血清晚期糖基化终产物及其可溶性受体对特发性肺纤维化与肺纤维化实质性疾病的鉴别诊断价值

doi:10.3969/j.issn.1003-9198.2022.06.006

摘要/Abstract

摘要： 目的探究老年特发性肺纤维化(IPF)病人血清晚期糖基化终产物(AGEs)、可溶性晚期糖基化终产物受体(sRAGE)的表达及其与肺功能指标的相关性,分析两指标对IPF、慢性过敏性肺炎(cHP)、纤维化非特异性间质性肺炎(fNSIP)的鉴别诊断价值。方法纳入我院2016年2月至2021年8月就诊的79例老年IPF病人(IPF组)、30例老年cHP病人(cHP组)和30例老年fNSIP病人(fNSIP组),另外纳入同期30例老年健康志愿者作为对照组。比较4组血清AGEs、sRAGE、AGEs/sRAGE以及肺功能指标[用力肺活量占预计值百分比(FVC%)、一氧化碳弥散量占预计值百分比(DLCO%)、肺总容量(TLC)]水平。采用ROC曲线和似然比检验分析血清AGEs、sRAGE、AGEs/sRAGE鉴别诊断3种疾病的价值。采用Pearson相关系数描述老年IPF病人血清AGEs、sRAGE水平与肺功能指标的关系。结果 cHF组、fNSIP组、IPF组病人的FVC%、DLCO%、TLC水平均显著低于对照组(P<0.05)。IPF组和cHP组的血清sRAGE水平低于对照组和fNSIP组(P＜0.05),AGEs、AGEs/sRAGE水平高于对照组和fNSIP组(P<0.05);但对照组与fNSIP组血清AGEs、sRAGE水平差异均无统计学意义(P>0.05)。ROC曲线分析结果显示,AGEs、sRAGE、AGEs/sRAGE对IPF与fNSIP有良好的鉴别诊断价值(AUC均>0.7),且AGEs/sRAGE对IPF与fNSIP的鉴别准确率、似然比均高于血清AGEs和sRAGE。Pearson相关分析结果显示,老年IPF病人血清AGEs与sRAGE呈负相关(r=-0.541,P<0.001),血清sRAGE与FVC%、DLCO%、TLC均呈正相关(r=0.445、0.452、0.312,P均<0.001),但血清AGEs与FVC%、DLCO%、TLC无关(P均>0.05)。结论 AGEs/sRAGE比值有助于对IPF与fNISP进行鉴别诊断,而且血清sRAGE水平可以在一定程度上反映老年IPF病人的肺功能损伤程度。

关键词: 特发性肺纤维化, 慢性过敏性肺炎, 纤维化非特异性间质性肺炎, 可溶性晚期糖基化终产物受体, 晚期糖基化终产物, 鉴别诊断

Abstract: Objective To investigate the expression of serum advanced glycation end products (AGEs) and soluble receptor for AGEs (sRAGEs) in the elderly patients with idiopathic pulmonary fibrosis (IPF) and the correlations with pulmonary function indexes, and to analyze the value of serum AGEs, sRAGEs in the differential diagnosis of IPF, chronic hypersensitivity pneumonitis (cHP) and fibrotic nonspecific interstitial pneumonia (fNSIP). Methods Seventy-nine elderly IPF patients (IPF group), 30 elderly cHP patients (cHP group) and 30 elderly fNSIP patients (fNSIP group) were enrolled in this study from February 2016 to August 2021, while 30 healthy elderly volunteers were enrolled as control group. The levels of serum AGEs, sRAGE, AGEs/sRAGE, pulmonary function indexes such as forced vital capacity predicted (FVC%), percentage of predicted diffusing capacity of lung for carbon monoxide (DLCO%) and total lung capacity (TLC) were detected and compared among the four groups. The diagnostic value of serum AGEs, sRAGE and AGEs/sRAGE were analyzed by receiver operating characteristic (ROC) curve and likelihood ratio test. Pearson correlation coefficient was used to describe the relationship between serum AGEs, sRAGE and pulmonary function in the elderly patients with IPF. Results The levels of FVC%, DLCO% and TLC in cHF group, fNSIP group and IPF group were significantly lower than those in control group (P＜0.05). The level of serum sRAGE in IPF group and CHP group was significantly lower than that in control group and fNSIP group (P＜0.05), and the level of AGEs and the ratio of AGEs/sRAGE were significantly higher than those in control group and fNSIP group (P＜0.05). However, there were no significant differences in serum levels of AGEs and sRAGE between control group and fNSIP group (P＞0.05). ROC curve analysis showed that AGEs, sRAGE, AGEs/sRAGE had good diagnostic value in the differential diagnosis between IPF and fNSIP (all AUC＞0.7). The accuracy and likelihood ratio of AGEs/sRAGE in the differential diagnosis of IPF and fNSIP were higher than those of serum AGEs and sRAGE. Pearson correlation analysis showed that serum AGEs was negatively correlated with sRAGE (r=-0.541, P<0.001), and serum sRAGE was positively correlated with FVC%, DLCO%, TLC (r=0.445,0.452,0.312, all P<0.001), however, AGEs was not correlated to FVC%, DLCO% or TLC (P＞0.05). Conclusions AGEs/sRAGE is helpful for the differential diagnosis of IPF and fNISP, and serum level of sRAGE can reflect the degree of lung function injury in the elderly patients with IPF to a certain extent.

