Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan.
Pulm Pharmacol Ther. 2012 Dec;25(6):478-82. doi: 10.1016/j.pupt.2012.09.001. Epub 2012 Sep 13.
Recently, increased levels of pentosidine, an intermolecular cross-linking type of advanced glycation end products, are observed in the airways of asthmatic patients. This study was designed to determine whether differences in bronchodilator response among individuals with asthma are attributable to pentosidine levels in their airways.
Fifty-six asthmatic patients (21 with airway obstruction, 35 without airway obstruction) and 10 normal controls were included in this study. For asthmatic patients, we evaluated the spontaneous reversibility of airway obstruction or the reversibility that can be obtained after methacholine provocation. And we also measured pentosidine levels and percentage of sputum eosinophils in induced sputum, and exhaled nitric oxide (NO) levels.
The pentosidine levels did not significantly differ between the two asthmatic subgroups with and without airway obstruction. In asthmatic patients without airway obstruction, airway hyperresponsiveness to methacholine (PC20 methacholine) was significantly correlated with sputum eosinophils and exhaled NO levels. In contrast, PC20 methacholine was not significantly correlated with pentosidine levels. In asthmatic patients with or without airway obstruction, bronchodilator response was not significantly correlated with sputum eosinophils and exhaled NO levels. However, bronchodilator response was closely correlated with pentosidine levels (asthmatics without airway obstruction: r = -0.54, p = 0.002; asthmatics with airway obstruction: r = -0.48, p = 0.03).
Our results showed that pentosidine might be a potential biomarker reflecting the reduced bronchodilator response in asthma. This study will provide new insights into the mechanisms underlying persistent airway obstruction.
最近,哮喘患者的气道中观察到戊糖素(一种交联型晚期糖基化终产物)水平升高。本研究旨在确定个体气道中戊糖素水平的差异是否导致了哮喘患者支气管扩张反应的差异。
本研究纳入 56 例哮喘患者(21 例气道阻塞,35 例无气道阻塞)和 10 例正常对照者。对于哮喘患者,我们评估了气道阻塞的自发性逆转或乙酰甲胆碱激发后可获得的逆转。我们还测量了诱导痰中的戊糖素水平和痰嗜酸性粒细胞百分比,以及呼气一氧化氮(NO)水平。
两组气道阻塞和无气道阻塞的哮喘患者之间,戊糖素水平无显著差异。在无气道阻塞的哮喘患者中,气道对乙酰甲胆碱的高反应性(PC20 乙酰甲胆碱)与痰嗜酸性粒细胞和呼气 NO 水平显著相关。相比之下,PC20 乙酰甲胆碱与戊糖素水平无显著相关性。在有或无气道阻塞的哮喘患者中,支气管扩张反应与痰嗜酸性粒细胞和呼气 NO 水平无显著相关性。然而,支气管扩张反应与戊糖素水平密切相关(无气道阻塞的哮喘患者:r=-0.54,p=0.002;有气道阻塞的哮喘患者:r=-0.48,p=0.03)。
我们的结果表明,戊糖素可能是反映哮喘患者支气管扩张反应降低的潜在生物标志物。本研究将为持续气道阻塞的机制提供新的见解。