Non-invasive prediction of olfactory recovery in severe CRSwNP: a cross-compartment translational nomogram based on secretory IL-17A
Frontiers in Allergy, 2026
Zhang H., Wang L., Lu T., Hou Y., Wei Y., Huang W., Liu S., Huang Y., Xu Z., Li J., Wen W., Zhong H.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Respiratory Diseases | Patient Stratification | Nasal Fluid |  Olink Target 96 |
Abstract
Background
Predicting olfactory recovery after surgery for severe chronic rhinosinusitis with nasal polyps (CRSwNP) remains challenging. To overcome the reliance on invasive tissue biopsies, this study aimed to identify non-invasive liquid biopsy biomarkers reflecting the deep mucosal inflammatory microenvironment, ultimately developing a point-of-care prognostic model.
Methods
A “tissue-to-secretion” dual-cohort validation strategy was employed. A Random Forest (RF) algorithm screened deep-tissue proteomes (Luminex) in a discovery cohort ( N = 67). An independent RF model evaluated non-invasive nasal secretions (Olink) in a validation cohort ( N = 62). Bidirectionally convergent targets were assessed for continuous dose-response relationships with absolute olfactory improvement [ Δ (visual analog scale)VAS] score at 6 months. A clinical-molecular nomogram was developed and internally validated using 1,000 bootstrap resamples.
Results
The tissue-based RF identified interleukin (IL)-17A as a core prognostic candidate. The independent secretion-based RF model also prioritized secretory IL-17A, achieving bidirectional convergence. While canonical Type 2 cytokines (IL-5, IL-13) lost predictive significance in secretions ( P > 0.05), secretory IL-17A demonstrated a robust dose-response correlation (r = 0.334, P = 0.0003) and emerged as an independent protective factor for olfactory recovery ([odds ratio] OR = 1.408, 95% [confidence interval] CI: 1.03–2.03). The joint nomogram, seamlessly integrating baseline VAS and secretory IL-17A, yielded an optimism-corrected (area under the receiver operating characteristic curve) AUC of 0.793 (95% CI: [0.6908–0.9079]) with adequate calibration and substantial net clinical benefit.
Conclusions
Through cross-compartment translation, we identified secretory IL-17A as a robust, non-invasive indicator of mucosal plasticity and olfactory reversibility. The derived joint nomogram provides an actionable framework for personalized pre-operative counseling and risk stratification in severe CRSwNP.