A bacterial lysate does not prevent preschool wheeze

Design

parallel-arm, double-blind, placebo-controlled randomised trial at 11 US sites, 24 months of treatment then 36 months off drug (ORBEX)

Population

822 children aged 6-18 months at high risk of asthma through atopic dermatitis, parental asthma or an affected sibling; mean age 11.8 months

Primary outcome

time to first wheezing lower respiratory tract illness during the 36-month off-treatment observation period

Effect

71/342 (21%) with OM-85 vs 61/339 (18%) with placebo; hazard ratio 1.16 (95% CI 0.82-1.64), log-rank P=0.35

The idea that training the immune system early might prevent asthma has been attractive for decades, and oral bacterial lysates have been the most tested version of it. ORBEX was designed to settle the question properly. It randomised 822 children aged 6 to 18 months at high risk of asthma, by virtue of atopic dermatitis, parental asthma or an affected older sibling, to OM-85 3.5 mg or identical placebo for ten days each month for 24 months at 11 US academic sites, then followed them for a further 36 months off the drug. The primary outcome was time to first wheezing lower respiratory tract illness during that off-treatment period.

Nothing separated the groups. At least one wheezing illness occurred in 71 of 342 children (21%) in the OM-85 group and 61 of 339 (18%) on placebo, hazard ratio 1.16 (95% CI 0.82 to 1.64), log-rank P=0.35. The commonest adverse events, fevers, coughs and colds, were no different.

This is a well-conducted negative trial and its value is in closing a question rather than opening one. Bacterial lysates are widely sold, including over the counter in many countries, on exactly the premise this trial tested: that repeated immune stimulation in early life reduces later wheezing. In a high-risk group, given for two years, with three further years of follow-up, it did not.

The practical use is the conversation with a parent who has read about immune-boosting supplements for a wheezy toddler. The honest answer is that the best trial of the best-studied product in this class found no benefit, and that the interventions with evidence behind them remain avoidance of tobacco smoke exposure, treating eczema properly, immunisation, and recognising and treating wheeze episodes when they occur.

• Do not recommend bacterial lysates to prevent wheeze or asthma in young children
• Redirect the conversation to tobacco smoke exposure, indoor air quality and immunisation
• Treat atopic dermatitis actively; it is the marker that put many of these children in the high-risk group
• Reassure parents that a negative trial of this quality is useful information, not a failure to find a treatment
• Keep managing wheezing episodes as they arise rather than pursuing prevention with unproven agents

The statistics, in plain English

The hazard ratio of 1.16 sits above 1.0, meaning the treated group did numerically slightly worse, but the interval from 0.82 to 1.64 includes no effect comfortably, so the honest reading is no difference rather than harm. With 132 events across 681 children followed, the trial had enough events to exclude a large benefit; a small benefit of a few percentage points cannot be ruled out, and would not justify two years of monthly dosing in any case. The design is the strength: identical capsules, masked staff and participants, central randomisation stratified by known risk factors, and a primary outcome measured after the drug had stopped.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.