Current Smoking Status Is Associated With Lower Quantitative CT Measures of Emphysema and Gas Trapping

Purpose: The purposes of this study were to evaluate the effect of smoking status on quantitative computed tomography CT measures of low-attenuation areas (LAAs) on inspiratory and expiratory CT and to provide a method of adjusting for this effect. Materials and Methods: A total of 6762 current and former smokers underwent spirometry and volumetric inspiratory and expiratory CT. Quantitative CT analysis was completed using open-source 3D Slicer software. LAAs were defined as lung voxels with attenuation values <=-950 Hounsfield units (HU) on inspiratory CT and <=-856 HU on expiratory CT and were expressed as percentage of CT lung volume (%LAA(I-950) and %LAA(E-856)). Multiple linear regression was used to determine the effect of smoking status on %LAA(I-950) and %LAA(E-856) while controlling for demographic variables, spirometric lung function, and smoking history, as well as total lung capacity (%LAA(I-950)) or functional residual capacity (%LAA(E-856)). Quantile normalization was used to align the %LAA(I-950) distributions for current and former smokers. Results: Mean %LAA(I-950) was 4.2 +/- 7.1 in current smokers and 7.7 +/- 9.7 in former smokers (P < 0.001). After adjusting for confounders, %LAA(I-950) was 3.5 percentage points lower and %LAA(E-856) was 6.0 percentage points lower in current smokers than in former smokers (P < 0.001). After quantile normalization, smoking status was an insignificant variable in the inspiratory regression model, with %LAA(I-950) being 0.27 percentage points higher in current smokers (P=0.13). Conclusions: After adjusting for patient demographics and lung function, current smokers display significantly lower %LAA(I-950) and %LAA(E-856) than do former smokers. Potential methods for adjusting for this effect would include adding a fixed value (eg, 3.5%) to the calculated percentage of emphysema in current smokers, or quantile normalization.