Abstract
Objective: Chronic rhinosinusitis with nasal polyps exhibits marked eosinophilic infiltration and its mucosal eosinophilia is associated with more severe symptoms. The Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis found that patients with nasal polyps required multiple surgeries when there were higher infiltrating eosinophils in the mucosa. In order to identify plasma biomarkers for local eosinophil infiltration in rhinosinusitis for surgery, we examined the levels of molecules in the plasma of patients and compared the number of infiltrating eosinophils in the nasal mucosa.Materials and Methods: Mucosal tissues from 97 patients with chronic rhinosinusitis (CRS) were obtained from the nasal polyps during surgery. Tissues were immediately fixed and sections were stained with hematoxylin-eosin. The number of eosinophils in the mucosa was counted at HPF (x 400). Blood samples were obtained and the plasma was stored at −80°C. We measured the plasma cytokine and chemokine levels using multiple assay systems according to the manufacturers' protocols. The tissues were divided into high- and low-eosinophil mucosal infiltration group for recurrence after endoscopic sinus surgery (ESS). We also observed chemokine secretion from nasal fibroblasts.Results: The plasma level of eotaxin-3/ CC chemokine ligand 26 (CCL26) was significantly higher in the high-eosinophil mucosal infiltration group (p < 0.005). The number of infiltrating eosinophils in the mucosa was significantly higher in the group with the higher eotaxin-3 level (p < 0.001), but there was no significant difference in the blood eosinophil numbers among two groups. A significant positive correlation was found between the mucosal eosinophil count and the plasma levels of eotaxin-3 (p < 0.005). The levels of interleukin 33 (IL-33) (p < 0.001) and thymic stromal-derived lymphopoietin (TSLP) (p < 0.005) were significantly higher in the high-level eotaxin-3 group. IL-13 strongly induced the secretion of eotaxin-3 from human nasal fibroblasts (p < 0.05).Conclusion: This is the first report suggesting eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration. Furthermore, the level of eotaxin-3 was found to be closely related to IL-33 and TSLP levels which indicate respiratory diseases.
Highlights
Chronic rhinosinusitis demonstrates marked heterogeneity, both at the molecular pathophysiological level and at the clinical phenotype level
A study conducted by 15 institutions participating in the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis revealed that the cut-off value of 70 mucosal eosinophils/high-power field (HPF) led to the most significant difference (P < 0.001) in the risk of recurrence in 1,716 patients treated by endoscopic sinus surgery (ESS) [12]
In the 37 patients that could be observed more than 3 years after surgeries, the receiver operating characteristic (ROC) curve for nasal mucosal eosinophil counts was used to discriminate the patients with recurrence from those without recurrence
Summary
Chronic rhinosinusitis demonstrates marked heterogeneity, both at the molecular pathophysiological level and at the clinical phenotype level. This disease is divided into 2 subgroups, chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) [1]. The clinical classification of CRSwNP according to the degree of eosinophilic infiltration in nasal polyps is controversial [5]. Eosinophilic chronic rhinosinusitis (ECRS) is an emerging classification of CRS, and is thought to more accurately reflect the underlying pathophysiology. Mucosal eosinophilia is defined as >10 eosinophils per high-power field (HPF) according to histopathology profiling and remodeling changes [6,7,8]. A study conducted by 15 institutions participating in the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis revealed that the cut-off value of 70 mucosal eosinophils/HPF led to the most significant difference (P < 0.001) in the risk of recurrence in 1,716 patients treated by ESS [12]
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