晚期糖基化终末产物受体(RAGE)、表面活性蛋白D(SP-D)、血管生成素2(ANG2)及高迁移率族蛋白B1(HMGB1)在社区获得性肺炎严重程度及预后评估中的价值

doi:10.19983/j.issn.2096-8493.2024088

摘要/Abstract

摘要：

目的: 探讨晚期糖基化终末产物受体(receptors for advanced glycation end products,RAGE)、表面活性蛋白D(surfactant protein D,SP-D)、血管生成素2(angiopoietin 2,ANG2)及高迁移率族蛋白B1(high mobility group protein B1,HMGB1)在社区获得性肺炎(community-acquired pneumonia,CAP)严重程度及预后评估中的价值。 方法: 连续纳入2022年1月至2023年1月于河南省人民医院呼吸与危重症医学科住院并确诊为CAP的患者,共112例,其中非重症CAP(non-severe community-acquired pneumonia,NSCAP)70例,重症CAP(severe community-acquired pneumonia,SCAP)42例;根据90d生存情况,分为生存组和死亡组,分别为83例和29例。ELISA法检测血浆RAGE、SP-D、ANG2及HMGB1的浓度,采用二元logistic回归分析评估发展为SCAP及90d死亡的危险因素,应用受试者工作特征(ROC)曲线分析上述指标单独及联合CURB-65评分预测SCAP、90d死亡风险的价值。结果:SCAP组RAGE、SP-D、ANG2、HMGB1的浓度中位数(四分位数)分别为2.09(0.90,4.99)ng/ml、3.48(2.22,6.98)ng/ml、3.59(2.50,6.31)ng/ml、47.52(25.99,80.58)ng/ml,均较CAP组[分别为1.21(0.88,2.26)ng/ml、2.45(1.36,3.77)ng/ml、0.90(0.53,1.64)ng/ml、14.09(7.96,25.31)ng/ml]显著升高,差异均有统计学意义(Z=-2.861,P=0.004;Z=-2.951,P=0.003;Z=-7.272,P<0.001;Z=-6.256,P<0.001)。其中,ANG2和HMGB1均是CAP发展为SCAP的独立危险因素(OR=3.889,95%CI:1.775~8.518,P=0.001;OR=1.047,95%CI:1.012~1.082,P=0.008),两者联合预测发展为SCAP取得的AUC值为0.923,敏感度和特异度分别为83.3%和85.7%。死亡组RAGE、SP-D、ANG2、HMGB1浓度中位数(四分位数)分别为2.73(0.82,4.59)ng/ml、3.41(2.49,6.86)ng/ml、4.30(2.98,6.63)ng/ml、64.01(35.32,89.34)ng/ml均明显高于生存组[分别为1.24(0.90,2.37)ng/ml、2.61(1.38,4.32)ng/ml、1.00(0.60,1.98)ng/ml、15.05(9.26,26.44)ng/ml],差异均有统计学意义(Z=-1.989,P=0.047;Z=-2.295,P=0.022;Z=-7.024,P<0.001;Z=-6.446,P<0.001),其中,ANG2、HMGB1、CURB-65评分均是CAP患者90d死亡的独立危险因素(OR=5.458,95%CI:1.374~21.683,P=0.016;OR=1.089,95%CI:1.030~1.151,P=0.003;OR=2.772,95%CI:1.097~7.003,P=0.031),ANG2、HMGB1联合CURB-65评分可以更准确地预测CAP患者90d死亡风险,其AUC值为0.970,敏感度和特异度分别为89.7%和92.8%。结论: SCAP组及90d死亡组RAGE、SP-D、ANG2、HMGB1显著升高,ANG2和HMGB1均是发展为SCAP的独立危险因素,ANG2、HMGB1和CURB-65评分均是CAP患者90d死亡的独立危险因素,三者联合可提高预测90d死亡风险的价值。

关键词: 社区获得性感染, 肺炎, 生物学标记, 晚期糖基化终末产物受体, 表面活性蛋白D, 血管生成素2

Abstract:

