title: The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  GlaxoSmithKline.
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, Canada. Electronic address: Harvey.coxson@vch.ca.
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.affiliation: Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Dirksen
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Edwards
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Yates
authors.affiliation: Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, and CIBER Enfermedades Respiratorias (CIBERES), Mallorca, Spain.
authors.forename: Alvar
authors.initials: A
authors.lastname: Agusti
authors.affiliation: Institute of Internal Medicine, University of Bergen, Bergen, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Peter Ma
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.affiliation: University of Cambridge, Cambridge, UK.
authors.forename: Annelyse
authors.initials: A
authors.lastname: Duvoix
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, Canada.
authors.forename: Paola Nasute
authors.initials: PN
authors.lastname: Fauerbach
authors.affiliation: University of Cambridge, Cambridge, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: University of Edinburgh, Edinburgh, UK.
authors.forename: William
authors.initials: W
authors.lastname: Macnee
authors.affiliation: GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Mayer
authors.affiliation: GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.affiliation: Department of Radiology, University of British Columbia, Vancouver, Canada.
authors.forename: Nestor L
authors.initials: NL
authors.lastname: Müller
authors.affiliation: University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Emiel Fm
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Odense University Hospital, University of Southern Denmark, Odense, Denmark; University of Manchester, Manchester, UK.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
mesh_terms: D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D004646:Emphysema / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D016015:Logistic Models; D008137:Longitudinal Studies; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology / Q000523:psychology; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D012123:Pulmonary Ventilation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D015415:Biomarkers; D037663:Pulmonary Surfactant-Associated Protein D; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic