Abstract Rationale Relatively lower volume of the small pulmonary vessels (referred to as vascular “pruning”) can be quantified using image analysis of chest CT scans and has demonstrated promise as an actionable biomarker of poor prognosis in individuals with chronic hypersensitivity pneumonitis (cHP) and other pulmonary conditions. However, a deeper understanding of the basis of the pruning signal is needed to improve clinical sub-phenotyping of cHP. In this study, we investigated whether arterial vs. venous pruning were separate predictors of mortality in cHP, and whether heterogeneity of pruning was associated with long-term outcomes. Methods The sample consisted of 34 patients with cHP evaluated at the Federal University of São Paulo (2011-2013). From clinical chest CTs, we measured the small-vessel (area 5mm²) volume fraction from all five lobes of the lung, including arteries, veins, and the combined vessels. More severe pruning was defined as lower small vessel fraction from the lowest-density lobe (i.e. least involved by ILD). We also calculated the coefficient of variation (CV) for pruning across all five lobes, with higher CV reflecting greater spatial heterogeneity. We constructed multivariable Cox proportional hazards models to evaluate the associations of each pruning metric with mortality. HRs expressed per standard deviation of more severe pruning. Results Over an average of 5.1±3.8 years of follow-up, we found that arterial, venous, and combined pruning were all associated with greater mortality. The effect of arterial pruning (HR = 1.87, 95%CI: 1.19-2.95; p = 0.007) was greater than venous pruning (HR = 1.63, 95%CI 0.99-2.67; p = 0.05). However, combined arterial and venous pruning had the greatest association (HR = 2.10, 95%CI 1.33-3.43; p = 0.002), suggesting complementary contributions from each side of the vasculature. We also found that more homogenous pruning was associated with greater mortality; for example, per standard deviation lower CV, the mortality rate was 2.22-fold higher (95%CI: 1.18-4.20; p = 0.01). This was driven by the arterial signal, whereas no association was seen between venous heterogeneity and mortality. Conclusion In a cohort of patients with cHP, both arterial and venous vascular pruning on CT contributed to greater risk of death, and a more homogenous pattern of arterial pruning was also associated with a higher mortality. These findings suggest that more detailed radiographic sub-phenotypes may improve identification of high-risk individuals with cHP. This abstract is funded by: AJS is supported by a grant from NHLBI/NIH (K23HL164976). TCFM and GOSC are supported by UNIFESP’s Pulmonary Hemodynamic Assessment Program Research Fund, Brazil. RKFO is supported by the Brazilian National Council for Scientific and Technological Development (313284/2021-0; 409180/2022-0; and 404797/2024-5).
Millan et al. (Fri,) studied this question.