Bacterial lysate therapy for the prevention of wheezing episodes and asthma exacerbations: a systematic review and meta-analysis

Geertje Maria de Boer, Jakub Żółkiewicz, Konrad Piotr Strzelec, Marek Ruszczyński, Rudi W Hendriks, Gert-Jan Braunstahl, Wojciech Feleszko, Gerdien A Tramper-Stranders, Geertje Maria de Boer, Jakub Żółkiewicz, Konrad Piotr Strzelec, Marek Ruszczyński, Rudi W Hendriks, Gert-Jan Braunstahl, Wojciech Feleszko, Gerdien A Tramper-Stranders

Abstract

Wheezing and asthma are a growing cause of morbidity in children and adults. Treatment is aimed at prevention of disease exacerbations and preservation of lung function. Respiratory viruses are involved in ∼40-60% of exacerbations. Bacterial lysates prevent recurrent respiratory tract infections and might reduce exacerbations. Moreover, immunomodulatory effects have been observed in human and animal studies. Here we aimed to assess the effects of bacterial lysate therapy on preschool wheezing episodes and asthma exacerbation frequency. We performed a systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement and a meta-analysis using Cochrane Review Manager. Out of 2016 retrieved articles, 22 studies were included, of which five provided sufficient data for a meta-analysis.The use of bacterial lysates showed a decrease of both wheezing episodes (mean difference -2.35 (-3.03- -1.67), p<0.001) and asthma exacerbations in children (mean difference -0.90 (-1.23- -0.57), p<0.001). Additionally, antibiotic use was reduced, and the duration of wheezing episodes was also decreased. No data for adults with asthma are currently available. The immunomodulatory effect seems to be dependent on increased T-helper (Th)1-cell activation and Th2-cell suppression.These favourable effects of bacterial lysates indicate that they show promise as add-on therapy in preschool wheezing and childhood asthma.

Conflict of interest statement

Conflict of interest: G.M. de Boer has nothing to disclose. Conflict of interest: J. Żółkiewicz has nothing to disclose. Conflict of interest: K. Strzelec has nothing to disclose. Conflict of interest: M. Ruszczyński has nothing to disclose. Conflict of interest: R.W. Hendriks has nothing to disclose. Conflict of interest: G.J. Braunstahl has nothing to disclose. Conflict of interest: W. Feleszko reports speaker honoraria from Vifor Pharma. Conflict of interest: G.A. Tramper-Stranders reports grants from European Society for Pediatric Infectious Diseases, Stichting Coolsingel, and a grant, personal fees and non-financial support from OM-Pharma for an affiliated project during the conduct of the study. All fees were paid to the research foundation.

Copyright ©ERS 2020.

Figures

FIGURE 1
FIGURE 1
Flowchart of included studies.
FIGURE 2
FIGURE 2
Bias included randomised controlled trials for meta-analysis.
FIGURE 3
FIGURE 3
a) Meta-analysis of wheezing episodes and asthma exacerbations. b) Meta-analysis of polyvalent chemical bacterial lysate (PCBL) and polyvalent mechanical bacterial lysate (PMBL). BL: bacterial lysate.
FIGURE 4
FIGURE 4
Immunological effects of Broncho-Vaxom (OM-85) in animals and humans. Red text: human only; italic text: animal only; bold text: human and animal. PAMP: pathogen-associated molecular pattern; NF-κB: nuclear factor-κB; MAPK: mitogen-activated protein kinase; GALT: gut-associated lymphoid tissue; TGF: transforming growth factor; TLR: Toll-like receptor; IL: interleukin; Ig: immunoglobulin; TNF: tumour necrosis factor; Treg: regulatory T-cell.