Objective: To evaluate the value of receptors for advanced glycation end products (RAGE), surfactant protein D (SP-D), angiopoietin 2 (ANG2) and high mobility group protein B1 (HMGB1) in assessing severity and prognosis of Community-acquired Pneumonia (CAP). Methods: A total of 112 patients hospitalized and diagnosed with CAP in the Department of Respiratory and Critical Care Medicine of Henan Provincial People’s Hospital from January 2022 to January 2023 were enrolled, including 70 patients with non-severe CAP (NSCAP) and 42 patients with severe CAP (SCAP). According to 90-day survival status, they were divided into survival group (83 patients) and death group (29 patients). The plasma concentrations of RAGE, SP-D, ANG2 and HMGB1 were determined by ELISA. Binary logistic regression analysis was used to assess risk factors for developing SCAP and 90-day mortality. Receiver worker characteristic curve (ROC) was used to analyze values of these indicators in predicting risks of SCAP and 90-day mortality alone and in combination with CURB-65 score. Results: The median plasma concentrations of RAGE, SP-D, ANG2, and HMGB1 in the SCAP group were 2.09 (0.90,4.99) ng/ml, 3.48 (2.22,6.98) ng/ml, 3.59 (2.50,6.31) ng/ml, and 47.52 (25.99,80.58) ng/ml, respectively, significantly higher than those in the NSCAP group which were 1.21 (0.88,2.26) ng/ml, 2.45 (1.36,3.77) ng/ml, 0.90 (0.53,1.64) ng/ml, and 14.09 (7.96,25.31) ng/ml, respectively (Z=-2.861,P=0.004;Z=-2.951,P=0.003;Z=-7.272,P<0.001;Z=-6.256,P<0.001). ANG2 and HMGB1 were independent risk factors for SCAP (OR=3.889,95%CI:1.775-8.518,P=0.001;OR=1.047,95%CI:1.012-1.082,P=0.008). ANG2 combined with HMGB1 had the highest AUC prediction value (0.923), while the sensitivity and specificity were 83.3% and 85.7%, respectively. The median plasma concentrations of RAGE, SP-D, ANG2, and HMGB1 in the death group were 2.73 (0.82,4.59) ng/ml, 3.41 (2.49,6.86) ng/ml, 4.30 (2.98,6.63) ng/ml, and 64.01 (35.32,89.34) ng/ml, respectively, significantly higher than those in the survival group (1.24 (0.90,2.37) ng/ml, 2.61 (1.38,4.32) ng/ml, 1.00 (0.60,1.98) ng/ml, and 15.05 (9.26,26.44) ng/ml, respectively). The differences were statistically significant (Z=-1.989,P=0.047;Z=-2.295,P=0.022;Z=-7.024,P<0.001;Z=-6.446,P<0.001). ANG2, HMGB1 and CURB-65 score were independent risk factors for 90-day mortality in patients with CAP (OR=5.458,95%CI:1.374-21.683,P=0.016;OR=1.089,95%CI:1.030-1.151,P=0.003;OR=2.772,95%CI:1.097-7.003,P=0.031). ANG2 and HMGB1 combined with CURB-65 score could more accurately predict the risk of 90-day mortality in CAP patients, for which the AUC value could reach 0.970, and the sensitivity and specificity were 89.7% and 92.8%, respectively. Conclusion: The plasma concentrations of RAGE, SP-D, ANG2, and HMGB1 significantly increased in SCAP and 90-day death group. ANG2 and HMGB1 were independent risk factors for SCAP. ANG2, HMGB1, and CURB-65 score were independent risk factors for 90-day mortality in patients with CAP. Combining these three factors could increase prediction value on assessing 90-day mortality risk.

