Бактериальный лизат ОМ-85: от механизмов действия к доказательствам клинической эффективности в педиатрической практике
Бактериальный лизат ОМ-85: от механизмов действия к доказательствам клинической эффективности в педиатрической практике
Овсянников Д.Ю. Бактериальный лизат ОМ-85: от механизмов действия к доказательствам клинической эффективности
в педиатрической практике. Педиатрия. Consilium Medicum. 2019; 3: 92–97.
DOI: 10.26442/26586630.2019.3.190645
________________________________________________
Ovsyannikov D.Iu. Bacterial lysate OM-85: from the mechanisms of action to the evidence of clinical efficacy in a pediatric practice. Pediatrics. Consilium Medicum. 2019; 3: 92–97. DOI: 10.26442/26586630.2019.3.190645
Бактериальный лизат ОМ-85: от механизмов действия к доказательствам клинической эффективности в педиатрической практике
Овсянников Д.Ю. Бактериальный лизат ОМ-85: от механизмов действия к доказательствам клинической эффективности
в педиатрической практике. Педиатрия. Consilium Medicum. 2019; 3: 92–97.
DOI: 10.26442/26586630.2019.3.190645
________________________________________________
Ovsyannikov D.Iu. Bacterial lysate OM-85: from the mechanisms of action to the evidence of clinical efficacy in a pediatric practice. Pediatrics. Consilium Medicum. 2019; 3: 92–97. DOI: 10.26442/26586630.2019.3.190645
В статье обсуждаются проблемы этиологии, эпидемиологии, профилактики и терапии респираторных инфекций у детей, применение бактериального лизата ОМ-85 в педиатрической практике. Подробно описаны многокомпонентные механизмы действия препарата ОМ-85 на антигенпрезентирующие клетки, систему врожденного и приобретенного иммунитета, противовирусная и антибактериальная активность препарата, влияние на патогенез заболеваний, протекающих с бронхиальной обструкцией и атопией за счет действия на баланс Т-хелперов 1 и 2-го типа, воспаление дыхательных путей, иммуноглобулины. На основании метаанализа, рандомизированных зарубежных исследований приведены доказательства клинической эффективности препарата при острых и рецидивирующих респираторных инфекциях, а также заболеваниях, протекающих с бронхиальной обструкцией (острый бронхиолит, обструктивный бронхит, бронхиальная астма) у детей. На фоне терапии препаратом ОМ-85 по сравнению с контрольной группой отмечены статистически значимое сокращение частоты и длительности острых респираторных инфекций, длительности лихорадки, кашля, бронхиальной обструкции, антибактериальной терапии, увеличение содержания сывороточных иммуноглобулинов G, A, M. При этом установлены хорошая переносимость препарата ОМ-85 и его безопасность. Обоснованы показания для профилактического и терапевтического применения бактериального лизата ОМ-85 в детском возрасте. Ключевые слова: респираторная инфекция, обструктивный бронхит, бронхиальная астма, профилактика, дети, ОМ-85.
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The article discusses the issues of etiology, epidemiology, prevention and treatment of respiratory infections in children and the use of a bacterial lysate OM-85 in pediatric practice. It considers in details the multicomponent mechanisms of action of the OM-85 on antigen-presenting cells, the innate and acquired immunity, the drug antiviral and antibacterial activity, the effect on a pathogenesis of diseases which are associated with bronchial obstruction and atopy due its effect on a balance of type 1 and type 2 T-helpers, inflammation of the respiratory tract, immunoglobulins. Based on the meta-analysis and foreign randomized studies, the evidence of clinical efficacy of the drug in acute and recurrent respiratory infections, as well as in diseases which are associated with bronchial obstruction (acute bronchiolitis, obstructive bronchitis, bronchial asthma) in children are given. Compared with the control group, the treatment with the OM-85 showed a statistically significant reduction in the rate and duration of acute respiratory infections, the duration of fever, cough, bronchial obstruction, antibiotic therapy as well as an increase in serum IgG, IgA and IgM levels. The OM-85 was also safe and well tolerated. The article provides the rationale for indications for a preventive and therapeutic use of the bacterial lysate OM-85 in children. Key words: respiratory infection, obstructive bronchitis, bronchial asthma, prevention, children, OM-85.
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17. Liao JY, Zhang T. Influence of OM-85 BV on hBD-1 and immunoglobulin in children with asthma and recurrent respiratory tract infection. Zhongguo Dang Dai Er Ke Za Zhi 2014; 16: 508–12.
18. Roth M, Pasquali C, Stolz D, Tamm M. Broncho Vaxom (OM-85) modulates rhinovirus docking proteins on human airway epithelial cells via Erk1/2 mitogen activated protein kinase and cAMP. PLoS One 2017; 12: e0188010.
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26. Navarro S, Cossalter G, Chiavaroli C et al. The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 2011; 4: 53–65.