References

    1. Selroos O, Kupczyk M, Kuna P, et al. . National and regional asthma programmes in Europe. Eur Respir Rev 2015; 24: 474–483. doi:10.1183/16000617.00008114
    1. Papi A, Brightling C, Pedersen SE, et al. . Asthma. Lancet 2018; 391: 783–800. doi:10.1016/S0140-6736(17)33311-1
    1. Rabe KF, Watz H. Chronic obstructive pulmonary disease. Lancet 2017; 389: 1931–1940. doi:10.1016/S0140-6736(17)31222-9
    1. Jartti T, Gern JE. Role of viral infections in the development and exacerbation of asthma in children. J Allergy Clin Immunol 2017; 140: 895–906. doi:10.1016/j.jaci.2017.08.003
    1. Bacharier LB, Guilbert TW. Diagnosis and management of early asthma in preschool-aged children. J Allergy Clin Immunol 2012; 130: 287–296. doi:10.1016/j.jaci.2012.04.025
    1. Brand PL, Caudri D, Eber E, et al. . Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J 2014; 43: 1172–1177. doi:10.1183/09031936.00199913
    1. Adamiec A, Ambrozej D, Ryczaj K, et al. . Preschool wheezing diagnosis and management: survey of physicians’ and caregivers’ perspective. Pediatr Allergy Immunol 2020; 31: 206–209. doi:10.1111/pai.13142
    1. Edwards MR, Walton RP, Jackson DJ, et al. . The potential of anti-infectives and immunomodulators as therapies for asthma and asthma exacerbations. Allergy 2018; 73: 50–63. doi:10.1111/all.13257
    1. Hekking PP, Wener RR, Amelink M, et al. . The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015; 135: 896–902. doi:10.1016/j.jaci.2014.08.042
    1. Jackson DJ, Hartert TV, Martinez FD, et al. . Asthma: NHLBI workshop on the primary prevention of chronic lung diseases. Ann Am Thorac Soc 2014; 11: Suppl. 3, S139–S145. doi:10.1513/AnnalsATS.201312-448LD
    1. van der Meer V, van Stel HF, Bakker MJ, et al. . Weekly self-monitoring and treatment adjustment benefit patients with partly controlled and uncontrolled asthma: an analysis of the SMASHING study. Respir Res 2010; 11: 74. doi:10.1186/1465-9921-11-74
    1. Le Souef P. Viral infections in wheezing disorders. Eur Respir Rev 2018; 27: 170133. doi:10.1183/16000617.0133-2017
    1. 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. Curr Opin Allergy Clin Immunol 2018; 18: 198–209. doi:10.1097/ACI.0000000000000433
    1. Cirauqui C, Benito-Villalvilla C, Sanchez-Ramon S, et al. . Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. Eur J Immunol 2018; 48: 180–193. doi:10.1002/eji.201747024
    1. Cazzola M, Rogliani P, Curradi G. Bacterial extracts for the prevention of acute exacerbations in chronic obstructive pulmonary disease: a point of view. Respir Med 2008; 102: 321–327. doi:10.1016/j.rmed.2007.11.002
    1. Del-Rio-Navarro BE, Espinosa Rosales F, Flenady V, et al. . Immunostimulants for preventing respiratory tract infection in children. Cochrane Database Syst Rev 2006;4 : CD004974.
    1. Chyrek-Borowska S, Moniuszko T, Szymanski W, et al. . Broncho-vaxom in the treatment and prophylaxis of recurrent respiratory tract infections in bronchial asthma. Pneumonol Alergol Pol 1992; 60: Suppl. 2, 117–119.
    1. Kearney SC, Dziekiewicz M, Feleszko W. Immunoregulatory and immunostimulatory responses of bacterial lysates in respiratory infections and asthma. Ann Allergy Asthma Immunol 2015; 114: 364–369.
    1. 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 (Lausanne) 2014; 1: 41.
    1. Yin J, Xu B, Zeng X, et al. . Broncho-Vaxom in pediatric recurrent respiratory tract infections: a systematic review and meta-analysis. Int Immunopharmacol 2018; 54: 198–209. doi:10.1016/j.intimp.2017.10.032
    1. 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. doi:10.1371/journal.pone.0082867
    1. 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. doi:10.1038/mi.2010.51
    1. 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. doi:10.1038/mi.2010.43
    1. Liberati A, Altman DG, Tetzlaff J, et al. . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009; 62: e1–34. doi:10.1016/j.jclinepi.2009.06.006
    1. Moher D, Liberati A, Tetzlaff J, et al. . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62: 1006–1012. doi:10.1016/j.jclinepi.2009.06.005
    1. Review Manager (RevMan) . Version 5.3. Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration. 2014.
    1. Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Chichester, Wiley-Blackwell, 2011.
