Reply to Marruchella: Preserved Ratio Impaired Spirometry and Interstitial Lung Abnormalities in Smokers.

From the Authors:

On behalf of our coauthors, we thank Dr. Marruchella for his interest in the longitudinal analysis of Preserved Ratio Impaired Spirometry (PRISm) (FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted) in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study (1) and for bringing attention to the possible role of interstitial lung abnormalities in PRISm. Among the first 2,500 subjects enrolled in phase 1 of the COPDGene study, a significantly higher prevalence of interstitial lung abnormalities on chest computed tomography imaging was noted among the PRISm subgroup, then referred to by the moniker “GOLD-Unclassified,” relative to the remainder of the COPDGene cohort (22% vs. 10–13% among GOLD 0–4) (2). This same research group subsequently extended their visual assessment of interstitial lung abnormalities to a subset of individuals with 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.