| Title: | Lifestyle-associated metabolite signatures and the risk of late-onset asthma |
| Journal: | The Journal of Allergy and Clinical Immunology |
| Published: | 3 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41046934/ |
| DOI: | https://doi.org/10.1016/j.jaci.2025.09.020 |
Publication 19306
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Abstract
BACKGROUND: Unhealthy lifestyle behaviors, leading to systemic metabolic disturbances, are significantly linked to the risk of late-onset asthma. However, the underlying metabolism-related mechanisms remain unclear.</p>
OBJECTIVE: We sought to identify lifestyle-related metabolites and assess their predictive value for incident asthma.</p>
METHODS: Using nuclear magnetic resonance metabolomics data from the UK Biobank population (ages 40-69), plasma metabolites associated with healthy lifestyle scores were identified through multiple linear regression. Cox proportional hazards regression was used to further screen metabolites linked to late-onset asthma risk. Elastic net regularization selected critical metabolites for developing an asthma risk prediction model, incorporating conventional clinical characteristics and lifestyle factors. A metabolic score based on nonzero regularization coefficients was derived, and its association with asthma risk was evaluated through survival analysis. Models and metabolic score performance were validated in unused internal UK Biobank participants and an external China Kadoorie Biobank cohort.</p>
RESULTS: Among 198,607 participants (mean age 56.4 years), 159 plasma metabolites were significantly related to healthy lifestyle scores, 103 of which were associated with incident asthma risk. Nine metabolites were selected and incorporated into the asthma risk prediction model, significantly improving its predictive performance (area under the curve 0.812 vs 0.758). Individuals with an unfavorable metabolic signature exhibited a 77.0% increased risk (hazard ratio 1.770, 95% CI 1.634-1.918) of developing asthma compared with individuals with a favorable metabolic signature, with a stronger effect observed in women (hazard ratio 1.914, 95% CI 1.729-2.118). The results for the predictive model and metabolic score were confirmed in both internal and external validations.</p>
CONCLUSIONS: Multiple lifestyle-related metabolites are associated with late-onset asthma risk and can help stratify asthma risk, particularly among women.</p>
19 Authors
- Qinyu Chang
- Lu Chen
- Yiqun Zhu
- Ben Liu
- Xin Zhou
- Huaying Liang
- Fengyu Lin
- Dianwu Li
- Zhuanxing Zhu
- Zhaojun Pan
- Xiang Chen
- Hong Liu
- Dianjianyi Sun
- Jun Lv
- Liming Li
- Pinhua Pan
- Canqing Yu
- Yan Zhang
- China Kadoorie Biobank Collaborative Group
1 Application
| Application ID | Title |
|---|---|
| 84979 | Associations of Lifestyle and Genetic Risk with Incidence of Respiratory Diseases |
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