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Precision targeting of type 2 inflammation in COPD: identifying candidates for dupilumab therapy

Year: 2026

Type: article

Abstract: Type 2 (T2) inflammation represents a clinically important and therapeutically tractable endotype in 20%-40% of patients with chronic obstructive pulmonary disease (COPD). This subgroup is characterised by elevated blood eosinophil counts, increased fractional exhaled nitric oxide (FeNO), and activation of the interleukin (IL)-4/IL-13 pathway, and is associated with higher exacerbation risk and greater corticosteroid responsiveness. Dupilumab, a fully human monoclonal antibody that blocks the shared IL-4 receptor α subunit, became the first biologic approved for COPD following the replicate phase 3 BOREAS and NOTUS trials, which demonstrated approximately 30%-34% reductions in moderate or severe exacerbations in eosinophil-enriched populations receiving triple inhaled therapy. Pooled analyses have reinforced these findings, while post-hoc biomarker studies show that higher baseline eosinophil counts and FeNO independently predict greater treatment response. Dual IL-4/IL-13 blockade also reduces circulating IgE, eotaxin-3 and pulmonary and activation-regulated chemokine, providing mechanistic evidence of pathway modulation beyond eosinophil depletion. Patient selection should prioritise individuals who meet the pivotal trial criteria, confirmed COPD, frequent exacerbations despite optimised triple therapy, blood eosinophils ≥300 cells/µL, and chronic bronchitis features, while recognising that lower eosinophil thresholds and additional T2 markers remain incompletely validated. Real-world evidence remains sparse and limited by small sample sizes and observational designs. Realising the full potential of T2-targeted therapy will require pragmatic trials with broader inclusion criteria, prospective validation of multi-marker strategies, longer-term outcome data, and head-to-head comparisons with other biologics.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1971309

Authors: Kezhuo Zhong, Kaiying Lv, Qun Liang

Institutions: Heilongjiang University of Chinese Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Language: English

Topic: Chronic Obstructive Pulmonary Disease (COPD) Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801