Efficacy of OM-85 (Broncho-Vaxom) for prevention of acute exacerbations in patients with chronic airway diseases or chronic bronchitis: a systematic review and meta-analysis
Jonghoo Lee1#
, Jae-Uk Song2#
Contributions: (I) Conception and design: J Lee; (II) Administrative support: J Lee; (III) Provision of study materials or patients: Both authors; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.
#These authors contributed equally to this work as co-first authors.
Background: The oral immunostimulant OM-85 (Broncho-Vaxom) has been suggested to reduce exacerbation frequency in patients with chronic obstructive pulmonary disease (COPD) or chronic bronchitis; however, its efficacy remains unclear. This study aimed to evaluate the effectiveness of OM-85 in preventing acute exacerbations in this patient population.
Methods: We conducted a systematic review and meta-analysis using PubMed, Embase, and the Cochrane Central Register through April 2025. Eligibility was limited to peer-reviewed, full-length randomized controlled trials (RCTs) in English. Odds ratios (ORs) and mean difference (MD) with 95% confidence intervals (CIs) were calculated for between-group (OM-85 and placebo) comparisons. The methodological quality of the included studies was assessed the Cochrane risk of bias guidelines. The primary outcome was acute exacerbation rates on predefined outcomes. The secondary outcome was the rate of adverse events.
Results: A total of five RCTs involving 1,724 patients were included. The methodological quality of the included studies was generally acceptable, with selection bias related to inadequate sequence generation and allocation concealment identified as the most frequent source of potential bias. The proportion of patients free from acute exacerbations was 39.2% with OM-85 and 30.3% with placebo (OR, 1.73; 95% CI: 1.04 to 2.87; P=0.03). As substantial heterogeneity was detected among the included studies (I2=80%), a random-effects model was applied. And the pooled estimates showed no statistically significant difference in the cumulative number of exacerbation episodes per patient between the OM-85 and placebo groups (0.63 vs. 0.77; MD, –0.14; 95% CI: –0.28 to 0; P=0.05; I2=75%). Adverse event rates were comparable between the two groups (OR, 1.13; 95% CI: 0.86 to 1.50; P=0.38; I2=0%).
Conclusions: Our findings suggest that OM-85 therapy provides some benefits in improving exacerbation outcomes compared with placebo in patients with COPD or chronic bronchitis. Additional research is required to verify these findings due to the small number of trials and between-study heterogeneity.
Keywords: Broncho-Vaxom; lung diseases; obstructive; meta-analysis; symptom flare up
Submitted Jun 10, 2025. Accepted for publication Sep 05, 2025. Published online Oct 23, 2025.
doi: 10.21037/jtd-2025-1166
Highlight box
Key findings
• OM-85 (Broncho-Vaxom) was associated with significant improvements in exacerbation outcomes compared with placebo in patients with chronic obstructive pulmonary disease or chronic bronchitis.
What is known and what is new?
• OM-85 has been proposed to reduce the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease or chronic bronchitis, but its clinical effectiveness remains uncertain.
• This meta-analysis shows that OM-85 leads to a greater proportion of patients remaining free from acute exacerbations.
What is the implication, and what should change now?
• The findings suggest that OM-85 may offer some protective benefits against acute exacerbations in these patient populations.
• Due to small sample size and study heterogeneity, our results should be interpreted with caution. Further high-quality, large-scale randomized controlled trials are needed to clarify its role and identify which patient subgroups may benefit the most.
Introduction
Chronic obstructive lung diseases (COPDs) are a major public health concern, contributing to high morbidity and mortality worldwide (1). Acute exacerbations, defined as sudden worsening of respiratory symptoms requiring therapeutic adjustment, are a common manifestation of these diseases (1). These events trigger airway and systemic inflammation, increasing ventilatory demand. In patients with limited expiratory flow, tachypnea causes air trapping and dyspnea, which can be alleviated by bronchodilators and noninvasive ventilation (1). While hypoxemia occurs in milder cases, severe disease may lead to ventilatory failure and hypercapnia, both linked to poor outcomes (1). Recovery is often prolonged, with reduced quality of life, exercise capacity, and lung function (1).
