阿奇霉素联合孟鲁司特钠治疗不同严重程度儿童肺炎支原体肺炎的临床研究OA
Clinical trial of azithromycin combined with montelukast sodium in children with Mycoplasma pneumoniae pneumonia of different severity
目的 观察阿奇霉素注射液和颗粒联合孟鲁司特钠片对不同严重程度儿童肺炎支原体肺炎(MPP)的临床疗效和安全性.方法 将本院收治的MPP患儿根据治疗方法分为对照组和试验组.所有患儿均静脉滴注阿奇霉素注射液10 mg·kg-1qd,持续滴注5 d直至体温恢复正常,后改用阿奇霉素颗粒冲服,剂量同上,连服3 d停4 d,总疗程3周.试验组在此基础上加服孟鲁司特钠片,≤5岁患儿剂量为4 mg·d-1,5岁以上患儿剂量为5 mg·d-1,总疗程3周.根据MPP严重程度将患儿分为轻症MPP组和重症MPP组.治疗后,比较2组患儿不同严重程度下的临床疗效、NLRP3炎症小体通路相关指标和小气道功能指标;用多元线性回归分析NLRP3炎症小体通路相关指标与小气道功能的相关性;用广义估计方程模型(GEE)分析NLRP3炎症小体通路相关指标在不同时间点、不同组别、不同程度的变化情况.结果 本研究共纳入92例患儿,其中试验组和对照组各46例,用倾向评分匹配法(PSM)矫正混杂因素,匹配后2组均入组40例,轻症MPP组47例、重症MPP组33例.重症患儿与轻症患儿的白细胞计数(WBC)分别为(10.82±1.59)和(10.06±1.47)× 109·L-1,C-反应蛋白(CRP)分别为(19.45±8.94)和(8.67±4.08)mg·L-1,白细胞介素-6(IL-6)分别为(18.25±4.48)和(13.65±4.33)pg·mL-1,白细胞介素-10(IL-10)分别为(6.70±1.89)和(5.26±1.35)pg·mL-1,上述指标在亚组间比较,在统计学上差异均有统计学意义(均P<0.05).试验组和对照组的轻症MPP患儿治疗有效率分别为100.00%(22例/22例)和88.00%(22例/25例);重症MPP患儿治疗有效率分别为88.89%(16例/18例)和60.00%(9例/15例),上述指标在组间比较,在统计学上差异均有统计学意义(均P<0.05).治疗后,试验组轻症与重症MPP患儿NLRP3 mRNA分别为0.89±0.11与1.11±0.10,凋亡相关斑点样蛋白(ASC)mRNA分别为0.77±0.10与0.95±0.15,半胱氨酸天冬氨酸蛋白水解酶-1(caspase-1)mRNA分别为0.69±0.09与0.82±0.10;呼吸初期瞬间流量(FEF25%)分别为(2.72±0.24)与(2.28±0.19)L·s-1,呼吸中期瞬间流量(FEF50%)分别为(2.90±0.40)与(2.37±0.31)L·s-1,呼吸后期瞬间流量(FEF75%)分别为(2.13±0.32)与(1.73±0.35)L·s-1,上述指标在亚组间比较,在统计学上差异均有统计学意义(均P<0.05).相关性分析显示,MPP患儿NLRP3炎症小体通路相关指标NLRP3、ASC和caspase-1 mRNA与小气道功能指标FEF25%、FEF50%和FEF75%水平之间均呈负相关关系,负相关性在统计学上差异均具有统计学意义(均P<0.001).GEE结果显示,试验组NLRP3 mRNA的降低幅度均大于对照组.在轻症MPP中,试验组与对照组估计值分别为-0.76和-0.56;试验组ASC mRNA的降低幅度均大于对照组,试验组与对照组估计值分别为-0.56和-0.26;试验组caspase-1 mRNA的降低幅度均大于对照组,试验组与对照组估计值分别为-0.32和-0.26,交互项在统计学上差异均显著(均P<0.05).结论 阿奇霉素注射液和颗粒联合孟鲁司特钠片治疗可以明显提升不同严重程度MPP患儿的临床疗效,通过靶向抑制NLRP3炎症小体通路,减轻不同严重程度MPP患儿的过度炎症反应,改善小气道功能,尤其对轻症患儿疗效更明显.
