Cytokine profile and vitamin D concentration in children with acute bronchiolitis depending on respiratory distress severity

A. E. Andzhel; A. B. Malakhov; I. A. Antonyan; T. A. Gutyrchik; P. V. Berezhanskiy; E. V. Deeva

doi:10.21518/ms2025-381

Cytokine profile and vitamin D concentration in children with acute bronchiolitis depending on respiratory distress severity

A. E. Andzhel, A. B. Malakhov, I. A. Antonyan, T. A. Gutyrchik, P. V. Berezhanskiy, E. V. Deeva

https://doi.org/10.21518/ms2025-381

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Abstract

Introduction. Acute bronchiolitis is one of the most frequent manifestations of viral infection of early age, in particular in children under 1 year of age. The course of acute bronchiolitis is characterized by a marked variability of the clinical picture in the direction of aggravation in separate groups of patients.

Aim. To reveal the peculiarities of cytokine profile and vitamin D concentration in blood serum of children with acute bronchiolitis depending on respiratory distress (RD) severity.

Materials and methods. In the pulmonology department of the Morozovsky Municipal Children Clinical Hospital in 2021–2022, 56 patients aged from 1 to 12 months with the diagnosis of acute bronchiolitis with different degrees of RD were examined. In addition to the standard methods of investigation (anamnesis, physical examination, general and biochemical blood tests, assessment of CRP concentration), all patients underwent determination of interleukin-6 (IL-6), interleukin-4 (IL-4) and vitamin D concentrations in blood.

Results. With a mean vitamin D concentration of less than 14.8 ng/mL, the number of acute respiratory infections (ARIs) suffered was more than 3 episodes, and with a value of less than 21.5 ng/mL, the number of ARI episodes was 2. The level of proinflammatory cytokine IL-6 and anti-inflammatory cytokine IL-4 decreased with increasing degree of RD. A direct moderate correlation between vitamin D and IL-4 concentration in blood (r = 0.44) was revealed, respectively, a higher level of vitamin D will result in a higher level of IL-4.

Conclusion. In patients with acute bronchiolitis, changes in cytokine concentrations correlate with the degree of respiratory failure: a decrease in IL-4 and IL-6 concentrations is observed with an increase in the degree of RD. Patients with low vitamin D concentration have lower resistance to upper respiratory tract infections.

Keywords

bronchiolitis, vitamin D, interleukins, cytokine profile, respiratory distress, children

About the Authors

A. E. Andzhel

Morozovsky Municipal Children Clinical Hospital
Россия

Andrey E. Andzhel, Deputy Chief Physician

1/9, 4^th Dobryninsky Lane, Moscow, 119049

A. B. Malakhov

Morozovsky Municipal Children Clinical Hospital; Research Clinical Institute of Childhood; Sechenov First Moscow State Medical University (Sechenov University)
Россия

Alexander B. Malakhov, Dr. Sci. (Med.), Professor of the Department of Children’s Diseases, Clinical Institute of Child Health named after N.F. Filatov; Chief Freelance Pediatric Specialist-Pulmonologist of the Department of Health of Moscow and the Ministry of Health of the Moscow Region; Head of the Pediatrics Department; Pulmonologist

1/9, 4^th Dobryninsky Lane, Moscow, 119049

8, Bldg. 2, Trubetskaya St., Moscow, 119991

62, Bolshaya Serpukhovskaya St., Moscow, 115093

I. A. Antonyan

Morozovsky Municipal Children Clinical Hospital
Россия

Inga A. Antonyan, Resident

1/9, 4^th Dobryninsky Lane, Moscow, 119049

T. A. Gutyrchik

Morozovsky Municipal Children Clinical Hospital
Россия

Tatiana A. Gutyrchik, Pulmonologist, Pediatrician

1/9, 4^th Dobryninsky Lane, Moscow, 119049

P. V. Berezhanskiy

Morozovsky Municipal Children Clinical Hospital; Sechenov First Moscow State Medical University (Sechenov University); Research Clinical Institute of Childhood; Peoples’ Friendship University of Russia named after Patrice Lumumba”
Россия

Pavel V. Berezhanskiy, Dr. Sci. (Med.), Professor of the Department of Children’s Diseases; Pulmonologist; Senior Researcher of the Department of Pediatrics; Assistant of the Department of Clinical Immunology, Allergology and Adaptology, Faculty of Continuing Medical Education of the Medical Institute

