medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-271medsovet-10358Research ArticleБРОНХОПУЛЬМОНОЛОГИЯ И ОТОЛАРИНГОЛОГИЯBRONCHOPULMONOLOGY, OTORHINOLARYNGOLOGYЦитокины эпителиально‑Т‑клеточной оси и статус витамина D при различных фенотипах бронхиальной астмы у детей на фоне приема препаратов холекальциферолаEpithelial‑T‑cell axis cytokines and vitamin D status in different asthma phenotypes in childrenhttps://orcid.org/0000-0002-2056-153XДолбняС. В.DolbnyaS. V.

Долбня Светлана Викторовна - к.м.н., доцент кафедры факультетской педиатрии, Ставропольский ГМУ; врач-пульмонолог, Краевая ДКБ.

355017, Ставрополь, ул. Мира, д. 310; 355029, Ставрополь, ул. Семашко, д. 3.

Svetlana V. Dolbnya - Cand. Sci. (Med.), Assistant Professor of the Department of Faculty Pediatrics, Stavropol State Medical University; Pulmonologist, RCCH.

310, Mira St., Stavropol, 355017; 3, Semashko St., Stavropol, 355029.

svet-lana.dolbnya@yandex.ruhttps://orcid.org/0009-0007-9505-3349ПонамареваВ. Р.PonamaryovaV. R.

Понамарева Виктория Романовна - врач-ординатор кафедры госпитальной педиатрии имени академика В.А. Таболина, РНИМУ имени Н.И. Пирогова.

117513, Москва, ул. Островитянова д. 1

Viktoriya R. Ponamaryova - Resident of the Department of Hospital Pediatrics named after Academician V.A. Tabolin.

Ostrovityanov St., Moscow, 117513

viktoriaponamarevaaa@yandex.ruhttps://orcid.org/0000-0003-4200-4598ЗахароваИ. Н.ZakharovaI. N.

Захарова Ирина Николаевна - д.м.н., профессор, заслуженный врач Российской Федерации, заведующая кафедрой педиатрии имени академика Г.Н. Сперанского.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Irina N. Zakharova - Dr. Sci. (Med.), Professor, Head of the Department of Pediatrics named after Academician G.N. Speransky.

2/1, Вldg. 1, Barrikadnaya St., Moscow, 125993

zakharova-rmapo@yandex.ruhttps://orcid.org/0000-0001-7248-1614КлимовЛ. Я.KlimovL. Ya.

Климов Леонид Яковлевич - д.м.н., профессор, заведующий кафедрой факультетской педиатрии.

355017, Ставрополь, ул. Мира, д. 310

Leonid Ya. Klimov - Dr. Sci. (Med.), Professor, Head of the Department of Faculty Pediatrics.

310, Mira St., Stavropol, 355017

klimov_leo@mail.ruhttps://orcid.org/0000-0001-6983-0967ТолкуноваА. А.TolkunovaA. A.

Толкунова Анна Александровна - к.м.н., ассистент кафедры факультетской педиатрии, Ставропольский ГМУ; врач-пульмонолог, Краевая ДКБ.

355029, Ставрополь, ул. Семашко, д. 3; 355017, Ставрополь, ул. Мира, д. 310

Anna А. Tolkunova - Cand. Sci. (Med.), Assistant of the Department of Faculty Pediatrics, Stavropol State Medical University; Pulmonologist, RCCH.

310, Mira St., Stavropol, 355017; 3, Semashko St., Stavropol, 355029

anndiatlova@mail.ruhttps://orcid.org/0000-0002-4069-0566БарычеваЛ. Ю.BarychevaL. Yu.

Барычева Людмила Юрьевна - д.м.н., профессор, заведующая кафедрой иммунологии с курсом ДПО, Ставропольский ГМУ; врач-аллерголог-иммунолог, Краевая ДКБ.

355017, Ставрополь, ул. Мира, д. 310; 355029, Ставрополь, ул. Семашко, д. 3

Liudmila Yu. Barycheva - Dr. Sci. (Med.), Professor, Head of the Department Immunology with a Course of Additional Professional Education.310, Mira St., Stavropol, 355017

for_ludmila@inbox.ruhttps://orcid.org/0009-0003-5246-0527КузнецоваВ. В.KuznetsovaV. V.

Кузнецова Вера Валентиновна, ассистент кафедры иммунологии с курсом ДПО, Ставропольский ГМУ, врач-аллерголог-иммунолог, Краевая ДКБ.

355017, Ставрополь, ул. Мира, д. 310; 355029, Ставрополь, ул. Семашко, д. 3

Vera V. Kuznetsova - Assistant of the Department of Immunology with a Course of Additional Professional Education, Stavropol State Medical University; 310, Mira St., Stavropol, 355017; Allergist-Immunologist, RCCH.

310, Mira St., Stavropol, 355017; 3, Semashko St., Stavropol, 355029

kuznetsovavera96@mail.ruhttps://orcid.org/0000-0002-5306-8223ЕнинаЕ. А.EninaE. A.

Енина Елена Александровна, к.м.н., доцент кафедры госпитальной педиатрии, Ставропольский ГМУ; 355017, Ставрополь, ул. Мира, д. 310; заведующая отделением пульмонологии, Краевая ДКБ.

