Significance of neutrophil extracellular trap and its markers in the early diagnosis of community-acquired pneumonia in children / 中国当代儿科杂志

OBJECTIVE@#To study the significance of plasma neutrophil extracellular trap (NET) and its markers in the diagnosis of community-acquired pneumonia (CAP) in children.@*METHODS@#A total of 160 children with CAP were enrolled as the CAP group, and 50 healthy children were enrolled the control group. According to disease severity, the CAP group was further divided into a mild CAP subgroup with 137 children and a severe CAP subgroup with 23 children. According to the pathogen, the CAP group was further divided into a bacterial pneumonia subgroup with 78 children, a Mycoplasma pneumonia subgroup with 35 children, and a viral pneumonia subgroup with 47 children. The levels of plasma NET and its markers [antibacterial peptide (LL-37), extracellular free DNA (cfDNA), and deoxyribonuclease I (DNase I)] were measured. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in diagnosing CAP and assessing its severity.@*RESULTS@#Compared with the control group, the CAP group had significant increases in the levels of NET, LL-37, and cfDNA and a significant reduction in the activity of DNase I (P0.05). In the CAP group, plasma NET levels were positively correlated with white blood cell count (WBC), percentage of neutrophils, and serum levels of C-reactive protein (CRP), procalcitonin and tumor necrosis factor-α (r=0.166, 0.168, 0.275, 0.181 and 0.173 respectively, P<0.05); LL-37 and cfDNA levels were positively correlated with WBC (r=0.186 and 0.338 respectively, P<0.05) and CRP levels (r=0.309 and 0.274 respectively, P<0.05); the activity of DNase I was negatively correlated with CRP levels (r=-0.482, P<0.05). The ROC curve analysis showed that NET, LL-37, cfDNA, and DNase I had an area under the ROC curve (AUC) of 0.844, 0.648, 0.727, and 0.913 respectively in the diagnosis of CAP, with optimal cut-off values of 182.89, 46.26 ng/mL, 233.13 ng/mL, and 0.39 U/mL respectively, sensitivities of 88.12%, 35.63%, 54.37%, and 91.25% respectively, and specificities of 74.00%, 92.00%, 86.00%, and 76.00% respectively. In the assessment of the severity of CAP, NET, LL-37, cfDNA, and DNase I had an AUC of 0.873, 0.924, 0.820, and 0.778 respectively, with optimal cut-off values of 257.7, 49.11 ng/mL, 252.54 ng/mL, and 0.29 U/mL respectively, sensitivities of 83.21%, 86.96%, 78.26%, and 95.65% respectively, and specificities of 78.26%, 83.94%, 76.64%, and 56.93% respectively.@*CONCLUSIONS@#Plasma NET and its related markers have a certain value in diagnosing CAP and assessing its severity in children.

Value of simultaneous amplification and testing in early diagnosis of Mycoplasma pneumoniae pneumonia and related influencing factors / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the value of simultaneous amplification and testing (SAT) in the early diagnosis of Mycoplasma pneumoniae pneumonia (MPP) in children and related influencing factors.</p><p><b>METHODS</b>A total of 526 children with community-acquired pneumonia who were hospitalized between December 2016 and December 2017 were enrolled. Particle agglutination was used to measure serum Mycoplasma pneumoniae (MP) antibody (MP-Ab). The value of SAT in the diagnosis of MPP was evaluated based on these results.</p><p><b>RESULTS</b>Based on the results of serum MP-Ab measurement, 165 children were diagnosed with MPP. MP-SAT had a sensitivity of 90.9% (150/165), a specificity of 97.9% (368/376), and high accuracy (Youden index=0.89) in the diagnosis of MPP, suggesting that there was good consistency between these two methods (Kappa=0.90). The diagnostic sensitivity of MP-SAT in children with a short course of disease was significantly higher than that in children with a long course of disease (P=0.031). The diagnostic sensitivity of MP-SAT was significantly higher than that of single serum MP-Ab measurement (P=0.018), with poor consistency between these two methods (Kappa=0.039). MP-SAT had good consistency with double serum MP-Ab measurement (Kappa=0.91). The multivariate logistic regression analysis showed that course of disease (≥7 days) and out-of-hospital macrolide treatment were the main factors influencing the results of MP-SAT (P<0.05).</p><p><b>CONCLUSIONS</b>MP-SAT has high value in the early diagnosis of MPP and can effectively cover the shortage of single serum MP-Ab test in the acute stage and thus provide help for early clinical diagnosis. MP-SAT test should be performed in the early stage of the disease (<7 days) and before the application of macrolide treatment.</p>

