Longitudinal Study of Spatially Heterogeneous Emphysema Progression in Current Smokers with Chronic Obstructive Pulmonary Disease

Background: Cigarette smoke is the main risk factor for emphysema, which is a key pathology in chronic obstructive pulmonary disease (COPD). Low attenuation areas (LAA) in computed tomography (CT) images reflect emphysema, and the cumulative size distribution of LAA clusters follows a power law characterized by the exponent D. This property of LAA clusters can be explained by model simulation, where mechanical force breaks alveolar walls causing local heterogeneous lung tissue destruction. However, a longitudinal CT study has not investigated whether continuous smoking causes the spatially heterogeneous progression of emphysema. Methods: We measured annual changes in ratios of LAA (LAA%), D and numbers of LAA clusters (LAN) in CT images acquired at intervals of ≥3 years from 22 current and 31 former smokers with COPD to assess emphysema progression. We constructed model simulations using CT images to morphologically interpret changes in current smokers. Results: D was decreased in current and former smokers, whereas LAA% and LAN were increased only in current smokers. The annual changes in LAA%, D, and LAN were greater in current, than in former smokers (1.03 vs. 0.37%, p = 0.008; −0.045 vs. −0.01, p = 0.004; 13.9 vs. 1.1, p = 0.007, respectively). When LAA% increased in model simulations, the coalescence of neighboring LAA clusters decreased D, but the combination of changes in D and LAN in current smokers could not be explained by the homogeneous emphysema progression model despite cluster coalescence. Conversely, a model in which LAAs heterogeneously increased and LAA clusters merged somewhat in relatively advanced emphysematous regions could reflect actual changes. Conclusions: Susceptibility to parenchymal destruction induced by continuous smoking is not uniform over the lung, but might be higher in local regions of relatively advanced emphysema. These could result in the spatially heterogeneous progression of emphysema in current smokers.