Modern Pediatrics. Ukraine. (2025).4(148): 84-89. doi: 10.15574/SP.2025.4(148).8489
Umanets T. R., Dzisiak V. O., Buratynska A. A., Harashchenko T. A., Bondarenko Yu. M.
SI «Ukrainian center of maternity and childhood of the NAMS of Ukraine», Kyiv

For citation: Umanets TR, Dzisiak VO, Buratynska AA, Harashchenko TA, Bondarenko YuM. (2025). Modern approaches to diagnosis and treatment of respiratory epithelial dysfunction. Modern Pediatrics. Ukraine. 4(148): 84-89. doi: 10.15574/SP.2025.4(148).8489.
Article received: Feb 17, 2025. Accepted for publication: Jun 10, 2025.

The integrity of the respiratory epithelium protects the airways from the penetration of external harmful agents. Impairments in the structure and function of the epithelial barrier can lead to chronic inflammatory processes that underlie the pathogenesis of numerous allergic and inflammatory respiratory diseases, particularly in children.
Аim – to review contemporary scientific literature on the role of epithelial barrier dysfunction in the development of allergic diseases, and to examine methods for the diagnosis and treatment of respiratory epithelial dysfunction (RED) based on the latest scientific evidence.
An analysis of literature from international databases, including PubMed, ScienceDirect, and Google Scholar, for the period 2018-2025 was conducted. RED involves the disruption of its structural integrity, leading to a compromised barrier function and increased permeability to external agents such as allergens, pollutants, and pathogens. In patients with asthma, a decreased expression of proteins that form tight junctions between epithelial cells is observed, constituting a critical pathogenetic mechanism in the development of respiratory allergic diseases. The combined use of modern methods—such as histological and immunohistochemical analyses, electron microscopy, mass spectrometry, proteomics, and the study of alarmins — allows for a more effective assessment of the respiratory epithelial barrier's status. Modern therapeutic strategies for RED are aimed at restoring the structure and function of epithelial tight junctions.
Conclusions. RED is a key factor in the development of asthma and other respiratory diseases, especially in the pediatric population. Early diagnosis and timely intervention to enhance epithelial barrier function are critical for achieving successful disease control. Future research prospects include the development of novel preventive and therapeutic approaches aimed at restoring and maintaining the integrity of the respiratory epithelium.
The authors declare no conflict of interest.
Keywords: respiratory epithelial dysfunction, asthma, epithelial barrier, ectoine, children, allergic diseases, microbiota, diagnostic methods, prevention, treatment.

REFERENCES

1. Aghapour M, Ubags ND, Bruder D, Hiemstra PS et al. (2022). Role of air pollutants in airway epithelial barrier dysfunction in asthma and COPD. Eur Respir Rev. 31(163): 210112. https://doi.org/10.1183/16000617.0112-2021; PMid:35321933 PMCid:PMC9128841

2. Arias-Pérez RD, Taborda NA, Gómez DM, Narvaez JF et al. (2020). Inflammatory effects of particulate matter air pollution. Environ Sci Pollut Res Int. 27(34): 42390-42404. https://doi.org/10.1007/s11356-020-10574-w; PMid:32870429

3. Bourdin A, Brusselle G, Couillard S, Fajt ML, et al. (2024). Phenotyping of Severe Asthma in the Era of Broad-Acting Anti-Asthma Biologics. J Allergy Clin Immunol Pract. 12(4):809-823. https://doi.org/10.1016/j.jaip.2024.01.023; PMid:38280454

4. Carlier FM, de Fays C, Pilette C. (2021). Epithelial Barrier Dysfunction in Chronic Respiratory Diseases. Front Physiol. 12: 691227. https://doi.org/10.3389/fphys.2021.691227; PMid:34248677 PMCid:PMC8264588

5. Celebi Sozener Z, Özdel OB, Cerci P et al. (2022). Epithelial barrier hypothesis: effect of the external exposome on the microbiome and epithelial barriers in allergic disease Allergy. 77(5): 1418-1449. https://doi.org/10.1111/all.15240; PMid:35108405 PMCid:PMC9306534