355017, Ставрополь, ул. Мира, д. 310; 355029, Ставрополь, ул. Семашко, д. 3

Elena A. Enina, Cand. Sci. (Med.), Associate Professor, Department of Hospital Pediatrics, Stavropol State Medical University; Head of the Pulmonology Department, RCCH.

310, Mira St., Stavropol, 355017; 3, Semashko St., Stavropol, 355029

enina_ea@rambler.ruhttps://orcid.org/0000-0002-0311-4068ФедькоН. А.FedkoN. A.

Федько Наталья Александровна, д.м.н., профессор, заведующая кафедрой поликлинической педиатрии, Ставропольский ГМУ.

355017, Ставрополь, ул. Мира, д. 310

Natalya A. Fedko - Dr. Sci. (Med.), Professor, Head of the Department of Outpatient Pediatrics.

310, Mira St., Stavropol, 355017

fedko_natalya@mail.ruhttps://orcid.org/0009-0009-9178-1634ЗарытовскаяН. В.ZaritovskayaN. V.

 

Зарытовская Наталья Владимировна - д.м.н., профессор кафедры пропедевтики детских болезней с курсом дополнительного профессионального образования.

355017, Ставрополь, ул. Мира, д. 310

Natalia V. Zaritovskaya - Dr. Sci. (Med.), Professor of the Department of Propaedeutics of Childhood Diseases with a Course of Additional Professional Education.

310, Mira St., Stavropol, 355017

leda54@mail.ruhttps://orcid.org/0009-0000-9259-8342ТаглановВ. Р.TaglanovV. R.

Тагланов Владислав Рамазанович - ординатор по специальности «Педиатрия».

355017, Ставрополь, ул. Мира, д. 310

Vladislav R. Taglanov - Resident in the Specialty "Pediatrics".

310, Mira St., Stavropol, 355017

vlad.taglanov@yandex.ruСтавропольский государственный медицинский университет; Краевая детская клиническая больницаРоссияStavropol State Medical University; Regional Children’s Clinical HospitalRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian FederationРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuing Professional EducationRussian FederationСтавропольский государственный медицинский университетРоссияStavropol State Medical UniversityRussian Federation2026110920260116069Copyright © Долбня С.В., Понамарева В.Р., Захарова И.Н., Климов Л.Я., Толкунова А.А., Барычева Л.Ю., Кузнецова В.В., Енина Е.А., Федько Н.А., Зарытовская Н.В., Тагланов В.Р., 20262026Долбня С.В., Понамарева В.Р., Захарова И.Н., Климов Л.Я., Толкунова А.А., Барычева Л.Ю., Кузнецова В.В., Енина Е.А., Федько Н.А., Зарытовская Н.В., Тагланов В.Р.Dolbnya S.V., Ponamaryova V.R., Zakharova I.N., Klimov L.Y., Tolkunova A.A., Barycheva L.Y., Kuznetsova V.V., Enina E.A., Fedko N.A., Zaritovskaya N.V., Taglanov V.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/10358Введение

Введение. Бронхиальная астма (БА) является гетерогенным заболеванием, проявляющимся различными фенотипами, определение которых предусматривает возможность индивидуального подбора терапии, что особенно важно среди пациентов детского возраста.

Цель

Цель. Определить значимость ИЛ-17 и ИЛ-33 на фоне профилактического приема холекальциферола у детей с различными фенотипами БА.

Материалы и методы

Материалы и методы. Обследовано 156 детей и подростков Ставропольского края, страдающих БА, в возрасте 13,5 [10,0; 15,9] года. За период 2024–2025 гг. у детей выполнено двухэтапное исследование обеспеченности витамином D, уровня ИЛ-17А и ИЛ-33 на фоне трехмесячного курса приема водного раствора холекальциферола в дозе 1000 МЕ/сут.

Результаты

Результаты. Выявлено три ведущих фенотипа БА у пациентов исследуемой группы: атопическая БА – 125 (80,1%), неатопическая БА – 9 (5,8%), астма, ассоциированная с ожирением, – 22 (14,1%). Статистически весомые различия выявлены в параметрах, определяющих фенотипическую принадлежность пациентов: в уровне общего IgE (p = 0,016) и SDS индекса массы тела к возрасту (p < 0,001). Значимых отличий в уровне кальцидиола сыворотки, ИЛ-17А и ИЛ-33 в зависимости от фенотипа получено не было, имеет место тенденция к снижению уровня витамина D и увеличению уровней цитокинов при нарастании степени тяжести астмы. На фоне курса профилактического приема препаратов холекальциферола наблюдался значимый прирост обеспеченности витамином D (р < 0,001), который сопровождался снижением уровня ИЛ-17А (p = 0,002). Значимого влияния на уровень ИЛ-33 выявлено не было.

Заключение

Заключение. Трехмесячный курс профилактического приема препаратов холекальциферола приводит к значимому сокращению дефицита витамина D у детей и подростков с БА и снижению уровня ИЛ-17А, а также в комплексе со стандартной ступенчатой терапией позволяет повысить уровень контроля над заболеванием.

Introduction

Introduction. Bronchial asthma (BA) is a heterogeneous disease that manifests in various phenotypes; identifying these phenotypes allows for the individualization of treatment, which is particularly important among pediatric patients.

