Age-associated changes in chronic rhinosinusitis endotypes

Background: Immunologic function in innate and adaptive immunity changes with the ageing process. Thus, age-related cytokine profiles in chronic rhinosinusitis (CRS) need to be investigated for precision medicine. Objective: The objective of this study was to characterize age-related changes in immunologic profiles according to CRS subtypes. Methods: Subjects in control (n = 29), CRS without nasal polyps (CRSsNP, n = 86), and CRS with nasal polyps (eosinophilic NP: ENP, n = 81; non-eosinophilic NP: NENP, n = 113) were enrolled in this study. Twenty markers for type 1/2/3 inflammation and other inflammatory processes were measured in homogenates of sinonasal tissues and statistically analysed. Results: In control tissues, type 2/3 and proinflammatory mediators showed an inverse correlation with age. CRSsNP and NENP showed an age-related increase in type 2 cytokines and a decline in type 3 cytokines. Interestingly, the age-related decrease in type 3 mediators was associated with those of CT scores in NENP. ENP showed an age-related increase in type 3 cytokines with type 2 mediators sustained at high levels. Smokers with ENP demonstrated age-associated increases in type 1/2/3 mediators as well as CT scores. These age-related patterns in each CRS were confirmed by statistically adjusting atopy status, smoking history, and disease duration. Conclusion: Age-associated cytokine changes differed among CRS subtypes and control tissues. CRSsNP and NENP demonstrated a decline in type 3 mediators and increase in type 2 mediators, whereas type 3 mediators increased with age in ENP.