Clinical Evaluation of Bacterial Lysate for Immune Regulation and Exacerbation Reduction in Stable Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and is accompanied by systemic immune dysfunction, and recurrent acute exacerbations are the main determinants of disease progression, hospitalisation and poor prognosis. Oral bacterial lysates stimulate mucosa-associated lymphoid tissue and have been reported to reduce respiratory infections and exacerbations, but evidence on their immunomodulatory effect in patients with stable COPD is still limited. This single-centre retrospective cohort study, based on clinical data collected during routine care, was designed to investigate whether bacterial lysate Broncho-Vaxom (OM85-BV) can reduce the frequency of acute exacerbations in patients with stable COPD by regulating immune function.Methods: 102 patients with stable COPD admitted to outpatient and inpatient departments were included between January 2025 and October 2025. Based on the treatment methods, they were classified into a control group (CG, basic treatment) and an OM85-BV group (basic treatment combined with oral bacterial lysate). Propensity score matching (PSM) was performed at a ratio of 1:1 using the nearest-neighbour method with a caliper of 0.100. In addition, healthy individuals of the same age group who underwent physical examination in The Fourth People’s Hospital of Lin’an District during the same period were collected as a healthy control group (HC). HC received no drug treatment, and only admission indicators were collected. HC served solely as a descriptive reference for the distribution of immune indicators in individuals of comparable age and sex without COPD. The primary outcome measures in patients with COPD were the modified Medical Research Council (mMRC) dyspnea questionnaire and the COPD Assessment Test (CAT) at the 6-month follow-up, as well as the frequency of acute exacerbations within 6 months. The secondary outcome measures included albumin (ALB), immunoglobulins IgG, IgA and IgM, secretory immunoglobulin A (sIgA), CD4+ cells, CD8+ cells, CD4+/CD8+, natural killer (NK) cells, interleukin-6 (IL-6), interleukin-11 (IL-11), tumor necrosis factor-α (TNF-α) and safety indicators.Results: In the descriptive comparison with HC, patients with stable COPD in the OM85-BV group and CG showed significantly decreased CD4+, CD4+/CD8+ and NK cells, as well as significantly increased CD8+ (p < 0.001). In repeated-measures analysis of variance (ANOVA), the time × group interaction was significant for CD4+ (F(2,156) = 6.9, p = 0.001), CD8+ (F(2,156) = 8.9, p < 0.001), CD4+/CD8+ (F(2,156) = 18.200, p < 0.001), and NK cells (F(2,156) = 3.1, p = 0.046). At the 6-month follow-up, the median CAT score in the OM85-BV group was lower than that in the CG [10.00 (4.75, 12.25) points vs 12.50 (7.00, 20.00) points, p = 0.028], and the mMRC grade was lower compared to CG [1.00 (0.00, 2.00) vs 2.00 (1.00, 3.00), p = 0.023]. The OM85-BV group had fewer acute exacerbations [1.00 (0.00, 1.00) vs 1.00 (1.00, 2.00), p < 0.001]. In the negative binomial regression model, the incidence-rate ratio (IRR) of the OM85-BV group relative to CG was 0.630 (95% confidence interval (CI) 0.440 to 0.900, p = 0.011). The CD4+, CD4+/CD8+ and NK cells in the OM85-BV group at the 6-month follow-up were higher than those in the CG, whereas the CD8+ was lower (all p < 0.05). At the 6-month follow-up, the levels of sIgA, ALB, IgG, IgA and IgM in the OM85-BV group were higher than those in the CG, while IL-11 (T2: median 8.20 vs 11.10, Z = –4.285, p < 0.001) and TNF-α (T2: median 13.10 vs 15.20, Z = –2.267, p = 0.023) were lower than those in the CG (p < 0.05). Because Shapiro-Wilk tests indicated IL-6, IL-11, and TNF-α at T2 did not meet the normality assumption (Shapiro-Wilk p < 0.05), these markers were re-analysed non-parametrically. IL-6 at T2 did not differ significantly between groups (Z = –1.002, p = 0.318). Adverse events occurred in 4 cases (10.00%) in the CG and 6 cases (15.00%) in the OM85-BV group, including gastrointestinal discomfort and transient skin reactions. The incidence rate of adverse reactions revealed no significant difference between the two groups (p = 0.48).Conclusion: For patients with stable COPD, treatment with bacterial lysate was associated with more favourable changes in cellular immunity (CD4+, CD8+, CD4+/CD8+, NK cells) and humoral immunity (sIgA and immunoglobulins), as well as lower IL-11 and TNF-α levels and significantly reduced acute exacerbations within 6 months. Because the data are observational, these findings are consistent with an immunomodulatory effect of the combination of bacterial lysate and standard treatment but do not establish a causal relationship.