Correlation of Local Nasal Biomarkers and Olfactory Dysfunction in Chronic Rhinosinusitis: A Systematic Review and...

To systematically evaluate the local biomarkers correlated with olfactory dysfunction (OD) in chronic rhinosinusitis (CRS).

A systematic review was conducted in CINAHL, Cochrane Library, PubMed, and Scopus from inception to July 2025. Studies on CRS patients who underwent olfactory testing and measurement of biomarkers within olfactory mucus were included. Collected variables included CRS phenotype, olfactory test, mucus protein levels, quantification method, and reported correlation coefficients. Meta-analysis of outcome measures in 351 participants included continuous measures (mean), proportions (%), and correlations (r) with 95% confidence intervals (CIs).

Seven prospective studies met criteria, with 4 studies comprising 201 patients with CRS with nasal polyps (CRSwNP) and 150 with CRS without nasal polyps (CRSsNP) for meta-analysis. The CRSwNP and CRSsNP cohorts were 53.08% and 58.09% male, respectively, with a mean age of 49.09 (1.36) and 46.84 (0.4), respectively. In participants with CRSwNP, IL-5, IL-6, IL-10, IL-13, IgE, CCL2, and CCL3 were inversely correlated with olfactory function scores (r = -0.223 to -0.333; all p ≤ 0.016). CXCL5 and VEGF-A were positively correlated in CRSwNP (r = 0.240-0.247, both p < 0.01). Other Type 2 cytokines, including IL-4, IL-23, and IL-33, did not show any significant correlations. In CRSsNP, IL-8 was negatively correlated (r = -0.182, p = 0.028) and CXCL5 was positively correlated with olfactory function scores (r = 0.274, p = 0.01).

OD in CRSwNP is moderately or mildly associated with specific Type 2 cytokines and other biomarkers. OD in CRSsNP is weakly correlated with IL8 and CXCL5, but not Type 2 cytokines. Further prospective studies are needed to elucidate causal relationships and prognostic utility between local biomarkers and OD.