1/9, 4^th Dobryninsky Lane, Moscow, 119049

8, Bldg. 2, Trubetskaya St., Moscow, 119991

62, Bolshaya Serpukhovskaya St., Moscow, 115093

6, Miklukho-Maklai St., Moscow, 117198

E. V. Deeva

Morozovsky Municipal Children Clinical Hospital
Россия

Evgenia V. Deeva, Cand. Sci. (Med.), Head of the Pulmonology Department

1/9, 4^th Dobryninsky Lane, Moscow, 119049

References

1. Chuchalin AG, Geppe NA, Rozinova NN, Volkov IK, Mizernitskiy YuL, Artamonov RG et al. Modern classification of clinical forms of bronchopulmonary diseases in children. Pediatriya – Zhurnal im G.N. Speranskogo. 2010;89(4):6–15. (In Russ.) Available at: https://pediatriajournal.ru/files/upload/mags/306/2010_4_2687.pdf.

2. Ghazaly M, Nadel S. Characteristics of children admitted to intensive care with acute bronchiolitis. Eur J Pediatr. 2018;177(6):913–920. https://doi.org/10.1007/s00431-018-3138-6.

3. Janssen R, Bont L, Siezen CL, Hodemaekers HM, Ermers MJ, Doornbos G et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis. 2007;196(6):826–834. https://doi.org/10.1086/520886.

4. Figueras-Aloy J, Carbonell-Estrany X, Quero J. Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33-35 weeks in Spain. Pediatr Infect Dis J. 2004;23(9):815–820. https://doi.org/10.1097/01.inf.0000136869.21397.6b.

5. Law BJ, Langley JM, Allen U, Paes B, Lee DS, Mitchell I et al. The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation. Pediatr Infect Dis J. 2004;23(9):806–814. https://doi.org/10.1097/01.inf.0000137568.71589.bd.

6. Stensballe LG, Kristensen K, Simoes EA, Jensen H, Nielsen J, Benn CS, Aaby P. Atopic disposition, wheezing, and subsequent respiratory syncytial virus hospitalization in Danish children younger than 18 months: a nested case-control study. Pediatrics. 2006;118(5):1360–1368. https://doi.org/10.1542/peds.2006-0907.

7. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474–e1502. https://doi.org/10.1542/peds.2014-2742.

8. Jones LL, Hashim A, McKeever T, Cook DG, Britton J, Leonardi-Bee J. Parental and household smoking and the increased risk of bronchitis, bronchiolitis and other lower respiratory infections in infancy: systematic review and meta-analysis. Respir Res. 2011;12(1):5. https://doi.org/10.1186/1465-9921-12-5.

9. Malakhov AB, Berezhansky PV, Vlasova AV, Shubina YuF, Gutyrchik TA, Andzhel AE et al. Experience of using syndromic approaches to the diagnosis of respiratory infections. Clinical Practice in Pediatrics. 2023;18(5):27–33. (In Russ.) https://doi.org/10.20953/1817-7646-2023-5-27-33.

10. Risnes KR, Belanger K, Murk W, Bracken MB. Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a cohort of 1,401 US children. Am J Epidemiol. 2011;173(3):310–318. https://doi.org/10.1093/aje/kwq400.

11. Kabra SK, Ghai OP. Respiratory disorders. In: Ghai OP, Gupta P, Paul VK (eds.). Ghai Essentials Pediatrics. 6th ed. New Delhi: CBS Publishers and Distributors; 2004, pp. 352–354.

12. Delyagin VM. Acute bronchiolitis in children. Meditsinskiy Sovet. 2013;(1):64–68. (In Russ.) Available at: https://www.med-sovet.pro/jour/article/view/860.

13. Xu Q, Shen L, Lu M, Ran S, Jiang W, Hua J, Li L. Establishment and validation of a prediction model for apnea on bronchiolitis. Front Pediatr. 2024;12:1397750. https://doi.org/10.3389/fped.2024.1397750.

14. Malakhov AB, Andzhel AE, Ozerskaya IV, Kovalenko IV, Gorev VV, Kolosova NG, Sokolina IA. Modern approaches to diagnosis and treatment of acute bronchiolitis in young children. Lechebnoe Delo. 2020;(4):54–59. (In Russ.) https://doi.org/10.24412/2071-5315-2020-12271.