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28. Han L, Zheng CP, Sun YQ et al. A bacterial extract of OM-85 Broncho-Vaxom prevents allergic rhinitis in mice. Am J Rhinol Allergy 2014; 28: 110–6.
29. Rodrigues A, Gualdi LP, de Souza RG et al. Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model. Allergol Immunopathol 2016; 44: 504–11.
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1.Brady M. Respiratory viral infections. Infectious disease. D.Murray ed. Moscow: Praktika, 2006; p. 604–30 (in Russian).
2. Acute respiratory diseases in children: treatment and prevention. Manual for doctors. Moscow: Union of pediatricians of Russia, 2002 (in Russian).
3. Lozano R, Naghavi M, Foreman K et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2095–128.
4. Furman E.G., Mazunina E.S., Boitsova E.V., Ovsiannikov D.Iu. Zatiazhnoi bakterial'nyi bronkhit – "novaia" "staraia" bolezn'. Pediatriia. 2017; 96 (2): 136–44 (in Russian).
5. Ovsiannikov D.Iu., Illarionova T.Iu., Pushko L.V., Kuz'menko L.G. Chasto boleiushchie deti: chto eshche krome infektsii? Vopr. sovremennoi pediatrii. 2013; 12 (1): 74–86 (in Russian).
6. Zaplatnikov A.L., Girina A.A., Lokshina E.E. et al. Chasto boleiushchie deti: vse li resheno? Med. sovet. 2018; 17: 206–14 (in Russian).
7. Feleszko W, Ruszczynski M, Zalewski BM. Non-specific immune stimulation in respiratory tract infections. Separating the wheat from the chaff. Paediatr Respir Rev 2014; 15: 200e–6.
8. Karnaushkina M.A., Strutynskaia A.D., Ovsiannikov D.Iu. Nedonoshennost' i perenesennaia v rannem detstve infektsiia nizhnikh dykhatel'nykh putei kak faktory riska razvitiia khronicheskoi obstruktivnoi bronkholegochnoi patologii u vzroslykh. Sovr. tekhnologii v meditsine. 2017; 9 (1): 129–34 (in Russian).
9. Rachina S.A., Kozlov R.S., Tatochenko V.K. et al. Praktika lecheniia ostrykh respiratornykh infektsii u detei v ambulatorno-poliklinicheskikh uchrezhdeniiakh RF: rezul'taty mnogotsentrovogo farmakoepidemiologicheskogo issledovaniia. Klin. farmakologiia i terapiia. 2016; 2: 20–7 (in Russian).
10. Esposito S, Soto-Martinezb ME, Feleszkoc W et al. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol 2018, 18: 198–208.
11.Khaitov M.R., Il'ina N.I., Luss L.V., Babakhin A.A. Mukozal'nyi immunitet respiratornogo trakta i ego rol' pri professional'nykh patologiiakh. Meditsina ekstremal'nykh situatsii. 2017; 61 (3): 8–24 (in Russian).
12. Kaliuzhin OV. OM-85 v profilaktike/lechenii respiratornykh infektsii i obostrenii khronicheskikh zabolevanii legkikh: kriterii vybora, mekhanizmy i dokazatel'stva. Lechashchii vrach. 2018; 3:77–82 (in Russian).
13. Dronov I.A., Denisova A.R. Bakterial'nyi lizat OM-85: voprosy effektivnosti u detei i potentsial'naia rol' v sderzhivanii rosta antimikrobnoi rezistentnosti. Vopr. prakticheskoi pediatrii. 2019; 14 (1): 76–83 (in Russian).
14. Luan H, Zhang Q, Wang L et al. OM85-BV induced the productions of IL-1beta, IL-6, and TNF-alpha via TLR4- and TLR2-mediated ERK1/2/NF-kB pathway in RAW264.7 cells. J Interferon Cytokine Res 2014; 34: 526e–36.
15. Parola C, Salogni L, Vaira X et al. Selective activation of human dendritic cells by OM-85 through a NF-kB and MAPK dependent pathway. PLoS One 2013; 8: e82867.
16. Manolova V, Flace A, Jeandet P et al. Biomarkers induced by the immunomodulatory bacterial extract OM-85: unique roles for Peyer’s patches and intestinal epithelial cells. J Clin Cell Immunol 2017; 8: 494.
17. Liao JY, Zhang T. Influence of OM-85 BV on hBD-1 and immunoglobulin in children with asthma and recurrent respiratory tract infection. Zhongguo Dang Dai Er Ke Za Zhi 2014; 16: 508–12.
18. Roth M, Pasquali C, Stolz D, Tamm M. Broncho Vaxom (OM-85) modulates rhinovirus docking proteins on human airway epithelial cells via Erk1/2 mitogen activated protein kinase and cAMP. PLoS One 2017; 12: e0188010.