Aim

Aim. To determine the role of IL-17A and IL-33 in identifying bronchial asthma phenotypes in children receiving prophylactic cholecalciferol.

Material and methods

Material and methods. A total of 156 children and adolescents from the Stavropol Krai with asthma, aged 13.5 [10.0; 15.9] years, were studied. During the period 2024–2025, a two-stage study of vitamin D status and IL-17A and IL-33 levels was conducted in children against the background of a 3-month intake of an aqueous solution of cholecalciferol at a dose of 1000 IU/day.

Results

Results. We identified three main asthma phenotypes in the study group: atopic asthma – 125 (80.1%), non-atopic asthma – 9 (5.8%), and asthma associated with obesity – 22 (14.1%). Statistically significant differences were found only in parameters determining the patients’ phenotypic classification: total IgE level (p = 0.016) and age-adjusted BMI SDS (p < 0.001). No significant differences in serum calcidiol, IL-17A, and IL-33 levels were observed depending on the phenotype. No significant differences in serum calcidiol, IL-17A, and IL-33 levels were observed across phenotypes; however, there was a trend toward lower vitamin D levels and higher cytokine levels as asthma severity increased. Against the background of a prophylactic course of CC medication, a significant increase in vitamin D sufficiency was observed (p < 0.001), which was accompanied by a decrease in IL-17A levels (p = 0.002). No significant effect on IL-33 levels was detected.

Conclusion

Conclusion. A three-month course of prophylactic cholecalciferol supplementation leads to a significant reduction in vitamin D deficiency in children and adolescents with asthma and a decrease in IL-17A levels; when combined with standard stepwise therapy, it improves disease control.

