Precision targeting of type 2 inflammation in COPD: identifying candidates for dupilumab therapy
- 1Heilongjiang University of Chinese Medicine, Harbin, China
- 2The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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.
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BibTeX
@article{zhong2026precision,
title = {{Precision targeting of type 2 inflammation in COPD: identifying candidates for dupilumab therapy}},
author = {Kezhuo Zhong and Kaiying Lv and Qun Liang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1971309},
url = {https://doi.org/10.3389/fphar.2026.1971309},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Precision targeting of type 2 inflammation in COPD: identifying candidates for dupilumab therapy
AU - Kezhuo Zhong
AU - Kaiying Lv
AU - Qun Liang
PY - 2026
DA - 2026/10/12
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1971309
UR - https://doi.org/10.3389/fphar.2026.1971309
AB - 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.
SN - 1663-9812
ER -