重度肺炎患儿血清Clara细胞分泌蛋白16和肺表面活性蛋白D水平及临床意义
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摘要
目的探讨肺炎患儿血清Clara细胞分泌蛋白16(CC16)、肺表面活性蛋白D(SP-D)的变化及其临床意义。方法选取社区获得性肺炎患儿81例,其中重度肺炎机械通气组(21例)、重度肺炎非机械通气组(30例)与轻度肺炎组(30例),对照组为同期体检健康儿童(20例);采用ELISA法检测四组儿童血清CC16、TNF-α、IL-6、SP-D浓度,运用ROC曲线评价CC16、TNF-α、IL-6、SP-D对于重度肺炎的诊断价值;记录机械通气患儿肺动态顺应性(Cdyn)、气道阻力(Raw)、气道峰压(PIP)、呼吸做功(WOB)等呼吸力学参数,分析CC16与TNF-α、IL-6、SP-D及呼吸力学参数间的相关性。结果肺炎组患儿血清CC16浓度均明显低于对照组,重度肺炎组低于轻度肺炎组,机械通气组低于非机械通气组;肺炎组患儿血清TNF-α、IL-6、SP-D浓度均明显高于对照组,重度肺炎组高于轻度肺炎组,机械通气组高于非机械通气组,差异均有统计学意义(P<0.05)。与撤机前相比,重度肺炎组机械通气1小时血清CC16浓度明显降低,机械通气72小时更低;而机械通气1小时血清TNF-α、IL-6、SP-D明显升高,机械通气72小时更高,差异均有统计学意义(P<0.05);与撤机前相比,重度肺炎组机械通气72小时,Cdyn值明显下降,机械通气1小时更低;而机械通气72小时Raw、PIP、WOB值明显升高,机械通气1小时更高,差异均有统计学意义(P<0.05)。血清CC16浓度与TNF-α、IL-6、SP-D均呈负相关,与Cdyn呈正相关(P均<0.01)。ROC曲线中,CC16、TNF-α、IL-6、SP-D诊断重度肺炎的曲线下面积分别为0.905、0.704、0.832、0.825(P均<0.01)。结论社区获得性肺炎患儿血清CC 16、SP-D浓度与疾病严重程度相关;机械通气患儿CC 16浓度水平与Cdyn呈正相关关系;CC16对于重度肺炎病情变化具有较好的预测及评价作用。
Objective To explore the changes of serum Clara cell secretory protein 16(CC 16), pulmonary surfactant protein D(SP-D) in children with pneumonia and its clinical significance. Methods A total of 81 pediatric patients with community-acquired pneumonia were selected, including severe pneumonia with mechanical ventilation group(n= 21), severe pneumonia with non-mechanical ventilation group(n= 30), mild pneumonia group(n= 30), and the control group(n= 20) was selected in the physical examination of healthy children over the same period. We detected the concentration of serum CC 16, TNF-α, IL-6 and SP-D for the 4 groups by ELISA, and evaluated the clinical values of serum CC16, TNF-α, IL-6 and SP-D for severe pneumonia by using ROC curve. We recorded pulmonary dynamic compliance(Cdyn), airway resistance(Raw), peak inspiratory pressure(PIP), work of breathing(WOB) and other respiratory mechanical parameters, and analyzed the correlations between CC16 and TNF-α, IL-6, SP-D and respiratory mechanical parameters. Results The concentrations of serum CC16 in pneumonia group were all significantly lower than that in the control group, and those in severe pneumonia groups were lower than that in mild pneumonia group, and mechanical ventilation group was lower than that in non-mechanical ventilation; the concentration of serum TNF-α, IL-6 and SP-D in pneumonia groups were all obviously higher than that in the control group, and severe pneumonia group were higher than that in mild pneumonia group, and those in mechanical ventilation group were also higher than that in non-mechanical ventilation group(P<0.05). Compared to that before removing the ventilator, concentration of serum CC16 in severe pneumonia with mechanical ventilation group decreased significantly at 1 hour and lowered down at 72 hours; but the concentration of serum TNF-α, IL-6 and SP-D in severe pneumonia with mechanical ventilation increased significantly at 1 hour and went higher at 72 hours, the differences were all statistically significant(all of P<0.05); compared to that before weaning from the ventilator, the value of Cdyn decreased obviously in severe pneumonia with mechanical ventilation at 72 hours and lowered down at 1 hour; but the values of Raw, PIP, WOB in severe pneumonia with mechanical ventilation increased obviously at 72 hours and more higher at 1 hour, the differences were all statistically significant(all of P<0.05). The concentration of serum CC16 showed all negative correlations with TNF-α, IL-6 and SP-D, but it showed positive correlation with Cdyn( all of P<0.01). In the ROC curve, the area under the ROC curve of CC16, TNF-α, IL-6 and SP-D in serum was 0.905, 0. 704, 0. 832, 0. 825, respectively(for all of which P< 0. 01). Conclusion The concentrations of serum CC 16 and SP-D were associated with the severity of community acquired-pneumonia in children. The level of serum CC 16 was positive associated with Cdyn in children with mechanical ventilation. CC16 has better prediction and evaluation effect on the change of severe pneumonia.