бронхиальная астмаинтерлейкин-17интерлейкин-33витамин Dхолекальциферол25(ОН)Dдетиbronchial asthmainterleukin-17interleukin-33vitamin Dcholecalciferol25(OH)DchildrenСтатья опубликована в рамках выполнения государственного задания «Разработка персонализированной схемы профилактики и коррекции гиповитаминоза D при различных фенотипах и эндотипах бронхиальной астмы у детей» (государственный № 1023022000021-3-3.2.3)The article was published as part of the state assignment “Development of a personalized scheme for the prevention and correction of hypovitaminosis D in various phenotypes and endotypes of bronchial asthma in children” (state number 1023022000021-3-3.2.3)ReferencesАвдеев СН, Айсанов ЗР, Астафьева НГ, Баранов АА, Белевский АС, Бухтияров ИВ и др. Бронхиальная астма: клинические рекомендации. М.; 2024. 204 с. Режим доступа: https://cr.minzdrav.gov.ru/preview-cr/359_3.Авдеев СН, Айсанов ЗР, Астафьева НГ, Баранов АА, Белевский АС, Бухтияров ИВ и др. Бронхиальная астма: клинические рекомендации. М.; 2024. 204 с. Режим доступа: https://cr.minzdrav.gov.ru/preview-cr/359_3.Авдеев CН, Айсанов ЗР, Архипов ВВ, Астафьева НГ, Баранов АА, Белевский АС и др. Современные рекомендации по ведению пациентов с бронхиальной астмой. Педиатрическая фармакология. 2025;22(4):432–494. https://doi.org/10.15690/pf.v22i4.2938.Avdeev SN, Aysanov ZR, Arkhipov VV, Astafieva NG, Baranov AA, Belevskiy AS et al. Asthma management current guidelines. Pediatric pharmacology. 2025;22(4):432–494. (In Russ.) https://doi.org/10.15690/pf.v22i4.2938.Dolbnya SV, Tolkunova AA, Ponamareva VR, Klimov LYa, Barycheva LYu, Atanesyan RA et al. Immune and non-immune mechanisms behind the interaction between bronchial asthma and obesity in children: a modern perspective. Medical News of North Caucasus. 2025;20(2):190–197. https://doi.org/10.14300/mnnc.2025.20044.Dolbnya SV, Tolkunova AA, Ponamareva VR, Klimov LYa, Barycheva LYu, Atanesyan RA et al. Immune and non-immune mechanisms behind the interaction between bronchial asthma and obesity in children: a modern perspective. Medical News of North Caucasus. 2025;20(2):190–197. https://doi.org/10.14300/mnnc.2025.20044.Komlósi ZI, van de Veen W, Kovács N, Szűcs G, Sokolowska M, O’Mahony L et al. Cellular and molecular mechanisms of allergic asthma. Mol Aspects Med. 2022;85:100995. https://doi.org/10.1016/j.mam.2021.100995.Komlósi ZI, van de Veen W, Kovács N, Szűcs G, Sokolowska M, O’Mahony L et al. Cellular and molecular mechanisms of allergic asthma. Mol Aspects Med. 2022;85:100995. https://doi.org/10.1016/j.mam.2021.100995.Celebi Sozener Z, Ozdel Ozturk B, Cerci P, Turk M, Gorgulu Akin B, Akdis M et al. Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease. Allergy. 2022;77(5):1418–1449. https://doi.org/10.1111/all.15240.Celebi Sozener Z, Ozdel Ozturk B, Cerci P, Turk M, Gorgulu Akin B, Akdis M et al. Epithelial barrier hypothesis: Effect of the external exposome on the microbiome and epithelial barriers in allergic disease. Allergy. 2022;77(5):1418–1449. https://doi.org/10.1111/all.15240.Eguiluz-Gracia I, Mathioudakis AG, Bartel S, Vijverberg SJH, Fuertes E, Comberiati P et al. The need for clean air: The way air pollution and climate change affect allergic rhinitis and asthma. Allergy. 2020;75(9):2170–2184. https://doi.org/10.1111/all.14177.Eguiluz-Gracia I, Mathioudakis AG, Bartel S, Vijverberg SJH, Fuertes E, Comberiati P et al. The need for clean air: The way air pollution and climate change affect allergic rhinitis and asthma. Allergy. 2020;75(9):2170–2184. https://doi.org/10.1111/all.14177.Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021;21(11):739–751. https://doi.org/10.1038/s41577-021-00538-7.Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021;21(11):739–751. https://doi.org/10.1038/s41577-021-00538-7.Jackson ND, Everman JL, Chioccioli M, Feriani L, Goldfarbmuren KC, Sajuthi SP et al. Single-cell and population transcriptomics reveal panepithelial remodeling in type 2-high asthma. Cell Rep. 2020;32(1):107872. https://doi.org/10.1016/j.celrep.2020.107872.Jackson ND, Everman JL, Chioccioli M, Feriani L, Goldfarbmuren KC, Sajuthi SP et al. Single-cell and population transcriptomics reveal panepithelial remodeling in type 2-high asthma. Cell Rep. 2020;32(1):107872. https://doi.org/10.1016/j.celrep.2020.107872.Heijink IH, Kuchibhotla VNS, Roffel MP, Maes T, Knight DA, Sayers I, Nawijn MC. Epithelial cell dysfunction, a major driver of asthma development. Allergy. 2020;75(8):1902–1917. https://doi.org/10.1111/all.14421.Heijink IH, Kuchibhotla VNS, Roffel MP, Maes T, Knight DA, Sayers I, Nawijn MC. Epithelial cell dysfunction, a major driver of asthma development. Allergy. 2020;75(8):1902–1917. https://doi.org/10.1111/all.14421.Abu Khweek A, Kim E, Joldrichsen MR, Amer AO, Boyaka PN. Insights into mucosal innate immune responses in house dust mite-mediated allergic asthma. Front Immunol. 