Factor Analysis‐Based Quantitative Endotyping Improves Associations With CRS Cross‐Sectional and Longitudinal Outcomes

Background Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease characterized by persistent sinonasal inflammation. There is increasing interest in endotype‐based classification, which categorizes CRS based on underlying inflammatory pathways. We applied factor analysis to facilitate continuous endotype assignment to CRS patients and assess cross‐sectional and longitudinal CRS outcomes. Methods We prospectively enrolled 203 patients (52 controls, 88 CRSsNP, and 63 CRSwNP) undergoing endoscopic nasal or sinus surgery (ESS). Middle meatal mucus biomarkers were analyzed pre‐ESS (V0) and 6–12 months post‐ESS (V1). Factor analysis was performed to identify latent factors. Factor scores were generated, and statistical analyses were conducted to assess correlations with radiographic (Lund–Mackay [LM]) and patient‐reported (SNOT‐22, CRS‐PRO) outcomes measured at V0, V1, and V2 (1.5–5 years post‐ESS). Results Four factors were identified: Type 1 (T1), Type 2 (T2), Type 3 (T3), and macrophage‐associated (M). CRSwNP patients had higher T2 and M factor scores than CRSsNP and controls. T2, T3, and M factor scores demonstrated stronger or equivalent associations with radiographic and patient‐reported outcomes compared to individual biomarkers. Following ESS, median T2 and M factor scores significantly declined, while T1 and T3 remained stable. V0 T1 and T2 were weakly associated with long‐term (V2) radiographic and symptom scores. V1 factor scores were more consistently predictive of long‐term (V2) outcomes, with T2, T3, and M demonstrating modest correlations with radiographic severity and CRS‐PRO. Conclusions Factor analysis identifies distinct, quantifiable patterns of inflammation in CRS, offering improved associations with cross‐sectional and longitudinal outcomes compared to individual biomarkers.