TY - JOUR
T1 - The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression
T2 - A prospective analysis from the ECLIPSE study
AU - Coxson, Harvey O.
AU - Dirksen, Asger
AU - Edwards, Lisa D.
AU - Yates, Julie C.
AU - Agusti, Alvar
AU - Bakke, Per
AU - Calverley, Peter M.A.
AU - Celli, Bartolome
AU - Crim, Courtney
AU - Duvoix, Annelyse
AU - Fauerbach, Paola Nasute
AU - Lomas, David A.
AU - Macnee, William
AU - Mayer, Ruth J.
AU - Miller, Bruce E.
AU - Müller, Nestor L.
AU - Rennard, Stephen I.
AU - Silverman, Edwin K.
AU - Tal-Singer, Ruth
AU - Wouters, Emiel F.M.
AU - Vestbo, Jørgen
N1 - Funding Information:
HOC has received payment, travel expenses, and contract service agreements from GlaxoSmithKline (GSK), has a service agreement with Spiration Inc, and has received payment and travel expenses from AstraZeneca (Australia). AA has received reimbursements, fees, or funding from GSK, Almirall, AstraZeneca, Boheringer Ingelheim, Roche, Nycomed, Novartis, and Procter & Gamble. PB has received lecture fees from AstraZeneca, GSK, and Nycomed, and has participated in clinical research studies sponsored by GSK, Pfizer, and Boehringer Ingelheim. PMAC has received consulting fees from AstraZeneca, GSK, Nycomed, and Pfizer, speaking fees from GSK and Nycomed, and grant support from Boehringer Ingelheim and GSK. BC has received grants and fees from GSK, Boehringer Ingelheim, Forrest Medical, AstraZeneca, and Aeris, has served on advisory boards for GSK, Boehringer Ingelheim, Almirall, AstraZeneca, Aeris, and Deep Breeze, has received speaker fees from GSK, Boehringer Ingelheim, AstraZeneca, Almirall, and Esteve, does not have shares or interest in any company, and has not received tobacco money nor has stocks in any tobacco-related companies. LDE, JCY, CC, RJM, BEM, and RT-S are employees and shareholders of GSK, the sponsor of ECLIPSE. DAL has received grant funding, honoraria, and travel expenses from GSK, and serves on the Respiratory CEDD Board of GSK. WMacN has been reimbursed for travel by GSK, Zambon, AstraZeneca, Boehringer Ingelheim, Pfizer, and Micromet for attending conferences; has received honoraria from GSK and AstraZeneca for participating as a speaker in scientific meetings, serves on advisory boards for GSK, Pfizer, Almirall, Amgen, Bayer, and Micromet, and serves as a consultant for Pfizer and SMB Pharmaceuticals. NLM received a service contract from GSK for the analysis of the CT scans in the ECLIPSE Study. SIR has received industry-sponsored grants from: AstraZeneca, Biomarck, Centocor, Mpex, Nabi, Novartis, Otsuka, and has consulted or participated in advisory boards for: Able Associates, Adelphia Research, Almirall/Prescott, APT Pharma/Britnall, Aradigm, AstraZeneca, Boehringer Ingelheim, Chiesi, CommonHealth, Consult Complete, COPDForum, DataMonitor, Decision Resources, Defined Health, Dey, Dunn Group, Eaton Associates, Equinox, Gerson, GSK, Infomed, KOL Connection, M Pankove, MedaCorp, MDRx Financial, Mpex, Novartis, Nycomed, Oriel Therapeutics, Otsuka, Pennside Partners, Pfizer (Varenicline), PharmaVentures, Pharmaxis, Price Waterhouse, Propagate, Pulmatrix, Reckner Associates, Recruiting Resources, Roche, Schlesinger Medical, Scimed, Sudler and Hennessey, TargeGen, Theravance, UBC, Uptake Medical, VantagePoint Management. SIR has given lectures for: American Thoracic Society, AstraZeneca, Boehringer Ingelheim, California Allergy Society, Creative Educational Concept, France Foundation, Information TV, Network for Continuing Ed, Novartis, Pfizer, SOMA. EKS has received an honorarium for talks, grant support, and consulting fees from GSK and AstraZeneca. EFMW serves on an advisory board for Nycomed, has received lecture fees from GSK, AstraZeneca, and Novartis, and has received research grants from GSK and AstraZeneca. JV has received fees for advising or presenting from GSK, Bioxydyn, AstraZeneca, Pfizer, Boehringer Ingelheim, Nycomed, Hoffmann-La Roche, Talecris, Kamada, and Sounds Biotech, and has received research support from GSK. ADi, ADu, and PNF declare that they have no conflicts of interest.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878642324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878642324&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(13)70006-7
DO - 10.1016/S2213-2600(13)70006-7
M3 - Article
C2 - 24429093
AN - SCOPUS:84878642324
SN - 2213-2600
VL - 1
SP - 129
EP - 136
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 2
ER -