2020;11:534501. https://doi.org/10.3389/fimmu.2020.534501.Abu Khweek A, Kim E, Joldrichsen MR, Amer AO, Boyaka PN. Insights into mucosal innate immune responses in house dust mite-mediated allergic asthma. Front Immunol. 2020;11:534501. https://doi.org/10.3389/fimmu.2020.534501.Saikumar Jayalatha AK, Hesse L, Ketelaar ME, Koppelman GH, Nawijn MC. The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention. Pharmacol Ther. 2021;225:107847. https://doi.org/10.1016/j.pharmthera.2021.107847.Saikumar Jayalatha AK, Hesse L, Ketelaar ME, Koppelman GH, Nawijn MC. The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention. Pharmacol Ther. 2021;225:107847. https://doi.org/10.1016/j.pharmthera.2021.107847.Gauvreau GM, Bergeron C, Boulet LP, Cockcroft DW, Côté A, Davis BE et al. Sounding the alarmins – the role of alarmin cytokines in asthma. Allergy. 2023;78(2):402–417. https://doi.org/10.1111/all.15609.Gauvreau GM, Bergeron C, Boulet LP, Cockcroft DW, Côté A, Davis BE et al. Sounding the alarmins – the role of alarmin cytokines in asthma. Allergy. 2023;78(2):402–417. https://doi.org/10.1111/all.15609.Tsai ML, Tsai MK, Tsai YG, Lin YC, Hsu YL, Chen YT et al. Montelukast increased IL-25, IL-33, and TSLP via epigenetic regulation in airway epithelial cells. Int J Mol Sci. 2023;24(2):1227. https://doi.org/10.3390/ijms24021227.Tsai ML, Tsai MK, Tsai YG, Lin YC, Hsu YL, Chen YT et al. Montelukast increased IL-25, IL-33, and TSLP via epigenetic regulation in airway epithelial cells. Int J Mol Sci. 2023;24(2):1227. https://doi.org/10.3390/ijms24021227.Zhao Y, Patel J, Fan J, Wang X, Chen L, Li Y, Luo Z. Integrated analysis reveals that EGR1 promotes epithelial IL33 production in T2 asthma. J Transl Med. 2025;23(1):203. https://doi.org/10.1186/s12967-025-06116-y.Zhao Y, Patel J, Fan J, Wang X, Chen L, Li Y, Luo Z. Integrated analysis reveals that EGR1 promotes epithelial IL33 production in T2 asthma. J Transl Med. 2025;23(1):203. https://doi.org/10.1186/s12967-025-06116-y.Miranda-Katz MR, Gern JE, Bochkov YA, Wilson JL. The rhinovirus puzzle: linking virus and host factors to childhood asthma. J Allergy Clin Immunol. 2026;157(4):787–795. https://doi.org/10.1016/j.jaci.2026.01.009.Miranda-Katz MR, Gern JE, Bochkov YA, Wilson JL. The rhinovirus puzzle: linking virus and host factors to childhood asthma. J Allergy Clin Immunol. 2026;157(4):787–795. https://doi.org/10.1016/j.jaci.2026.01.009.Potaczek DP, Miethe S, Schindler V, Alhamdan F, Garn H. Role of airway epithelial cells in the development of different asthma phenotypes. Cell Signal. 2020;69:109523. https://doi.org/10.1016/j.cellsig.2019.109523.Potaczek DP, Miethe S, Schindler V, Alhamdan F, Garn H. Role of airway epithelial cells in the development of different asthma phenotypes. Cell Signal. 2020;69:109523. https://doi.org/10.1016/j.cellsig.2019.109523.Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219–233. https://doi.org/10.1007/s12016-018-8712-1.Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219–233. https://doi.org/10.1007/s12016-018-8712-1.Chang-Chien J, Huang JL, Tsai HJ, Wang SL, Kuo ML, Yao TC. Vitamin D ameliorates particulate matter induced mitochondrial damages and calcium dyshomeostasis in BEAS-2B human bronchial epithelial cells. Respir Res. 2024;25(1):321. https://doi.org/10.1186/s12931-024-02951-7.Chang-Chien J, Huang JL, Tsai HJ, Wang SL, Kuo ML, Yao TC. Vitamin D ameliorates particulate matter induced mitochondrial damages and calcium dyshomeostasis in BEAS-2B human bronchial epithelial cells. Respir Res. 2024;25(1):321. https://doi.org/10.1186/s12931-024-02951-7.Ketelaar ME, Portelli MA, Dijk FN, Shrine N, Faiz A, Vermeulen CJ et al. Phenotypic and functional translation of IL33 genetics in asthma. J Allergy Clin Immunol. 2021;147(1):144–157. https://doi.org/10.1016/j.jaci.2020.04.051.Ketelaar ME, Portelli MA, Dijk FN, Shrine N, Faiz A, Vermeulen CJ et al. Phenotypic and functional translation of IL33 genetics in asthma. J Allergy Clin Immunol. 2021;147(1):144–157. https://doi.org/10.1016/j.jaci.2020.04.051.Saikumar Jayalatha AK, Ketelaar ME, Hesse L, Badi YE, Zounemat-Kermani N, Brouwer S et al. IL-33 induced gene expression in activated Th2 effector cells is dependent on IL-1RL1 haplotype and asthma status. Eur Respir J. 2024;63(6):2400005. https://doi.org/10.1183/13993003.00005-2024.Saikumar Jayalatha AK, Ketelaar ME, Hesse L, Badi YE, Zounemat-Kermani N, Brouwer S et al. IL-33 induced gene expression in activated Th2 effector cells is dependent on IL-1RL1 haplotype and asthma status. Eur Respir J. 2024;63(6):2400005. https://doi.org/10.1183/13993003.00005-2024.McAlees JW, Baker T, Houshel L, McKnight C, Lindsley A, Strait RT et al. Increased nasal epithelial cell responsiveness to IL-17A in paediatric asthmatics with low blood neutrophil count, low traffic-related air pollution exposure and good asthma control. Clin Exp Allergy. 