ABSTRACT 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.
Park et al. (Thu,) studied this question.