Major goals in the management of chronic obstructive lung diseases include prevention of exacerbations and timely and effective treatment of those that do occur (2). Preventive measures include smoking cessation, regular exercise, appropriate medications, vaccinations, and avoiding environmental pollution (2). Preventive pharmacological strategies play a central role in reducing the burden of COPD exacerbations. Long-acting bronchodilators, including β2-agonists and muscarinic antagonists, have been shown to significantly decrease exacerbation frequency in patients with moderate to severe disease. Inhaled corticosteroids, particularly when combined with long-acting bronchodilators, provide additional benefit in patients with frequent exacerbations and elevated eosinophil counts (2). For individuals who continue to experience exacerbations despite optimal inhaler therapy, long-term macrolide antibiotics can further reduce exacerbation risk, although concerns remain regarding antibiotic resistance and ototoxicity (2). Phosphodiesterase-4 inhibitors, such as roflumilast, are also recommended for patients with severe COPD with chronic bronchitis and recurrent exacerbations (2). While conventional therapies lower exacerbation risk, they offer only partial protection and may cause adverse effects, including pneumonia, antibiotic resistance, and gastrointestinal or psychiatric issues (2). These drawbacks highlight the need for additional strategies, and oral immunomodulators such as OM-85 (Broncho-Vaxom) has been investigated as an adjunctive option, demonstrating the potential to decrease exacerbation incidence, limit hospitalization time, and lessen antibiotic utilization (3-5).
The orally administered immunomodulatory agent OM-85 is composed of a lyophilized bacterial lysate derived from eight common respiratory pathogens (6). OM-85 enhances immune defenses by stimulating the production of salivary immunoglobulin A (IgA), bronchoalveolar IgA, and serum IgA and immunoglobulin G (IgG)4. Since its introduction in 1980, OM-85 has been used in both adults and children to prevent recurrent respiratory tract infections and to increase IgA and IgG levels (6). The efficacy of OM-85 in preventing COPD exacerbations has been investigated in prior studies, and existing systematic reviews and meta-analyses using different approaches, populations, and outcomes have reported conflicting results (3-5). Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of OM-85 for preventing acute exacerbations in adult patients with COPD or chronic bronchitis. We present this article in accordance with the PRISMA reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1166/rc).
Methods
Data sources and search strategy
The systematic review and meta-analysis were prospectively registered in the PROSPERO database (www.crd.york.ac.uk/prospero CRD420251040370) (7). A comprehensive search of three electronic databases (PubMed, Embase, and the Cochrane Central Register of Controlled Trials) was conducted from their inception up to April 2025. The following terms were used: “OM-85”, “broncho-vaxom”, “chronic obstructive lung disease”, “chronic bronchitis” and “acute exacerbation”. Full search strategies for all databases are reported in Table S1. Only RCTs published as full-length, peer-reviewed articles in English and conducted on human subjects were included. Studies such as reviews, abstracts, crossover trials, single-arm studies, letters, case reports or case series, and commentaries were excluded. Because this study involved analysis of previously published data, ethical approval and informed consent were not required.
Study selection, data extraction, and clinical outcomes
Studies were selected according to the Population, Intervention, Comparison, Outcomes, and Study criteria: (I) Population, adults aged 18 years or older who were diagnosed with COPD or chronic bronchitis by physicians; (II) Intervention, OM-85 as adjunct therapy; (III) Comparison, placebo; (IV) Outcomes, acute exacerbation rate and adverse events; (V) Study design, RCTs. As this study was designed to investigate COPD or chronic bronchitis, individuals with asthma, bronchiectasis, pneumonia, tuberculosis, or interstitial lung diseases were excluded from the analysis.
Two independent reviewers (J.L. and J.U.S.) screened the titles and abstracts of all identified studies based on predefined eligibility criteria. Full-text articles of potentially relevant studies were subsequently retrieved and assessed for final inclusion. Data extraction was performed independently by the same reviewers using a standardized form, and discrepancies were resolved through discussion and consensus. The following data were collected from each included study: first author, year of publication, study design, sample size, patient characteristics (age and sex), height, weight, forced expiratory volume in one second, forced vital capacity, intervention details, comparator information, and clinical outcomes, including the incidence of exacerbations and adverse events.
The primary outcome measure for data extraction was an acute exacerbation, defined as worsened dyspnea, deteriorating cough, purulent secretions, or fever. The analysis of acute exacerbation rates was conducted with respect to two predefined outcomes: the proportion of patients who remained free from acute exacerbations and the cumulative number of episodes over a 6-month period. The secondary outcome was the rate of adverse events.