Objective To explore the changes of serum Clara cell secretory protein 16(CC 16), pulmonary surfactant protein D(SP-D) in children with pneumonia and its clinical significance. Methods A total of 81 pediatric patients with community-acquired pneumonia were selected, including severe pneumonia with mechanical ventilation group(n= 21), severe pneumonia with non-mechanical ventilation group(n= 30), mild pneumonia group(n= 30), and the control group(n= 20) was selected in the physical examination of healthy children over the same period. We detected the concentration of serum CC 16, TNF-α, IL-6 and SP-D for the 4 groups by ELISA, and evaluated the clinical values of serum CC16, TNF-α, IL-6 and SP-D for severe pneumonia by using ROC curve. We recorded pulmonary dynamic compliance(Cdyn), airway resistance(Raw), peak inspiratory pressure(PIP), work of breathing(WOB) and other respiratory mechanical parameters, and analyzed the correlations between CC16 and TNF-α, IL-6, SP-D and respiratory mechanical parameters. Results The concentrations of serum CC16 in pneumonia group were all significantly lower than that in the control group, and those in severe pneumonia groups were lower than that in mild pneumonia group, and mechanical ventilation group was lower than that in non-mechanical ventilation; the concentration of serum TNF-α, IL-6 and SP-D in pneumonia groups were all obviously higher than that in the control group, and severe pneumonia group were higher than that in mild pneumonia group, and those in mechanical ventilation group were also higher than that in non-mechanical ventilation group(P<0.05). Compared to that before removing the ventilator, concentration of serum CC16 in severe pneumonia with mechanical ventilation group decreased significantly at 1 hour and lowered down at 72 hours; but the concentration of serum TNF-α, IL-6 and SP-D in severe pneumonia with mechanical ventilation increased significantly at 1 hour and went higher at 72 hours, the differences were all statistically significant(all of P<0.05); compared to that before weaning from the ventilator, the value of Cdyn decreased obviously in severe pneumonia with mechanical ventilation at 72 hours and lowered down at 1 hour; but the values of Raw, PIP, WOB in severe pneumonia with mechanical ventilation increased obviously at 72 hours and more higher at 1 hour, the differences were all statistically significant(all of P<0.05). The concentration of serum CC16 showed all negative correlations with TNF-α, IL-6 and SP-D, but it showed positive correlation with Cdyn( all of P<0.01). In the ROC curve, the area under the ROC curve of CC16, TNF-α, IL-6 and SP-D in serum was 0.905, 0. 704, 0. 832, 0. 825, respectively(for all of which P< 0. 01). Conclusion The concentrations of serum CC 16 and SP-D were associated with the severity of community acquired-pneumonia in children. The level of serum CC 16 was positive associated with Cdyn in children with mechanical ventilation. CC16 has better prediction and evaluation effect on the change of severe pneumonia.
