Alleviating symptoms of paediatric acute rhinosinusitis and acute otitis media with otorrhea using nasal-spraying Bacillus probiotics: a randomized controlled trial

Abstract

Acute rhinosinusitis (ARS) in children may be accompanied by acute otitis media (AOM) which is often associated with bacterial co-infections. These conditions are among the primary reasons that children visit hospitals and require antibiotic treatment. This study evaluated the efficacy of the nasal-spraying probiotics (LiveSpo Navax containing 5 billion Bacillus subtilis and B. clausii spores/5 mL) as a supportive treatment for dual ARS and AOM with otorrhea in a randomized, single-blind, controlled clinical trial. Eighty-two patients (41 per group), aged 1 month to 12 years, received standard care along with nasal spraying of either physiological saline (Control group) or LiveSpo Navax (Navax group), administered three times daily over a 7-day follow-up period. A total of sixty-one patients (30-31 per group) completed the trial. The Navax group experienced 68.00% and 96.77% reductions in nasal congestion (by day 3) and rhinorrhea (by day 7), respectively, which were 2.04 and 1.94-fold higher than the Control group, with odds ratios (OR) of 4.31 and 30.00 (p < 0.05). Endoscopic results indicated 8% and 11% higher reductions in nasal mucopurulent discharge and tympanic membrane hyperemia in the Navax group compared to the Control group. By day 3, compared to day 0, the Navax group exhibited > 1200-fold reduction in Streptococcus pneumoniae and ≥ 4-fold reduction in Haemophilus influenzae concentrations (p < 0.05) in both nasopharyngeal and middle ear fluid samples, whereas the Control group showed no significant reductions. Navax treatment reduced IL-6 by 1.35- to 1.74-fold and TNF-α by 1.17- to 1.45-fold, more effectively than the Control group (p < 0.05). These results suggest that nasal-spray Bacillus spore probiotics, with their ability to reduce bacterial load and modulate immune responses, provide a cost-effective and safe solution for alleviating symptoms of both ARS and AOM in children.Trial registration: ClinicalTrials.gov, Identifier NCT05804123 on April 7, 2023.

Keywords: Acute; Bacterial co-infection; Cytokine; Nasal-spraying Bacillus spores; Otitis media; Rhinosinusitis.

Fig. 1

A CONSORT flowchart illustrating the patient recruitment and allocation process adopted in this study. It outlines the recruitment and allocation of participants, the standard treatment of care, follow-up, and analysis at the endpoint, conducted between July 2022 and March 2024.

Fig. 2

Percentages of patients exhibiting typical symptoms of acute rhinosinusitis and acute otitis media in the Control and Navax groups at days 0, 3, and 7: nasal congestion (A), rhinorrhea (B), otorrhea (C), and rhinorrhea in children < 24 months (D). The difference between data distribution was confirmed using the Chi-square and Fisher’s exact test.

Fig. 3

Endoscopic results demonstrating changes in nasal mucopurulent discharge and tympanic membrane hyperemia in the Control and Navax groups at day 3 compared to day 0. Percentages of patients exhibiting mucopurulent discharge from the middle meatus (A) and tympanic membrane hyperemia (B) in the Control and Navax groups at days 0 and 3. The difference between data distribution was confirmed using the Chi-square and Fisher’s exact test. Representative endoscopic images of the nose (C) and ear (D) show the locations of mucopurulent discharge from the middle meatus and tympanic membrane hyperemia (indicated by white arrows) in patients from the Control and Navax groups at days 0 and 3.

Fig. 4

Real time PCR results showing C_t values, reducing-fold levels (2^ΔCt), and amplification curves for S. pneumoniae, H. influenzae, B. subtilis, and B. clausii in nasopharyngeal (NOSE) and middle ear fluid (EAR) samples from Control and Navax groups at days 0 and 3. C_t and 2^ΔCt of fluorescence signals for S. pneumoniae and H. influenzae measured in samples of Control and Navax groups (A, B). C_t of fluorescence signals for B. subtilis and B. clausii measured in samples from the Control and Navax groups at day 3 (C). Real-time PCR TaqMan probe amplification curves for S. pneumoniae and H. influenzae from representative NOSE (D) and EAR (E) samples of the Control and Navax groups; real-time PCR SYBR Green amplification curves for B. subtilis and B. clausii (F) from samples of the Control and Navax groups at day 3; PC and NC are positive and negative controls. The Wilcoxon signed-rank test was used to determine the difference in C_t values of bacteria within a single group between days 0 and 3.

Fig. 5

Pro-inflammatory cytokine levels (pg/mL) and immunoglobulin A (ng/mL) in nasopharyngeal (NOSE) and middle ear fluid (EAR) samples from the Control and Navax groups at day 3 compared to those at day 0. The Wilcoxon signed-rank test was used to calculate the median differences in IL-6 (A), TNF-α (B), IL-8 (C) and IgA (D) levels at days 0 and 3 in each group. The 95% CI for median in each group and the median difference between the two groups were shown in figure A–D. The significance level of all analyses was set at the p < 0.05.