Conclusions
We have shown that two previously-described gas trapping measures based on paired inspiratory and expiratory chest CT scans (E/I MLA and RVC856–950) may serve as markers of small airway disease in smokers, including subjects with severe and very severe COPD. Although we cannot claim that one measure is superior to the other, the expiratory to inspiratory ratio of mean lung attenuation may be more straightforward than RVC856–950, and has more support in the published COPD literature. For clinical applicability, it will be important to define thresholds for these gas trapping parameters that delineate normal from small airway disease; a large sample of never smokers with normal lung function is necessary for this effort. Additionally, thresholds to define airway-predominant vs. emphysema-predominant COPD subtypes are also desirable. The current data do not allow for assessment of changes in these measures with treatment, an important area for future investigation. Large studies of smokers will have to include expiratory CT scans to further these efforts. In COPDGene and future studies, these gas trapping variables can be used in genetic analyses, to better understand the pathobiology of COPD subtypes.