Assessing the Mucosal Inflammatory Endotype of Obesity in Chronic Rhinosinusitis

ABSTRACT Background Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory syndrome of the paranasal sinuses that is defined phenotypically as either with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP). More recently, inflammatory markers have been used to cluster patients into putative endotypes that are presumed to have a common underlying etiology. Obesity is known to create a proinflammatory state in similar chronic inflammatory conditions such as asthma. However, the potential impact of obesity in CRS has not been investigated. Methods Samples were collected from 512 patients with CRS (235 CRSsNP, 277 CRSwNP) and 100 control patients undergoing surgery in a prospective longitudinal study. Mucus inflammatory cytokines were measured using a multiplex cytometric bead assay targeting IL‐1a, IL‐1b, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐9, IL‐10, IL‐11, IL‐12, IL‐13, IL‐17, IL‐18, IL‐21, TNF‐⍺, IFN‐𝛾, eotaxin, RANTES, and GM‐CSF. Cytokine levels were then compared between obese and non‐obese patients using categorical and continuous measures of BMI. Results In patients with CRSwNP, there were significant elevations in multiple pro‐inflammatory cytokines. Levels of IL‐2 (185 pg/mL vs. 39 pg/mL, p = 0.02), IL‐4 (17.7 pg/mL vs. 6.3 pg/mL, p = 0.04), TNF‐⍺ (58 pg/mL vs. 45 pg/mL, p = 0.04), IFN‐ɣ (18.5 pg/mL vs. 17.3 pg/mL, p = 0.009), and GM‐CSF (8.5 pg/mL vs. 2.5 pg/mL, p = 0.007) were elevated in obese CRSwNP patients. Continuous regression analysis did not confirm these results, potentially due to non‐linear effects of obesity on sinonasal inflammation. Conclusions Obese CRSwNP patients have elevations in Type 1 and 2 cytokines compared to non‐obese patients, potentially indicative of a pro‐inflammatory bias in the sinonasal mucosa of obese patients. As such, there may be a role for weight loss and medical weight management in the treatment of CRSwNP, although further research is needed.