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

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.