G.A. IGNATENKO¹, S.YA. YAROSHENKO¹, E.S. MIKHALEVА²

 ¹M. Gorky Donetsk State Medical University, Donetsk, Donetsk People’s Republic

²Central City Clinical Hospital № 3 of Donetsk, Donetsk, Donetsk People’s Republic

Contact details:

Yaroshenko S.Ya. — MD, Associate Professor, Professor of the Department of Pediatric Propaedeutics

Address: 16 prospekt Ilyicha, 283003 Donetsk, Russian Federation, tel.: +7-949-362-65-15, e-mail: yaroshenkosy@yandex.ru

The article considers pathophysiological and immunological aspects of bronchial asthma in children and prospects for using hypoxytherapy as a non-pharmacological treatment method. Hypoxic stimulation was shown to have a modulating effect on the key links of bronchial asthma pathogenesis: it reduces inflammation, promotes bronchial remodeling, activates antioxidant protection and normalizes the immune response. Special attention was paid to the intermittent hypoxia as a way of preconditioning which promotes activation of adaptive mechanisms in children. Data from clinical and experimental studies are provided confirming the effectiveness of the method. It is concluded that hypoxytherapy should be part of comprehensive rehabilitation programs for children with bronchial asthma.

Key words: bronchial asthma, children, hypoxytherapy, hypoxia, inflammation, bronchial remodeling, non-pharmacological therapy.

