Association of “Emptying Emphysema” with Clinical and Radiographic Features in People with Smoking History

RATIONAL: Emphysema is a hallmark of chronic obstructive pulmonary disease (COPD), yet its presumed coexistence with small airway disease remains debated. OBJECTIVE: To investigate the clinical significance of a novel CT-feature, "emptying emphysema," characterized by preserved expiratory density despite inspiratory attenuation consistent with emphysematous changes. METHODS: We analyzed data from 8,171 COPDGene participants with paired inspiratory-expiratory CT scans. Emptying emphysema was quantified using Parametric Response Mapping (%PRMEE) as the percentage of lung voxels with attenuation < -950 HU on inspiration and ≥ -856 HU on expiration. Multivariable models assessed associations between %PRMEE and clinical, functional, and radiographic outcomes. MEASUREMENTS AND MAIN RESULTS: Each one standard deviation (SD) higher in baseline %PRMEE was independently associated with less dyspnea (OR = 0.89; 95%CI: 0.94 to 0.95; P < .001) and impaired quality of life (OR = 0.87; 95%CI 0.83 to 0.93; P < .001). Each SD higher in %PRMEE was associated with a 11.2-meter increase in 6-minute walk distance (95%CI 8.7 to 13.6; P < .001). Higher %PRMEE was associated with lower FRC/TLC. Given the correlation between %PRMEE and traditional emphysema, we performed stratified analyses. Within each traditional emphysema quartile, higher %PRMEE was generally associated with higher FEV1% predicted and FEV1/FVC. Longitudinally, higher baseline %PRMEE was associated with attenuated lung density decline, and reduced mortality (HR = 0.90 per SD increase; 95%CI 0.86 to 0.95; P < .001). CONCLUSIONS: Emptying emphysema represents a CT-defined feature associated with preserved lung function and favorable clinical outcomes. Although it remains unclear whether this reflects a true pathological entity, these findings raise the possibility that emptying emphysema reflects alveolar-predominant changes occurring without significant airway disease, warranting further investigation.