Iwamoto Hiroshi, Gao Jing, Pulkkinen Ville, Toljamo Tuula, Nieminen Pentti, Mazur Witold
Heart and Lung Center, Division of Pulmonary medicine, University of Helsinki and Helsinki University Central Hospital, 00014 Helsinki, Finland.
BMC Pulm Med. 2014 Apr 24;14:68. doi: 10.1186/1471-2466-14-68.
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.
晚期糖基化终产物受体（RAGE）在肺中高表达，据信其在肺中具有稳态作用。据报道，慢性阻塞性肺疾病（COPD）患者的可溶性RAGE（sRAGE）血浆水平降低。本研究的目的是评估血浆sRAGE水平与肺功能纵向下降之间的关联。我们还测量了高迁移率族蛋白B1（HMGB1）的血浆水平，HMGB1是一种RAGE配体，与包括COPD在内的慢性炎症性疾病有关。
测量了非吸烟者（n = 32）、无COPD的吸烟者（n = 212）和患有COPD的吸烟者（n = 51）的sRAGE和HMGB1的基线血浆浓度，并分析了血浆sRAGE和HMGB1水平与4年随访期内肺功能纵向下降之间的关联。
与非吸烟者相比，无COPD的吸烟者和患有COPD的吸烟者的血浆sRAGE水平显著降低。血浆sRAGE水平与用力肺活量（FVC）和第一秒用力呼气容积（FEV1）呈正相关，与体重指数（BMI）和吸烟包年数呈负相关。在所有参与者中，较低的sRAGE水平与4年内FEV1/FVC的更大下降相关。此外，多变量回归分析表明，基线血浆sRAGE浓度是所有组中FEV1/FVC下降的独立预测因子。亚组分析显示，sRAGE水平降低与COPD吸烟者中FEV1/FVC的更快下降显著相关。血浆HMGB1水平与肺功能的纵向下降之间无显著相关性。
较低的血浆sRAGE浓度与气流受限随时间的更大进展相关，尤其是在COPD吸烟者中，这表明RAGE可能在肺中具有保护作用。