Key words: idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, fibrotic nonspecific interstitial pneumonia, soluble receptor for advanced glycation end products, advanced glycation end products, differential diagnosis

中图分类号:

R 563.1

张旋, 钱媛媛, 陈晓辰, 郭春燕. 血清晚期糖基化终产物及其可溶性受体对特发性肺纤维化与肺纤维化实质性疾病的鉴别诊断价值[J]. 实用老年医学, 2022, 36(6): 570-574.

ZHANG Xuan, QIAN Yuan-yuan, CHEN Xiao-chen, GUO Chun-yan. Value of serum advanced glycation end products (AGEs) and soluble receptor for AGEs in differential diagnosis of idiopathic pulmonary fibrosis and fibrotic parenchymal lung disease[J]. Practical Geriatrics, 2022, 36(6): 570-574.

参考文献

[1] SALTON F,VOLPE M C,CONFALONIERI M. Epithelial-mesenchymal transition in the pathogenesis of idiopathic pulmonary fibrosis[J]. Medicina: Kaunas, 2019, 55(4):83.
[2] 赵玉月,连宏建,李姗, 等.B细胞活化因子对自身免疫性疾病引起的寻常型间质性肺炎与特发性肺纤维化的鉴别诊断[J]. 中华结核和呼吸杂志,2018,41(7):544-550.
[3] SERVEAUX-DANCER M,JAHAUDON M,CREVEAUX I,et al. Pathological implications of receptor for advanced glycation end-product (AGER) gene polymorphism[J]. Dis Markers, 2019. DOI: 10.1155/2019/2067353.
[4] PERRONE A,GIOVINO A,BENNY J,et al.Advanced glycation end products (AGEs): biochemistry, signaling, analytical methods, and epigenetic effects[J]. Oxid Med Cell Longev, 2020. DOI:10.1155/2020/3818196.
[5] SCAVELLO F,ZENI F,TEDESCO C C, et al.Modulation of soluble receptor for advanced glycation end-products (RAGE) isoforms and their ligands in healthy aging[J]. Aging: Albany NY, 2019, 11(6):1648-1663.
[6] RAGHU G,COLLARD H R,EGAN J J,et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management[J]. Am J Respir Crit Care Med, 2011,183(6):788-824.
[7] TRAVIS W D, COSTABEL U, HANSELL D M, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias[J]. Am J Respir Crit Care Med, 2013, 188(6):733-748.
[8] 祝望才.不同类型间质性肺炎患者临床特点及CT征象特点分析[J]. 中国CT和MRI杂志,2019,17(10):44-46, 95.
[9] 苏奕亮,翁东,周瑛, 等.血清LN、Ⅳ C、P Ⅲ NP、HA与特发性肺纤维化严重度和预后的相关性[J]. 中华急诊医学杂志,2018,27(2):188-193.
[10] 尹成胜,张苑,李惠萍, 等.特发性肺纤维化急性加重的研究进展[J]. 中华医学杂志,2019,99(8):637-640.
[11] 王瑞, 王建华, 柴海强.特发性肺间质纤维化MSCT影像学征象及与肺功能指标的相关性研究[J]. 中国CT和MRI杂志, 2020, 18(3):62-65.
[12] MACHAHUA C,MONTES-WORBOYS A,PLANAS-CEREZALES L, et al. Serum AGE/RAGEs as potential biomarker in idiopathic pulmonary fibrosis[J]. Respir Res, 2018, 19(1):215.
[13] YAMAGUCHI K,IWAMOTO H,MAZUR W,et al.Reduced endogenous secretory RAGE in blood and bronchoalveolar lavage fluid is associated with poor prognosis in idiopathic pulmonary fibrosis[J]. Respir Res, 2020, 21(1):145.
[14] MACHAHUA C, MONTES-WORBOYS A,LLATJOS R,et al.Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis[J]. Respir Res, 2016, 17(1):144.
[15] ASADIPOOYA K,UY E M.Advanced glycation end products (AGEs), receptor for AGEs, diabetes, and bone: review of the literature[J]. J Endocr Soc, 2019, 3(10):1799-1818.
[16] DAI J Z,CHEN H,CHAI Y M. Advanced glycation end products (AGEs) induce apoptosis of fibroblasts by activation of NLRP3 inflammasome via reactive oxygen species (ROS) signaling pathway[J]. Med Sci Monit, 2019, 25:7499-7508.
[17] ENGLERT J M,HANFORD L E,KAMINSKI N,et al. A role for the receptor for advanced glycation end products in idiopathic pulmonary fibrosis[J]. Am J Pathol, 2008, 172(3):583-591.