| 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*
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¸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. |