正五聚体蛋白3对脓毒症患儿病情及心血管功能损害的诊断价值

Clinical study of Pentraxin 3 in diagnosing the severity and cardiovascular function of the children with sepsis

目的探讨正五聚体蛋白3（PTX3）对脓毒症患儿病情及心血管功能损害的诊断价值。方法2013年10月至2014年4月在湖南省儿童医院儿科重症监护病房（PICU）住院的〉28d、存在呼吸系统或神经系统感染的急性起病且排除慢性或特殊疾病的178例患儿，其中男102例、女76例，年龄1个月-13岁1个月。原发病为呼吸系统疾病101例，神经系统疾病77例。用酶联免疫吸附试验法分别于入院1d内、3d,7d检测所有患儿血浆PTX3浓度，同时收集相同时间点测得的肌钙蛋白、心肌酶、N-末端脑钠肽（BNP）、乳酸、C反应蛋白（CRP）、降钙素原、白细胞计数等，根据入院1d内血浆PTX3值分为3组：轻度升高组（〈44μg／L）41例；中度升高组（44～〈132μg/L）66例；重度升高组（≥132μg/L）71例；根据感染程度分为：非脓毒症组（78例）、脓毒症组（70例）、严重脓毒症组（30例），每组根据心力衰竭诊断标准分别存在19、28、17例心力衰竭病例。分析患儿不同临床表现、病情变化、器官功能损害和预后中血浆PTX3浓度的表达变化。连续变量比较使用t检验、F检验、H检验，分类变量应用χ2检验，相关性采用Pearson相关分析。结果非脓毒症组、脓毒症组、严重脓毒症组1d内PTX3值差异有统计学意义[50．4（35．2，70．4），175．8（99．6，309．9），419．9（168．3，468．6）μg/L，H=88．345、P=0．000]。随时间变化PTX3水平逐渐下降，而其中严重脓毒症组下降速度较慢（P〈0．05）；与其他炎性指标比较，PTX3较CRP、PCT、白细胞、中性粒细胞在诊断脓毒症方面ROC曲线下面积大，前三位依次为PTX3、降钙素原、CRP，其敏感度和特异度分别为0．77，0．68；0．66，0．60；0．47，0．55。PTX3轻、中、重度升高组中存在3个及3个以上器官功能衰竭患儿所占的比例差异有统计学意义[1（2．4％）、4（6．1％）、14（19．7％），χ2=16．16，P=0．000]；预后好和差的比例差异均有统计学意义[33（80．5％）和8（19．5％）、35（53．0％）和31（47．0％）、28（39．4％）和43（60．6％），χ2=17．663，P=0．000]，其中，重度升高组预后差的比例明显高于轻、中度升高组（P均〈0．05）；PTX3轻、中、重度升高组的生存时间曲线示差异有统计学意义（χ2=7．086，P=0．029）。不同感染程度的178例患儿中各组患儿出现心力衰竭时PTX3值均明显高于非心力衰竭患儿（U=-3．446、-4．586、-2．408，P=0．001、0．000、0．016）；PTX3随着心肌酶学（肌钙蛋白、肌酸激酶同工酶、BNP）升高而升高，在诊断心力衰竭方面PTX3、BNP、肌酸激酶同工酶、肌钙蛋白ROC曲线下面积分别为0．824、0．772、0．643、0．671，敏感度和特异度分别为0．80和0．58、0．56和0．79、0．60和0．69、0．73和0．58；在预测脓毒症心力衰竭患儿预后方面，PTX3的ROC曲线下面积比BNP大（0．844比0．472）。结论PTX3是一个可以诊断脓毒症的客观生化指标，可以反映脓毒症的严重程度及其预后；在脓毒症心血管功能损害方面具有一定的诊断价值。

