Distinct Profiles of Patient-Reported Outcomes Across Allergen Signatures in Chronic Rhinosinusitis

Abstract

Background: Chronic rhinosinusitis (CRS) exhibits marked symptom heterogeneity that is not fully explained by anatomy or endotypes. Although allergen types shape symptom patterns in allergic rhinitis, largescale systematic analyses linking allergen sensitization profiles to patient-reported outcome measures in patients with CRS are limited. Methods: We conducted a multicenter, retrospective surgical cohort study (n = 1880) including patients with CRS who underwent preoperative specific IgE testing for 35 inhalant allergens and completed the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaire within 1 year. Using a previously validated nonnegative matrix factorization model, we deconvolved each patient's IgE profile into four allergen signatures (Mite, Grass/Weed, Pet, and Tree) and defined a dominant group. Associations between signature contributions and SNOT-22 items, domain subscores, and total score were estimated by ordinary least squares, adjusting for age, sex, nasal polyps, and asthma, with coefficients scaled per 10-percentage-point increase. Item-level multiplicity was controlled for using the false discovery rate. Seasonality was assessed using monthly means and the coefficient of variation of the dominant group. Results: Dominant groups were nonallergic (50%), mite (26%), grass/weed (9%), pet (9%), and tree (5%). Symptoms varied by age and sex, characterized by notably low nasal scores with aging and a high female burden for several items, motivating covariate adjustment. Signature-symptom associations were domain-specific: the pet signature showed the strongest and most consistent associations with nasal domain (such as rhinorrhea and nasal obstruction) and emotion domain (feelings of embarrassment); mite and grass/weed signatures were linked to the function domain (daytime fatigue/productivity); whereas the tree signature showed no significant associations. Seasonal patterns aligned with exposure ecology: grass/weed and tree groups had the largest relative variation (high coefficient of variations), the pet group showed the highest absolute burden year-round, and the mite group varied modestly with winter-spring predominance. Conclusions: Allergen signatures distilled from routine IgE panels explained meaningful variations in CRS patient-reported outcome measures, mapping to distinct symptom domains and seasonal profiles. Incorporating signature information into clinical assessments may support personalized counseling, anticipatory management around exposure windows, and targeted evaluation of environmental or immunologic interventions.