CT imaging-based study of ventilation heterogeneity in smokers :the respective roles of unequal lung expansion and peripheral lung structure

Smoking-induced ventilation heterogeneity is thought to occur in air spaces down to the lung periphery, and the multiple breath washout (MBW) test has been proposed to serve as a non-invasive diagnostic tool. We separately examined the roles of unequal lung expansion and of peripheral heterogeneity (independent of expansion) on MBW N2 curves. We first extracted 3D maps of local lung expansion from registered CT images in 50 smokers (GOLD 0-III) to predict for each subject, the N2 washout concentration curve solely attributable to local expansion. By a head-on comparison with MBW N2 concentrations measured at the mouth in the same subjects supine, we could observe that : (1) lung clearance index (LCI) increased from 4.82+0.16(SD) to 6.58+0.77(SD) due to unequal lung expansion alone, and further increased to 8.99+1.46(SD) independent of local expansion, (2) alveolar mixing efficiency (AME) derived from the beginning of the washout curve, decreased (from 100% by definition) to 95+2(SD)% due to unequal expansion alone, and further decreased to 75+7(SD)% independent of local expansion. In a multiple regression between ventilation heterogeneity and CT derived parametric response mapping indices (PRMfSAD and PRMemphys), LCI was related to PRMfSAD (r=+0.58;P