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Clinical and transcriptomic characterization of mixed granulocytic phenotype in chronic obstructive pulmonary disease
Clarus Leung1, Jung-Wan Yoo2, Hye Yun Park3
1Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, Canada; Centre for Heart Lung Innovation, St Paul's Hospital, University of British Columbia, Vancouver, Canada.
The Journal of Allergy and Clinical Immunology
|June 30, 2026
Summary
Patients with mixed granulocytic COPD experience worse outcomes due to complex immune responses and increased tissue remodelling in airways. This phenotype is linked to more severe airflow limitation and emphysema.
Area of Science:
- Pulmonary Medicine
- Immunology
- Genetics
Background:
- Chronic obstructive pulmonary disease (COPD) is a progressive lung disease.
- A subset of COPD patients, termed
Purpose of the Study:
- To investigate immune response and lung tissue remodeling pathways in mixed granulocytic COPD.
- To compare these pathways across different COPD phenotypes.
Main Methods:
- Post hoc analysis of the DISARM randomized controlled trial.
- Defined mixed granulocytic COPD by specific eosinophil and neutrophil counts in bronchoalveolar lavage (BAL).
- Analyzed gene expression of immune responses and tissue remodeling in BAL cells using gene set enrichment analysis.
Main Results:
- Mixed granulocytic COPD (33% of patients) showed worse clinical outcomes, including lower FEV1, more emphysema, and higher exacerbation rates.
- Upregulated gene expression of type 1 (TNF-alpha, IL-6, IFN-gamma) and type 2 (IL-4/13) immune responses was observed.
- Increased expression of immune cell (NK, B, T cells) and tissue remodeling gene signatures correlated with reduced FEV1.
Conclusions:
- Mixed granulocytic COPD is characterized by intricate immune responses in peripheral airways.
- This phenotype is associated with heightened tissue remodeling, which correlates with more severe airflow limitation.
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