细菌裂解物治疗变应性鼻炎的研究进展

doi:10.6040/j.issn.1673-3770.0.2023.278

摘要/Abstract

摘要： 变应性鼻炎(allergic rhinitis, AR)作为耳鼻咽喉科的常见疾病,可严重影响患者的工作生活并带来经济负担,是日益严重的全球公共卫生问题。尽管随着AR发病机制研究的深入,治疗方法不断完善,但其患病率仍呈上升趋势。寻找新的、经济有效的治疗方法迫在眉睫。根据“卫生学假说”,病原体接触与变应性疾病发生之间具有高度相关性,通过病原体接触调节宿主免疫反应成为相关疾病的治疗靶点。细菌裂解物(bacterial lysates, BLs)在呼吸道疾病治疗中的应用已有数十年的历史,BLs是通过裂解呼吸道感染中常见病原体获得的抗原混合物,具有免疫调节功能,可降低炎症和恢复Th1/Th2平衡。近年来,越来越多的研究证据表明BLs在AR的预防和治疗中也有较好的临床效果。本文将对近年来BLs在AR治疗中的作用机制及临床效果的研究进展进行综述,以期提高临床工作者对BLs在AR治疗中的认识。

关键词: 变应性鼻炎, 细菌裂解物, 免疫调节, 2型炎症, 免疫球蛋白E

Abstract: Allergic rhinitis(AR), a common disease in otorhinolaryngology, can seriously affect patients' work and life and impose an economic burden and is increasingly being considered a serious global public health problem. However, despite the growing in-depth study of the pathogenesis of AR and continuous improvement in its treatment methods, its prevalence rate is still rising. Finding a new, economical, and effective treatment is therefore an urgent issue. The hypothesis of hygiene holds that there is a high correlation between pathogen exposure and the prevalence of allergic diseases, and regulating host immune responses through pathogen exposure has therefore become a therapeutic target in the treatment of related diseases. Bacterial lysates(BLs)have been used in the treatment of respiratory diseases for decades. BLs constitute an antigen mixture that is obtained by cracking common pathogens in respiratory infections; it has an immunomodulatory function, can reduce inflammation, and can restore Th1/Th2 balance. In recent years, an increasing amount of research evidence has shown that BLs also have a good clinical effect in AR prevention and treatment. This article will review the research progress of BLs' functional mechanisms and clinical effects in AR treatment in recent years in order to improve clinical workers' understanding of BLs in AR treatment.

Key words: Allergic rhinitis, Bacterial lysates, Immunomodulation, Th2, IgE

中图分类号:

R765.21

王曼娴,郑泉,杨亮. 细菌裂解物治疗变应性鼻炎的研究进展[J]. 山东大学耳鼻喉眼学报, 2025, 39(1): 141-145.

WANG Manxian, ZHENG Quan, YANG Liang. Research progress in the treatment of allergic rhinitis with bacterial lysates[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(1): 141-145.