2022;52:569–573. https://doi.org/10.1111/cea.14080.McAlees JW, Baker T, Houshel L, McKnight C, Lindsley A, Strait RT et al. Increased nasal epithelial cell responsiveness to IL-17A in paediatric asthmatics with low blood neutrophil count, low traffic-related air pollution exposure and good asthma control. Clin Exp Allergy. 2022;52:569–573. https://doi.org/10.1111/cea.14080.Wilburn AN, McAlees JW, Haslam DB, Graspeuntner S, Schmudde I, Laumonnier Y et al. Delayed microbial maturation durably exacerbates Th17-driven asthma in mice. Am J Respir Cell Mol Biol. 2023;68(5):498–510. https://doi.org/10.1165/rcmb.2022-0367OC.Wilburn AN, McAlees JW, Haslam DB, Graspeuntner S, Schmudde I, Laumonnier Y et al. Delayed microbial maturation durably exacerbates Th17-driven asthma in mice. Am J Respir Cell Mol Biol. 2023;68(5):498–510. https://doi.org/10.1165/rcmb.2022-0367OC.Messaoud-Nacer Y, Culerier E, Rose S, Maillet I, Boussad R, Veront C et al. STING-dependent induction of neutrophilic asthma exacerbation in response to house dust mite. Allergy. 2025;80(3):715–737. https://doi.org/10.1111/all.16369.Messaoud-Nacer Y, Culerier E, Rose S, Maillet I, Boussad R, Veront C et al. STING-dependent induction of neutrophilic asthma exacerbation in response to house dust mite. Allergy. 2025;80(3):715–737. https://doi.org/10.1111/all.16369.Lunding LP, Weckmann M, Zissler UM, Jakwerth C, Bodenstein-Sgró R, Webering S et al. Immune training of the interleukin 6 gene in airway epithelial cells is central to asthma exacerbations. Allergy. 2026;81(1):157–169. https://doi.org/10.1111/all.70070.Lunding LP, Weckmann M, Zissler UM, Jakwerth C, Bodenstein-Sgró R, Webering S et al. Immune training of the interleukin 6 gene in airway epithelial cells is central to asthma exacerbations. Allergy. 2026;81(1):157–169. https://doi.org/10.1111/all.70070.Briceno Noriega D, Savelkoul HFJ. Vitamin D and allergy susceptibility during gestation and early life. Nutrients. 2021;13(3):1015. https://doi.org/10.3390/nu13031015.Briceno Noriega D, Savelkoul HFJ. Vitamin D and allergy susceptibility during gestation and early life. Nutrients. 2021;13(3):1015. https://doi.org/10.3390/nu13031015.Alolayan A, Al-Wutayd O. Association between vitamin D status and asthma control levels among children and adolescents: a retrospective cross sectional study in Saudi Arabia. BMC Pediatr. 2025;25(1):585. https://doi.org/10.1186/s12887-025-05969-y.Alolayan A, Al-Wutayd O. Association between vitamin D status and asthma control levels among children and adolescents: a retrospective cross sectional study in Saudi Arabia. BMC Pediatr. 2025;25(1):585. https://doi.org/10.1186/s12887-025-05969-y.Fangal VD, Kılıç A, Mirzakhani H, Litonjua AA, Demay MB, Levy BD, Weiss ST. Vitamin D exerts endogenous control over TH2 cell fate and immune plasticity. iScience. 2025;28(4):112117. https://doi.org/10.1016/j.isci.2025.112117.Fangal VD, Kılıç A, Mirzakhani H, Litonjua AA, Demay MB, Levy BD, Weiss ST. Vitamin D exerts endogenous control over TH2 cell fate and immune plasticity. iScience. 2025;28(4):112117. https://doi.org/10.1016/j.isci.2025.112117.Sapartini G, Wong GWK, Indrati AR, Kartasasmita CB, Setiabudiawan B. The Association between vitamin D, interleukin-4, and interleukin-10 levels and CD23+ expression with bronchial asthma in stunted children. Biomedicines. 2023;11(9):2542. https://doi.org/10.3390/biomedicines11092542.Sapartini G, Wong GWK, Indrati AR, Kartasasmita CB, Setiabudiawan B. The Association between vitamin D, interleukin-4, and interleukin-10 levels and CD23+ expression with bronchial asthma in stunted children. Biomedicines. 2023;11(9):2542. https://doi.org/10.3390/biomedicines11092542.Alvi S, Syed JG, Nusrat B, Abbas Razvi SK, Shah ZZ, Shafaat Khan Y et al. Frequency of vitamin D deficiency in patients of asthma. Cureus. 2021;13(5):e14828. https://doi.org/10.7759/cureus.14828.Alvi S, Syed JG, Nusrat B, Abbas Razvi SK, Shah ZZ, Shafaat Khan Y et al. Frequency of vitamin D deficiency in patients of asthma. Cureus. 2021;13(5):e14828. https://doi.org/10.7759/cureus.14828.Shadid IL, Brustad N, Lu M, Chawes BL, Bisgaard H, Zeiger RS et al. The impact of baseline 25-hydroxyvitamin D level and gestational age on prenatal vitamin D supplementation to prevent offspring asthma or recurrent wheezing. Am J Clin Nutr. 2023;117(6):1342–1352. https://doi.org/10.1016/j.ajcnut.2023.04.019.Shadid IL, Brustad N, Lu M, Chawes BL, Bisgaard H, Zeiger RS et al. The impact of baseline 25-hydroxyvitamin D level and gestational age on prenatal vitamin D supplementation to prevent offspring asthma or recurrent wheezing. Am J Clin Nutr. 2023;117(6):1342–1352. https://doi.org/10.1016/j.ajcnut.2023.04.019.Dong L, Li Y. Vitamin D deficiency and asthma morbidity in school-age children: a single-center cohort study. Front Public Health. 2025;13:1717912. https://doi.org/10.3389/fpubh.2025.1717912.Dong L, Li Y. Vitamin D deficiency and asthma morbidity in school-age children: a single-center cohort study. Front Public Health. 