Objective To study the value of Pentraxin 3 （FTX3） in diagnosing the severity and cardiovascular function of the critically ill children. Method A total of 178 patients who were older than 28days, with acute infection of respiratory or neurological system, excluding chronic or special disease, and admitted to the pediatric intensive care unit （PICU） of Hunan Children＇s Hospital from October 1, 2013 to April 30, 2014 were enrolled, including 102 male cases and 76 female cases. The ages ranged from 1 month to 13 years and 1 month, 78 of them were less than 1 year old ; 58 cases were between 1 to 3 years old; 42 cases were above 3 years old; 101 cases were diagnosed as respiratory system diseases, 77 cases had nervous system diseases. PTX5 was detected with enzyme-linked immunosorbent assay （ELISA） within 1 d after enrollment, at 5 days and 7 days, meanwhile, troponin, myocardial enzyme, brain-type natriuretic peptide （BNP）, C-reactive protein （ CRP）, plasma calcitonin （PCT） and WBC etc. Were measured. According to the plasma PTX3 value which were measured within 24 h after enrollment the patients were divided into three groups： mildly elevated group （ 〈 44 μg/L） 41 cases; moderately elevated group （44 - 〈 132 μg/L） in 66 cases; severely elevated group 71 cases （132μg/L or higher）. Those 178 patients were divided into 3 groups according to the degree of infection： non-sepsis group （78 cases）, sepsis group （70 cases）, severe sepsis group （30 cases）, and in each group, those with heart failure were respectively 19 cases, 28 cases, 17 cases. Analysis of the plasma PTX3 expression changes in different clinical manifestations, different condition, different degrees of organ damages and prognosis for the patient. The continuous variables were analyzed with t-test, F-test, H-test, the categorical variables were analyzed with Chi-square test, and the correlation analysis was performed to calculate Pearson coefficients. Result The PTX3 value measured within 24 h after enrollment increased with the degree of infection （50.4（35.2,70. 4） μg/L;175.8 （99. 6, 309. 9） μg/L;419. 9 （ 168.3, 468. 6） μg/L; H = 88. 345, P = 0. 000）. PTX3 level gradually declined, while in severe sepsis group decreased slowly （ P 〈 0. 05 ） ; the area under the ROC curve of Plasma PTX3 was larger than that of other inflammatory markers such as CRP and PCT, white blood cells and neutrophils in the diagnosis of sepsis ; while the former three are PTX3, PCT and CRP （the sensitivity and specificity respectively were 0. 77, 0. 68 ; 0. 66, 0. 6 ; 0.47, 0. 55） ; the PTX3 value of the severely elevated group was significantly higher than those of the mildly and moderately elevated groups （ P 〈 0. 05 ）. The proportion of having 3 or more organs failure increased as the PTX3 rising among the groups of mildly elevated group, moderately elevated group and severely elevated group （ 1 （ 2.4 % ） ,4 （ 6. 1% ）, 14 （ 19. 7 % ） χ2 = 16. 16, P = 0. 000） ; and in each group, the proportion of having good and poor prognosis for these three groups were different （ 33 （ 80. 5% ） and 8 （ 19. 5% ）, 35 （ 53% ） and 31 （47%）, 28 （ 39.4% ） and 43 （ 60. 6% ）, χ2 = 17. 663 ,P =0. 000）. The K-M curve for these three groups had statistically significant difference （χ2 = 7. 086 ,P = 0. 029）. Those with heart failure had higher PTX3 value than those in non-heart failure at the same degree of infection. PTX3 value increased with myocardial enzyme （troponin, creatine kinase isoenzyme, BNP） levels. In the diagnosis of heart failure, the area under the ROC curve were respectively PTX3 0. 824; BNP 0.772; CM-KB 0. 643; CNTI0. 671, the sensitivity and specificity were PTX3 0. 8, 0. 58 ; CK-MB 0. 56,0. 79 ; CTNI 0. 60,0. 69 ; BNP 0. 73,0. 58. In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value＇ s area under ROC curve was larger than that of BNP （ respectively 0. 844, 0. 472）. Conclusion The PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage.