Early-life wheeze trajectories are associated with distinct asthma transcriptomes later in life.

Summary

Across 743 children from 12 birth cohorts, latent wheeze trajectories (infrequent, transient, late-onset, persistent) mapped to distinct nasal transcriptomic programs in later life. Transient wheeze associated with antiviral responses; late-onset with reduced insulin/glucose signaling; persistent wheeze with type 2 inflammation/epithelial development. Children with persistent wheeze plus current asthma showed enrichment of neuronal and ciliated epithelial gene sets.

Key Findings

• Four early-life wheeze trajectories were identified and linked to distinct later-life nasal transcriptomes.
• Transient wheeze mapped to antiviral response modules; late-onset wheeze to decreased insulin/glucose signaling.
• Persistent wheeze aligned with type 2 inflammation and epithelial development; in those with current asthma, neuronal and ciliated epithelial genes were further enriched.

Clinical Implications

Potential to risk-stratify children based on wheeze trajectories and target early-life interventions toward specific immune–epithelial pathways before fixed disease emerges.

Limitations

• Observational design limits causal inference
• Heterogeneity across cohorts and potential batch effects despite harmonization

Future Directions

Prospective intervention trials targeting trajectory-specific pathways (e.g., antiviral training, metabolic/epithelial modifiers) and validation in airway/lung tissues.