Factor Analysis-Based Quantitative Endotyping Improves Associations With CRS Cross-Sectional and Longitudinal Outcomes
Journal
International forum of allergy & rhinology
Journal Volume
16
Journal Issue
1
Start Page
32
End Page
42
ISSN
2042-6984
Date Issued
2026-01
Author(s)
Gleason, Brooke N
Luo, Zhidi
Agarwal, Aditi
Dong, Siyuan
Harmon, Regan L
Bai, Junqin
Huang, Julia
Conley, David B
Welch, Kevin C
Kern, Robert C
Smith, Stephanie S
Peters, Anju T
Stevens, Whitney S
Kato, Atsushi
Muhammad, Lutfiyya N
Tan, Bruce K
Abstract
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.
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).
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.
Factor analysis identifies distinct, quantifiable patterns of inflammation in CRS, offering improved associations with cross-sectional and longitudinal outcomes compared to individual biomarkers.
Subjects
biomarker
chronic rhinosinusitis
disease severity
endoscopic sinus surgery
endotype
patient reported outcomes
Type
journal article