Objective To investigate the therapeutic effects and safety of the combination of azithromycin(injection and granules)and montelukast sodium tablets on the treatment of Mycoplasma pneumoniae pneumonia(MPP)in children of different severity.Methods The children with MPP treated in our hospital were divided into control group and treatment group based on the treatment method.All children received intravenous infusion of azithromycin injection at a dose of 10 mg·kg-1 qd for 5 days until body temperature returned to normal,followed by oral administration of azithromycin granules at the same dose for 3 days,then 4 days off,for a total course of 3 weeks.On this basis,the treatment group was additionally given montelukast sodium tablets,with a dose of 4 mg·d-1 for children≤5 years old,and 5 mg·d-1 for children over 5 years old,for a total course of 3 weeks.According to the severity of MPP,patients were divided into mild MPP group and severe MPP group.After treatment,the clinical efficacy,NLRP3 inflammasome pathway-related indicators and small airway function indicators were compared between the two groups of children with different severity levels;multiple linear regression was used to analyze the correlation between NLRP3 inflammasome pathway-related indicators and small airway function;and generalized estimating equation(GEE)model was used to analyze the changes in NLRP3 inflammasome pathway-related indicators at different time points,in different groups,and with different severities.Results This study included a total of 92 patients,with 46 cases in each group.Confounding factors were adjusted using propensity score matching(PSM),and after matching,40 cases were included in each group,while 47 cases in mild MPP group and 33 cases in severe MPP group.The white blood cell count(WBC)in severe MPP and mild MPP groups were(10.82±1.59)and(10.06±1.47)× 109·L-1,C-reactive protein(CRP)were(19.45±8.94)and(8.67±4.08)mg·L-1,interleukin-6(IL-6)were(18.25±4.48)and(13.65±4.33)pg·mL-1,and interleukin-10(IL-10)were(6.70±1.89)and(5.26±1.35)pg·mL-1.Comparisons of these indicators between subgroups showed statistically significant differences(all P<0.05).The effective treatment rates of children with mild MPP in treatment group and control group were 100.00%(22 cases/22 cases)and 88.00%(22 cases/25 cases),respectively;the effective treatment rates of children with severe MPP were 88.89%(16 cases/18 cases)and 60.00%(9 cases/15 cases),respectively.Comparisons between groups showed that these differences were statistically significant(all P<0.05).After treatment,the mild and severe MPP children in treatment group had NLRP3 mRNA levels of 0.89±0.11 and 1.11±0.10,apoptosis-associated speck-like protein(ASC)mRNA levels of 0.77±0.10 and 0.95±0.15,caspase-1 mRNA levels of 0.69±0.09 and 0.82±0.10;forced expiratory flow at 25%of the pulmonary volume(FEF25%)levels were(2.72±0.24)and(2.28±0.19)L·s-1,forced expiratory flow at 50%(FEF50%)levels were(2.90±0.40)and(2.37±0.31)L·s-1,forced expiratory flow at 75%(FEF75%)levels were(2.13±0.32)and(1.73±0.35)L·s-1,all showing statistically significant differences(all P<0.05).Correlation analysis showed that in children with MPP,the NLRP3 inflammasome pathway-related indicators NLRP3,ASC and caspase-1 mRNA were all negatively correlated with small airway function indicators FEF25%,FEF50%and FEF75%,and the negative correlations were statistically significant(all P<0.001).GEE results indicated that the reduction in NLRP3 mRNA levels in treatment group was greater than that in control group.In mild MPP,the estimated values for treatment and control groups were-0.76 and-0.56,respectively;the reduction in ASC mRNA in treatment group was greater than in the control group,with estimated values of-0.56 and-0.26,respectively;the reduction in caspase-1 mRNA in treatment group was greater than in control group,with estimated values of-0.32 and-0.26,respectively,and all interaction terms were statistically significant(all P<0.05).Conclusion Azithromycin combined with montelukast sodium can significantly improve the clinical efficacy of children with different severity of MPP,reduce the excessive inflammatory response of children with different severity of MPP by targeting and inhibit the NLRP3 inflammasome pathway,and improve the function of the small airway,especially in children with mild disease.
董育哲;王一平
扬州大学医学院附属淮安市妇幼保健院药学部,江苏淮安 223002扬州大学医学院附属淮安市妇幼保健院药学部,江苏淮安 223002
医药卫生
阿奇霉素注射液阿奇霉素颗粒孟鲁司特钠片肺炎支原体肺炎核苷酸结合寡聚化结构域样受体蛋白3小气道功能
azithromycin injectionazithromycin granulemontelukast sodium tabletMycoplasma pneumoniae pneumonianucleotide-binding oligomerization domain-like receptor protein 3small airway function
《中国临床药理学杂志》 2026 (1)
7-14,8
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