Statistical analysis
Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models depending on dichotomous or continuous data. Heterogeneity among studies was evaluated using the I2 statistic, with values ranging from 0% to 100% (8). An I2>50% indicated substantial heterogeneity (8). In the absence of significant heterogeneity, a fixed-effects model was applied; otherwise, a random-effects model was used.
The methodological quality of the included studies was evaluated by assessing the risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (9). Each RCT was evaluated for risk of bias in each domain as low, high, or unclear (9). Any discrepancies arising during study selection, data extraction, or quality assessment were resolved through discussion and consensus between the reviewers.
A P value <0.05 was regarded as statistically significant. Statistical analyses were conducted using Review Manager Software, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).
Results
Initially, 168 titles were identified through database searches. After removing duplicates, 154 articles remained for potential inclusion. Title and abstract screening resulted in the exclusion of 133 studies. Subsequently, 21 articles were reviewed in full, and 5 were included in the final analysis (Figure 1) (10-14). The characteristics of the included study characteristics are shown in Table 1, and an overview of the primary outcomes of each study is presented in Table 2. The included articles were published between 1990 and 2015, with patient numbers ranging from 273 to 396 and a total sample size of 1,724.
Table 1
| Study (year) | Design, country | Patients | Age, years | Male, % | Current smoker, % | Height, cm | Weight, kg | FEV1, % predicted | FVC, % predicted | Adverse events, % | Population | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| O | P | O | P | O | P | O | P | O | P | O | P | O | P | O | P | O | P | |||||||||||
| Collet et al., 1997 (10) | Multi-center, double-blind placebo-controlled, Canada | 191 | 190 | 65.3 | 66.9 | 69.6 | 71.1 | 40.8 | 31.1 | NA | NA | NA | NA | 42.3 | 44.0 | 67.7 | 68.4 | NA | NA | COPD (heavy smokers >20 pack-years; FEV1 20–70% predicted; <15% reversibility post-salbutamol) | ||||||||
| Debbas et al., 1990 (11) | Multi-center, double-blind placebo-controlled, France | 198 | 198 | 81.8 | 81.9 | 45.4 | 47.5 | NA | NA | 161.0 | 161.1 | 59.7 | 59.5 | NA | NA | NA | NA | NA | NA | Chronic bronchitis with acute respiratory tract infections in the past year | ||||||||
| Orcel et al., 1994 (12) | Multi-center, double-blind placebo-controlled, France | 147 | 143 | 82 | 82 | 44.2 | 46.9 | NA | NA | 161 | 161 | 60.1 | 60.0 | 55 | 55 | 62 | 65 | 59.9 | 53.8 | Chronic bronchitis with antibiotic-treated lower respiratory tract infections in the past year | ||||||||
| Solèr et al., 2007 (13) | Multi-center, double-blind placebo-controlled, Switzerland and Germany | 142 | 131 | 57.3 | 57.9 | 54.9 | 43.5 | 33.1 | 28.2 | 168 | 167.7 | 74.5 | 74.7 | 85.0 | 82.6 | 91.0 | 89.7 | 30.8 | 27.5 | Chronic bronchitis or mild COPD | ||||||||
| Tang et al., 2015 (14) | Multi-center, double-blind placebo-controlled, China | 192 | 192 | 63.0 | 63.2 | 73.4 | 69.3 | 25.0 | 24.0 | 164.1 | 164.5 | 61.8 | 45.4 | 54.0 | 55.0 | NA | NA | 27.9 | 27.7 | Chronic bronchitis or COPD with acute exacerbation | ||||||||
COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; NA, not available; O, OM-85; P, placebo.
Table 2
| Study (year) | Primary outcome | OM-85 group | Placebo group | Effect estimate | P value |
|---|---|---|---|---|---|
| Collet et al., 1997 (10) | ≥1 acute exacerbation (patients) | 44.5% | 43.7% | No significant difference | 0.872 |
| Debbas et al., 1990 (11) | Total infections (episodes) | 113 | 156 | 39% reduction in favor of OM-85 | NA |
| Orcel et al., 1994 (12) | Lower respiratory tract infections (episodes) | 112/147 patients | 156/143 patients | 28% reduction | <0.05 |
| Solèr et al., 2007 (13) | Mean cumulative exacerbation rate | NA | NA | –0.22/patient (–23.7%) | 0.08 |
| Tang et al., 2015 (14) | Patients with recurrent exacerbations | 23.4% | 33.3% | Significant reduction | 0.03 |
NA, not available.
