A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Broncho-Vaxom Attenuates Lipopolysaccharide-Induced Inflammation in a Mouse Model of Acute Lung Injury.

Acute lung injury (ALI) is a condition associated with acute respiratory failure, resulting in significant morbidity and mortality. It involves cellular changes such as disruption of the alveolar-capillary membrane, excessive neutrophil migration, and release of inflammatory mediators. Broncho-Vaxom® (BV), a lyophilized product containing cell membrane components derived from eight bacteria commonly found in the respiratory tract, is known for its potential to reduce viral and bacterial lung infections. However, the specific effect of BV on ALI has not been clearly defined. This study explored the preventive effects of BV and its underlying mechanisms in a lipopolysaccharide (LPS)-induced ALI mouse model. Oral BV (1 mg/kg) gavage was administered one hour before the intratracheal injection of LPS to evaluate its preventive effect on the ALI model. The pre-administration of BV significantly mitigates inflammatory parameters, including the production of inflammatory mediators, macrophage infiltration, and NF-κB activation in lung tissue, and the increase in inflammatory cells in bronchoalveolar lavage fluid (BALF). Moreover, BV (3 µg/mL) pretreatment reduced the expression of M1 macrophage markers, interleukins (IL-1ß, IL-6), tumor necrosis factor α, and cyclooxygenase-2, which are activated by LPS, in both mouse alveolar macrophage MH-S cells and human macrophage THP-1 cells. These findings showed that BV exhibits anti-inflammatory effects by suppressing inflammatory mediators through the NF-κB pathway, suggesting its potential to attenuate bronchial and pulmonary inflammation.

Preventive effects of prenatal administration of OM-85/BV on asthma and respiratory infection risk in the offspring: A review of animal models.

Asthma is the most common chronic disease in childhood affecting the daily lives of many patients despite current treatment regimens. Therefore, the need for new therapeutic approaches is evident, where a primary prevention strategy is the ultimate goal. Studies of children born to mothers in farming environments have shown a lower risk of respiratory infections and asthma development. Already at birth, these newborns have demonstrated accelerated maturation and upregulation of host defense immune functions suggesting a prenatal transplacental training of the innate immune system through maternal microbial exposure. This mechanism could possibly be utilized to help prevent both respiratory infections and asthma in young children. Human studies exploring the potential preventative effects of pregnancy bacterial lysate treatment on asthma and respiratory infections are lacking, however, this has been studied in experimental studies using mice through administrations of the bacterial lysate OM-85. This review will present the current literature on the immunomodulatory effects relevant for respiratory infections and asthma in the offspring of mice treated with OM-85 throughout pregnancy. Further, the review will discuss the cellular and molecular mechanisms behind these effects. In conclusion, we found promising results of an accelerated immune competence and improved resistance to airway challenges as a result of prenatal bacterial lysate treatment that may pave the way for implementing this in human trials to prevent asthma and respiratory infections.

Effect of Broncho-Vaxom (OM-85) on the frequency of chronic obstructive pulmonary disease (COPD) exacerbations.

BACKGROUND: Efforts have been made to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations using a variety of measures. Broncho-Vaxom (BV) is an immunomodulating agent that has shown potential benefit by balancing between immune stimulation and regulation in patients with COPD. In this study, we evaluated the clinical efficacy of BV for reducing the risk of COPD exacerbations. METHODS: This study was based on the Korean National Health Insurance database, which contains reimbursement information for almost the entire population of South Korea. We extracted data from 2016 to 2019 for patients started on BV during 2017-2018. We collected baseline data on demographics, comorbidities, inhaler use, hospital type, and insurance type 1 year before starting BV. We also analyzed exacerbation history, starting from the year before BV initiation. RESULTS: In total, 238 patients were enrolled in this study. Their mean age was 69.2 ± 9.14 years, 79.8% were male, and 45% experienced at least one exacerbation. BV reduced the risk of moderate (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.38-0.91) and moderate-to-severe exacerbations compared to pre- and post-BV (OR = 0.571, 95% CI: 0.37-0.89). BV use also reduced the incidence of moderate and moderate-to-severe exacerbations (incidence rate ratio [IRR] = 0.75, p = 0.03; and IRR = 0.77, p = 0.03, respectively). The use of BV was significantly delayed moderate exacerbations (hazard ratio = 0.68, p = 0.02), but not with moderate-to-severe or severe exacerbations. CONCLUSION: The use of BV was associated with fewer moderate and moderate-to-severe exacerbations. Additionally, BV was associated with a delay in moderate COPD exacerbations.

