Harvey O Coxson1, Asger Dirksen2, Lisa D Edwards3, Julie C Yates3, Alvar Agusti4, Per Bakke5, Peter Ma Calverley6, Bartolome Celli7, Courtney Crim3, Annelyse Duvoix8, Paola Nasute Fauerbach9, David A Lomas8, William Macnee10, Ruth J Mayer11, Bruce E Miller11, Nestor L Müller9, Stephen I Rennard12, Edwin K Silverman7, Ruth Tal-Singer11, Emiel Fm Wouters13, Jørgen Vestbo14. 1. Department of Radiology, University of British Columbia, Vancouver, Canada. Electronic address: Harvey.coxson@vch.ca. 2. Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. 3. GlaxoSmithKline, Research Triangle Park, North Carolina, USA. 4. Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, and CIBER Enfermedades Respiratorias (CIBERES), Mallorca, Spain. 5. Institute of Internal Medicine, University of Bergen, Bergen, Norway. 6. University of Liverpool, Liverpool, UK. 7. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA. 8. University of Cambridge, Cambridge, UK. 9. Department of Radiology, University of British Columbia, Vancouver, Canada. 10. University of Edinburgh, Edinburgh, UK. 11. GlaxoSmithKline, King of Prussia, Pennsylvania, USA. 12. University of Nebraska Medical Center, Omaha, Nebraska, USA. 13. Maastricht University Medical Center, Maastricht, The Netherlands. 14. Odense University Hospital, University of Southern Denmark, Odense, Denmark; University of Manchester, Manchester, UK.
Abstract
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. FUNDING: GlaxoSmithKline.
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. FUNDING: GlaxoSmithKline.
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