C39-40 Imaging-Physiology Dissociation and the Role of Pulmonary Vasculature in Systemic Sclerosis-Associated ILD

Abstract Rationale Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a heterogeneous fibrosing condition in which the relationship between structural fibrosis and functional progression remains poorly characterized. Quantitative CT (qCT) biomarkers offer objective alternative measurement of disease severity for improving patient monitoring and endpoint selection in trials. Methods Patients with SSc-ILD were identified from a global imaging repository of ILD-specific data and two UK Healthcare Trusts. Volumetric evaluation of the airways, pulmonary vessels and parenchymal patterns, ground glass opacification and fibrosis were quantified using Air8™, Vascul8™, Glass8™, and Fibr8™, respectively, normalised against total lung volume. Annualised change in percent-predicted forced vital capacity (ΔppFVC%) and fibrosis (%Fibr8) were estimated using linear mixed-effects models from longitudinal spirometry. Associations between baseline CT biomakers, fibrosis progression, and % predicted FVC (ppFVC) trends were assessed by linear regression. An IPF-derived optimal fibrosis threshold (15.3%) for predicting 12-month ppFVC decline was tested for generalizability. Results Sixty-four patients were included (mean age 55.3±13.7 years; 73.4% female). Baseline fibrosis extent averaged 16.9±13.8%, and baseline ppFVC was 75.5±19.7% predicted. Baseline fibrosis was inversely correlated with baseline ppFVC (β = -0.89±0.0.14, R² = 0.37, p 0.001) but did not predict subsequent ppFVC decline (β = -0.03±0.07, p = 0.67). Increasing normalised pulmonary vascular volume was associated with physiological decline (β = -4.90 ± 2.02, p = 0.018, R² = 0.07) but normalised airway volume and extent of ground glass opacification were not (β = 0.48±, p = 0.87 and β = 0.03 ± 0.12, p = 0.84). Mean fibrosis progression was +10.80 ± 41.39% and mean annualized ppFVC change -0.81 ± 7.67%. Overall, fibrosis progression and ppFVC decline were only weakly related (β = 0.04 ± 0.02, p = 0.09). No significant difference in 12-month ppFVC was demonstrated in patient groups stratified by a baseline fibrosis threshold of 15.3% (p = 0.427) Conclusions In SScl-ILD, baseline fibrosis extent did not predict physiological decline, confirming a dissociation between baseline disease severity and short-term progression. Stratification using an IPF-derived fibrosis threshold further underscored this disconnect, failing to separate ppFVC decline. Pulmonary vascular volume, rather than fibrosis, inflammatory or airway measures, was most closely associated with ppFVC loss, consistent with the vasculopathy component of SSc-ILD. These findings indicate conventional lung function endpoints incompletely capture disease dynamics; qCT biomarkers-particularly vascular and fibrotic metrics-offer complementary measures for assessing progression and therapeutic response in clinical trials. This abstract is funded by: None