孟鲁司特治疗毛细支气管炎的多中心随机三盲对照研究

Montelukast in the Treatment of Bronchiolitis,A Multi-center,Randomized,Three-blind,Placebo-controlled Trial

目的探讨孟鲁司特(白三烯受体拮抗剂)对毛细支气管炎继发的气道高反应性的改善作用。方法将2007年1月～2008年1月在乌鲁木齐市儿童医院儿科、新疆医科大学第一附属医院儿科、军区总医院儿科住院且符合纳入标准的400例毛细支气管炎患者完全随机分为4组。对照组(n=92):给予常规治疗+安慰剂口服;布地奈德组(n=91例):对照组治疗+布地奈德吸入7天,孟鲁司特短程组(n=88):常规治疗+孟鲁司特口服7天,孟鲁司特长程组(n=90):常规治疗+孟鲁司特口服28天。观察各组T-IgE水平、ECP水平变化,并对其进行为期1.5年的随访,统计毛细支气管炎后反复喘息次数及哮喘发生率,由两个试验助理分别负责统计受试者短期指标和长期指标的随访记录。直到试验完成揭盲时各参与人员均不知道受试对象的分组情况。揭盲后数据交由统计师统计分析。期间若患者出现药物副作用时中止试验并破盲。结果本研究共纳入400例患者,失访39例,最终纳入361例进行统计分析。结果显示,布地奈德组与对照组治疗前后在T-IgE(F=6.17,P=0.00)、ECP水平(F=8.13,P=0.00)、日后喘息反复发作次数(χ2=49.46,P=0.00)、哮喘发生率(χ2=27.21,P=0.00)方面的差异均有统计学意义;孟鲁司特短程组与对照组比较(F=12.56,P=0.00)、与布地奈德组比较(F=7.22,P=0.00);孟鲁司特长程组与对照组比较(F=20.48,P=0.00)、与布地奈德组比较(F=13.56,P=0.00),以及孟鲁司特短与长程组比较(F=1.04,P=0.00),差异均有统计学意义。结论吸入布地奈德7天后尚不能改善毛细支气管炎后继发的气道高反应性,孟鲁司特可改善毛细支气管炎后继发的气道高反应性,即能减少毛细支气管炎患者日后喘息反复发作次数、降低毛细支气管炎后哮喘发生率,且孟鲁司特长程组优于短程组。

Objective To study the effect of montelukast for improving bronchial hyperresponsiveness （BHR） in treatment of bronchiolitis.Methods Four hundreds infants,3 to 24 months old,hospitalized with acute bronchiolitis in three Hospitals （Urumqi Children＇s Hospital,Pediatrics Department of First Affiliated Hospital of Xinjiang Medical University,and Pediatrics Department of Army General Hospital） from January,2007 to January,2008,were randomly assigned into four groups：placebo group （n=92）,budesonide group （n=91）,montelukast short-course group （7 days,n=88）,and montelukast long-course group （28 days,n=90）.Main outcome measure was BHR after treatment,including recurrent bronchiolitis wheezing and asthma incidence rate.Secondary measures were changes in serum T-IgE level and eosinophilic cationic protein （ECP） level.Results All four groups were comparable at baseline.No significant differences were observed between placebo group and budesonide group in changes of serum T-IgE （F=6.17,P=0.00）,ECP （F=8.13,P=0.00）,recurrent post-bronchiolitis-wheezing （χ^2=49.46,P=0.00） and asthma incidence rate （χ^2=27.21,P=0.00）.After treatment with montelukast,there was statistical significance in T-IgE and ECP level,times of recurrent bronchiolitis wheezing and asthma incidence rate,as follows,montelukast short-course group versus placebo group （F=12.56,P=0.00）,montelukast short-course group versus budesonide group （F=7.22,P=0.00）,montelukast long-course group versus placebo group （F=20.48,P=0.00）,montelukast long-course group versus budesonide group （F=13.56,P=0.00）,montelukast short-course group versus montelukast long-course group （F=1.04,P=0.00）.Conclusions Budesonide treatment for 7 days can not improve bronchial hyperresponsiveness induced by bronchiolitis,while montelukast does,that is,montelukast can decrease both the times of bronchiolitis wheezing and asthma incidence rate.Long-course treatment of montelukast is superior to that of short-course.