Bacterial lysate add-on therapy in adult and childhood asthma: a systematic review and meta-analysis

Abstract

Background It has been proposed that bacterial lysates may serve as a suitable immunomodulatory oral medication to improve and control asthma symptoms. However, the difference in its efficacy in adults and children remains unclear. Methods Randomized controlled trials (RCTs) evaluating OM-85 add-on therapy in asthma patients up to December 2021 were searched using PubMed, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, and WP (WeiPu) database. Risk of bias was evaluated using the Cochrane risk of bias assessment tool. Results A total of 36 studies were included. The results showed that OM-85 add-on treatment provided a 24% improvement in asthma symptom control [relative rates (RR) =1.24, 95% confidence intervals (CI): 1.19–1.30], and also significantly improved lung function, increased numbers of T-lymphocytes and the subtypes, and elevated levels of interferon-γ (IFN-γ), interleukin-10 (IL-10), and IL-12. Levels of serum immunoglobulin E (IgE), eosinophil cationic protein (ECP) and pro-inflammatory cytokines (including IL-4 and IL-5) were suppressed in the OM-85 add-on treatment group. Moreover, OM-85 add-on treatment showed more prominent effects in asthmatic children than in asthmatic adults. Conclusions OM-85 add-on therapy showed important clinical benefits for patients with asthma, especially asthmatic children. Further studies focusing on the immunomodulatory function of OM-85 in personalized asthma treatment are warranted.

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

“…They did report a second RCT on OM-85 that showed significant improvements, but for unclear reasons that study was not part of the pooled analysis. Yao et al 29 reported 22% improvement in asthma symptoms in the OM-85 groups vs. controls, but no separate data was presented in terms of intervention or placebo group. The number of asthma exacerbations during treatment was lower in the OM-85 group than in controls but with high heterogeneity (I 2 = 95%).…”

“…And children in the OM-85 group showed greater improvement in FEV 1 % (I 2 = 52.2%) than controls. Among those two systematic reviews 26,29 on wheezing/asthma exacerbations or asthma control, one 26 had "critical low confidence" and one 29 had "low confidence" (i.e., the review has one critical flaw and may not provide an accurate and comprehensive summary of the available studies that address the question of interest). One systematic review 30 we did not include, because not separately data exclusively on the pediatric population was presented, was done on 12 RCTs (10 RCTswere in children, accounting for 84% of participants) and showed asthma symptoms control was 22% higher and FEV1 improved more in the OM-85 group compared to controls (placebo or routine therapy, without analyze separately).…”

“…Based on evidence obtained in vitro, in animal models, and many studies in humans, four (non-mutually exclusive) cellular mechanisms may be involved: gut-associated lymphoid tissue (GALT)-mediated activation of dendritic cells, T-lymphocytes, and B-lymphocytes; migration of GALT-generated immune cells into the upper and lower respiratory tract; increased production of immunoglobulins resulting in decreased susceptibility to pathogens; and prevention (or early correction) of an imbalance in T1/T2-mediated immunological responses [32][33][34]. Yao et al29 examined some immunological measurements and found that OM-85 add-on therapy did present immunomodulatory effects such as increased numbers of T-lymphocytes, increased IgA concentration in serum and sputum, elevated levels of T1 inflammatory cytokines, and decreased intensity of T2-mediated inflammatory responses. Conclusions: Based on this updated extensive review, it is not feasible to reach clear recommendations on the efficacy of OM-85 for acute RTIs, asthma development, or acute exacerbations in children.…”

Advances in Bacterial Lysate Immunotherapy for Infectious Diseases and Cancer

“…OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, and Vaxoral®) is an over-the-counter oral preparation of lyophilized bacterial lysates of eight common respiratory pathogens ( H. influenzae , Diplococcus pneumoniae , Klebsiella pneumoniae , Klebsiella ozaenae , Staphylococcus aureus , S. pyogenes , Streptococcus viridans , and Neisseria catarrhalis ). OM-85 has been used for several decades in different countries (excluding the USA as OM-85 or similar products are not yet approved by the FDA) in both adults and children to treat and prevent recurrent respiratory infections, including COPD, asthma, and rhinosinusitis [ 17 , 40 ]. However, in a review in 2019, the European Medicines Agency recommended the use of BLs only for the prevention of RRTIs except for pneumonia, and they also stated that there are no adequate data to support that the BLs are effective in treating existing respiratory infections or preventing pneumonia [ 41 ].…”

“…Potential future developments in genomics and immune profiling technologies might facilitate the identification of blood-based immune signals that can be used to predict a patient's response to bacterial lysate immunotherapy under individualized treatment regimens. Subsequent investigations may concentrate on ascertaining if bacterial lysates may be used to create a tumor microenvironment that is more conducive to antitumor immune responses [ 40 , 192 , 202 ].…”