6. Dong X, Ding M, Zhang J, Ogülür I et al. (2022). Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma. Chin Med J (Engl). 135(5): 519-531. https://doi.org/10.1097/CM9.0000000000001983; PMid:35170505 PMCid:PMC8920422

7. Dorscheid D, Gauvreau GM, Georas SN, Hiemstra PS et al. (2025). Airway epithelial cells as drivers of severe asthma pathogenesis. Mucosal Immunol. 18(3): 524-536. https://doi.org/10.1016/j.mucimm.2025.03.003; PMid:40154790

8. Esnault S, Dill-McFarland KA, Altman MC, Rosenkranz MA et al. (2025). Identification of bronchial epithelial genes associated with type 2 eosinophilic inflammation in asthma. J Allergy Clin Immunol. 155(5): 1510-1520. https://doi.org/10.1016/j.jaci.2024.12.1089; PMid:39793714

9. Frey A, Lunding LP, Wegmann M. (2023). The Dual Role of the Airway Epithelium in Asthma: Active Barrier and Regulator of Inflammation. Cells. 12(18): 2208. https://doi.org/10.3390/cells12182208; PMid:37759430 PMCid:PMC10526792

10. Gohy S, Hupin C, Ladjemi MZ, Hox V, Pilette C. (2020). Key role of the epithelium in chronic upper airways diseases. Clin Exp Allergy. 50(2): 135-146. https://doi.org/10.1111/cea.13539; PMid:31746062

11. Heijink IH, Kuchibhotla VNS, Roffel MP, Maes T et al. (2020). Epithelial cell dysfunction, a major driver of asthma development. Allergy. 75(8): 1902-1917. https://doi.org/10.1111/all.14421; PMid:32460363 PMCid:PMC7496351

12. Hellings PW, Steelant B. (2020). Epithelial barriers in allergy and asthma. J Allergy Clin Immunol. 145(6): 1499-1509. https://doi.org/10.1016/j.jaci.2020.04.010; PMid:32507228 PMCid:PMC7270816

13. Inoue H, Akimoto K, Homma T, Tanaka A et al. (2020). Airway Epithelial Dysfunction in Asthma: Relevant to Epidermal Growth Factor Receptors and Airway Epithelial Cells. J. Clin. Med. 9: 3698. https://doi.org/10.3390/jcm9113698; PMid:33217964 PMCid:PMC7698733

14. Jakwerth CA, Ordovas-Montanes J, Blank S, Schmidt-Weber CB et al. (2022). Role of Respiratory Epithelial Cells in Allergic Diseases. Cells. 11(9): 1387. https://doi.org/10.3390/cells11091387; PMid:35563693 PMCid:PMC9105716

15. Kayalar Ö, Rajabi H, Konyalilar N, Mortazavi D et al. (2024). Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms. Front Immunol. 15: 1324552. https://doi.org/10.3389/fimmu.2024.1324552; PMid:38524119 PMCid:PMC10957538

16. Khaytovych MV. (2021). Ektoin: mekhanizmy respiratornoyi tsytoprotektsiyi (Ectoine: mechanisms of respiratory cytoprotection). Zdorovya Ukrayiny. 16(509): 52-53. https://doi.org/10.21706/aep-16-1-52

17. Kucuksezer UC, Ozdemir C, Yazici D, Pat Y et al. (2023). The epithelial barrier theory: Development and exacerbation of allergic and other chronic inflammatory diseases. Asia Pac Allergy. 13(1): 28-39. https://doi.org/10.5415/apallergy.0000000000000005; PMid:37389096 PMCid:PMC10166244

18. Lee YG, Lee PH, Choi SM, An MH et al. (2021). Effects of Air Pollutants on Airway Diseases. Int J Environ Res Public Health. 18(18): 9905. https://doi.org/10.3390/ijerph18189905; PMid:34574829 PMCid:PMC8465980

19. Losol P, Sokolowska M, Hwang YK, Ogulur I et al. (2023). Epithelial Barrier Theory: The Role of Exposome, Microbiome, and Barrier Function in Allergic Diseases. Allergy Asthma Immunol Res. 15(6): 705-724. https://doi.org/10.4168/aair.2023.15.6.705; PMid:37957791 PMCid:PMC10643858

