Exploring associations between nasal fluid inflammatory proteins and patient-reported symptom burden in respiratory disease.

INTRODUCTION: Patient-reported outcome measures are widely used to assess symptom burden in respiratory disease, yet the extent to which symptom severity reflects underlying mucosal biology remains incompletely understood. Nasal fluid provides a non-invasive matrix for assessing airway inflammation within the unified airway framework. METHODS: In this exploratory study, nasal fluid samples were collected from 30 participants with heterogeneous respiratory conditions, and protein concentrations were measured using a multiplex immunoassay. Associations between protein concentrations and symptom burden, measured using the 22-item Sino-Nasal Outcome Test (SNOT-22), were assessed using Spearman correlations. RESULTS: Protein concentrations of 40 analytes were measured and were found to span a wide dynamic range across participants. The mean SNOT-22 score was 39.1 (range, 3-89). TRAIL and CXCL10 demonstrated positive correlations with SNOT-22 scores (rho = 0.563, p = 0.001 and rho = 0.520, p = 0.005, respectively). Heatmap analysis revealed marked inter-individual variability in nasal fluid protein expression, including among participants with similar SNOT-22 scores. DISCUSSION: These findings demonstrate the feasibility of linking non-invasive nasal fluid biomarkers with composite symptom scores in a heterogeneous respiratory cohort. Together, they support the potential of nasal fluid profiling to capture clinically relevant biological variation and inform larger, multimodal studies integrating complementary clinical and physiological measures.