    1. OM-Pharma . 2016. Summary of Product Characteristics. .
    1. Emeryk A, Bartkowiak-Emeryk M, Raus Z, et al. . Mechanical bacterial lysate administration prevents exacerbation in allergic asthmatic children: The EOLIA study. Pediatr Allergy Immunol 2018; 29: 394–401. doi:10.1111/pai.12894
    1. Koatz AM, Coe NA, Ciceran A, et al. . Clinical and immunological benefits of OM-85 bacterial lysate in patients with allergic rhinitis, asthma, and COPD and recurrent respiratory infections. Lung 2016; 194: 687–697. doi:10.1007/s00408-016-9880-5
    1. Chen ZG, Ji JZ, Li M, et al. . [Immunoregulants improves the prognosis of infants with wheezing]. Nan Fang Yi Ke Da Xue Xue Bao 2007; 27: 1612–1613.
    1. Han RF, Li HY, Wang JW, et al. . 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: 2151–2155.
    1. Sly PD, Galbraith S, Islam Z, et al. . Primary prevention of severe lower respiratory illnesses in at-risk infants using the immunomodulator OM-85. J Allergy Clin Immunol 2019; 144: 870–872. doi:10.1016/j.jaci.2019.05.032
    1. 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: 508–512.
    1. 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: 139–144. doi:10.1159/000377683
    1. Razi CH, Harmanci K, Abaci A, et al. . The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol 2010; 126: 763–769. doi:10.1016/j.jaci.2010.07.038
    1. Conejero L, Nieto A, Brandi P, et al. . Bacterial immunotherapy in children with wheezing attacks: clinical impact and mechanism of action. Eur Respir J 2019; 54: Suppl. 63, PA4998.
    1. 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: 3.
    1. Liao JY, Zhang T. [Effects of montelukast sodium and bacterial lysates on airway remodeling and expression of transforming growth factor-beta1 and Smad7 in guinea pigs with bronchial asthma]. Zhongguo Dang Dai Er Ke Za Zhi 2018; 20: 1063–1069.
    1. 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 (Madr) 2016; 44: 504–511. doi:10.1016/j.aller.2016.04.010
    1. Nemeth A, Magyar P. Broncho-Vaxom inhibits histamine release from rat mast cells induced by compound 48/80 and ionophore A23187. Agents Actions 1989; 27: 43–45. doi:10.1007/BF02222193
    1. Liu C, Huang R, Yao R, et al. . The immunotherapeutic role of bacterial lysates in a mouse model of asthma. Lung 2017; 195: 563–569. doi:10.1007/s00408-017-0003-8
    1. Fu R, Li J, Zhong H, et al. . Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3beta-related T regulatory cell insufficiency. PloS One 2014; 9: e92912. doi:10.1371/journal.pone.0092912
    1. Roth M, Pasquali C, Stolz D, et al. . 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. doi:10.1371/journal.pone.0188010
    1. Keul R, Roth M, Papakonstantinou E, et al. . Induction of interleukin 6 and interleukin 8 expression by Broncho-Vaxom (OM-85 BV) via C-Fos/serum responsive element. Thorax 1996; 51: 150–154. doi:10.1136/thx.51.2.150
    1. Weiss S, Fux T. [Effect of Broncho-Vaxom on serum IgE and IgG levels in patients with bronchial asthma and chronic obstructive lung disease. A placebo-controlled double-blind study]. Schweiz Med Wochenschr 1987; 117: 1514–1518.
    1. 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: 110–116. doi:10.2500/ajra.2013.27.4021
    1. Lau S. Bacterial lysates in food allergy prevention. Curr Opin Allergy Clin Immunol 2013; 13: 293–295. doi:10.1097/ACI.0b013e328360ede9
    1. Feleszko W, Jaworska J, Rha RD, et al. . Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy 2007; 37: 498–505. doi:10.1111/j.1365-2222.2006.02629.x
    1. Elazab N, Mendy A, Gasana J, et al. . Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics 2013; 132: e666–e676. doi:10.1542/peds.2013-0246
    1. Azad MB, Coneys JG, Kozyrskyj AL, et al. . Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis. BMJ 2013; 347: f6471. doi:10.1136/bmj.f6471
    1. Reddel HK, FitzGerald JM, Bateman ED, et al. . GINA 2019: a fundamental change in asthma management: treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J 2019; 53: 1901046. doi:10.1183/13993003.01046-2019
    1. Lefebvre P, Duh MS, Lafeuille MH, et al. . Acute and chronic systemic corticosteroid-related complications in patients with severe asthma. J Allergy Clin Immunol 2015; 136: 1488–1495. doi:10.1016/j.jaci.2015.07.046

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren