Safety and Efficacy of Two Courses of OM-85 BV in the Prevention of Respiratory Tract Infections in Children During 12 Months

doi:10.1378/chest.119.6.1742

Chest

Volume 119, Issue 6, June 2001, Pages 1742-1748

https://doi.org/10.1378/chest.119.6.1742 Get rights and content

Background

Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children. The bacterial extract OM-85 BV (bronchovaxom) has shown protective effect for ARTIs on children. We report a double-blind, placebo-controlled, parallel, prospective clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months.

Methods

Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected. They were randomized to receive either OM-85 BV or placebo (one capsule a day for 10 days a month for 3 consecutive months) at the beginning of the trial and 6 months later with the same schedule. Patients were followed up for 12 months, including the administration period. The trial began in July 1997 and ended in April 1999.

Results

The number (mean ± SD) of ARTIs was 5.04 ± 1.99 (median, 5.0) in the OM-85 BV group vs 8.0 ± 2.55 (median, 8.0) in the placebo group, with a mean difference of − 2.96 (95% confidence interval [CI],−4.22 to − 1.7). The number of antibiotic courses was 2.46 ± 2.08 (median, 1.5) in the treatment group vs 4.46 ± 2.08 (median, 4.0) in the control group, a difference of − 2.0 (95% CI,− 3.14 to − 0.86). The total duration of ARTIs was 35.23 ± 17.64 days (median, 30.5 days) in the OM-85 BV group vs 60.75 ± 25.44 days (median, 55.0 days) in the placebo group, ie, a difference of − 25.52 days (95% CI, − 37.56 to − 13.47 days),p < 0.001 by Student’s t test and Mann-Whitney U test for all the items. Four patients in the OM-85 BV group had five adverse events. Only one episode of skin rash was related to the medication intake. Six patients in the control group had six adverse events.

Conclusions

OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on the antibiotic requirements and the number of days of suffering ARTIs.

Section snippets

Materials and Methods

A placebo-controlled, parallel, prospective trial was conducted. The patients were children from 1 to 12 years of age living in the metropolitan area of Chihuahua City, Chihuahua State, Mexico. The families were cared for under the state (Pensiones Civiles de Chihuahua, free medical services for workers of state government).

An upper ARTI was defined as the presence of at least one of the following signs: rhinorrhea; sore throat or cough, without signs of lower ARTI, for ≥ 48 h. Lower ARTI was

Results

Fifty-four of 100 children were selected to enter the trial. The nonincluded children suffered seasonal or food-related wheezing or nasal itchiness. Patients were reminded of follow-up visits. Only one boy in the OM-85 BV group was unavailable for follow-up in the last assessment, and the rest of the trial participants completed the scheduled clinical assessments.

All the envelopes containing the double-blind code for the treatment numbers were collected after the end of the study. Based on the

Discussion

RTIs are important causes of morbidity, mortality, and disability in children,^1,^2,³ and therefore are one of the main costs for the health-care system.^36,³⁷ In order to reduce the incidence and complications of RTIs, it is necessary to explore new alternatives for the prevention of this kind of infection.

We have presented a trial to investigate the safety and efficacy of the bacterial extracts OM-85 BV covering a period of 12 months with two courses of administration. We tried to exclude the

ACKNOWLEDGMENT

We thank Miss Lucila Velasco and Dr. Jean Claude Farine for reviewing the article.

