Clinico-immunological Differences in Chronic Rhinosinusitis with and Without Obesity: Longitudinal Results from an Expanded Cohort

Introduction: Obesity is associated with chronic systemic inflammation, which may contribute to an increased risk of chronic rhinosinusitis (CRS). Our prior study identified an obesity-related CRS phenotype characterized by distinct clinical and cytokine profiles. To build on these findings, we expanded our cohort, allowing for a more comprehensive characterization of the clinico-immunological features associated with obesity in CRS patients.

Methods: This prospective study was conducted at the Cleveland Clinic, including patients with CRS undergoing functional endoscopic sinus surgery between 2021 and 2024. Data collected included demographics, body mass index (BMI), comorbidities, baseline sinonasal outcome test (SNOT)-22 and Lund-MacKay (LM) scores, local and systemic alarmins/T-helper cytokines, and postoperative SNOT-22 scores at 6 months. Group differences based on obesity status were assessed using the Wilcoxon test (p < 0.05).

Results: Among 88 patients, CRS patients with obesity (BMI ≥ 30 kg/m²) had lower systemic levels of interleukin(IL)-33 (147.3 ± 329.7 vs. 792.6 ± 1235.2 pg/μL, p = 0.01) and thymic stromal lymphopoietin (TSLP) (30.0 ± 88.2 vs. 779.9 ± 2015.6 pg/μL, p = 0.01) compared to non-obese patients. For CRS without nasal polyps (CRSsNP), individuals with obesity had lower systemic TSLP (5.3 ± 10.4 vs. 76.8 ± 55.3 pg/μL, p = 0.03) but higher nasal IL-33 (835.1 ± 416.0 vs. 427.6 ± 274.4 pg/μL, p = 0.04) compared to non-obese patients. In those with CRS with nasal polyps (CRSwNP), systemic cytokine levels did not differ by BMI, but patients with obesity had lower nasal IL-33 (316.8 ± 327.9 vs. 682.4 ± 384.4 pg/μL, p = 0.004) and eotaxin-3 (270.3 ± 238.8 vs. 474.2 ± 285.6 pg/μL, p = 0.02). BMI did not influence baseline and postoperative SNOT-22 and LM scores.

Conclusions: Our findings show that obesity in CRS is associated with lower systemic alarmins overall, with CRSwNP patients with obesity demonstrating reduced nasal alarmins and eotaxin-3 while CRSsNP patients with obesity exhibit elevated nasal alarmins. This suggests that obesity may differentially influence inflammatory profiles across CRS phenotypes.