One-year progression of CT emphysema subtypes predict lung function decline: SPIROMICS.

RATIONALE: Intermediate endpoints that predict lung function decline are needed to improve the efficiency of clinical trials in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To test if one-year progression of quantitative computed tomography (QCT) measures predicts subsequent FEV₁ decline. METHODS: SPIROMICS recruited individuals with ≥ 20 pack-years smoking history with or without COPD and nonsmoking controls who underwent four annual and a later fifth visit. We analyzed chest CT scans at visits one and two for machine-learned CT emphysema subtypes (combined bronchitic-apical emphysema [CBaE], diffuse emphysema) and standard QCT measures of emphysema (percent emphysema-950HU, 15th percentile HU, volume-adjusted lung density), airways, functional small airways, hyperinflation, parenchymal texture and vasculature. Linear mixed-effects models evaluated associations between one-year QCT measure changes and FEV₁ decline from visits two through five, adjusting for demographics, site, enrollment group, baseline QCT value, and time-varying anthropometrics and smoking. MEASUREMENTS AND MAIN RESULTS: Among 880 participants (43% mild/moderate COPD, 17% severe COPD, 29% smoking controls, 11% nonsmoking controls), FEV₁ declined -30.4mL/year (95% CI: -34.5, -26.3). A standard deviation (SD) one-year increase in CBaE and diffuse emphysema predicted an accelerated decline in FEV1 of - 4.2 mL/year (95% CI: -8.3, -0.2) and -6.2 mL/year (95% CI: -10.7, -1.8), respectively. Changes in standard QCT emphysema measures also predicted change in FEV1 decline, but only CBaE and diffuse emphysema remained independently predictive of accelerated FEV1 decline when all were considered together. CONCLUSIONS: One-year progression of CT emphysema subtypes predicted accelerated FEV₁ decline, supporting their potential use as intermediate endpoints in COPD trials.