Appropriate Medical Therapy Primarily Modifies Type 2 and Severity Biomarkers in Chronic Rhinosinusitis

BACKGROUND: Appropriate medical therapy (AMT) is first-line treatment for patients with chronic rhinosinusitis (CRS). We evaluated inflammatory structure, treatment-induced changes, and biomarker-outcome associations in AMT-managed patients. METHODS: Fifty-one CRS patients were evaluated before and after AMT which included a combination of oral antibiotics, oral steroids, or intranasal steroids tailored to CRS phenotype and severity. At each visit, patients completed the SNOT-22, CRS-PRO, Brief Smell Identification Test (BSIT), CT scan (Lund-Mackay Score [LM]), and endoscopy (Modified Lund-Kennedy Score [MLK]). Middle-meatal mucus was analyzed for IL-1b, IL-5, IL-13, IFN-g, and MIP1a using Luminex and ELISA. Principal components analysis (PCA) was performed on baseline cytokine data to identify key biomarker axes. Paired-sample Wilcoxon tests compared cytokine changes, and Spearman's correlation assessed relationships between biomarkers and disease measures. RESULTS: PCA revealed two major components: PC-1 (inflammation severity) dominated by ECP and MIP1a, and PC-2 (endotype axis) with positive weighting of IL-5 and IL-13 (T2) and negative weighting of IFN-g and IL-1b (T1/3). AMT significantly reduced inflammatory severity and T2 biomarker burden, driven by decreases in IL-5, IL-13, ECP, and MIP1a (all p < 0.01), while T1/3 biomarker remained unchanged. Clinical outcomes, including MLK, SNOT-22, CRS-PRO, and BSIT, improved and showed stronger correlations with T2 than T1/3 biomarkers. CONCLUSION: AMT for CRS is associated with reduction in index biomarkers across inflammatory severity and T2 endotype with minimal effects on T1/3 inflammation. T2-driven inflammation appears to be the most AMT-responsive axis found in this study, aligning with measurable improvements in endoscopic, patient reported, and nasal airflow outcomes.