CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis

Abstract

Background: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone.

Objective: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS.

Methods: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry.

Results: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τ_b = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm², p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar.

Conclusions: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

Keywords: CCAD; Th2; allergic rhinitis; allergy; central compartment; chronic rhinosinusitis; endotype; eosinophils; inhalant allergy; middle turbinate oedema; phenotype; polyps; type 2.

Figure 1.

Visual guide for identification of eosinophils. Representative microscopic images of nucleated and anucleated eosinophils on haematoxylin and eosin (H&E) stained sinonasal tissue, visualised on digital whole slide imaging at high power (40×).

Figure 2.

Grading of intensity of eotaxin-3 staining. Representative microscopic images of sinonasal tissue stained for eotaxin-3 on immunohistochemistry, visualised on digital whole slide imaging at high power (20×). Intensity of staining was scored according to a 4-point scale: (A) 0 = no staining, (B) 1 = minimal (light brown), (C) 2 = moderate (medium brown) and (D) 3 = excessive (dark brown). The black line represents a scale of 50 µm.

Figure 3.

Visual guide for identification of immunoglobulin E (IgE)-positive mast cells. Representative microscopic images of sinonasal tissue stained for IgE on immunohistochemistry, showing (A) cytoplasmic IgE-positive mast cells and (B) membrane IgE-positive mast cells, visualised on digital whole slide imaging at high power (20×). The black line represents a scale of 50 µm.