Blood Exosomal Multi-omics and Lung Radiomics for Predicting Efficacy and Prognosis of Severe Eosinophilic ACOS With Biologics

Firstly, eligible patients (age ≥14 years, diagnosis of severe eosinophilic ACOS, blood eosinophils ≥150/μL within 3 months or ≥300/μL within 1 year, and clinician decision to start a biologic) will be enrolled. Exclusion criteria include concurrent trial participation, allergy to biologics, malignancy, or prior biologic use.

Then, patients are followed for 48 weeks after the first biologic dose. Visits occur at weeks 0, 1, 2, 4, 8, 16, 24, 40, and 48. Data collected include demographics, medical history, ACQ-6, MiniAQLQ, pre-BD FEV1, exacerbations, medication use, adverse events, and blood routine tests (residual samples for exosome analysis). HRCT and Xe129MRI are optional.

Next, the primary outcome is the composite endpoint of efficacy and prognosis at week 48, defined as: no ACOS exacerbation, no oral corticosteroids, pre-BD FEV1 improvement ≥100 mL from baseline, and ACQ-6 score <1.5 (or ≤0.75). Secondary outcomes include changes in ACQ-6, FEV1, annualized exacerbation rate, MiniAQLQ, OCS dose reduction, and blood exosomal multi-omics and lung radiomics biomarkers.

Finally, statistical analyses include descriptive statistics, paired t-test/Wilcoxon, ANOVA/Kruskal-Wallis, mixed-effects model for repeated measures (MMRM), differential expression analysis (DESeq2/limma), pathway enrichment, machine learning (LASSO, random forest), ROC curves, logistic regression, and Cox regression. A total of 500 patients will be enrolled from multiple centers in China.

Inclusion criteria

• Age ≥ 14 years
• Clinician decision to start biologic (benralizumab, mepolizumab, or dupilumab) for severe eosinophilic ACOS
• Blood eosinophils ≥150/μL within 3 months prior to informed consent, or ≥300/μL within 1 year prior
• Signed written informed consent

Exclusion criteria

• Currently participating in any other interventional clinical trial
• Known allergy or hypersensitivity to any component of the study drugs
• Any type of malignancy
• Prior or current biologic treatment for ACOS