OM-85 Broncho-Vaxom®, a Bacterial Lysate, Reduces SARS-CoV-2 Binding Proteins on Human Bronchial Epithelial Cells.

In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by human bronchial epithelial cells. Human bronchial epithelial cells were treated with OM-85 over 5 days. The expression of SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2), transmembrane protease serine subtype 2 (TMPRSS2), dipeptidyl peptidase-4 (DPP4), and a disintegrin and metalloprotease 17 (ADAM17) were determined by Western blotting and quantitative RT-PCR. Soluble (s)ACE2, heparan sulfate, heparanase, and hyaluronic acid were assessed by ELISA. OM-85 significantly reduced the expression of ACE2 (p < 0.001), TMPRSS2 (p < 0.001), DPP4 (p < 0.005), and cellular heparan sulfate (p < 0.01), while ADAM17 (p < 0.02) expression was significantly upregulated. Furthermore, OM-85 increased the level of sACE2 (p < 0.05), hyaluronic acid (p < 0.002), and hyaluronan synthase 1 (p < 0.01). Consequently, the infection by a SARS-CoV-2 spike protein pseudo-typed lentivirus was reduced in cells pretreated with OM-85. All effects of OM-85 were concentration- and time-dependent. The results suggest that OM-85 might reduce the binding of SARS-CoV-2 S-protein to epithelial cells by modification of host cell membrane proteins and specific glycosaminoglycans. Thus, OM-85 might be considered as an add-on for COVID-19 therapy.

Broncho-Vaxom in pediatric recurrent respiratory tract infections: A systematic review and meta-analysis.

OBJECTIVES: Assess the efficacy and safety of Broncho-Vaxom in pediatric recurrent respiratory tract infections (RRTIs). METHODS: Published randomized controlled trials (RCTs) of Broncho-Vaxom for pediatric RRTI were searched using PubMed, Embase, Cochrane Library, CBM, CNKI, WanFang Data, and VIP databases up to January 2017. Risk of bias was evaluated in accordance to the guidelines of the Cochrane collaboration and the level of evidence was graded according to the GRADE. RESULTS: 53 RCTs involving 4851 pediatric patients were included in this meta-analysis. It showed that Broncho-Vaxom was positively correlated with a reduction in the frequency of respiratory infection [MD=-2.33, 95% CI (-2.75, -1.90), P<0.00001] compared to the control group. The Broncho-Vaxom group was more effective than control groups in relation to the duration of antibiotics course, infections, fever, cough, and wheezing, increasing serum immunoglobulin levels (IgG, IgA or IgM), and T-lymphocytes subtype (CD3+, CD4+, or CD8+). However, Broncho-Vaxom had higher adverse event rates [RR=1.39, 95% CI (1.02, 1.88), P=0.04]; these were not serious and did not influence the treatment course. CONCLUSION: Broncho-Vaxom shows a good efficacy for pediatric RRTIs on the basis of routine therapy (e.g. anti-infection and antiviral therapy). However, the level of evidence was low and more international multicenter clinical trials are needed to explore the efficacy and safety of Broncho-Vaxom.