19. Dang AT, Pasquali C, Ludigs K, Guarda G. OM-85 is an immunomodulator of interferon-b production and inflammasome activity. Sci Rep 2017; 7: 43844.
20. Zelle-Rieser C, Ramoner R, Bartsch G, Thurnher M. A clinically approved oral vaccine against pneumotropic bacteria induces the terminal maturation of CD83(þ) immunostimulatory dendritic cells. Immunol Lett 2001; 76: 63–7.
21. Roth M, Block LH. Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines. Thorax 2000; 55: 678–84.
22. Pasquali C, Salami O, Taneja M et al. Enhanced mucosal antibody production and protection against respiratory infections following an orally administered bacterial extract. Front Med 2014; 1: 41.
23. Yin J, Xu B, Zeng X, Shen K. Broncho-Vaxom in pediatric recurrent respiratory tract infections: A systematic review and meta-analysis. Int Immunopharmacol 2018, 54: 98–209.
24. Byl B, Libin M, Ge´rard M et al. Bacterial extract OM85-BV induces interleukin-12-dependent IFN-gamma production by human CD4(þ) T cells. J Interfer Cytok Res 1998; 18: 817–21.
25. Triantafillou V, Workman AD, Patel NN et al. Broncho-Vaxom (OM-85 BV) soluble components stimulate sinonasal innate immunity. Int Forum Allergy Rhinol 2018; 00: 1–8.
26. Navarro S, Cossalter G, Chiavaroli C et al. The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 2011; 4: 53–65.
27. Huber M, Mossmann H, Bessler WG. Th1-orientated immunological properties of the bacterial extract OM-85-BV. Eur J Med Res 2005; 10: 209–17.
28. Han L, Zheng CP, Sun YQ et al. A bacterial extract of OM-85 Broncho-Vaxom prevents allergic rhinitis in mice. Am J Rhinol Allergy 2014; 28: 110–6.
29. Rodrigues A, Gualdi LP, de Souza RG et al. Bacterial extract (OM-85) with human-equivalent doses does not inhibit the development of asthma in a murine model. Allergol Immunopathol 2016; 44: 504–11.
30. Chen ZG, Ji JZ, Li M et al. Effect and analysis of clinical efficacy of immunomodulator on serum levels of IL-4 and IFN-gamma in asthmatic children. J Sun Yat-sen Univ Med Sci 2009; 30: 100–3.
31. Lu Y, Li Y, Xu L et al. Bacterial lysate increases the percentage of natural killer T cells in peripheral blood and alleviates asthma in children. Pharmacology 2015; 95: 139–44.
32. Han RF, Li HY, Wang JW, Cong XJ. Study on clinical effect and immunologic mechanism of infants capillary bronchitis secondary bronchial asthma treated with bacterial lysates Broncho-Vaxom. Eur Rev Med Pharmacol Sci 2016; 20: 2151–5.
33. Strickland DH, Judd S, Thomas JA et al. Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control. Mucosal Immunol 2011; 4: 43–52.
34. Zhong H, Wei J, Yao Y et al. A bacterial extract of OM-85 Broncho-Vaxom suppresses ovalbumin-induced airway inflammation and remodeling in a mouse chronic allergic asthma model. Int J Clin Exp Pathol 2017; 10: 1149–57.
35. Kaliuzhin O.V. Topicheskie bakterial'nye lizaty v profilaktike i lechenii respiratornykh infektsii. Prakticheskaia meditsina. 2016; 2 (94): 69–74 (in Russian).
36. Gomez Barreto D, De la Torre C, Alvarez A et al. Safety and efficacy of OM-85-BV plus amoxicillin/clavulanate in the treatment of subacute sinusitis and the prevention of recurrent infections in children. Allergol Immunopathol 1998; 26: 17–22.
37. Zagar S, Löfler-Badzek D. Broncho-Vaxom in children with rhinosinusitis: a double-blind clinical trial. J Otorhinolaryngol Relat Spec 1988; 50 (6): 397–404.
38. Liu YW, Dong SH, Zhan GY et al. Analysis of the effect of bacterial lysate and the immunologic mechanism in treating infant bronchiolitis. Eur Rev Med Pharmacol Sci 2017; 21 (14): 3332–6.
39. Berber AC, Del-Rio-Navarro BE. Use of Broncho-Vaxom in private practice: phase IV trial in 587 children. Clin Ther 1996; 18 (6): 1068–79.
40. Ryabova M.A., Galkina O.V., Pestakova L.V., Posobilo E.E. The question of treatment of acute diseases of the upper respiratory tract. Pediatrics (Suppl. Consilium Medicum). 2016; 3: 51–4.
41. Razi CH, Harmancı K, Abaci A et al. The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol 2010; 126: 763–9.
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Авторы
Д.Ю. Овсянников*
ФГАОУ ВО «Российский университет дружбы народов» Министерства науки и высшего образования,
Москва, Россия
*mdovsyannikov@yahoo.com