引文
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[8]杜春艳,卢强,李玉品,等.大叶性肺炎患儿血清肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8、白细胞介素-10和高迁移率族蛋白B1表达意义[J].中华实用儿科临床杂志,2014,29(16):1224-1226.
[9]王鹂鹂,郑首燕,任洛,等.肺炎患儿支气管肺泡灌洗液中肺表面活性蛋白A和D表达及其与肺炎临床特征的相关性[J].中国当代儿科杂志,2016,18(5):386-390.
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[11]Delgado C,Krotzsch E,Jimenez-Alvarez LA,et al.Serum surfactant protein D(SP-D)is a prognostic marker of poor outcome in patients with A/H1N1 virus infection[J].Lung,2015,193(1):25-30.
[12]Schleh C,Rothen-Rutishauser BM,Blank F,et al.Surfactant Protein D modulates allergen particle uptake and infl amatory response in a human epithelial airway model[J].Respir Res,2012,13:8.
[13]Han S,Mallampalli RK.The role of surfactant in lung disease and host defense against pulmonary infections[J].Ann Am Thorac Soc,2015,12(5):765-774.
[14]Mcauley DF,Matthay MA.Clara cell protein CC16.A new lung epithelial biomarker for acute lung injury[J].Chest,2009,135(6):1408-1410.
[15]Martin AC,Laing IA,Khoo S K,et al.Acute asthma in children:relationships among CD14 and CC16 genotypes,plasma levels,and severity[J].Am J Respir Crit Care Med,2006,173(6):617-622.
[16]Pang M,Yuan Y,Wang D,et al.Recombinant CC16 protein inhibits the production of pro-inflammatory cytokines via NF-kappa B and p38 MAPK pathways in LPS-activated RAW264.7 macrophages[J].Acta Biochim Biophys Sin(Shanghai),2017,49(5):435-443.
[17]Wang XY,Keefe KM,Jensen-Taubman SM,et al.Novel method for isolation of murine clara cell secretory proteinexpressing cells with traces of stemness[J].Plo S One,2012,7(8):e43008.
[18]Guzman-Barcenas J,Calderon-Moore A,Baptista-Gonzalez H,et al.Clara cell protein expression in mechanically ventilated term and preterm infants with respiratory distress syndrome and at risk of bronchopulmonary dysplasia:A pilot study[J].Can Respir J,2017,2017:8074678.
[19]Laucho-Contreras ME,Polverino F,Tesfaigzi Y,et al.Club cell protein 16(CC16)augmentation:a potential diseasemodifying approach for chronic obstructive pulmonary disease(COPD)[J].Expert Opin Ther Targets,2016,20(7):869-883.
[20]Magill SS,Klompas M,Balk R,et al.Developing a new,national approach to surveillance for ventilator-associated events:executive summary[J].Clin Infect Dis,2013,57(12):1742-1746.
[21]Engstrom G,Lindberg C,Gerhardsson de Verdier M,et a1.Blood biomarkers and measures of pulmonary function-a study from the Swedish twin registry[J].Respir Med,2012,106(9):1250-1257.
[2]Wang H,Tang J,Xiong Y,et al.Neonatal communityacquired pneumonia:pathogens and treatment[J].J Paediatr Child Health,2010,46(11):668-672.
[3]郁志伟,钱俊,顾晓虹,等.婴幼儿喘息性社区获得性肺炎患儿血清炎症因子的变化[J].中国当代儿科杂志,2015,17(8):815-818.
[4]中华医学会儿科学分会呼吸学组,中华儿科杂志编辑委员会.儿童社区获得性肺炎管理指南(2013修订)(上)[J].中华儿科杂志,2013,51(10):745-752.