参考文献

[1] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组, 中华医学会耳鼻咽喉头颈外科学分会鼻科学组. 中国变应性鼻炎诊断和治疗指南(2022年,修订版)[J]. 中华耳鼻咽喉头颈外科杂志, 2022, 57(2): 106-129. doi:10.3760/cma.j.cn115330-20211228-00828
[2] 倪璟滋, 万文锦. 变应性鼻炎健康相关生活质量研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3)110-115, 122. doi: 10.6040/j.issn.1673-3770.1.2021.165 NI Jingzi, WAN Wenjin. Research progress on health-related quality of life in allergic rhinitis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3)110-115, 122. doi: 10.6040/j.issn.1673-3770.1.2021.165
[3] Biering LMK, Tea S, Allan L. Allergic rhinitis and allergic sensitisation are still increasing among Danish adults[J]. Allergy, 2020, 75(3): 660-668. doi:10.1111/all.14046.
[4] Tong H, Gao L, Deng YQ, et al. Prevalence of allergic rhinitis and associated risk factors in 6 to 12 years schoolchildren from Wuhan in central China: a cross-sectional study[J]. Am J Rhinol Allergy, 2020, 34(5): 632-641. doi:10.1177/1945892420920499
[5] Li F, Zhou YC, Li SH, et al. Prevalence and risk factors of childhood allergic diseases in eight metropolitan cities in China: a multicenter study[J]. BMC Public Health, 2011, 11: 437. doi:10.1186/1471-2458-11-437
[6] Ma TT, Wang XD, Zhuang Y, et al. Prevalence and risk factors for allergic rhinitis in adults and children living in different grassland regions of Inner Mongolia[J]. Allergy, 2020, 75(1): 234-239. doi:10.1111/all.13941
[7] Sasaki M, Morikawa E, Yoshida K, et al. The change in the prevalence of wheeze, eczema and rhino-conjunctivitis among Japanese children: findings from 3 nationwide cross-sectional surveys between 2005 and 2015[J]. Allergy, 2019, 74(8): 1572-1575. doi:10.1111/all.13773
[8] Avdeeva KS, Reitsma S, Fokkens WJ. Direct and indirect costs of allergic and non-allergic rhinitis in the Netherlands[J]. Allergy, 2020, 75(11): 2993-2996. doi:10.1111/all.14457
[9] Esposito S, Soto-Martinez ME, Feleszko W, et al. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence[J]. Curr Opin Allergy Clin Immunol, 2018, 18(3): 198-209. doi:10.1097/ACI.0000000000000433
[10] Meng Q, Li P, Li Y, et al. Broncho-vaxom alleviates persistent allergic rhinitis in patients by improving Th1/Th2 cytokine balance of nasal mucosa[J]. Rhinology, 2019, 57(6): 451-459. doi:10.4193/Rhin19.161
[11] Okubo K, Kurono Y, Ichimura K, et al. Japanese guidelines for allergic rhinitis 2020[J]. Allergol Int, 2020, 69(3): 331-345. doi:10.1016/j.alit.2020.04.001
[12] Muñoz-Bellido FJ, Moreno E, Dávila I. Dupilumab: a review of present indications and off-label uses[J]. J Investig Allergol Clin, 2022, 32(2): 97-115. doi:10.18176/jiaci.0682
[13] Gonzalez-Figueroa P, Roco JA, Papa I, et al. Follicular regulatory T cells produce neuritin to regulate B cells[J]. Cell, 2021, 184(7): 1775-1789.e19. doi:10.1016/j.cell.2021.02.027
[14] Golebski K, Layhadi JA, Sahiner U, et al. Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response[J]. Immunity, 2021, 54(2): 291-307.e7. doi:10.1016/j.immuni.2020.12.013
[15] Edwards MR, Walton RP, Jackson DJ, et al. The potential of anti-infectives and immunomodulators as therapies for asthma and asthma exacerbations[J]. Allergy, 2018, 73(1): 50-63. doi:10.1111/all.13257
[16] Yin J, Xu BP, Zeng XT, et al. Broncho-Vaxom in pediatric recurrent respiratory tract infections: a systematic review and meta-analysis[J]. Int Immunopharmacol, 2018, 54: 198-209. doi:10.1016/j.intimp.2017.10.032
[17] Ferrara F, Rial A, Suárez N, et al. Polyvalent bacterial lysate protects against pneumonia independently of neutrophils, IL-17A or caspase-1 activation[J]. Front Immunol, 2021, 12: 562244. doi:10.3389/fimmu.2021.562244
[18] 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[J]. PLoS One, 2013, 8(12): e82867. doi:10.1371/journal.pone.0082867
[19] Luan H, Zhang Q, Wang L, et al. OM85-BV induced the productions of IL-1β, IL-6, and TNF-α via TLR4- and TLR2-mediated ERK1/2/NF-κB pathway in RAW264.7 cells[J]. J Interf Cytokine Res, 2014, 34(7): 526-536. doi:10.1089/jir.2013.0077
[20] Sun Yuting, Zhou Liyu, Chen Weikai, et al. Immune metabolism: a bridge of dendritic cells function[J]. Int Rev Immunol, 2022, 41(3):313-325. doi: 10.1080/08830185.2021.1897124
[21] Suárez N, Ferrara F, Rial A, et al. Bacterial lysates as immunotherapies for respiratory infections: methods of preparation[J]. Front Bioeng Biotechnol, 2020, 8: 545. doi:10.3389/fbioe.2020.00545
[22] Kearney SC, Dziekiewicz M, Feleszko W. Immunoregulatory and immunostimulatory responses of bacterial lysates in respiratory infections and asthma[J]. Ann Allergy Asthma Immunol, 2015, 114(5): 364-369. doi:10.1016/j.anai.2015.02.008
[23] Le Souëf P. Viral infections in wheezing disorders[J]. Eur Respir Rev, 2018, 27(147): 170133. doi:10.1183/16000617.0133-2017
