Except for the additional subjects obtained for longitudinal analysis, all CT data and analysis were performed as part of the COPDGene project. Whole-lung volumetric multi-detector CT acquisition was performed at full inspiration and normal expiration using a standardized previously published protocol.3 (link) Data reconstructed with the standard reconstruction kernel was used for quantitative analysis. All CT data were presented in Hounsfield Units (HU), where stability of CT measurement for each scanner was monitored monthly using a custom COPDGene phantom.3 (link) For reference, air and water attenuation values are −1000 and 0 HU; healthy lung parenchyma is approximately −700 HU. Quantitative analysis of emphysema severity was performed on segmented lung images using Slicer (www.Slicer.org). The percentage of emphysema (% emphysema) was defined as all lung voxels with a CT attenuation value of less than −950 Hounsfield units (HU) divided by the total lung volume at full inflation, multiplied by 100. The total percent gas trapping (GT) was defined as the fraction of lung with a CT attenuation value of less than −856 HU divided by the total lung volume at expiration, multiplied by 100. Automated airway analysis was performed using VIDA Pulmonary Workstation version 2.0 (www.vidadiagnostics.com) using previously validated segmentation methods (details in Supplemental Methods).28 (link) All analytical measurements not pertaining to the discussed PRM approach were performed by COPDGene personnel. Similar data acquisition and post-processing were performed on the additional retrospective longitudinal data sets which were not obtained as part of the COPDGene study.