A Novel Method of Estimating Small Airway Disease Using Inspiratory-to-Expiratory Computed Tomography

Abstract

Disease accumulates in the small airways withoutbeing detected by conventional measurements. Objectives: 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. Methods: Participants from the population-based CanCOLD study were evaluated using full-inspiration/fullexpiration CT and pulmonary function measurements. Fullinspiration 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). Results: The participants included neversmokers (n = 135), at risk (n = 97), Global Initiative for Chronic Obstructive Lung Disease I (GOLD I) (n = 140), and GOLD II chronic obstructive pulmonary disease (n = 96). PRM GasTrap and DPM GasTrap measurements were significantly elevated in GOLD II compared to never-smokers (p 0.01) and at risk (p 0.01), and for GOLD I compared to at risk (p 0.05). Gas trapping measurements were significantly elevated in GOLD II compared to GOLD I (p 0.0001) using the DPM classification only. Overall, DPM classified significantly more voxels as gas trapping than PRM (p 0.0001); a spatial comparison revealed that the expiratory CT Hounsfield units (HU) for voxels classified as DPM GasTrap but PRM Normal (PRM Normal - DPM GasTrap = -785 ± 72 HU) were significantly reduced compared to voxels classified normal by both approaches (PRM Normal -DPM Normal = -722 ± 89 HU; p 0.0001). DPM and PRM GasTrap measurements showed similar, significantly associations with forced expiratory volume in 1 s (FEV 1) (p 0.01), FEV 1 /forced vital capacity (p 0.0001), residual volume/total lung capacity (p 0.0001), bronchodilator response (p 0.0001), and dyspnea (p 0.05). Conclusion: CT inspiratoryto- 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..