Soluble receptor for advanced glycation end-products and progression of airway disease.
BACKGROUND
The receptor for advanced glycation end-products (RAGE) is highly expressed in the lung, where it is believed to have a homeostatic role. Reduced plasma levels of soluble RAGE (sRAGE) have been reported in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the association of plasma sRAGE levels with a longitudinal decline of lung function. We have also measured plasma levels of high mobility group box 1 (HMGB1), a RAGE ligand which has been associated with chronic inflammatory diseases including COPD.


METHODS
Baseline plasma concentrations of sRAGE and HMGB1 were measured in non-smokers (n = 32), smokers without COPD (n = 212), and smokers with COPD (n = 51), and the associations of the plasma sRAGE and HMGB1 levels with longitudinal declines of lung function during a 4-year follow-up period were analysed.


RESULTS
The plasma levels of sRAGE were significantly lower in smokers without COPD and in smokers with COPD, as compared to those of non-smokers. Plasma sRAGE levels positively correlated with FVC and FEV1 and inversely correlated with BMI and pack-years. Lower sRAGE levels were associated with greater declines of FEV1/FVC over 4 years in all participants. Moreover, multivariate regression analysis indicated that the baseline plasma sRAGE concentration was an independent predictor of FEV1/FVC decline in all groups. A subgroup analysis showed that decreased sRAGE levels are significantly associated with a more rapid decline of FEV1/FVC in smokers with COPD. There was no significant correlation between plasma HMGB1 levels and longitudinal decline of lung function.


CONCLUSIONS
Lower plasma concentrations of sRAGE were associated with greater progression of airflow limitations over time, especially in smokers with COPD, suggesting that RAGE might have a protective role in the lung.
Heart and Lung Center, Division of Pulmonary medicine, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland. iwamotohiroshig@gmail.com.
Hiroshi
H
Iwamoto
Jing
J
Gao
Ville
V
Pulkkinen
Tuula
T
Toljamo
Pentti
P
Nieminen
Witold
W
Mazur
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005387:Finland; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012044:Regression Analysis; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D012907:Smoking / Q000097:blood*; D014797:Vital Capacity
D015415:Biomarkers; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic