Supplementary Material for: A Novel Method of Estimating Small Airway Disease Using Inspiratory-to-Expiratory Computed Tomography

<p><b><i>Background:</i></b> Disease accumulates in the small airways without being detected by conventional measurements. <b><i>Objectives:</i></b> To quantify small airway disease using a novel computed tomography (CT) inspiratory-to-expiratory approach called the disease probability measure (DPM) and to investigate the association with pulmonary function measurements. <b><i>Methods:</i></b> Participants from the population-based CanCOLD study were evaluated using full-inspiration/full-expiration CT and pulmonary function measurements. Full-inspiration and full-expiration CT images were registered, and each voxel was classified as emphysema, gas trapping (GasTrap) related to functional small airway disease, or normal using two classification approaches: parametric response map (PRM) and DPM (VIDA Diagnostics, Inc., Coralville, IA, USA). <b><i>Results:</i></b> The participants included never-smokers (<i>n</i> = 135), at risk (<i>n</i> = 97), Global Initiative for Chronic Obstructive Lung Disease I (GOLD I) (<i>n</i> = 140), and GOLD II chronic obstructive pulmonary disease (<i>n</i> = 96). PRM<sub>GasTrap</sub> and DPM<sub>GasTrap</sub> measurements were significantly elevated in GOLD II compared to never-smokers (<i>p</i> < 0.01) and at risk (<i>p</i> < 0.01), and for GOLD I compared to at risk (<i>p</i> < 0.05). Gas trapping measurements were significantly elevated in GOLD II compared to GOLD I (<i>p</i> < 0.0001) using the DPM classification only. Overall, DPM classified significantly more voxels as gas trapping than PRM (<i>p</i> < 0.0001); a spatial comparison revealed that the expiratory CT Hounsfield units (HU) for voxels classified as DPM<sub>GasTrap</sub> but PRM<sub>Normal</sub> (PRM<sub>Normal</sub>- DPM<sub>GasTrap</sub> = -785 ± 72 HU) were significantly reduced compared to voxels classified normal by both approaches (PRM<sub>Normal</sub>-DPM<sub>Normal</sub> = -722 ± 89 HU; <i>p</i> < 0.0001). DPM and PRM<sub>GasTrap</sub> measurements showed similar, significantly associations with forced expiratory volume in 1 s (FEV<sub>1</sub>) (<i>p</i> < 0.01), FEV<sub>1</sub>/forced vital capacity (<i>p</i> < 0.0001), residual volume/total lung capacity (<i>p</i> < 0.0001), bronchodilator response (<i>p</i> < 0.0001), and dyspnea (<i>p</i> < 0.05). <b><i>Conclusion:</i></b> CT inspiratory-to-expiratory gas trapping measurements are significantly associated with pulmonary function and symptoms. There are quantitative and spatial differences between PRM and DPM classification that need pathological investigation.</p>