Key words: Community-acquired infections, Pneumonia, Biological markers, RAGE, SP-D, ANG2

中图分类号:

胡莎莎, 常晓青, 李英, 李丹丹. 晚期糖基化终末产物受体(RAGE)、表面活性蛋白D(SP-D)、血管生成素2(ANG2)及高迁移率族蛋白B1(HMGB1)在社区获得性肺炎严重程度及预后评估中的价值[J]. 结核与肺部疾病杂志, 2024, 5(6): 526-532. doi: 10.19983/j.issn.2096-8493.2024088

Hu Shasha, Chang Xiaoqing, Li Ying, Li Dandan. The value of RAGE, SP-D, ANG2, and HMGB1 in the assessment of severity and prognosis of community-acquired pneumonia[J]. Journal of Tuberculosis and Lung Disease, 2024, 5(6): 526-532. doi: 10.19983/j.issn.2096-8493.2024088

图/表 8

表1

表2

表3

logistic回归分析评估4种生物标志物与CAP严重程度的关系

变量	β值	$s x ˉ$ 值	Wald χ²值	P值	OR值	95%CI值
RAGE	0.143	0.194	0.541	0.462	1.154	0.788~1.689
SP-D	-0.063	0.105	0.366	0.545	0.939	0.765~1.152
ANG2	1.358	0.400	11.523	0.001	3.889	1.775~8.518
HMGB1	0.046	0.017	7.131	0.008	1.047	1.012~1.082
年龄	-1.504	0.869	2.992	0.084	0.222	0.040~1.222
并发冠心病	1.316	0.744	3.131	0.077	3.727	0.868~16.007
并发糖尿病	0.736	0.779	0.892	0.345	2.087	0.453~9.601

表3

图1

表4

表5

表6

logistic回归分析评估4种生物标志物及CURB-65评分与CAP患者90d死亡风险的关系

变量	β值	$s x ˉ$ 值	Wald χ²值	P值	OR值	95%CI值
RAGE	-0.327	0.227	2.072	0.150	0.721	0.462~1.125
SP-D	-0.218	0.113	3.715	0.054	0.804	0.645~1.004
ANG2	1.697	0.704	5.814	0.016	5.458	1.374~21.683
HMGB1	0.085	0.028	8.949	0.003	1.089	1.030~1.151
CURB-65评分	1.020	0.473	4.651	0.031	2.772	1.097~7.003
年龄	-0.444	1.258	0.125	0.724	0.641	0.054~7.550
并发冠心病	0.890	1.040	0.713	0.392	2.434	0.317~18.697
并发糖尿病	1.448	1.132	1.637	0.201	4.225	0.463~39.113

表6

图2

参考文献 19

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临床特征	NSCAP组(70例)	SCAP组(42例)	χ²值	P值
年龄组[例(构成比,%)]			8.020	0.005
≥65岁	29(41.4)	29(69.0)
<65岁	41(58.6)	13(31.0)
性别[例(构成比,%)]			0.747	0.388
男性	48(68.6)	32(76.2)
女性	22(31.4)	10(23.8)
吸烟史[例(发生率,%)]	29(41.4)	22(52.4)	1.270	0.260
饮酒史[例(发生率,%)]	30(42.9)	14(33.3)	0.998	0.318
并发症[例(发生率,%)]
高血压	16(22.9)	15(35.7)	2.168	0.141
冠心病	7(10.0)	14(33.3)	9.381	0.002
糖尿病	10(14.3)	15(35.7)	6.952	0.008
慢性阻塞性肺病	1(1.4)	3(7.1)	1.106	0.293
脑梗死	9(12.9)	7(16.7)	0.311	0.577

临床特征	生存组(83例)	死亡组(29例)	χ²值	P值
年龄组[例(构成比,%)]			15.035	<0.001
≥65岁	34(41.0)	24(82.8)
<65岁	49(59.0)	5(17.2)
性别[例(构成比,%)]			0.019	0.891
男性	59(71.1)	21(72.4)
女性	24(28.9)	8(27.6)
吸烟史[例(发生率,%)]	38(45.8)	13(44.8)	0.008	0.929
饮酒史[例(发生率,%)]	34(41.0)	10(34.5)	0.378	0.538
并发症[例(发生率,%)]
高血压	20(24.1)	11(37.9)	2.055	0.152
冠心病	12(14.5)	9(31.0)	3.876	0.049
糖尿病	14(16.9)	11(37.9)	5.499	0.019
慢性阻塞性肺疾病	2(2.4)	2(6.9)	0.291	0.589
脑梗死	12(14.5)	4(13.8)	<0.001	1.000