REFERENCES

1. Vsemirnaya organizatsiya zdravookhraneniya. Global’naya strategiya po astme [World Health Organization. Global Asthma Strategy]. Zheneva: VOZ, 2023.
2. FGBU «TsNIIOIZ» Minzdrava Rossii — Glavnaya stranitsa []. (n.d.). Retrieved February 9, 2024, from https://mednet.ru/
3. Papadopoulos N.G. et al. International consensus on (ICON) pediatric asthma. Allergy, 2012, vol. 67 (8), pp. 976–997.
4. Natsional’naya programma «Bronkhial’naya astma u detey. Strategiya lecheniya i profilaktika» [National Program «Bronchial Asthma in Children. Treatment Strategy and Prevention»]. Moscow: Original-maket, 2017. ISBN 978-5-9909505-3-5
5. Huerta-Yepez S. et al. Hypoxia-inducible factors and their role in asthma. Am. J. Resp. Cell Mol. Biol, 2011,  vol. 45 (6),  pp. 1104–1112.
6. Poryadin Yu.A., Pimenov A.V. Hypoxic signaling pathways in the pathogenesis of asthma. Voprosy sovremennoy pediatrii, 2021,  vol. 20, no. 4,  pp. 185–190.
7. Ryvkin A.I., Glazova T.G., Pobedinskaya N.S., Laryushkina R.M., Reshetova T.G. Pathogenetic mechanisms of bronchial remodeling in bronchial asthma in children. Meditsinskiy al’manakh, 2017,  no. 2 (47) (in Russ.).
8. Comhair S.A.A., Erzurum S.C. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxidants & Redox Signaling. ISSN: 1523-0864 EISSN: 1557-7716 r. 93–124.
9. Rahman I., MacNee W. Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J, 2000,  vol. 16,  pp. 534–554.
10. Sies H., Jones D.P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol, 2020,  vol. 21 (7),  pp. 363–383. DOI: 10.1038/s41580-020-0230-3
11. Larsson-Callerfelt A-K. et al. Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders. Front. Physiol, 2023,  vol. 14. 1094245. DOI: 10.3389/fphys.2023.1094245
12. Verges S., Chacaroun S., Godin-Ribuot D., Baillieul S. Hypoxic conditioning as a new therapeutic modality. Front. Pediatr, 2015,  vol. 3,  p. 58. DOI: 10.3389/fped.2015.00058
13. Uryas’ev O.M., Isaeva I.A., Byalovskiy Yu.Yu. Non-drug therapy of patients with bronchial asthma with concomitant cardiovascular diseases (hypertension, coronary heart disease) at the hospital stage. ZV, 2017,  no. 1 (in Russ.).
14. Millan I., Korral’-Debriski M., Vento M. i Torres-Kuevas I. Hypoxic preconditioning induces neuroprotection against oxidative stress. Redox Exp. Med, 2022,  no. 1,  rr. R159–R167 (in Russ.). DOI: 10.1530/REM-22-0011
15. Tanveer A., Manish K., Ulaganathan M., Bijay P., Shilpi A., Ranjana S. et al. Hypoxia response in asthma differential modulation on inflammation and epithelial injury. Am. J. Resp. Cell Mol. Biol, vol. 47 (1).
16. Berggren-Nylund R., Ryde M., Löfdahl A., Ibáñez-Fonseca A., Kåredal M. et al. Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders. Sec. Resp. Physiol. Pathophysiol, 2023,  vol. 14. DOI: 10.3389/fphys.2023.1094245
17. Kolchinskaya A.Z., Tsyganova T.N., Ostapenko L.A. Normobaricheskaya interval’naya gipoksicheskaya trenirovka v meditsine i sporte: pukovodstvo dlya vrachey [Normobaric interval hypoxic training in medicine and sports: a guide for doctors]. Moscow: Meditsina, 2003. 406 p.
18. Zhang C., Gao J., Zhu S. Hypoxia-inducible factor-1α promotes proliferation of airway smooth muscle cells through miRNA-103-mediated signaling pathway under hypoxia. In Vitro Cell Dev. Biol. Anim, 2021,  vol. 57 (10),  pp. 944–952. DOI: 10.1007/s11626-021-00607-0
19. Struchkov P.V. Fizicheskie faktory v korrektsii gipoksicheskikh narusheniy u bol’nykh khronicheskim obstruktivnym bronkhitom i bronkhial’noy astmoy: avtoref. diss. … d.m.n. [Physical factors in the correction of hypoxic disorders in patients with chronic obstructive bronchitis and bronchial asthma. Synopsis of Dis. Dr med. Sciences]. Moscow, 2004.
20. Ignatenko G.A., Dubovaya A.V., Naumenko Yu.V. Possibilities of using normobaric hypoxic therapy in therapeutic and pediatric practices. Rossiyskiy vestnik perinatologii i pediatrii, 2022,  vol. 67, no. 6,  pp. 46–53 (in Russ.). DOI: 10.21508/1027-4065-2022-67-6-46-53
21. Kolchinskaya A.Z. Mekhanizmy deystviya interval’noy gipoksicheskoy trenirovki. Interval’naya gipoksicheskaya trenirovka [Mechanisms of action of interval hypoxic training. Interval hypoxic training]. Kiev, 1992. Pp. 107–111.
22. Kolchinskaya A.Z., Beloshitskiy P.V., Monogarov V.D. Physical performance of mountain climbers under conditions of extremely low PO2 in inspired air. Fiziol. zhurn. USSR, 1989,  vol. 35,  pp. 68–73 (in Russ.).
23. Semenza Dzh.L. Hypoxia and HIF factors: physiology and medicine. Cell, 2012, vol. 148, no. 3,  pp. 399–408 (in Russ.).
24. P’yu K.U., Retkliff P.Dzh. Regulation of angiogenesis during hypoxia: the role of the HIF system. Nat. Med, 2003,  vol. 9, no. 6, pp. 677–684 (in Russ.).
25. Berendt T., Belitski R., Berens M., Kherol’d F., Shega L. The effect of intermittent hypoxia-hyperxia on performance and health in humans: a systematic review. Sports Med. Open, 2022,  no. 8 (1),  p. 70 (in Russ.). DOI: 10.1186/s40798-022-00450-x
26. Ivanov A.B., Borukaeva I.Kh., Abazova Z.Kh., Shkhagumov K.Yu., Molov A.A. Intermittent hypoxic therapy in the treatment of patients with bronchial asthma, taking into account chronotypes. Ul’yanovskiy mediko-biologicheskiy zhurnal, 2021,  no. 2.
27. Borukaeva I.Kh., Abazova Z.Kh., Ivanov A.B., Shkhagumov K.Yu., Shavaeva F.V., Molov A.A. et al. The effect of interval hypoxic therapy on the immune status of patients with hypertension. Rossiyskiy immunologicheskiy zhurnal, 2024,  vol. 27, no. 2,  pp. 273–280 (in Russ.).
28. Barabash E.Yu., Kalinina E.P., Gvozdenko T.A., Denisenko Yu.K., Novgorodtseva T.P., Antonyuk M.V., Khodosova K.K. Regulation of the immune response in patients with partially controlled and controlled bronchial asthma. Meditsinskaya immunologiya, 2017,  no. 1 (in Russ.).
29. Novikov V.E., Levchenkova O.S. Hypoxia-induced factor (hif-1α) as a target for pharmacological action. Obzory po klinich. farmakol. i lek. terapii, 2013, no. 2 (in Russ.).
30. Alemanova G.D., Popova L.Yu., Vivtanenko T.V. Efficiency of intermittent hyperbaric hypoxia in bronchial asthma in children and adolescents. Rossiyskiy immunologicheskiy zhurnal, 2018,  vol. 12, no. 3,  pp. 211–215 (in Russ.).
31. Strelkov R.B. Prospects for the use of intermittent normobaric hypoxic therapy in medical practice. Kurortnye vedomosti, 2006,  no. 5 (38),  p. 50 (in Russ.).
32. Ponomareva A.V., Raspertov M.M., Yakovlev M.Yu., Fesyun A.D. Innovative methods of an interdisciplinary approach to medical rehabilitation in children with bronchial asthma. Vestnik vosstanovitel’noy meditsiny, 2021,  vol. 20, no. 4,  pp. 50–56 (in Russ.).
33. Borukaeva I.Kh., Aslanov A.D. The effect of interval hypoxic training and enteral oxygen therapy on the bioelectrical activity of the brain in children with bronchial asthma. Vestnik RUDN. Seriya: Meditsina, 2012,  no. 4 (in Russ.).
34. Uyanaeva A.I., Khan M.A., Tupitsyna Yu.Yu., Chukina I.M., Lyan N.A., MaksimovaG.A. Climatotherapy in the treatment and rehabilitation of children with bronchial asthma complicated by increased meteosensitivity. Allergologiya i immunologiya v pediatrii,  2020,  no. 3 (62),  pp. 23–28 (in Russ.). DOI: 10.24411/2500-1175-2020-00003
35. Lyan N.A., Uyanaeva A.I., Rassulova M.A., Tupitsyna Yu.Yu., Ivanova I.I., Kalinovskaya I.I. Meteopathic reactions and their prevention in children with bronchial asthma in the Moscow region: a prospective cohort study of patients with increased meteosensitivity. Bull. Rehab. Med, 2022,  vol. 21, no. 4,  pp. 97–105 (in Russ.).
36. Alemanova G.D. Intermittent hypoxic hypobaria in the treatment of bronchial asthma in children at the rehabilitation stage. Pediatricheskaya farmakologiya, 2009,  no. 6 (3), pp. 126–129 (in Russ.).