新生儿气管插管后呼吸道感染影响因素及与TLR4基因的关联

Influencing factors for respiratory tract infection in neonates with tracheal intubation and its association with TLR4 gene

目的 探讨新生儿气管插管后呼吸道感染的病原菌特点、高危因素,并分析感染与Toll样受体4(TLR4)基因表达的关联。方法 选取2016年1月-2020年12月嘉兴市妇幼保健院收治的581例行气管插管机械通气的新生儿。根据是否发生呼吸道感染,分为感染组116例与未感染组465例。病原菌培养及鉴定,收集临床资料,单因素和多因素分析新生儿气管插管后呼吸道感染的危险因素,采用实时荧光定量聚合酶链式反应(qPCR)检测TLR4 mRNA表达水平以及TLR4-2381 A/G位点的基因分型。结果 116例呼吸道感染新生儿送检标本中共检出病原菌126株,革兰阴性菌109株占比86.51%,革兰阳性菌11株占比8.73%,真菌6株占比4.76%。极低出生体质量儿、气管插管时间>7 d、气管插管内吸痰>1/d、肺不张、血清白蛋白<30 g/L是新生儿气管插管后呼吸道感染的危险因素(P<0.05)。感染组TLR4 mRNA表达水平高于未感染组(P<0.05)。感染组TLR4-2381 A/G位点的AA基因型频率低于未感染组(P<0.05)。结论 新生儿气管插管后呼吸道感染以革兰阴性菌为主,极低出生体质量儿、气管插管时间过长、吸痰频次过高、肺不张、血清白蛋白过低是导致患儿感染的高危因素。TLR4基因表达上调可能增加呼吸道感染风险,TLR4-2381 A/G位点AA基因型突变可能与感染易感性有关。

OBJECTIVE To explore the etiological characteristics and high risk factors for respiratory tract infection in neonates with tracheal intonation and analyze the relationship between the infection and the expression of Toll-like receptor 4(TLR4) gene. METHODS A total of 581 neonates who underwent endotracheal intubation for mechanical ventilation in Jiaxing Maternal and Child Health Hospital from Jan 2016 to Dec 2020 were enrolled in the study and divided into the infection group with 116 cases and the no infection group with 465 cases according to the status of respiratory tract infection. The pathogens were cultured and identified, the clinical data were collected, univariate analysis and multivariate analysis were performed for risk factors for the respiratory tract infection in the neonates with tracheal intubation, the expression level of TLR4 mRNA and genotypes at TLR4-2381 A/G locus were detected by real-time fluorescent quantitative polymerase chain reaction(qPCR). RESULTS Totally 126 strains of pathogens were isolated from submitted specimens of the 116 neonates with respiratory tract infection, 109(86.51%) of which were gram-negative bacteria, 11(8.73%) were gram-positive bacteria, and 6(4.86%) were fungi. Very low birth weight, endotracheal intubation time more than 7 days, sputum suction of tracheal intubation more than once per day, atelectasis and serum albumin level less than 30 g/L were the risk factors for the respiratory tract infection in the neonates with tracheal intubation(P<0.05). The expression level of TLR4 mRNA of the infection group was significantly higher than that of the no infection group(P<0.05). The frequency of AA genotype at TLR4-2381 A/G locus was significantly lower in the infection group than in the no infection group(P<0.05). CONCLUSION The gram-negative bacteria are dominant among the pathogens isolated from the tracheal intubation neonates with respiratory tract infection. The very low birth weight, over long time of tracheal intubation, over high frequency of sputum suction, atelectasis and over low level of serum albumin are the high risk factors for the infection. The upregulation of TLR4 gene may increase the risk of respiratory tract infection, and the mutation of AA genotype at TLR4-2381 A/G locus may be associated with the susceptibility to the infection.