Inflammatory and clinical risk factors for asthma attacks (ORACLE2): a patient-level meta-analysis of control groups of 22 randomised trials.

Summary

Across 6513 patients from 22 RCT control groups, both blood eosinophils and FeNO independently increased severe asthma attack risk (RR 1.48 and 1.44 per 10-fold increase). Attack history and greater disease severity added prognostic value, supporting biomarker-driven risk stratification.

Key Findings

• Higher baseline blood eosinophil count and FeNO independently increased severe attack risk (per 10-fold increase: RR 1.48 and 1.44).
• Attack history (RR 1.94) and severe vs moderate disease (RR 1.57) further stratified risk.
• IPD from 22 RCTs (n=6513) with negative binomial models and GRADE assessment underpin high-certainty evidence.

Clinical Implications

Incorporating blood eosinophils and FeNO with attack history and severity can refine risk stratification to guide inhaled corticosteroid optimization and biologic therapy selection.

Limitations

• Findings derive from RCT control arms rather than population-based cohorts
• Potential residual heterogeneity and limited applicability to mild asthma not well represented

Future Directions

Develop and validate pragmatic risk calculators integrating eosinophils, FeNO, and clinical factors; test biomarker-guided treatment strategies in prospective trials.