702677. https://doi.org/10.3389/fphar.2021.702677Totani L, Amore C, Piccoli A, Dell'Elba G, Di Santo A, et al. Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis. Front Pharmacol. 2021;12:702677. https://doi.org/10.3389/fphar.2021.702677Chalmers JD, Burgel PR, Daley CL, De Soyza A, Haworth CS, et al. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med. 2025;392(16):1569-1581. https://doi.org/10.1056/NEJMoa2411664Chalmers JD, Burgel PR, Daley CL, De Soyza A, Haworth CS, et al. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med. 2025;392(16):1569-1581. https://doi.org/10.1056/NEJMoa2411664Weisel JW, Litvinov RI. Visualizing thrombosis to improve thrombus resolution. Res Pract Thromb Haemost. 2021;5(1):38-50. https://doi.org/10.1002/rth2.12469Weisel JW, Litvinov RI. Visualizing thrombosis to improve thrombus resolution. Res Pract Thromb Haemost. 2021;5(1):38-50. https://doi.org/10.1002/rth2.12469

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