Type 2 Inflammation in Chronic Rhinosinusitis without Nasal Polyps: Another Relevant Endotype.

Abstract Background Chronic rhinosinusitis without nasal polyps (CRSsNP) is mainly considered a type 1 mediated disease. The role and clinical significance of type 2 immune responses in CRSsNP have not been addressed sufficiently; a recent cluster analysis for CRS described the existence of a subgroup of CRSsNP patients with a type 2 inflammation. Objective We aimed to characterize the underlying type 2 immune response and its clinical significance in CRSsNP patients. Methods 240 CRSsNP patients were endotyped and subdivided based on the expression of marker cytokines. Clinical data as recurrence, comorbid asthma and allergy, and numbers of blood eosinophils and neutrophils were collected from all patients. A selection of 15 patients was further characterized for the presence of eosinophils, neutrophils, Charcot-Leyden crystals (CLCs) and eosinophil extracellular traps (EETs) in the mucosae. Results A type 2 immune response with increased levels of IL-4, IL-5, ECP, IgE and Staphylococcus aureus enterotoxin-specific IgE (SE-IgE) was observed in 49% of CRSsNP patients. Those patients showed increased numbers of blood and tissue eosinophils, and displayed a considerable eosinophilic inflammation associated with EETosis and CLCs. A significantly increased prevalence of recurrence and asthma was observed in type 2 vs. non-type 2 CRSsNP patients. However, only 4 out of 117 type 2 CRSsNP patients developed nasal polyps within 12 years. Conclusion This study shows that type 2 immune responses in CRSsNP follow similar patterns, but are less pronounced than in CRSwNP. Also CRSsNP with a moderate type 2 immune response showed a considerable eosinophilic inflammation with clinical impact.