2025;13:1717912. https://doi.org/10.3389/fpubh.2025.1717912.Malheiro APG, Gianfrancesco L, Nogueira RJN, Grotta MB, Morcillo AM, Ribeiro JD, Toro AADC. Association between serum vitamin D levels and asthma severity and control in children and adolescents. Lung. 2023;201(2):181–187. https://doi.org/10.1007/s00408-023-00605-x.Malheiro APG, Gianfrancesco L, Nogueira RJN, Grotta MB, Morcillo AM, Ribeiro JD, Toro AADC. Association between serum vitamin D levels and asthma severity and control in children and adolescents. Lung. 2023;201(2):181–187. https://doi.org/10.1007/s00408-023-00605-x.Bhat KG, Mahalingam S, Soumya VC. Vitamin D and its association with severity and control of childhood bronchial asthma. Indian J Public Health. 2023;67(1):3–7. https://doi.org/10.4103/ijph.ijph_1507_21.Bhat KG, Mahalingam S, Soumya VC. Vitamin D and its association with severity and control of childhood bronchial asthma. Indian J Public Health. 2023;67(1):3–7. https://doi.org/10.4103/ijph.ijph_1507_21.Vaghela DM, Makwana NK, Aravind A, Shankar DKM. Association of vitamin D level in hyperreactive airway diseases: a case-control study. Cureus. 2025;17(1):e77037. https://doi.org/10.7759/cureus.77037.Vaghela DM, Makwana NK, Aravind A, Shankar DKM. Association of vitamin D level in hyperreactive airway diseases: a case-control study. Cureus. 2025;17(1):e77037. https://doi.org/10.7759/cureus.77037.Барычева ЛЮ, Долбня СВ, Толкунова АА, Климов ЛЯ, Кузнецова ВВ, Понамарева ВР, Захарова ИН. Обеспеченность витамином D, респираторные вирусные инфекции и персистирующие хрипы у детей: насколько значима взаимосвязь? Медицинский совет. 2024;18(1):72–81. https://doi.org/10.21518/ms2024-007.Barycheva LYu, Dolbnya SV, Tolkunova AA, Klimov LYa, Kuznetsova VV, Ponamaryova VR, Zakharova IN. Vitamin D supply, respiratory viral infections and persistent wheezing in children: how significant is the relationship? Meditsinskiy Sovet. 2024;18(1):72–81. (In Russ.) https://doi.org/10.21518/ms2024-007.Долбня СВ, Понамарева ВР, Захарова ИН, Климов ЛЯ, Толкунова АА, Барычева ЛЮ и соавт. Эффективность коррекции гиповитаминоза D на фоне стандартной ступенчатой терапии бронхиальной астмы у детей. Медицинский совет. 2025;19(11):188–196. https://doi.org/10.21518/ms2025-279.Dolbnya SV, Ponamaryova VR, Zakharova IN, Klimov LYa, Tolkunova AA, Barycheva LYu et al. Effectiveness of correction of hypovitaminosis D against the background of standard step therapy of bronchial asthma in children. Meditsinskiy Sovet. 2025;19(11):188–196. (In Russ.) https://doi.org/10.21518/ms2025-279.Krasowski R, Kamińska K, Głodek K, Ostrowska J, Zajda K, Pawliczak R, Kleniewska P. The therapeutic potential of vitamin D supplementation in asthma. Pharmacol Rep. 2025;77(4):874–888. https://doi.org/10.1007/s43440-025-00734-5.Krasowski R, Kamińska K, Głodek K, Ostrowska J, Zajda K, Pawliczak R, Kleniewska P. The therapeutic potential of vitamin D supplementation in asthma. Pharmacol Rep. 2025;77(4):874–888. https://doi.org/10.1007/s43440-025-00734-5.Fedora K, Setyoningrum RA, Aina Q, Rosyidah LN, Ni’mah NL, Titiharja FF. Vitamin D supplementation decrease asthma exacerbations in children: a systematic review and meta-analysis of randomized controlled trials. Ann Med. 2024;56(1):2400313. https://doi.org/10.1080/07853890.2024.2400313.Fedora K, Setyoningrum RA, Aina Q, Rosyidah LN, Ni’mah NL, Titiharja FF. Vitamin D supplementation decrease asthma exacerbations in children: a systematic review and meta-analysis of randomized controlled trials. Ann Med. 2024;56(1):2400313. https://doi.org/10.1080/07853890.2024.2400313.Kumar J, Kumar P, Goyal JP, Thakur C, Choudhary P, Meena J et al. Vitamin D supplementation in childhood asthma: a systematic review and metaanalysis of randomised controlled trials. ERJ Open Res. 2021;8(1):006622021. https://doi.org/10.1183/23120541.00662-2021.Kumar J, Kumar P, Goyal JP, Thakur C, Choudhary P, Meena J et al. Vitamin D supplementation in childhood asthma: a systematic review and metaanalysis of randomised controlled trials. ERJ Open Res. 2021;8(1):006622021. https://doi.org/10.1183/23120541.00662-2021.Devulapalli CS. Vitamin D and asthma in pediatrics: evidence and clinical implications. World J Pediatr. 2025;21(8):760–765. https://doi.org/10.1007/s12519-025-00947-x.Devulapalli CS. Vitamin D and asthma in pediatrics: evidence and clinical implications. World J Pediatr. 2025;21(8):760–765. https://doi.org/10.1007/s12519-025-00947-x.Чучалин АГ, Геппе НА, Колосова НГ, Кондюрина ЕГ, Малахов АБ, Мизерницкий ЮЛ, Ревякина ВА. Национальная программа «Бронхиальная астма у детей. Стратегия лечения и профилактика». 5-е изд. М.; 2017. 160 с. Режим доступа: https://astgmu.ru/wp-content/uploads/2018/10/Natsionalnaya-programma-BA-u-detej.-Strategiya-lecheniya-i-profilaktika.pdf.Чучалин АГ, Геппе НА, Колосова НГ, Кондюрина ЕГ, Малахов АБ, Мизерницкий ЮЛ, Ревякина ВА. Национальная программа «Бронхиальная астма у детей. Стратегия лечения и профилактика». 5-е изд. М.; 2017. 