Use of the bacterial lysate OM-85 for the primary prevention of wheezing lower respiratory illness in preschool children: a randomised, placebo-controlled trial.

September 7, 2026| Source: Lancet (London, England)

Wheezing lower respiratory tract illnesses are a major health concern in preschool children. We report the results of the ORBEX trial which evaluated the safety and efficacy of the bacterial lysate, OM-85, in the primary prevention of wheezing lower respiratory tract illness. ORBEX is a parallel-arm, double-blind, placebo-controlled trial for the primary prevention of wheezing lower respiratory tract illness in young children at increased risk for asthma due to atopic dermatitis, parental asthma, or asthma in a blood sibling aged 4 years or older. Children aged 6-18 months were centrally randomly assigned (1:1) at 11 academic clinical sites with experience in recruiting young children in the USA to receive OM-85 3·5 mg or placebo orally for 10 days each month for 24 months and then followed for an additional 36 months to evaluate outcomes while they were off the study drug. Identical openable capsules were used for active drug and placebo, and staff, investigators, and participants were masked to treatment assignment. Participants received usual treatment for wheezing illness as per US guidelines. Randomisation was stratified by sex, age group, family history of asthma, and clinical site. The primary outcome was the time to first wheezing lower respiratory tract illness during the 36-month observation period off the study drug analysed in the intention-to-treat population, which included all randomly assigned participants. The trial is registered with clinicaltrials.gov, NCT02148796, and is completed. Between Jan 3, 2017, and Nov 30, 2020, 984 children were screened for eligibility, 162 were excluded, and 822 were randomly assigned (411 to the OM-85 intervention group and 411 to the placebo group). 492 participants were male (59·9%) and 330 (40·1%) were female and the mean age of participants was 11·8 months (SD 3·8). 681 children completed the 24-month treatment period, and 596 children completed the 36-month observation period. 132 children experienced at least one wheezing lower respiratory tract illness during the observation period; 71 (21%) of 342 in the OM-85 group and 61 (18%) of 339 in the placebo group. There was no significant difference between OM-85 and placebo with respect to the time to first wheezing lower respiratory tract illness (log-rank test p value 0·35; hazard ratio 1·16 [95% CI 0·82-1·64]). The most frequent adverse events, fevers, coughs, and colds, did not differ between groups. Oral administration of OM-85 in early life did not decrease the incidence of wheezing lower respiratory tract illness in this high-risk population. Bacterial lysates are not efficacious for the primary prevention of asthma-like symptoms during the preschool years. National Heart, Lung, and Blood Institute and OM Pharma with supplemental funding and provision of study drug and placebo from OM Pharma.

Read the original source →

An innervated and vascularized HNSCC-on-a-chip model built on defined and tunable engineered extracellular matrices.

Understanding the tumor microenvironment requires experimental platforms that faithfully recapitulate its key components. Here, we present an innervated and vascularized head and neck squamous cell carcinoma (HNSCC)-on-a-chip platform built with fully defined and tunable engineered extracellular matrices (eECMs). In a stepwise increase of complexity, we first cocultured patient-derived HNSCC cells, cancer-associated fibroblasts, and endothelial cells within tailored eECMs, revealing extracellula

Septin binding restricts Shigella growth and triggers intracellular tolerance.

Pathogen survival relies on their ability to adapt to changing environments, yet how intracellular bacteria tolerate cell-autonomous immunity remains unclear. Septins assemble into cage-like structures around cytoplasmic Shigella targeted by autophagy, but their antibacterial activity was unknown. Using advanced microscopy and cell-free reconstitution, we show that septins polymerize into circumferentially oriented filaments that inhibit bacterial growth. RNA-sequencing reveals that septin bindi

DCAF6 reprograms TGF-β responses through TRIM33 destruction.

TGF-β signaling plays a pivotal role in regulating numerous cellular processes, primarily through the Smad-dependent pathway. Disruptions of the pathway are associated with developmental disorders and life-threatening diseases, such as cancer. It has been reported that TRIM33 inactivates Smad4 signaling and also drives its own signaling responses. However, the mechanism controlling TRIM33 activity has remained unclear. In this study, we identify DCAF6 as a previously unrecognized ubiquitin

Stimulated protein degradation to promote mitochondrial function and neuronal survival.

Targeted protein degradation is a promising modality to treat cancer or inflammation, but whether it can provide a similar benefit for disorders caused by pervasive protein dysregulation is unclear. We describe stimulated protein degradation (SPD) as a strategy that leverages agonists of stress-responsive E3 ubiquitin ligases to simultaneously eliminate multiple pathogenic factors. Specifically, we show that activators of the reductive stress response E3 CUL2 FEM1B boost degradation of multiple

Spatial coordination in the codevelopment of the human urogenital system during organogenesis.

The human urogenital system originates from a common embryonic domain, yet the mechanisms guiding its spatiotemporal coordination remain understudied. Here, we combined high-resolution spatial transcriptomics with single-cell multiomics to profile human embryos from Carnegie stages 15 to 23, capturing the codevelopmental dynamics of the urogenital system. We revealed mesonephros- and adrenal primordium-derived signals that promote gonadal specification and enable efficient in vitro generation of