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

Blood Exosomal Multi-omics and Lung Radiomics for Predicting Efficacy and Prognosis of Severe Eosinophilic ACOS (Asthma-COPD Overlap Syndrome) Treated With Different Biologics: A Real-World Observational Study

Firstly, to screen blood exosomal multi-omics (transcriptomics, proteomics, metabolomics) and lung radiomics (HRCT, Xe129MRI) biomarkers that can predict efficacy and prognosis in severe eosinophilic ACOS (asthma-COPD overlap) patients treated with different biologics (benralizumab, mepolizumab, dupilumab). Then, to prospectively follow patients for 48 weeks after biologic initiation and collect clinical data, blood samples, and imaging features. Finally, to build a multi-dimensional predictive model for efficacy and prognosis of severe eosinophilic ACOS.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Eosinophilic ACOS (Asthma-COPD Overlap)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Qi Huang; Phone Number: +86 15827329098; Email: huangqi66@126.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Qi Huang; Phone Number: +86 15827329098; Email: huangqi66@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 14 years or older with a confirmed diagnosis of severe eosinophilic ACOS (asthma-COPD overlap) who are prescribed a biologic (benralizumab, mepolizumab, or dupilumab) by their treating physician according to routine clinical practice. The study population is recruited from outpatient and inpatient respiratory departments of multiple hospitals in China, including Union Hospital (Tongji Medical College, Huazhong University of Science and Technology) and its collaborating centers.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Benralizumab Group; Patients with severe eosinophilic ACOS receiving benralizumab as prescribed by their treating physician according to routine clinical practice.
Mepolizumab Group; Patients with severe eosinophilic ACOS receiving mepolizumab as prescribed by their treating physician according to routine clinical practice.
Dupilumab Group; Patients with severe eosinophilic ACOS receiving dupilumab as prescribed by their treating physician according to routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite efficacy and prognosis endpoint at week 48 in severe eosinophilic ACOS	We define the composite endpoint as achieving ALL of the following at week 48: (1) no ACOS exacerbation (worsening of respiratory symptoms requiring systemic corticosteroids ≥3 days, emergency visit <24h, or hospitalization ≥24h); (2) no use of oral corticosteroids (OCS); (3) pre-bronchodilator FEV1 improvement ≥100 mL from baseline; (4) ACQ-6 score <1.5 (or ≤0.75). The proportion of patients meeting all four criteria will be calculated.	48 weeks after the first dose of biologic

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Asthma Control Questionnaire-6 (ACQ-6) score	ACQ-6 is a validated questionnaire (6 items, score 0-6, lower = better control). Change from baseline will be assessed at weeks 1,2,4,8,16,24,40,48. Mean difference and standard deviation will be reported.	Baseline to 48 weeks
Change in pre-bronchodilator FEV1 (mL)	FEV1 (forced expiratory volume in 1 second) will be measured using spirometry according to international standards (ATS/ERS). Change in mL from baseline will be calculated at weeks 8, 16, and 48.	Baseline to 48 weeks
Annualized rate of ACOS exacerbations	Number of ACOS exacerbations per year during the 48-week follow-up. Exacerbation defined as worsening of respiratory symptoms requiring systemic corticosteroids (≥3 days), emergency department visit (<24 hours), or hospitalization (≥24 hours). Rate = (total exacerbations × 365.25) / follow-up days.	48 weeks
Change in Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score	MiniAQLQ is a 15-item questionnaire (score 1-7, higher = better quality of life). Change from baseline will be assessed at weeks 8, 16, 24, and 48.	Baseline to 48 weeks
Change in blood exosomal multi-omics biomarkers	Residual blood from routine tests (2-3 mL per time point at weeks 0,4,8,16,24,40,48) will be used to isolate exosomes. Transcriptomics (RNA-seq), proteomics (mass spectrometry), and metabolomics (LC-MS) profiles will be compared between baseline and week 48. Differentially expressed features (|log2FC|>1, FDR<0.05) will be reported.	Baseline to 48 weeks
Change in lung radiomics features	For patients who undergo HRCT or Xe129MRI (optional), radiomics features (e.g., texture, shape, intensity) will be extracted using standard software. Changes from baseline to week 24 and 48 will be analyzed.	Baseline to 48 weeks

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 17, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Biologics; Radiomics; Exosomal Multi-omics; Severe Eosinophilic ACOS
• Other Study ID Numbers: XHJY202605

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No