Abstract
BackgroundThe 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.MethodsBaseline 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.ResultsThe 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.ConclusionsLower 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.
Highlights
The receptor for advanced glycation end-products (RAGE) is highly expressed in the lung, where it is believed to have a homeostatic role
We examined the association between longitudinal changes of spirometric variables during 4 years and baseline plasma levels of soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1) along with demographic variables at the baseline visit including age, BMI, smoking status, and spirometric measurements
There was no significant difference in mean plasma HMGB1 concentrations among the three groups
Summary
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). We have measured plasma levels of high mobility group box 1 (HMGB1), a RAGE ligand which has been associated with chronic inflammatory diseases including COPD. RAGE is a pattern-recognition receptor that binds multiple ligands, and in most normal tissues it is typically expressed at low levels or is undetectable. In the lung, RAGE is highly expressed even under normal physiological conditions, and it is believed to have a homeostatic function [2]. We have previously reported that the expression of RAGE is significantly decreased in the COPD lung, especially in severe disease [3]. Circulatory HMGB1 levels are elevated in patients with COPD, especially in those with more severe airflow limitation or in cases complicated by comorbid lung cancer [13,14,15]
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