CT-derived pulmonary blood volume distribution may be modifiable in asthma

Background A smaller relative volume of the peripheral pulmonary vasculature in asthma, termed “vascular pruning”, has been linked to greater disease severity, exacerbations, and airflow obstruction. It is not known if this is reversible. Therefore, the study objective was to determine if “loss” of computed tomography (CT) measures of peripheral pulmonary vasculature is a modifiable feature of asthma pathophysiology by assessing its response to dupilumab. Methods Twenty-seven adults with moderate-to-severe asthma received dupilumab (n=19) or placebo (n=8) every 2-weeks for 16-weeks. Chest CT scans acquired at baseline and follow-up were analyzed to quantify pulmonary blood vessel volumes categorized by cross-sectional area (≤5 mm 2 as BV5 and ≥10 mm 2 as BV10). These volumes were reported relative to the total blood volume (TBV) as BV5% and BV10%. Change in blood vessel volumes from baseline to follow-up were evaluated and correlated with changes in patient-reported outcomes, type-2 inflammatory biomarkers, and measurements of airway structure and function. Results Following dupilumab treatment (but not placebo), BV5% increased by 1.0% (95% CI: −0.2% to 4.5%, p=0.02) and BV10% decreased by 1.0% (95% CI: −3.6% to 0.7%, p=0.03). The between-group difference in median change was 3.0% for BV5% (95% CI: 0.6% to 5.5%, p=0.008) and −3.0% for BV10% (95% CI: −5.2% to −1.0%, p=0.007). In dupilumab-treated participants, the increase in BV5% and decrease in BV10% was associated with improved ACQ-5, FEV 1 , FeNO, and sputum eosinophil percent (all p<0.05). Conclusion A redistribution of pulmonary blood volume toward smaller vessels was observed following dupilumab, suggesting that CT-derived pulmonary vascular measurements may be modifiable in asthma.