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Childhood acute respiratory tract infections (ARTIs) are a significant cause of morbidity and mortality, so, immunostimulants have been used as a preventative measure. Despite this, there is no updated evidence regarding the safety and efficacy of immunostimulant drugs for this purpose. This study aimed to determine the effectiveness and safety of immunostimulants in preventing ARTIs in children based on the most recent scientific evidence. Data sources such as PubMed, Cochrane Central Register of Controlled Trials, Embase, Google Scholar, and Scopus were searched from 1965 to 10 January 2022 to identify randomized controlled trials (RCTs) comparing immunostimulants administered by any method, with placebo to prevent ARTIs on children under 18 years of age without immunodeficiencies, anatomical, genetic, or allergic conditions. In order to analyze data from the studies, we used Review Manager 5.4 (The Cochrane Collaboration, 2020), assessed the certainty of the evidence with Grading of Recommendations, Assessment, Development and Evaluations (GRADE), and assessed the quality and risk of bias of the studies using the RoB tool 1.0. Further, outcomes were combined and analyzed using meta-analysis, subgroup analysis, and sensitivity analysis. Throughout the review, we included 72 placebo-controlled clinical trials involving 12,229 children. The meta-analyses, however, included only 38 studies (52.8%) with 4643 children (38% of the total) with data on mean number of ARTIs. These studies demonstrated a reduction in the ARTIs (MD –1.12 [95%CI –1.39 to −0.85]) and ratio of means of ARTIs (0.61 [95%CI 0.54–0.69]), corresponding to a percentage reduction of 39% (95%CI, 46%–31%) with moderate-quality data. Nevertheless, since there was considerable to substantial heterogeneity and bias was unclear in all domains in 32 out of 72 trials, the quality of the evidence for efficacy was deemed low. Only 14 trials reported adverse events.
The review indicates that immunostimulants reduce the incidence of ARTIs by 40% on average in susceptible children, despite low-quality evidence, heterogeneity, and the possibility of publication bias. However, further studies are needed to establish immunostimulants' safety and efficacy profiles.
This review was conducted without the support of any funding and has no registered number.
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Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2.
ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein–pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro.
OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein–pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.
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Exacerbations are a main characteristic of asthma. In childhood, the risk is increasing with severity. Exacerbations are a strong phenotypic marker, particularly of severe and therapy-resistant asthma. These early-life events may influence the evolution and be involved in lung function decline.
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The aim of this review is to synthesize studies exploring immune mechanisms impairment against viruses and bacteria promoting asthma attacks in children. The potential influence of the nature of infectious agents and/or preexisting microbiota on the development of exacerbation is also addressed. We then discuss our understanding of how these diverse host-microbiota interactions in children may account for the heterogeneity of endotypes and clinical presentations. Finally, improving the knowledge of the pathophysiological processes induced by infections has led to offer new opportunities for the development of preventive or curative therapeutics for acute asthma. A better definition of asthma endotypes associated with precision medicine might lead to substantial progress in the management of severe childhood asthma.
Broncho-Vaxom in pediatric recurrent respiratory tract infections: A systematic review and meta-analysis
2018, International Immunopharmacology
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The quality of the evidence was assessed by GRADEpro GTD software. 823 relevant references were identified initially and 53 [10–62] were subsequently retained after step-by-step screening, including 11 studies published in English [40,52–54,56–62] and 42 in Chinese [10–39,41–51,55]. 4851 pediatric patients were included totally, of which 2491 were in Broncho-Vaxom group and 2360 in control group.
Assess the efficacy and safety of Broncho-Vaxom in pediatric recurrent respiratory tract infections (RRTIs).
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.
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.
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View all citing articles on Scopus

Supported by Química Knoll de México SA de CV.

Dr. Berber is the medical man ager for OM-85 BV in Mexico.

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Chest

Clinical InvestigationsPediatric PulmonologySafety and Efficacy of Two Courses of OM-85 BV in the Prevention of Respiratory Tract Infections in Children During 12 Months

Background

Methods

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

ACKNOWLEDGMENT

Int J Pediatr Otorhinolaryngol

Am J Med

Int J Immunopharmacol

Biochem Biophys Res Comm

Int J Immunopharmacol

Chest

Cur Ther Res

Clin Ther

Am J Med

Otolaryngol Head Neck Surg

Acute respiratory infections: the forgotten pandemic

Bull WHO

Day care and illness: evidence, costs, and public policy

Pediatrics

Illness associated with child day care: a study of incidence and cost

Am J Public Health

Otitis media in infancy and intellectual ability, school achievement, speech, and language at age 7 years: Greater Boston Otitis Media Study Group

J Infect Dis

Recurrent otitis media during infancy and linguistic skills at the age of nine years

Pediatr Infect Dis J

A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion

N Engl J Med

Prevalence of various respiratory viruses in the middle ear during acute otitis media

N Engl J Med

Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial

Pediatrics

Clinical Investigations
Pediatric Pulmonology
Safety and Efficacy of Two Courses of OM-85 BV in the Prevention of Respiratory Tract Infections in Children During 12 Months