Abstract
BACKGROUND: Chronic rhinosinusitis (CRS) is increasingly linked to systemic inflammation, however, research on peripheral blood metabolic patterns in CRS patients remains limited. This study aimed to investigate peripheral blood metabolic profiles in eosinophilic CRS and non-eosinophilic CRS, while exploring the mediating role of metabolites in the relationship between body mass index and CRS. METHODS: Clinical data were collected from 1,151 CRS patients and 814 healthy controls, classifying patients into eosinophilic CRS and non-eosinophilic CRS groups based on tissue eosinophil counts. Peripheral blood metabolic profiles were compared across different CRS endotypes and between CRS patients and healthy controls. Causal mediation analysis assessed the mediating effects of metabolites on the relationship between body mass index and CRS. RESULTS: CRS patients exhibited distinct metabolic profiles, with dysregulated lipid metabolism characterized by increased triglycerides, free fatty acids, and lipoprotein(a), but patients with eosinophilic CRS had higher triglycerides, while non-eosinophilic CRS had higher free fatty acids. Cystatin-C effectively differentiated CRS endotypes (area under the curve = 0.735). Elevated body mass index was a risk factor for both eosinophilic CRS and non-eosinophilic CRS patients, with peripheral free fatty acids and Cystatin-C mediating this effect. CONCLUSIONS: This study reveals distinct metabolic profiles in patients with CRS, supporting its link to systemic inflammation. Promoting healthy dietary habits and weight control is therefore a cornerstone of sustainable, preventive care, offering a practical strategy to improve long-term patient well-being, particularly in refractory cases.