[5]Li T,Luo N,Du L,et al.Tumor necrosis factor-alpha plays an initiating role in extracorporeal circulation-induced acute lung injury[J].Lung,2013,191(2):207-214.
[6]Mihara M,Hashizume M,Yoshida H,et al.IL-6/IL-6receptor system and its role in physiological and pathological conditions[J].Clin Sci(Lond),2012,122(4):143-159.
[7]Zhang Y,Zhou Y,Li S,et al.The clinical characteristics and predictors of refractory Mycoplasma pneumoniae pneumonia in children[J].PLo S One,2016,11(5):e0156465.
[8]杜春艳,卢强,李玉品,等.大叶性肺炎患儿血清肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8、白细胞介素-10和高迁移率族蛋白B1表达意义[J].中华实用儿科临床杂志,2014,29(16):1224-1226.
[9]王鹂鹂,郑首燕,任洛,等.肺炎患儿支气管肺泡灌洗液中肺表面活性蛋白A和D表达及其与肺炎临床特征的相关性[J].中国当代儿科杂志,2016,18(5):386-390.
[10]Shu LH,Lu Q,Han LY,et al.SP-D,KL-6,and HTI-56 levels in children with Mycoplasma pneumoniae pneumonia[J].Int J Clin Exp Pathol,2015,8(9):11185-11191.
[11]Delgado C,Krotzsch E,Jimenez-Alvarez LA,et al.Serum surfactant protein D(SP-D)is a prognostic marker of poor outcome in patients with A/H1N1 virus infection[J].Lung,2015,193(1):25-30.
[12]Schleh C,Rothen-Rutishauser BM,Blank F,et al.Surfactant Protein D modulates allergen particle uptake and infl amatory response in a human epithelial airway model[J].Respir Res,2012,13:8.
[13]Han S,Mallampalli RK.The role of surfactant in lung disease and host defense against pulmonary infections[J].Ann Am Thorac Soc,2015,12(5):765-774.
[14]Mcauley DF,Matthay MA.Clara cell protein CC16.A new lung epithelial biomarker for acute lung injury[J].Chest,2009,135(6):1408-1410.
[15]Martin AC,Laing IA,Khoo S K,et al.Acute asthma in children:relationships among CD14 and CC16 genotypes,plasma levels,and severity[J].Am J Respir Crit Care Med,2006,173(6):617-622.
[16]Pang M,Yuan Y,Wang D,et al.Recombinant CC16 protein inhibits the production of pro-inflammatory cytokines via NF-kappa B and p38 MAPK pathways in LPS-activated RAW264.7 macrophages[J].Acta Biochim Biophys Sin(Shanghai),2017,49(5):435-443.
[17]Wang XY,Keefe KM,Jensen-Taubman SM,et al.Novel method for isolation of murine clara cell secretory proteinexpressing cells with traces of stemness[J].Plo S One,2012,7(8):e43008.
[18]Guzman-Barcenas J,Calderon-Moore A,Baptista-Gonzalez H,et al.Clara cell protein expression in mechanically ventilated term and preterm infants with respiratory distress syndrome and at risk of bronchopulmonary dysplasia:A pilot study[J].Can Respir J,2017,2017:8074678.
[19]Laucho-Contreras ME,Polverino F,Tesfaigzi Y,et al.Club cell protein 16(CC16)augmentation:a potential diseasemodifying approach for chronic obstructive pulmonary disease(COPD)[J].Expert Opin Ther Targets,2016,20(7):869-883.
[20]Magill SS,Klompas M,Balk R,et al.Developing a new,national approach to surveillance for ventilator-associated events:executive summary[J].Clin Infect Dis,2013,57(12):1742-1746.
[21]Engstrom G,Lindberg C,Gerhardsson de Verdier M,et a1.Blood biomarkers and measures of pulmonary function-a study from the Swedish twin registry[J].Respir Med,2012,106(9):1250-1257.