In four trials, patients received one 7 mg OM-85 capsule daily for 10 consecutive days per month over three consecutive months (10-12,14). In one study, patients received OM-85 daily for 30 days from the initial visit, followed by three 10-day courses administered at the beginning of months 3, 4, and 5 (13). A quality assessment of the studies included is presented in Table 3. The overall quality of the studies was satisfactory. The most common potential source of bias was selection bias resulting from a lack of sequence generation and allocation concealment.
Table 3
| Study (year) | Sequence generation | Allocation concealment | Blinding of participants and researchers | Blinding of outcome assessment | Incomplete outcome data addressed | Free of selective reporting |
|---|---|---|---|---|---|---|
| Collet et al., 1997 (10) | Low risk | Low risk | Low risk | Low risk | Low risk | Low risk |
| Debbas et al., 1990 (11) | Unclear | Unclear | Low risk | Low risk | Low risk | Low risk |
| Orcel et al., 1994 (12) | Unclear | Unclear | Low risk | Low risk | Low risk | Low risk |
| Solèr et al., 2007(13) | Unclear | Unclear | Low risk | Low risk | Low risk | Low risk |
| Tang et al., 2015 (14) | Unclear | Unclear | Low risk | Low risk | Low risk | Low risk |
All included trials were evaluated to determine the proportion of patients who remained free from acute exacerbations when treated with OM-85 compared with placebo. The rate of patients remaining free from acute exacerbations was 39.2% in the OM-85 group and 30.3% in the placebo group. The pooled estimates revealed a significant improvement in the rate of patients remaining free from acute exacerbations in the OM-85 group compared with the placebo group (OR, 1.73; 95% CI: 1.04 to 2.87; P=0.03; Figure 2). Because substantial between-study heterogeneity was observed (I2=80%), the random effects model was used for our meta-analysis.
We also assessed the cumulative number of acute exacerbation episodes over 6 months in patients with COPD or chronic bronchitis (10-14). The pooled analysis showed that there was no statistically significant difference in the cumulative number of exacerbation episodes per patient between the OM-85 and placebo groups (0.63 vs. 0.77; MD, –0.14; 95% CI: –0.28 to 0; P=0.05; I2=75%; Figure 3).
A total of 3 trials assessed the adverse events of OM-85 therapy (12-14). The pooled estimates using a fixed effects model demonstrated that the rate of any adverse events at the end point of the study did not differ significantly between the two groups (38.6% in the OM-85 and 36.0% in the placebo group; OR, 1.13; 95% CI: 0.86 to 1.50; P=0.38; I2=0%; Figure 4).
Discussion
Previous systematic reviews and meta-analyses on the role of OM-85 therapy in patients with chronic bronchitis and COPD have reported inconsistent results regarding its effect on exacerbation rates (3-5). To enhance the clarity of our findings, we sought to provide more definitive evidence by defining exacerbation rate both as the proportion of patients who remained free from acute exacerbations and as the cumulative number of episodes over 6 months.
In the present study, add-on therapy with OM-85 (Broncho-Vaxom) significantly increased the proportion of patients who remained free from acute exacerbations compared with placebo in patients with COPD or chronic bronchitis. Specifically, OM-85 therapy led to an approximately 9% higher proportion of patients remaining exacerbation-free. However, significant differences were not observed in the cumulative number of acute exacerbations per patient at 6 months. OM-85 was also well tolerated, with a comparable incidence of adverse events between the OM-85 and placebo groups. Taken together, these findings support a potential role for OM-85 therapy in reducing the burden of acute exacerbations among patients with COPD or chronic bronchitis.
A number of studies have evaluated OM-85 add-on therapy in the pediatric population, and recent meta-analyses have established its clinical benefits in managing recurrent respiratory infections in this group (15-17). In particular, among children with asthma, OM-85 add-on therapy has been shown to significantly improve asthmatic symptoms, lower the frequency of asthma exacerbations, and enhance airway function (15). Additionally, OM-85 treatment has demonstrated immune-modulatory effects, as indicated by increased serum immunoglobulin levels, elevated counts of T-lymphocytes and their subsets, and decreased interleukin-4 (IL-4) levels (15).
