Inflammatory Signatures Beyond Th1/Th2 Endotypes Provide Insights Into Postoperative Recurrence in Chronic Rhinosinusitis
- 1Department of Otolaryngology Head and Neck and Maxillofacial Surgery Tel Aviv Sourasky Medical Center Gray Faculty of Medical and Health Sciences, Tel Aviv University Tel Aviv Israel
- 2Head and Neck Cancer Research Laboratory Tel Aviv Sourasky Medical Center Gray Faculty of Medical and Health Sciences, Tel Aviv University Tel Aviv Israel
- 3Pathology and Cancer Research Institute Tel Aviv Sourasky Medical Center Gray Faculty of Medical and Health Sciences, Tel Aviv University Tel Aviv Israel
Abstract
Background: Chronic rhinosinusitis (CRS) represents a spectrum of inflammatory endotypes, driven by distinct T helper (Th) immune responses. The high rate of recurrent disease despite appropriate medical and surgical interventions highlights the need for improved characterization beyond the traditional type 2 and non‐type 2 phenotypes to better inform personalized treatment.
Methods: Sinonasal tissue samples were obtained from 105 CRS patients undergoing endoscopic sinus surgery. Histopathologic evaluation classified inflammatory patterns by predominant cell type and severity. Levels of Th1, Th2, and Th17‐ and epithelial‐derived cytokines were quantified using a multiplex immunoassay targeting 12 markers. Clinical, radiologic, and follow‐up data were correlated with inflammatory patterns and cytokine profiles.
Results: Type 2 CRS, identified in 65 patients (62%), was associated with higher levels of IL‐5, IL‐13, and TSLP (p = 0.0002, <0.0001, and 0.02, respectively), whereas IL‐8 was elevated in non‐type 2 disease (p = 0.022). Recurrence occurred in 22 patients (21%) and was associated with asthma (p = 0.002), anosmia (p = 0.006), prior steroids use (p = 0.044), lymphoplasmacytic inflammatory pattern (p = 0.022), higher IL‐13 (p = 0.045), and IL‐33 (p = 0.031). Recurrence rates did not differ between inflammatory profiles (Th2, Th1/Th17, and mixed). Asthma remained the only independent predictor of recurrence in multivariable Cox model (HR 2.48, 95% CI 1.003–8.042, p = 0.049).
Conclusion: Elevated IL‐33 levels and lymphoplasmacytic inflammation were associated with postoperative recurrence, underscoring the role of epithelial‒immune signaling in persistent mucosal inflammation, whereas comorbid asthma remained the only independent predictor of refractory CRS.
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BibTeX
@article{kampel2026inflammatory,
title = {{Inflammatory Signatures Beyond Th1/Th2 Endotypes Provide Insights Into Postoperative Recurrence in Chronic Rhinosinusitis}},
author = {Liyona Kampel and Narin N. Carmel and Shaun Edalati and Hen Chaushu and Forsan Jahshan and Yaniv Hadi and Timur Pestrikov and Leonor Leider Trejo and Nidal Muhanna and Avraham Abergel},
journal = {International Forum of Allergy \& Rhinology},
year = {2026},
month = jun,
doi = {10.1002/alr.70210},
url = {https://doi.org/10.1002/alr.70210},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Inflammatory Signatures Beyond Th1/Th2 Endotypes Provide Insights Into Postoperative Recurrence in Chronic Rhinosinusitis
AU - Liyona Kampel
AU - Narin N. Carmel
AU - Shaun Edalati
AU - Hen Chaushu
AU - Forsan Jahshan
AU - Yaniv Hadi
AU - Timur Pestrikov
AU - Leonor Leider Trejo
AU - Nidal Muhanna
AU - Avraham Abergel
PY - 2026
DA - 2026/06/24
JO - International Forum of Allergy & Rhinology
DO - 10.1002/alr.70210
UR - https://doi.org/10.1002/alr.70210
AB - Background: Chronic rhinosinusitis (CRS) represents a spectrum of inflammatory endotypes, driven by distinct T helper (Th) immune responses. The high rate of recurrent disease despite appropriate medical and surgical interventions highlights the need for improved characterization beyond the traditional type 2 and non‐type 2 phenotypes to better inform personalized treatment. Methods: Sinonasal tissue samples were obtained from 105 CRS patients undergoing endoscopic sinus surgery. Histopathologic evaluation classified inflammatory patterns by predominant cell type and severity. Levels of Th1, Th2, and Th17‐ and epithelial‐derived cytokines were quantified using a multiplex immunoassay targeting 12 markers. Clinical, radiologic, and follow‐up data were correlated with inflammatory patterns and cytokine profiles. Results: Type 2 CRS, identified in 65 patients (62%), was associated with higher levels of IL‐5, IL‐13, and TSLP (p = 0.0002, <0.0001, and 0.02, respectively), whereas IL‐8 was elevated in non‐type 2 disease (p = 0.022). Recurrence occurred in 22 patients (21%) and was associated with asthma (p = 0.002), anosmia (p = 0.006), prior steroids use (p = 0.044), lymphoplasmacytic inflammatory pattern (p = 0.022), higher IL‐13 (p = 0.045), and IL‐33 (p = 0.031). Recurrence rates did not differ between inflammatory profiles (Th2, Th1/Th17, and mixed). Asthma remained the only independent predictor of recurrence in multivariable Cox model (HR 2.48, 95% CI 1.003–8.042, p = 0.049). Conclusion: Elevated IL‐33 levels and lymphoplasmacytic inflammation were associated with postoperative recurrence, underscoring the role of epithelial‒immune signaling in persistent mucosal inflammation, whereas comorbid asthma remained the only independent predictor of refractory CRS.
SN - 2042-6976
SN - 2042-6984
ER -