Open Access Open Badges Research article

Soluble receptor for advanced glycation end-products and progression of airway disease

Hiroshi Iwamoto12*, Jing Gao1, Ville Pulkkinen1, Tuula Toljamo3, Pentti Nieminen4 and Witold Mazur1

Author Affiliations

1 Heart and Lung Center, Division of Pulmonary medicine, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland

2 Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 734-8551 Hiroshima, Japan

3 Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland

4 Medical Informatics and Statistics Group, University of Oulu, Oulu, Finland

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BMC Pulmonary Medicine 2014, 14:68  doi:10.1186/1471-2466-14-68

Published: 24 April 2014



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.


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.


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.


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.