Temporal and spatial distribution of VIP, CGRP and their receptors in the development of airway hyperresponsiveness in the lungs / 生理学报

To explore the role of intrapulmonary neuropeptides in the development of airway hyperresponsiveness, we established an animal model of airway hyperresponsiveness (AHR) in rabbits by using ozone exposure. With the model, after test of the mechanics of respiration and bronchoalveolar lavage assay, the levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the lungs were determined by radioimmunoassay, and the expression of mRNA coding receptors of these two neuropeptides was evaluated by reverse transcriptional-polymerase chain reaction (RT-PCR). At the same time, the distribution of VIP receptor-1 (VIPR1) and CGRP receptor-1 (CGRPR1) in lung tissues and its time-course were examined by in situ hybridization. The results showed: (1) in ozone-stressing groups, airway resistance increased significantly and typical inflammatory pathological changes were observed in pulmonary tissue slides, including neutrophil and eosinophil infiltration, mucus exudation and bronchial epithelial cells (BECs) shedding; (2) with elongation of ozone exposure, the levels of VIP and CGRP in the lungs increased at first, reaching a peak on d 2 to 4, then decreased slowly, and CGRP peaked somewhat earlier than VIP; (3) mRNA expression of the two neuropeptide receptors in the lungs changed in a similar manner like VIP and CGRP, but the high level of mRNA expression of VIPR1 lasted longer than that of CGRPR1; and (4) in situ hybridization for neuropeptide receptors demonstrated that, in unstressed control, VIPR1 and CGRPR1 positive cells appeared in the airway epithelium, pulmonary interstitial and focal areas of airway and vascular smooth muscles. With the elongation of ozone exposure, hybridization stained deeper and the majority of positive cells were located around the vessels and bronchus except a few in the alveoli. At 8 d, only a small number of positive cells were seen in the lungs. From the results, it is concluded that ozone-stressing can induce the development of AHR, in which VIP and CGRP may play important roles. That implies, through binding to CGRPR1, CGRP stimulates an early inflammation response which contributes in cleaning up of irritants, while VIP exerts a later dampening of pulmonary inflammation response. These two neuropeptides may play sequential and complementary roles in the development of AHR.

Influence of regulatory peptides on the secretion of interleukins from bronchial epithelial cells of the rabbit / 生理学报

To explore the role of regulatory peptides in the secretion of bronchial epithelial cells (BECs), we observed the effects of four peptides, i.e.vasoactive intestinal peptide (VIP), epidermal growth factor (EGF), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP), on the secretion of ILs from unstimulated or O3-stressed BECs. The results of the experiments showed that VIP exerted an inhibitory effect on the secretion of IL-1 and IL-8 from unstimulated and O3-stressed BECs, VIP also decreased the secretion of IL-5 from O3-stressed BECs; EGF promoted secretion of IL-1 and IL-8 from unstimulated BECs, but decreased the secretion of ILs from O3-stressed BECs; ET-1 and CGRP enhanced the secretion of IL-1, IL-5, and IL-8 from unstimlated BECs, CGRP also increased the secretion of ILs from O3-stressed BECs. The results obtained demonstrate that intrapulmonary regulatory peptides modulate the secretion of ILs from BECs, and may play an important part in transduction of inflammatory signals.