Clinical and Prognostic Differences in Mild to Moderate COPD With and Without Emphysema

BACKGROUND: The clinical and prognostic characteristics of mild-to-moderate COPD with and without emphysema remain inadequately investigated. RESEARCH QUESTION: Do the clinical and prognostic characteristics differ between mild-to- moderate COPD with and without emphysema? STUDY DESIGN AND METHODS: We obtained clinical data of 989 participants with mild-to- moderate COPD from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). They were categorized into two groups based on their baseline low- attention lung voxels with a density <-950 Hounsfield units of < 5% on CT scans: mild-to-moderate COPD with emphysema (EC) group and mild-to-moderate COPD without emphysema (NEC) group. Linear mixed-effects models were used to assess the differences in the decline of lung function, health-related quality of life, and quantitative CT indexes between these two groups. Zero-inflated negative binomial regressions were used to evaluate the rates of acute respiratory exacerbations between the groups. RESULTS: Among participants with mild-to-moderate COPD, 428 (43.3%) exhibited emphysema on CT scans. The annual decline in FEV1 was-56.1 mL/y for the EC group and-46.9 mL/y for the NEC group, with a nonsignificant between-group difference of 9.1 mL/y (95% CI,-24.0 to 5.7 mL/y). The rate of emphysema progression in the EC group was significantly lower than in the NEC group (natural logarithm(%LAA-950),-0.173%; 95% CI,-0.252% to-0.094%). The EC group also showed a more pronounced annual increase in the St. George's Respiratory Questionnaire score (0.9 points) compared with the NEC group. The EC group had a higher rate of acute respiratory exacerbations (0.36 per person-year) than the NEC group (0.25 per person- year), with a rate ratio of 1.42 (95% CI, 1.27-1.54). INTERPRETATION: The EC group did not have accelerated rates of decline in FEV1, but they experienced significantly worse health-related quality of life and a higher rate of acute respiratory exacerbations. The nonemphysema subtype demonstrated increased emphysema progression. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. clinicaltrials.gov CHEST 2025; 167(3):724-735