20. Lu HF, Zhou YC, Yang LT, Zhou Q et al. (2024). Involvement and repair of epithelial barrier dysfunction in allergic diseases. Front Immunol. 15: 1348272. https://doi.org/10.3389/fimmu.2024.1348272; PMid:38361946 PMCid:PMC10867171

21. Noureddine N, Chalubinski M, Wawrzyniak P. (2022). The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development. J Asthma Allergy. 15: 487-504. https://doi.org/10.2147/JAA.S324080; PMid:35463205 PMCid:PMC9030405

22. Ozdemir C, Kucuksezer UC, Ogulur I, Pat Y et al. (2024). Lifestyle Changes and Industrialization in the Development of Allergic Diseases. Curr Allergy Asthma Rep. 24(7): 331-345. https://doi.org/10.1007/s11882-024-01149-7; PMid:38884832 PMCid:PMC11233349

23. Pat Y, Yazici D, D'Avino P, Li M, et al. (2024). Recent advances in the epithelial barrier theory. Int Immunol. 36(5):211-222. https://doi.org/10.1093/intimm/dxae002; PMid:38227765 PMCid:PMC10989673

24. Raby KL, Michaeloudes C, Tonkin J, Chung KF, Bhavsar PK. (2023). Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD. Front Immunol. 14: 1201658. https://doi.org/10.3389/fimmu.2023.1201658; PMid:37520564 PMCid:PMC10374037

25. Russell RJ, Boulet L-P, Brightling CE et al. (2024). The airway epithelium: an orchestrator of inflammation, a key structural barrier and a therapeutic target in severe asthma. Eur Respir J. 63(4): 2301397. https://doi.org/10.1183/13993003.01397-2023; PMid:38453256 PMCid:PMC10991852

26. Schleimer RP, Berdnikovs S. (2017). Etiology of epithelial barrier dysfunction in type 2 inflammatory diseases J Allergy Clin Immunol. 139(6): 17521761. https://doi.org/10.1016/j.jaci.2017.04.010; PMid:28583447 PMCid:PMC5753806

27. Sharma M, Huber E, Arnesdotter E, Behrsing HP et al. (2025). Minimum information for reporting on the TEER (trans-epithelial/endothelial electrical resistance) assay (MIRTA). Arch Toxicol. 99(1): 57-66. https://doi.org/10.1007/s00204-024-03879-z; PMid:39365315 PMCid:PMC11742365

28. Sugita K, Soyka MB, Wawrzyniak P, Rinaldi AO, et al. (2020). Outside-in hypothesis revisited: The role of microbial, epithelial, and immune interactions. Ann Allergy Asthma Immunol. 125(5): 517-527. https://doi.org/10.1016/j.anai.2020.05.016; PMid:32454094

29. Tran BH, Dao VA, Bilstein A, Unfried K et al. (2019). Ectoine-Containing Inhalation Solution versus Saline Inhalation Solution in the Treatment of Acute Bronchitis and Acute Respiratory Infections: A Prospective, Controlled, Observational Study. Biomed Res Int. 2019: 7945091. https://doi.org/10.1155/2019/7945091; PMid:30834276 PMCid:PMC6374829

30. Werkhäuser N, Bilstein A, Mahlstedt K, Sonnemann U. (2022). Observational study investigating Ectoin® Rhinitis Nasal Spray as natural treatment option of acute rhinosinusitis compared to treatment with Xylometazoline. Eur Arch Otorhinolaryngol. 279(3): 1371-1381. https://doi.org/10.1007/s00405-021-06916-0; PMid:34089097 PMCid:PMC8897346

31. Yazici D, Ogulur I, Pat Y, Babayev H et al. (2023). The epithelial barrier: The gateway to allergic, autoimmune, and metabolic diseases and chronic neuropsychiatric conditions. Semin Immunol. 70: 101846. https://doi.org/10.1016/j.smim.2023.101846; PMid:37801907

32. Zhou J, Zhou XD, Xu R, Du XZ et al. (2021). The Degradation of Airway Epithelial Tight Junctions in Asthma Under High Airway Pressure Is Probably Mediated by Piezo-1. Front Physiol. 12: 637790. https://doi.org/10.3389/fphys.2021.637790; PMid:33868003 PMCid:PMC8047413