Disease Duration and Latent Symptom Phenotypes in Medically Refractory Chronic Rhinosinusitis

Importance Chronic rhinosinusitis (CRS) symptom duration has not been associated with distinct patterns of symptom co-occurrence, limiting its utility for clinical phenotyping and treatment planning. Patients with longer-standing CRS may represent biologically or treatment-modified presentations, but it remains unclear whether symptom patterns differ systematically by duration. Objective To characterize symptom phenotypes based on CRS symptom duration and determine whether patterns of symptom co-occurrence differ systematically across duration categories. Design, Setting, and Participants A cross-sectional analysis of prospectively collected data in a large CRS cohort including patients in academic tertiary care center rhinology clinics aged 11 to 85 years with CRS who in whom appropriate medical therapy was not successful, met criteria, and underwent endoscopic sinus surgery between January 1, 2020, and May 1, 2025. Main Outcomes and Measures Binary sinonasal symptom indicators from a structured symptom checklist were analyzed using multiple correspondence analysis (MCA) to identify latent patterns of symptom co-occurrence. Dimension scores were then compared across duration categories (<6 months, 6 months to 3 years, >3 years) using Kruskal-Wallis tests with post hoc Dunn testing. As convergent evidence, the 22-item Sino-Nasal Outcome Test (SNOT-22) total and subdomain scores were compared across the same duration groups. Results Among 661 patients (mean [SD] age, 54.4 [16.7] years; 364 [55.1%] male; 85 [12.9%] Black and 289 [43.7%] Hispanic), MCA of 21 binary sinonasal symptom indicators identified 3 principal dimensions, explaining 40% of total variance. Dimension 1 reflected global symptom burden and increased monotonically with symptom duration (ε 2 = 0.035; 95% CI, 0.017-1.000). Dimension 2 captured a phenotypic shift between headache or pressure–dominant and chemosensory or drainage–dominant symptom patterns and varied across duration groups (ε 2 = 0.025; 95% CI, 0.012-1.000). Dimension 3 captured airway-irritative and sensory features and varied across duration groups (ε 2 = 0.019; 95% CI, 0.007-1.000), with post hoc testing showing separation between the 2 longer-duration groups. SNOT-22 total and subdomain scores replicated this threshold pattern across duration cohorts. Conclusions and Relevance This study found that, in medically refractory CRS, the duration of symptoms was associated with structural differences in symptom phenotypes rather than simple, linear increases in symptom severity. Early chronic disease (<6 months) is characterized by a lower overall symptom burden and headache/pressure predominance. Longer disease duration is associated with greater total symptom load and a predominance of chemosensory dysfunction and drainage-dominant concerns. Additional longitudinal validation of these phenotypic patterns and their association with clinical response is needed.