LAUSR

serial chest computed tomography data from the Framingham Heart Study and reported accelerated loss of FVC among individuals with radiographic progression of interstitial changes (relative to individuals without interstitial lung abnormalities or with stable interstitial lung abnormalities) (3). Within COPDGene, individuals who developed “incident PRISm” (i.e., transitioned from normal spirometry [“GOLD 0”] at phase 1 to PRISm at phase 2) also exhibited higher rates of lung function decline, albeit in both FEV1 and FVC rather than isolated declines in FVC (1). The degree to which interstitial lung abnormalities contribute to this transition has not yet been fully characterized. Assessment of the de novo development of interstitial lung abnormalities as well as progression of existing interstitial lung abnormalities are active areas of investigation within COPDGene. Notably, a significant number of subjects with PRISm in COPDGene had anatomical abnormalities that were not limited to interstitial parenchymal changes, including chest wall and diaphragmatic deformities as well as a smaller internal transverse thoracic diameter in phase 1 (4). In addition to anatomical and parenchymal changes, functional differences, such as small airway disease (5) and gas transfer abnormalities, represent additional domains that should be explored in PRISm. We continue to assert that the PRISm cohort is heterogeneous and is likely composed of subgroups with distinct pathobiological processes (6); interstitial lung abnormalities likely contribute to the development and progression of lung disease in a subset of subjects with PRISm. Future studies, both within and beyond COPDGene, to characterize the predictors and risks associated with distinct subgroups within PRISm are needed. n