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CLINICAL CHARACTERISTICS AND IMMUNOLOGICAL PROFILES OF CHRONIC RHINOSINUSITIS WITH MIXED EOSINOPHILIC AND NEUTROPHILIC INFLAMMATION
1YONSEI UNIVERSITY COLLEGE OF MEDICINE, SEOUL, REPUBLIC OF KOREA 2DEPARTMENT OF OTORHINOLARYNGOLOGY, YONSEI UNIVERSITY COLLEGE OF MEDICINE, SEOUL, REPUBLIC OF KOREA 3THE AIRWAY MUCUS INSTITUTE, YONSEI UNIVERSITY COLLEGE OF MEDICINE, SEVERANCE HOSPITAL, SEOUL, REPUBLIC OF KOREA *CORRESPONDENCE
YOUNGJOO PARK, YOUNGJOO PARK1, GYEONGYEOB KIM2, SOL LEE2, MIN-SEOK KOO2, HYUNG-JU CHO2,3, CHANG-HOON KIM2,3, MIN-SEOK RHA2,3*
¸ñÀû: Chronic rhinosinusitis (CRS) is an immunologically heterogeneous disease characterized by eosinophilic and/or neutrophilic inflammation. Recent studies have suggested that mixed eosinophilic-neutrophilic inflammation may be associated with severe disease. In the present study, we sought to investigate the clinical characteristics and immunological profiles of CRS with mixed inflammation. ¹æ¹ý:A total of 100 patients with CRS who underwent endoscopic sinus surgery were divided into four groups based on the presence or absence of tissue eosinophilia and neutrophilia: pauci- granulocytic, neutrophilic, eosinophilic, and mixed groups. Nasal tissue samples were obtained from the patients. A tissue eosinophil count of > 10 cells/high power field (HPF) and a tissue neutrophil count of > 10 cells/HPF were used as the cut-off for tissue eosinophilia and neutrophilia, respectively. The functional profiles of nasal CD4+ T cells were analyzed by flow cytometry. The expression levels of 48 proteins in nasal tissue homogenates were measured using Luminex multiplex immunoassays. °á°ú:The mixed group made up 41% of the total patients (41/100). Compared to the eosinophilic group, the mixed group showed significantly higher body mass index (BMI) and lower JESREC scores. Remarkably, the frequency of refractory disease was significantly higher in the mixed group. Flow cytometric analysis showed a tendency for a higher frequency of IFN-¥ã⁺ and IFN- ¥ã⁺TNF⁺ cells among CD4⁺ T cells in the mixed group compared to the eosinophilic group. In Luminex assays, CCL13, CCL24, CCL26, G-CSF, and IL-1¥â expression levels were significantly different among all groups. Additionally, the mixed group had significantly higher levels of MPO, MMP-8, Granzyme B, IL-1¥â, G-CSF, CCL19, CXCL13, IL-6, and IL-33, as well as lower levels of IL- 5, than the eosinophilic group. Among these proteins, MPO, MMP-8, Granzyme B, IL-1¥â, G-CSF, and IL-6 were significantly correlated with tissue neutrophil count. Furthermore, a combined analysis of the eosinophilic and mixed groups revealed that levels of IL-33 were significantly correlated with refractory disease. °á·Ð:The mixed endotype of CRS is associated with more obese and refractory patients. The mixed endotype can be distinguished by elevated expression of MPO, G- CSF, IL-1¥â, IL-6, and IL-33 compared to the pure eosinophilic endotype. Furthermore, IL-33 may serve as a prognostic biomarker for refractory disease in eosinophil-high CRS. Our study enhances the current understanding of the inflammatory characteristics of mixed CRS, providing a basis for the development of effective therapeutic strategies against mixed CRS.


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