抗菌药物降阶梯治疗对老年COPD合并肺部感染患者气道炎症和肺功能与TLR4及NF-κB水平的影响

Effect of antibacterial drug de-escalation therapy on airway inflammation,pulmonary function,TLR4 and NF-κB in elderly patients with COPD and pulmonary infection

目的抗菌药物降阶梯对老年慢性阻塞性肺疾病(COPD)合并肺部感染患者气道炎症、肺功能与Toll样受体4(TLR4)、核因子κB(NF-κB)的影响。方法纳入2017年8月-2019年8月南阳医学高等专科学校第一附属医院收治的COPD合并肺部感染患者108例,随机分为常规组和研究组,各54例;常规组采用抗菌药物常规治疗方案,研究组采用抗菌药物降阶梯治疗方案,观察两组患者临床疗效和安全性评价,对比治疗前后肺功能相关指标[用力肺活量(FVC)、一秒用力呼气容积(FEV_(1))和最大呼气峰值流速(PEF)]、气道炎症反应指标[C-反应蛋白(CRP)、降钙素原(PCT)、脑钠肽(BNP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)],收集两组患者外周血,分离外周血单个核细胞,采用实时荧光聚合酶链式反应检测细胞中TLR4、NF-κB的mRNA表达水平,分析TLR4/NF-κB通路与气道炎症指标的相关性。结果治疗前,两组患者肺功能指标FVC、FEV_(1)、PEF差异无统计学意义,治疗后,两组患者上述指标皆有明显改善,且研究组上述指标改善幅度优于常规组(P<0.05);研究组疗效优于常规组(P=0.028);研究组不良反应总发生率为3.70%低于常规组(P=0.046);治疗前两组患者气道炎症反应指标CRP、PCT、BNP、IL-6和TNF-α差异无统计学意义,治疗后,两组患者气道炎症反应指标CRP、PCT、BNP、IL-6和TNF-α皆降低,且研究组上述指标降低幅度高于常规组(P<0.05);治疗前两组TLR4 mRNA、NF-κB mRNA差异无统计学意义,治疗后,两组患者TLR4 mRNA、NF-κB mRNA皆降低,且研究组上述指标降低幅度高于常规组(P<0.05)。结论抗菌药物降阶梯治疗可提高COPD合并肺部感染患者的临床疗效及肺功能,降低TLR4、NF-κB水平,减轻气道炎症反应,该方案临床效果较好,安全可靠。

OBJECTIVE To explore the effect of de-escalation of antibacterial drugs on airway inflammation,pulmonary function and levels of Toll-like receptor 4(TLR4)and nuclear factorκB(NF-κB)in elderly patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary infection.METHODS Totally 108 patients with COPD complicated with pulmonary infection admitted to the First Affiliated Hospital of Nanyang Medical College were included between Aug.2017 and Aug.2019 were included and randomly divided into a conventional group and a study group,with 54 cases in each group.The conventional group was adopted routine treatment regimen of antibacterial drugs,and the study group was given de-escalation therapy of antibacterial drugs.The clinical efficacy and safety evaluation were observed in the two groups of patients,and the pulmonary function-related indexes[forced vital capacity(FVC),forced expiratory volume in one second(FEV_(1))and peak expiratory flow(PEF)]and airway inflammatory response indicators[C-reactive protein(CRP),procaicltonin(PCT),brain natriuretic peptide(BNP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were compared before and after treatment.Peripheral blood was collected from the two groups and peripheral blood mononuclear cells were isolated.The mRNA expression levels of TLR4 and NF-κB in the cells were detected by real-time fluorescence polymerase chain reaction,and the correlation between TLR4/NF-κB pathways and airway inflammatory indicators was analyzed.RESULTS Before treatment,there were no statistical differences in terms of pulmonary function indicators such as FVC,FEV_(1) and PEF between the two groups,and after treatment,the above indicators were significantly improved in both groups,and the improvements of the above indicators in the study group were better than those in the conventional group(P<0.05).The efficacy in the study group was better than that in the conventional group(P=0.028).The overall incidence of adverse reactions in the study group was 3.70%,lower than that in the conventional group(P=0.046).Before treatment,there were no statistical differences in the levels of airway inflammatory response indicators such as CRP,PCT,BNP,IL-6 and TNF-αbetween the two groups of patients,and after treatment,the airway inflammatory response indexes CRP,PCT,BNP,IL-6 and TNF-αwere reduced in both groups,and the reductions of the above indicators in the study group were higher than those in the conventional group(P<0.05).Before treatment,there were no statistical differences in the expressions of TLR4 mRNA and NF-κB mRNA between the two groups,and after treatment,the expressions of TLR4 mRNA and NF-κB mRNA were decreased in both groups,and the decreases of the above indicators were higher in the study group than those in the conventional group(P<0.05).CONCLUSION De-escalation therapy of antibacterial drugs could improve the clinical efficacy and pulmonary function,reduce the levels of LR4 and NF-κB,and relieve the airway inflammatory response in patients with COPD complicated with pulmonary infection.This regimen had good clinical effects and it was safe and reliable.