In contrast, the clinical benefits of OM-85 therapy in adult populations have been investigated in only a limited number of studies. The articles included in our analysis were published between 1990 and 2015, and more recent publications were not available. However, a recent study utilizing national health insurance reimbursement data demonstrated that OM-85 add-on therapy significantly reduced the rate of acute exacerbations in patients with COPD (18). This study, which compared the frequency of exacerbations before and after OM-85 therapy among OM-85 users, showed that the risk of moderate and moderate-to-severe exacerbations was markedly reduced with OM-85 add-on therapy (18). Moreover, OM-85 therapy delayed the onset of the first moderate exacerbation (18). Consistent with previous studies, our results also support the beneficial effects of OM-85 therapy in reducing exacerbation rates in patients with COPD (5,18). These findings suggest that, although OM-85 therapy has received limited attention in recent years, the accumulation of further evidence and the identification of factors associated with its effectiveness may support its role in contributing to individualized treatment strategies for patients with COPD or chronic bronchitis.
There remains limited evidence on the use of OM-85 therapy in adults with other chronic airway diseases, such as asthma and bronchiectasis. A recent RCT assessed the effects of add-on OM-85 therapy in adults with severe asthma and frequent exacerbations (19). This study found no significant benefit of OM-85 in reducing asthma exacerbations. However, a post hoc subgroup analysis indicated a potential trend toward reduced exacerbation frequency among patients with asthma characterized by type 2 inflammation (19). Similarly, in a trial involving adults with bronchiectasis who had experienced at least one exacerbation in the preceding year, OM-85 therapy did not demonstrate clinically meaningful benefits in reducing the cumulative number of exacerbations, delaying the time to first exacerbation, improving lung function, alleviating cough symptoms, or enhancing quality-of-life measures (20).
The benefits of OM-85 add-on therapy appear to be more pronounced in children. Although the exact mechanisms underlying these differences remain unclear, several hypotheses have been proposed to explain the observed effects. One possible explanation is the immature immune homeostasis in children (21). Early-life exposure to environmental microbes, particularly through gut bacteria, plays a key role in immune system development and T cell differentiation. Because OM-85 contains pathogen-associated molecular patterns that help restore immune balance, its effects may be more pronounced in children with developing immune systems (21). In contrast, adults have already been exposed to a wide range of antigens, resulting in a well-established immune system (16). Consequently, their response to additional immune stimulation may not be as robust as in children, potentially limiting the added benefits of OM-85 therapy. Furthermore, adults have developed immune memory through prior vaccinations and natural infections and might experience weaker effects of further immune stimulation (15).
Regarding adverse effects, OM-85 has a robust safety profile, supported by 40 years of clinical use (22). From 1979 to 2017, with an estimated 100 million patients exposed, only 1,974 adverse events were reported, mainly mild hypersensitivity reactions (22). Fatal reactions were rare, with only 28 severe cutaneous events and 3 reports of toxic epidermal necrolysis or Stevens-Johnson syndrome (22). In our study, the rate of any adverse events with OM-85 therapy was comparable with that of placebo.
This study has some limitations. First, despite a thorough search, a small number of trials was identified, which may have affected the strength of the conclusions. Second, substantial statistical heterogeneity was observed among the included studies and might be attributed to variations in population characteristics such as concomitant medication use, duration of OM-85 add-on therapy, influenza or pneumococcal vaccination status, and length of follow-up. And the criteria used to define exacerbations varied across studies (e.g., symptom-based definitions, or composite criteria including symptoms plus radiological changes), which may have contributed to heterogeneity in the pooled endpoints. Furthermore, COPD and chronic bronchitis are distinct clinical entities with different pathophysiological characteristics. Nevertheless, most of the studies included in our analysis reported outcomes by combining patients with COPD and chronic bronchitis, and the reported forced expiratory volume in one second values indicated a wide spectrum of disease severity. Although we attempted to perform a subgroup analysis to differentiate COPD from chronic bronchitis, this was not feasible due to limitations in the data available from the original studies. Third, the small number of studies hindered proper assessment of publication bias. The absence of certain data and unpublished findings may have contributed to this bias.
Conclusions
Add-on therapy with OM-85 (Broncho-Vaxom) increased the proportion of patients who remained free from acute exacerbations in COPD or chronic bronchitis, although it did not significantly reduce the cumulative number of episodes over 6 months. The treatment was well tolerated and may play a potential role in alleviating the burden of exacerbations in these patients. Due to the limited number of studies and the substantial heterogeneity observed among them, further large-scale clinical trials are warranted to confirm and extend the findings.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1166/rc
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1166/prf
Funding: This work was supported by a research grant from
Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1166/coif). J.L. reports receiving a research grant from the Jeju National University Hospital Research Fund of Jeju National University College of Medicine in 2024. However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other author has no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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