Longitudinal Mediastinal Lymph Node Dynamics Associate With Mortality and Fibrosis Progression in Fibrotic...

Although mediastinal lymph node (MLN) enlargement is common in fibrotic interstitial lung disease (ILD), its dynamic behavior and prognostic value are unclear.

Do MLN size, count, and progression on high-resolution chest CT imaging associate with physiological decline, fibrosis progression, and transplant-free survival, and do these factors improve risk models?

This study included a prospective cohort of patients with fibrotic ILD from a tertiary center (N = 1,122) with independent replication (n = 181). MLNs were scored by using standardized radiologic criteria; fibrosis was quantified according to deep texture analysis. Associations with outcomes were evaluated by using Cox and linear mixed-effects models; model discrimination was assessed by using Harrell's concordance index and net benefit by decision curve analysis.

Baseline MLN enlargement (≥ 10 mm) occurred in 67% and was independently associated with worse transplant-free survival (hazard ratio, 2.44; 95% CI, 2.01-2.96; P < .0001). MLN progression was associated with excess mortality (adjusted hazard ratio, 4.09; 95% CI, 2.34-7.17; P < .001) and modified the association between fibrosis progression and survival (interaction hazard ratio, 3.02; P = .001). Fibrosis remained the stronger prognostic marker, but MLN metrics added complementary information within fibrosis strata and modestly improved discrimination when added to clinical models based on ILD-GAP (gender, age, physiology) model score or progressive pulmonary fibrosis status. Findings were directionally consistent in the independent replication cohort.

MLN burden and progression are accessible, quantifiable imaging biomarkers associated with adverse outcomes in fibrotic ILD. Incorporating MLN metrics into existing clinical models improves risk discrimination and supports further evaluation of their role in ILD risk stratification.