Improvement of Mixed Inflammatory Environment in Nasal Secretions of Diffuse Type 2 Chronic Rhinosinusitis With Nasal Polyps Under Dupilumab
Clinical and Translational Allergy, 2026
Ryser F., Mauthe T., Brühlmann C., Soyka M., Steiner U.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Serum Nasal Fluid |  Olink Target 96 |
Abstract
Background
In Western countries, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is predominantly associated with a type 2 inflammatory endotype. While nasal secretion analysis shows promise for disease endotyping, current biomarkers remain limited for accurate stratification, disease monitoring, and prediction of treatment response.
Objective
This study aimed to investigate the inflammatory patterns in nasal secretions of patients with type 2 Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) undergoing treatment with dupilumab, an anti‐IL4Rα antibody. A second objective was to evaluate markers for therapy response and monitoring.
Methods
Nasal secretions and blood samples were collected at four time points from 23 patients with histological type 2 CRSwNP undergoing dupilumab treatment and compared with 10 healthy controls. Samples were analysed using proximity extension assay method by Olink.
Results
Proteomic analysis of nasal secretions revealed 50 differentially expressed proteins in type 2 CRSwNP compared to healthy controls. Nasal secretions of most patients revealed a mixed inflammatory endotype. Under dupilumab treatment, cytokines of all different endotypes decreased. The cytokines with the highest mean change (MCP‐4, CCL23, GDNF and CCL11) showed good associations with clinical variables and were effective predictors of dupilumab response and disease control.
Conclusion
The inflammatory environment of the nasal mucosa in histological type 2 CRSwNP is most often characterized by a mixed type 1, 2, and 3 inflammatory endotype. Targeting type 2 inflammation with dupilumab reduces inflammation markers of all three types of inflammation. GDNF has emerged as a valuable marker for stratifying therapy and monitoring success in type 2 CRSwNP under dupilumab treatment.