Quantitative Chest CT-derived Fibrosis and Vascular Remodeling and Acute Exacerbation Risk in Mild Idiopathic Pulmonary Fibrosis.

Background Acute exacerbations worsen outcomes in idiopathic pulmonary fibrosis (IPF), but the role of vascular remodeling remains unclear. Purpose To determine whether quantitative CT-derived vascular metrics are independently associated with acute exacerbations in mild IPF and whether arterial or venous remodeling mediates the effects of fibrosis burden. Materials and Methods In this retrospective cohort study, patients with mild IPF (forced vital capacity ≥ 80% and diffusing capacity for carbon monoxide ≥ 55%) underwent baseline volumetric high-spatial-resolution unenhanced chest CT between April 2011 and December 2021 at a single tertiary hospital. Fibrosis score (FS) and vascular metrics were assessed using deep learning-based software. The primary outcome was time to acute exacerbation; the secondary outcome was event-free survival for acute exacerbation, lung transplantation, and death (composite outcome). Multivariable Cox models were used to evaluate both outcomes, adjusting for age, smoking status, and pack-years. Mediation analysis was used to assess whether vascular remodeling mediated the association between FS and the outcomes. Results Among 313 patients (mean age, 66.4 years ± 7.1 [SD]; 245 male patients), 86 (27.5%) experienced acute exacerbation, two (0.6%) underwent lung transplantation, and 120 (38.3%) died during a median 6.3 years of follow-up. Higher FS was associated with a higher estimated risk of acute exacerbation (adjusted hazard ratio [aHR] range across models, 1.05-1.09; P value range, .001-.10) and of the composite outcome (aHR range, 1.08-1.20; all P ≤ .001). Venous dilatation (aHR, 7.93 [95% CI: 2.56, 24.59]) and venous diameter heterogeneity (aHR, 1.37 [95% CI: 1.16, 1.63]) were associated with increased acute exacerbation risk, whereas higher small-artery volume fraction was associated with reduced risk (aHR, 0.91 [95% CI: 0.86, 0.96]). FS effects on acute exacerbation were mediated by venous remodeling (57.1% mediation; P = .001) and by small-artery volume fraction (21.5%; P = .02). Conclusion In mild IPF, fibrosis burden and vascular remodeling were associated with acute exacerbation risk, with venous and arterial remodeling mediating fibrosis effects, and higher small-artery volume fraction associated with reduced acute exacerbation risk. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.