This study examined tissue-based biomarkers predicting post-FESS CRSwNP recurrence in 91 patients (dichotomized as rapid recurrence <1 year vs. slow/no recurrence >2 years), and assessed whether dupilumab modifies these mediators in a separate prospective cohort of 17 CRSwNP patients over 2 months.
23 tissue mediators predicted rapid recurrence (AUC >0.70), spanning T2 markers (IL-4, IL-13, IgE) and innate/myeloid markers (CCL3/4/7/8/13, CSF2, IL-1β, MMP12, HIF-1α, TNF-α); dupilumab reduced T2-linked mediators (IL-5Rα, CCL3, CCL4, CCL13) but left key myeloid mediators unchanged (CCL8, CSF2, IL-1β, MMP12, HIF-1α).
Retrospective design for the recurrence cohort introduces selection bias; the dupilumab cohort was small (n=17) and only followed for 2 months; nasal fluid rather than tissue was used to assess dupilumab effects, limiting direct comparability.
Clinicians should recognize that dupilumab does not suppress a parallel innate/myeloid inflammatory axis in CRSwNP, which may drive recurrence after T2 blockade is stopped or insufficient. Myeloid mediators like CSF2, IL-1β, and MMP12 are candidate targets worth monitoring in patients with rapid post-FESS recurrence.