[24] de Boer GM, Zókiewicz J, Strzelec KP, et al. Bacterial lysate therapy for the prevention of wheezing episodes and asthma exacerbations: a systematic review and meta-analysis[J]. Eur Respir Rev, 2020, 29(158): 190175. doi:10.1183/16000617.0175-2019
[25] Lu YM, Li YQ, Xu LY, et al. Bacterial lysate increases the percentage of natural killer T cells in peripheral blood and alleviates asthma in children[J]. Pharmacology, 2015, 95(3/4): 139-144. doi:10.1159/000377683
[26] Liu CT, Huang R, Yao RJ, et al. The immunotherapeutic role of bacterial lysates in a mouse model of asthma[J]. Lung, 2017, 195(5): 563-569. doi:10.1007/s00408-017-0003-8
[27] Bartkowiak-Emeryk M, Emeryk A, Roliński J, et al. Impact of polyvalent mechanical bacterial lysate on lymphocyte number and activity in asthmatic children: a randomized controlled trial[J]. Allergy Asthma Clin Immunol, 2021, 17(1): 10. doi:10.1186/s13223-020-00503-4
[28] Dang AT, Pasquali C, Ludigs K, et al. OM-85 is an immunomodulator of interferon-β production and inflammasome activity[J]. Sci Rep, 2017, 7(1): 1-9. doi:10.1038/srep43844
[29] Janeczek K, Emeryk A, Rachel M, et al. Polyvalent mechanical bacterial lysate administration improves the clinical course of grass pollen-induced allergic rhinitis in children: a randomized controlled trial[J]. J Allergy Clin Immunol Pract, 2021, 9(1):453-62. doi: 10.1016/j.jaip.2020.08.025
[30] Cardinale F, Lombardi E, Rossi O, et al. Epithelial dysfunction, respiratory infections and asthma: the importance of immunomodulation. A focus on OM-85[J]. Expert Rev Respir Med, 2020, 14(10):1019-1026. doi: 10.1080/17476348.2020.1793673
[31] Jurkiewicz D, Zielnik-Jurkiewicz B. Bacterial lysates in the prevention of respiratory tract infections[J]. Otolaryngol Pol, 2018, 72(5): 1-8. doi:10.5604/01.3001.0012.7216
[32] Cao CQ, Wang JH, Li YN, et al. Efficacy and safety of OM-85 in paediatric recurrent respiratory tract infections which could have a possible protective effect on COVID-19 pandemic: a meta-analysis[J]. Int J Clin Pract, 2021, 75(5): e13981. doi:10.1111/ijcp.13981
[33] Esposito S, Cassano M, Cutrera R, et al. Expert consensus on the role of OM-85 in the management of recurrent respiratory infections: a Delphi study[J]. Hum Vaccin Immunother, 2022, 18(6): 2106720. doi:10.1080/21645515.2022.2106720
[34] Cantarutti A, Barbieri E, Scamarcia A, et al. Use of the bacterial lysate OM-85 in the paediatric population in Italy: a retrospective cohort study[J]. Int J Environ Res Public Health, 2021, 18(13): 6871. doi:10.3390/ijerph18136871
[35] Esposito S, Bianchini S, Bosis S, et al. A randomized, placebo-controlled, double-blinded, single-centre, phase IV trial to assess the efficacy and safety of OM-85 in children suffering from recurrent respiratory tract infections[J]. J Transl Med, 2019, 17(1): 284. doi:10.1186/s12967-019-2040-y
[36] Koatz AM, Coe NA, Cicerán A, et al. Clinical and immunological benefits of OM-85 bacterial lysate in patients with allergic rhinitis, asthma, and COPD and recurrent respiratory infections[J]. Lung, 2016, 194(4): 687-697. doi:10.1007/s00408-016-9880-5
[37] Cinicola BL, Brindisi G, Capponi M, et al. The allergic phenotype of children and adolescents with selective IgA deficiency: a longitudinal monocentric study[J]. J Clin Med, 2022, 11(19): 5705. doi:10.3390/jcm11195705
[38] Banche G, Allizond V, Mandras N, et al. Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects[J]. Int J Immunopathol Pharmacol, 2007, 20(1): 129-138. doi:10.1177/039463200702000115
[39] Janeczek K, Emeryk A, Rapiejko P. Effect of polyvalent bacterial lysate on the clinical course of pollen allergic rhinitis in children[J]. Pdia, 2019, 36(4): 504-505. doi:10.5114/ada.2019.87457
[40] Kowalska M, Emeryk A, Janeczek K, et al. Effect of nasal polivalent bacterial lysate on the clinical course of seasonal allergic rhinitis in children-preliminary study[C] //Paediatric asthma and allergy. European Respiratory Society, 2020: 56(suppl 64): 1208. doi:10.1183/13993003.congress-2020.1208
[41] Kaczynska A, Klosinska M, Janeczek K, et al. Promising immunomodulatory effects of bacterial lysates in allergic diseases[J]. Front Immunol, 2022, 13: 907149. doi:10.3389/fimmu.2022.907149
[42] Janeczek K, Kaczyńska A, Emeryk A, et al. Perspectives for the use of bacterial lysates for the treatment of allergic rhinitis: a systematic review[J]. J Asthma Allergy, 2022, 15: 839-850. doi:10.2147/jaa.s360828
[43] Janeczek K, Kowalska W, Zarobkiewicz M, et al. Effect of immunostimulation with bacterial lysate on the clinical course of allergic rhinitis and the level of gdT, iNKT and cytotoxic T cells in children sensitized to grass pollen allergens: A randomized controlled trial[J]. Front Immunol, 2023, 14:1073788. doi: 10.3389/fimmu.2023.1073788

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