Association of Ground-Glass Opacities with Systemic Inflammation and Progression of Emphysema

Rationale: Ground-glass opacities (GGOs) in the absence of interstitial lung disease are understudied. Objectives: To assess the association of GGOs with white blood cells (WBCs) and progression of quantified chest computed tomography emphysema. Methods: We analyzed data of participants in the SPIROMICS study (Subpopulations and Intermediate Outcome Measures in COPD Study). Chest radiologists and pulmonologists labeled regions of the lung as GGOs, and the adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGOs (%GGO_AMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGO_AMFM with WBCs, changes in percentage emphysema, and clinical outcomes. Measurements and Main Results: Among 2,714 participants, 1,680 had chronic obstructive pulmonary disease (COPD) and 1,034 had normal spirometry. Among participants with COPD, on the basis of multivariable analysis, current smoking and chronic productive cough were associated with higher %GGO_AMFM. Higher %GGO_AMFM was cross-sectionally associated with higher WBC and neutrophil concentrations. Higher %GGO_AMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at 1-year follow-up visit by 11.7% (relative increase; 95% confidence interval, 7.5-16.1%; P < 0.001). We found no association between %GGO_AMFM and 1-year FEV₁ decline, but %GGO_AMFM was associated with exacerbations and all-cause mortality during a median follow-up of 1,544 days (interquartile interval, 1,118-2,059). Among normal spirometry participants, we found similar results, except that %GGO_AMFM was associated with progression to COPD at 1-year follow-up. Conclusions: Our findings suggest that GGO_AMFM is associated with increased systemic inflammation and emphysema progression.