Study on the effect of short course chemotherapy combined with broncho-vaxom on the prognosis of new smear positive pulmonary tuberculosis patients / 中国基层医药

Objective To investigate the effect of short course chemotherapy combined with broncho-vaxom on the prognosis of new smear positive pulmonary tuberculosis patients.Methods 80 patients with new smear positive pulmonary tuberculosis were selected as the research subjects.According to the random number table method,they were divided into observation group and control group,40 cases in each group.The control group was treated with 2HRZE/4HR chemotherapy,the observation group was treated with broncho-vaxom tablets based on the treatment of the control group.After 6 months of treatment,the sputum negative conversion rate,pulmonary lesions absorption,the incidence rate of adverse reaction and immune function were compared between the two groups.Results After 2,4,6 months of treatmentt,the sputum negative conversion rates of the observation group were 90.00％,95.00％ and 97.50％,respectively,which were significantly higher than those of the control group(x2 =4.020,4.114,3.914,all P ＜ 0.05).After 2,6 months of treatment,the total effective rates of the observation group were 87.50％ and 97.50％,which were significantly higher than those of the control group (x2 =4.588,5.000,all P ＜ 0.05).After 6 months of treatment,the IgA,IgG,IgM,CD3+,CD4+,CD4+/CD8+ in the observation group were (70.24 ± 6.19) ％,(46.89 ± 6.25) ％,(2.21 ± 0.39),(3.86 ± 1.43) g/L,(14.76 ± 2.58) g/L,(1.47 ± 0.65) g/L,respectively,which were significantly higher than those of the control group(t =-2.116,-2.575,-2.322,-2.138,-4.513,-2.599,all P ＜ 0.05),the CD8+ was (18.85 ± 2.08) ％,which was significantly lower than that in the control group (t =2.609,P ＜ 0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups (x2 =0.251,P ＞ 0.05).Conclusion Short course chemotherapy regimen combined with bronchovaxom can improve the new smear positive pulmonary tuberculosis patients with recent sputum negative conversion rate and lung lesions absorption effect,improve the immune function of patients and without increasing the incidence of adverse reactions,it is worthy of clinical attention.

Efficacy and Safety of Bacterial Lysates for Recurrent Respiratory Infection of Children:A Meta-analysis / 中国药房

OBJECTIVE:To evaluate the efficacy and safety of Bacterial lysates(hereinafter referred to as"Broncho-Vaxom") for recurrent respiratory tract infections (RRTIs) of children,and to provide evidence-based reference for clinic. METHODS:Retrieved from PubMed,EMBase,Cochrane Library,CBM,CNKI,Wanfang database and VIP database,domestic and foreign published randomized controlled trials (RCTs) about Broncho-Vaxom (trail group) vs. placebo (control group) for RRTIs of children were collected during database establishment to Jan. 2018. After literature scanning and data extraction,the risk of bias of included trials were evaluated by using Cochrane 5.1.0 risk bias evaluation tool. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS:A total of 13 RCTs involving 1 228 children were included. The results showed that the trial group was superior to control group in frequency of respiratory infection [MD＝－1.14,95%CI(－1.29,－0.99),P＜0.001],total response rate [RR＝9.47,95%CI(2.33,38.54),P＝0.002],the time of antibiotics use [MD＝－4.36,95%CI(－6.52,－2.21),P＜0.001], infection duration [MD＝－3.89,95%CI(－4.47,－3.04),P＜0.001],febrile time [MD＝－1.81,95%CI(－3.40,－0.22),P＝0.03],serum immunoglobulin (Ig)G level [MD＝1.25,95%CI(0.13,2.37)),P＝0.03],IgA level [MD＝0.77,95%CI(0.07, 1.46),P＝0.03] and the level of T cell subgroup CD4+[MD＝1.33,95%CI(0.90,1.76),P＜0.001] and CD8+[MD＝0.64,95%CI (0.24,1.04),P＝0.002],there was statistical significance. Trail group was similar to control group in respect of cough time [MD＝－6.00,95%CI(－13.86,1.86),P＝0.13] and IgM level [MD＝－0.10,95%CI(－0.32,0.12),P＝0.39] and the incidence of ADR [RR＝0.76,95%CI(0.43,1.35),P＝0.35]. CONCLUSIONS:The current evidence shows that Broncho-Vaxom could effectively prevent the RRTIs of children with good safety.

