The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study

Background Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a longitudinal, international cohort of patients with COPD. We also explored the potential relation between emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density. Methods We used a random coefficient model to assess predictors of both CT lung density and its longitudinal change over 3 years in 1928 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Lung density was measured for every voxel in the CT scan and after correcting for lung volume was expressed as the density at lowest 15th percentile point of the distribution. This study is registered with ClinicalTrials.gov, number NCT00292552. Findings Lung density at baseline was influenced by age, sex, body-mass index, current smoking status and smoking history, and severity of airflow limitation. The observed decline in lung density was variable (mean decline -1.13 g/L [SE 0.06] per year). The annual decline in lung density was more rapid in women (additional -0.41 [SE 0.14] g/L per year, p=0.003) than men and in current smokers (additional -0.29 [SE 0.14] g/L per year, p=0.047) than in former smokers. Circulating levels of the biomarkers surfactant protein D (SP-D) and soluble receptor for advanced glycation endproduct (sRAGE) were significantly associated with both baseline lung density and its decline over time. Interpretation This study shows that decline in lung density in COPD can be measured, that it is variable, and related to smoking and gender. We identified potential biochemical predictors of the presence and progression of emphysema.