15. Baranov AA, Namazova-Baranova LS, Tatochenko VK, Davydova IV, Bakradze MD, Vishnyova EA et al. Acute Bronchiolitis in Children. Current Approaches to Diagnosis and Therapy. Pediatric Pharmacology. 2015;12(4):441–446. (In Russ.) https://doi.org/10.15690/pf.v12i4.1426.

16. Malakhov AB, Andzhel AE, Berezhanskiy PV, Elagina VI, Gorev VV, Gorbunov AV, Sedova AYu. Interleukin Profile in Children with Acute Bronchiolitis (Raw Data). Doctor.Ru. 2021;20(10):12–17. (In Russ.) https://doi.org/10.31550/1727-2378-2021-20-10-12-17.

17. Ao T, Kikuta J, Ishii M. The Effects of Vitamin D on Immune System and Inflammatory Diseases. Biomolecules. 2021;11(11):1624. https://doi.org/10.3390/biom11111624.

18. Wimalawansa SJ. Infections and Autoimmunity – The Immune System and Vitamin D: A Systematic Review. Nutrients. 2023;15(17):3842. https://doi.org/10.3390/nu15173842.

19. Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D’s Effect on Immune Function. Nutrients. 2020;12(5):1248. https://doi.org/10.3390/nu12051248.

20. Xu Y, Baylink DJ, Chen CS, Reeves ME, Xiao J, Lacy C et al. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J Transl Med. 2020;18(1):322. https://doi.org/10.1186/s12967-020-02488-5.

21. Mailhot G, White JH. Vitamin D and Immunity in Infants and Children. Nutrients. 2020;12(5):1233. https://doi.org/10.3390/nu12051233.

22. Ismailova A, White JH. Vitamin D, infections and immunity. Rev Endocr Metab Disord. 2022;23(2):265–277. https://doi.org/10.1007/s11154-021-09679-5.

23. Manti S, Staiano A, Orfeo L, Midulla F, Marseglia GL, Ghizzi C et al. UPDATE – 2022 Italian guidelines on the management of bronchiolitis in infants. Ital J Pediatr. 2023;49(1):19. https://doi.org/10.1186/s13052-022-01392-6.

24. Baranov AA, Namazova-Baranova LS, Tatochenko VK, Davydova IV, Bakradze MD, Kulichenko TV et al. Modern Approaches in Management of Children with Acute Bronchiolitis. Pediatric Pharmacology. 2019;16(6):339–348. (In Russ.) https://doi.org/10.15690/pf.v16i6.2071.

25. Paluch L. Identifying and managing bronchiolitis. JAAPA. 2020;33(9):12–15. https://doi.org/10.1097/01.JAA.0000694944.22382.39.

26. Törmänen S, Lauhkonen E, Riikonen R, Koponen P, Huhtala H, Helminen M et al. Risk factors for asthma after infant bronchiolitis. Allergy. 2018;73(4):916–922. https://doi.org/10.1111/all.13347.

27. Caffrey Osvald E, Clarke JR. NICE clinical guideline: bronchiolitis in children. Arch Dis Child Educ Pract Ed. 2016;101(1):46–48. https://doi.org/10.1136/archdischild-2015-309156.

28. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT et al. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J. 1999;14(1):144–149. Available at: https://publications.ersnet.org/content/erj/14/1/144.

29. Emam AA, Shehab MMM, Allah MAN, Elkoumi MA, Abdelaal NM, Mosabah AAA et al. Interleukin-4 -590C/T gene polymorphism in Egyptian children with acute lower respiratory infection: A multicenter study. Pediatr Pulmonol. 2019;54(3):297–302. https://doi.org/10.1002/ppul.24235.

30. Spurling GK, Doust J, Del Mar CB, Eriksson L. Antibiotics for bronchiolitis in children. Cochrane Database Syst Rev. 2011;(6):CD005189. https://doi.org/10.1002/14651858.CD005189.pub3.

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For citations:

Andzhel AE, Malakhov AB, Antonyan IA, Gutyrchik TA, Berezhanskiy PV, Deeva EV. Cytokine profile and vitamin D concentration in children with acute bronchiolitis depending on respiratory distress severity. Meditsinskiy sovet = Medical Council. 2025;(19):329–337. (In Russ.) https://doi.org/10.21518/ms2025-381

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