細菌を用いた早期喘息予防試験、効果を示さず（Bacterial trial fails to demonstrate early asthma prevention）

2026-09-09

2026-09-08 アリゾナ大学

米アリゾナ大学主導の大規模臨床試験「ORBEX」は、幼少期の喘息発症リスクを低減する目的で、細菌抽出物OM-85を投与しても、重度の喘鳴や呼吸器疾患の発症を抑制できないことを示した。6～18か月齢で、家族歴や湿疹などから喘息リスクが高い822人を対象に、OM-85またはプラセボを2年間投与し、その後3年間追跡した。重度の喘鳴はOM-85群21%、プラセボ群18%で、6歳までの喘息診断率はいずれも21%と差がなかった。これは、幼少期の微生物曝露が免疫発達を促し喘息を防ぐとする「衛生仮説」の単純な応用に疑問を投げかける結果である。一方、既に頻繁な喘鳴がある子どもには治療効果がある可能性があり、今後は投与経路や出生前のエピジェネティック要因なども含め、喘息発症の複雑なメカニズムを検討する必要がある。

＜関連情報＞

就学前児童における喘鳴を伴う下気道疾患の一次予防のための細菌溶解物OM-85の使用：無作為化プラセボ対照試験 Use of the bacterial lysate OM-85 for the primary prevention of wheezing lower respiratory illness in preschool children: a randomised, placebo-controlled trial

Prof Wayne J Morgan ∙ Prof David T Mauger, PhD ∙ Prof Leonard B Bacharier, MD ∙ Cindy S Bauer, MD ∙ Prof Stephanie D Davis, MD ∙ Prof Anne M Fitzpatrick, PhD ∙ et al.
The Lancet Published: September 7, 2026
DOI:https://doi.org/10.1016/S0140-6736(26)01443-1

Summary

Background
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.

Methods
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.

Findings
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.

Interpretation
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.

Funding
National Heart, Lung, and Blood Institute and OM Pharma with supplemental funding and provision of study drug and placebo from OM Pharma.