Type 2 biomarkers in olfactory cleft mucus correlate with SNOT-22 in chronic rhinosinusitis independent of nasal polyp status

Background: Quantitative mucus cytokine analysis to examine the sinonasal microenvironment may bridge the gap between patient-reported outcome measures (PROMs) and empirical measures of inflammation in patients with chronic rhinosinusitis (CRS).

Objective: Investigate the correlation between mucus cytokine levels and Sino-Nasal Outcome Test (SNOT-22) scores, including individual subdomains.

Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a multi-institutional observational study. Mucus was collected from the olfactory cleft and evaluated for mucus cytokine biomarkers. Spearman correlations (ρ) between cytokine levels and SNOT-22 scores, including individual subdomains, Lund-Mackay (LM) CT and Lund-Kennedy (LK) endoscopy scores were assessed. Subgroup analysis based on nasal polyp status (CRSsNP-without nasal polyps; CRSwNP-with nasal polyps) was also performed. Linear regression was employed to identify multivariate associations between cytokine expression levels, clinical covariates, and SNOT-22 total and domain scores.

Results: A total of 127 patients were included in the study (CRSsNP = 53, CRSwNP = 74). IL-9 (ρ = 0.196, p < 0.05) was the only biomarker that correlated with the SNOT-22 total score. CRSwNP patients had a higher absolute expression level of Type 2 biomarkers (IgE, IL-5, and IL-13), compared to CRSsNP patients. IgE, IL-5, IL-9, and IL-13 significantly correlated with the SNOT-22 rhinologic subdomain scores (p < 0.001), LM scores, and patient reported sense of smell (Question 21). Notably, subgroup analysis showed that CRSsNP patients also demonstrated significant correlations between Type 2 markers (IL-4, IL-5, IL-9, and IL-13) and SNOT-22 rhinologic subdomain scores.

Conclusion: Type 2 mucus cytokine levels, especially IL-9, correlate with SNOT-22, and the rhinologic SNOT-22 subdomain scores for both CRSsNP and CRSwNP patients.