• Harvey O Coxson, Asger Dirksen, Lisa D Edwards, Julie C Yates, Alvar Agusti, Per Bakke, Peter Ma Calverley, Bartolome Celli, Courtney Crim, Annelyse Duvoix, Paola Nasute Fauerbach, David A Lomas, William Macnee, Ruth J Mayer, Bruce E Miller, Nestor L Müller, Stephen I Rennard, Edwin K Silverman, Ruth Tal-Singer, Emiel Fm Wouters, Jørgen Vestbo, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators.
• Department of Radiology, University of British Columbia, Vancouver, Canada. Electronic address: Harvey.coxson@vch.ca.
• Lancet Respir Med. 2013 Apr 1;1(2):129-36.

BackgroundEmphysema 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.MethodsWe 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.FindingsLung 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.InterpretationThis 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.FundingGlaxoSmithKline.Copyright © 2013 Elsevier Ltd. All rights reserved.

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