The purposes of this study are to evaluate the normal range of quantitative CT (QCT) measures of lung attenuation and airway parameters measurements in healthy non-smoking adults and to identify sources of variation in those measures and possible means to adjust for them.
Materials and Methods
Within the COPDGene® study, 92 healthy non-Hispanic White non-smokers [29 male, 63 female, mean age 62.7 (SD 9.0), BMI 28.1 (SD 5.1)] underwent volumetric CT at full inspiration and at the end of a normal expiration. On QCT analysis (Pulmonary Workstation 2, VIDA Diagnostics), inspiratory low attenuation areas were defined as lung tissue with attenuation values ≤ −950 Hounsfield Units (HU) on inspiratory CT (LAAI-950). Expiratory low attenuation areas were defined as lung tissue ≤ −856 HU on expiratory CT (LAAE-856). We used simple linear regression to determine the impact of age and gender on QCT parameters and multiple regression to assess the additional impact of total lung capacity and functional residual capacity measured by CT (TLCCT and FRCCT), scanner type, and mean tracheal air attenuation. Airways were evaluated using measures of airway wall thickness (AWT), inner luminal area (ILA), wall area percent (WA%) and standardized thickness of an airway with inner perimeter of 10mm (Pi10).
Mean %LAAI-950 was 2.0 (SD 2.7), and mean %LAAE-856 was 9.2 (SD 6.8). Mean %LAAI-950 was 3.6 (SD 3.2) % in men, compared with 1.3 (SD 2.0) in women (P<0.001). The %LAAI-950 did not change significantly with age (P=0.08) or BMI (P=0.52). %LAAE-856 did not show any independent relationship with age (P=0.33), gender (P=0.70), or BMI (P=0.32). On multivariate analysis, %LAAI-950 showed a direct relationship to TLCCT (P=0.002) and an inverse relationship to mean tracheal air attenuation (P=0.003), and %LAAE-856 was related to age (P=0.001), FRCCT (P=0.007) and scanner type (P<0.001). Multivariate analysis of segmental airways showed that ILA and WA% were significantly related to TLCCT (P<0.001) and age (0.006). WA% was also associated with gender (P=0.05), axial pixel size (P=0.03) and slice interval (P=0.04). Lastly, AWT is strongly influenced by axial pixel size (P<0.001).
Although the attenuation characteristics of normal lung differ by age and gender, these differences do not persist on multivariate analysis. Potential sources of variation in measurement of attenuation-based quantitative CT parameters include depth of inspiration/expiration, and scanner type. Tracheal air attenuation may partially correct variation due to scanner type. Sources of variation in QCT airway measurements may include age, gender, BMI, depth of inspiration, and spatial resolution.