The impact of bacterial lysate on asthma prevention in mouse / 临床儿科杂志

Objective To establish mouse allergic asthma model and observe the effect of bacterial lysates (OM-85BV) on airway inlfammation. Methods Forty-eight 4 to 6 weeks healthy male BALB/c mice were used as research subjects and randomly divided into six groups, a:control group;b:OM-85BV contral group;c:allergic asthma model;d:dexamethasone group (Dex group);e:OM-85BV A group;f:OM-85BV B group (the intervention time was prolonged 10 days than group e). BALB/c mice were sensitized and challenged with ovalbumin (OVA). Mice in groups c, d, e and f were intraperitoneally administered with antigen (OVA)-Al(OH)3 on days 1, 8 and 15, others were administered by PBS. From the 17th day to the 26th day, Mice in group f were treated with OM-85BV and others were treated with normal saline. In the next days, mice in groups c, d, e and f were intranasal given OVA for 5 consecutive days. Additionally, mice in groups b, e and f were treated with OM-85BV before challenge, while mice in the group d were administered by Dex, others were treated with normal saline at the same dose. Twenty four hours after the last intranasal administration, mice were anesthetized and dissected. Lungs were lavaged with PBS and bronchoalveolar lavage lfuid (BALF) was obtained. The total inlfammatory cells and eosinophils in BALF were counted. The total IgE levels of blood serum and IFN-γ/IL-4 levels of lavage were detected. The removed parts of lung tissue were collected for histological examination. Results Compared with groups a and b, lung tissue biopsies by HE staining from the asthma group showed obvious airway inlfammation. The situation of groups d and f was signiifcantly improved than group c, while the differences between groups e and c were not evident. Total cells and the number of eosinophils in BALF of group c (90.3±13.94×104/ml) were signiifcantly higher than that in groups a and b. Compared with the control group, levels of IL-4 in BALF (119.03±19.92 pg/ml) and IgE in serum (15.86±1.97 ng/ml) increased and levels of IFN-γin BALF (90.50±13.51 pg/ml) reduced signiifcantly. The corresponding levels of groups d, e and f were signiifcantly improved than group c (P<0.01). Conclusions Administered by OM-85BV helps regulate the balance between Th1/Th2 in asthmatic mice, reduce airway inlfammation, and prevent the occurrence and development of airway inlfammation.

OM-85 BV, un inmunoestimulante en las infecciones respiratorias recurrentes en pediatría: una revisión sistemática / OM-85 BV, an inmunostimulant in pediatric recurrent respiratory tract infections: a systematic review

Antecedentes: Meta-análisis para evaluar la eficacia de OM-85 BV (Broncho-Vaxom) en la prevención de las infecciones respiratorias recurrentes (IRRs) en niños. Se define a las IRRs como 23 infecciones por semestre (otoño e invierno) y se definen como el evento final primario. Métodos: Se identificaron los estudios en bases de datos. Se excluyó once estudios que no fueron doble-ciego y uno referente a la prevención primaria; y se incluyó en el meta-análisis ocho estudios controlados y randomizados. Se compararon los resultados a 6 meses. Se examinó la base de datos de acuerdo con los lineamientos Cochrane. Resultados: De los pacientes tratados con OM-85 BV (n= 435), un32% tuvo IRRs (esto es, 23 RTI/periodo de 6 meses) vs. 58.2% en la población que recibió placebo (n= 416; P<0.001). Los resultados también fueron positivos para el tratamiento activo con respecto a las variables secundarias. Conclusiones: El presente meta-análisis demuestra, que la población tratada con OM-85BV tuvo significativa y consistentemente menos casos del IRRs. El efecto es mayor en los pacientes con un mayor riesgo para desarrollar IRRs.