Disease accumulates in the small airways without being detected by conventional measurements. 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. 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). The participants included never-smokers (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). 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.