Osteoprotegerin in sputum is a potential biomarker in COPD.
BACKGROUND
COPD is characterized by chronic airflow limitation and inflammation of the respiratory tract. Several inflammatory biomarkers have been evaluated in COPD but are poorly related to disease severity and progression. Osteoprotegerin (OPG) is a glycoprotein mediator that is expressed in the lung and macrophages, so we have studied its concentration in induced sputum and macrophages of patients with COPD.


METHODS
OPG was measured by enzyme-linked immunosorbent assay in induced sputum of patients with COPD and control subjects.


RESULTS
OPG concentrations in induced sputum of patients with COPD (18.7 ± 18.6 ng/mL, n = 39) were significantly higher than those of healthy smokers (8.1 ± 5.6 ng/mL, n = 15), healthy nonsmokers (3.5 ± 3.8 ng/mL, n = 14), or patients with asthma (8.0 ± 5.4 ng/mL, n = 18). Sputum OPG levels in COPD negatively correlated with FEV(1) and positively correlated with residual volume to total lung capacity ratio (RV/TLC) (r = 0.55, P < .05), transfer factor of the lung for carbon monoxide (r = -0.53, P < .05), and carbon monoxide transfer coefficient (r = -0.61, P < .01). By contrast, sputum IL-8 concentrations were related to disease severity but not to RV/TLC or gas diffusion. Airway macrophages and neutrophils were positive for OPG by immunocytochemistry in sputum and peripheral lung tissue. OPG induced matrix metalloproteinase-9 release from sputum macrophages in vitro.


CONCLUSIONS
Sputum OPG may be a useful biomarker to monitor parenchymal destruction in COPD.
Airway Disease Section, National Heart and Lung Institute, Imperial College, London, England.
Masako
M
To
Airway Disease Section, National Heart and Lung Institute, Imperial College, London, England.
Kazuhiro
K
Ito
Airway Disease Section, National Heart and Lung Institute, Imperial College, London, England.
Pilar M
PM
Ausin
Airway Disease Section, National Heart and Lung Institute, Imperial College, London, England.
Sergei A
SA
Kharitonov
Airway Disease Section, National Heart and Lung Institute, Imperial College, London, England. Electronic address: p.j.barnes@imperial.ac.uk.
Peter J
PJ
Barnes
D015415:Biomarkers / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000378:metabolism*; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry*
D015415:Biomarkers; D053244:Osteoprotegerin