160 с. Режим доступа: https://astgmu.ru/wp-content/uploads/2018/10/Natsionalnaya-programma-BA-u-detej.-Strategiya-lecheniya-i-profilaktika.pdf.Боровик ТЭ, Громова ОА, Захарова ИН, Мальцев СВ, Мошетова ЛК, Намазова-Баранова ЛС и др. Недостаточность витамина D у детей и подростков Российской Федерации: современные подходы к коррекции: национальная программа. 2-е изд. М.; 2021. 116 с.Боровик ТЭ, Громова ОА, Захарова ИН, Мальцев СВ, Мошетова ЛК, Намазова-Баранова ЛС и др. Недостаточность витамина D у детей и подростков Российской Федерации: современные подходы к коррекции: национальная программа. 2-е изд. М.; 2021. 116 с.Ntinopoulou M, Cassimos D, Roupakia E, Kolettas E, Panopoulou M, Mantadakis E et al. Ιnterleukin-17A-Enriched neutrophil extracellular traps promote immunofibrotic aspects of childhood asthma exacerbation. Biomedicines. 2023;11(8):2104. https://doi.org/10.3390/biomedicines11082104.Ntinopoulou M, Cassimos D, Roupakia E, Kolettas E, Panopoulou M, Mantadakis E et al. Ιnterleukin-17A-Enriched neutrophil extracellular traps promote immunofibrotic aspects of childhood asthma exacerbation. Biomedicines. 2023;11(8):2104. https://doi.org/10.3390/biomedicines11082104.Zhou T, Huang X, Zhou Y, Ma J, Zhou M, Liu Y et al. Associations between Th17-related inflammatory cytokines and asthma in adults: A Case-Control Study. Sci Rep. 2017;7(1):15502. https://doi.org/10.1038/s41598-017-15570-8.Zhou T, Huang X, Zhou Y, Ma J, Zhou M, Liu Y et al. Associations between Th17-related inflammatory cytokines and asthma in adults: A Case-Control Study. Sci Rep. 2017;7(1):15502. https://doi.org/10.1038/s41598-017-15570-8.Agache I, Ciobanu C, Agache C, Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med. 2010;104(8):1131–1137. https://doi.org/10.1016/j.rmed.2010.02.018.Agache I, Ciobanu C, Agache C, Anghel M. Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med. 2010;104(8):1131–1137. https://doi.org/10.1016/j.rmed.2010.02.018.Pirogov AB, Prikhodko AG, Pirogova NA, Naumov DE, Gassan DA, Perelman JM. Content of Th17 related and Th2 cytokines in asthma patients with cold airway hyperresponsiveness. Medical Immunology (Russia). 2025;27(2):351–360. (In Russ.) https://doi.org/10.15789/15630625-COT-3020.Pirogov AB, Prikhodko AG, Pirogova NA, Naumov DE, Gassan DA, Perelman JM. Content of Th17 related and Th2 cytokines in asthma patients with cold airway hyperresponsiveness. Medical Immunology (Russia). 2025;27(2):351–360. (In Russ.) https://doi.org/10.15789/15630625-COT-3020.Zhao R, Shi Y, Liu N, Li B. Elevated levels of interleukin-33 are associated with asthma: A meta-analysis. Immun Inflamm Dis. 2023;11(4):e842. https://doi.org/10.1002/iid3.842.Zhao R, Shi Y, Liu N, Li B. Elevated levels of interleukin-33 are associated with asthma: A meta-analysis. Immun Inflamm Dis. 2023;11(4):e842. https://doi.org/10.1002/iid3.842.Wang Y, Wang L, Hua S. Interleukin-33 in children with asthma: A systematic review and meta-analysis. Allergol Immunopathol (Madr). 2017;45(4):387–392. https://doi.org/10.1016/j.aller.2016.12.007.Wang Y, Wang L, Hua S. Interleukin-33 in children with asthma: A systematic review and meta-analysis. Allergol Immunopathol (Madr). 2017;45(4):387–392. https://doi.org/10.1016/j.aller.2016.12.007.Geng L, Xiao R, Chang K. Changes and correlation of serum levels of interleukins 33, 15, 4, and interferon γ in children with bronchial asthma at different periods. Postepy Dermatol Alergol. 2024;41(5):473–478. https://doi.org/10.5114/ada.2024.143542.Geng L, Xiao R, Chang K. Changes and correlation of serum levels of interleukins 33, 15, 4, and interferon γ in children with bronchial asthma at different periods. Postepy Dermatol Alergol. 2024;41(5):473–478. https://doi.org/10.5114/ada.2024.143542.Ladeira JM, Zacas O, Ferreira AM, Stegun PCG, Grotta MB, Toro AADC. The role of vitamin D in severity and control of asthma in children and adolescents: a systematic review and meta-analysis. Pediatr Pulmonol. 2026;61(3):e71541. https://doi.org/10.1002/ppul.71541.Ladeira JM, Zacas O, Ferreira AM, Stegun PCG, Grotta MB, Toro AADC. The role of vitamin D in severity and control of asthma in children and adolescents: a systematic review and meta-analysis. Pediatr Pulmonol. 2026;61(3):e71541. https://doi.org/10.1002/ppul.71541.El Abd A, Dasari H, Dodin P, Trottier H, Ducharme FM. Associations between vitamin D status and biomarkers linked with inflammation in patients with asthma: a systematic review and meta-analysis of interventional and observational studies. Respir Res. 2024;25(1):344. https://doi.org/10.1186/s12931-024-02967-z.El Abd A, Dasari H, Dodin P, Trottier H, Ducharme FM. Associations between vitamin D status and biomarkers linked with inflammation in patients with asthma: a systematic review and meta-analysis of interventional and observational studies. Respir Res. 2024;25(1):344. https://doi.org/10.1186/s12931-024-02967-z.

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