不同剂量布地奈德福莫特罗用于高风险慢性阻塞性肺疾病急性加重期患者的疗效对比研究

Clinical efficacy of different doses of budesonide/formoterol in the treatment of an acute exacerbation of chronic obstructive pulmonary disease in patients

目的观察不同剂量布地奈德福莫特罗用于高风险慢性阻塞性肺疾病急性加重期患者的临床疗效。方法选择酒泉市人民医院2019年1-12月收治的高风险慢性阻塞性肺疾病急性加重期[慢性阻塞性肺疾病防治全球倡议(GOLD)分级C/D级]住院患者200例为研究对象,采用随机数字表法分为对照组和治疗组,每组100例。治疗组患者在抗感染、化痰治疗基础上给予大剂量布地奈德福莫特罗粉吸入剂(320 μg/9 μg)吸入治疗,对照组患者在抗感染、化痰治疗基础上给予小剂量布地奈德福莫特罗粉吸入剂(160 μg/4.5 μg)吸入治疗,疗程9 d。以治疗前、治疗第5天、治疗第9天为观察时间点,监测两组患者各时间点降钙素原(PCT)、超敏C反应蛋白(hs-CRP)、呼出气一氧化氮(FeNO)、血嗜酸性粒细胞百分比(EO%)、动脉氧分压(PaO2)、乳酸(HL)、白细胞介素6(IL-6)、第一秒用力呼气量(FEV1)、第一秒用力呼气量/用力肺活量(FEV1/FVC)等各项客观指标变化情况,观察慢性阻塞性肺疾病评估测试(CAT)评分、呼吸困难指数(mMRC)评分、6 min行走试验(6MWT)距离、症状积分改善情况。结果两组患者治疗前PCT、PaO2等指标比较,差异均无统计学意义(均P>0.05)。治疗第5天,两组PCT、PaO2、FeNO、hs-CRP、E0(%)、IL-6、FEV1/FVC、FEV1、6MWT、mMRC、咳嗽、咳痰、气短、CAT评分等指标比较,差异均有统计学意义(t=2.416、3.289、3.982、4.871、3.332、4.098、5.253、6.214、3.843、7.268、5.387、7.392、5.398、6.349,均P<0.05);治疗第9天两组比较,PCT、PaO2、FeNO、hs-CRP、E0(%)、IL-6、FEV1/FVC、FEV1、6MWT、mMRC、咳嗽、咳痰、气短、CAT评分等指标差异均有统计学意义(t=2.508、4.032、2.948、3.527、3.118、5.251、5.325、6.338、2.907、6.289、3.246、2.084、2.151、2.527,均P<0.05);治疗第5天,治疗组HL水平明显低于对照组(t=4.341,P<0.05),治疗第9天,两组HL水平差异无统计学意义(t=1.173,P>0.05)。治疗组不良反应发生率为4%(4/100),对照组不良反应发生率为5%(5/100),两组差异无统计学意义(P>0.05)。结论大剂量布地奈德福莫特罗吸入剂可以显著改善高风险慢性阻塞性肺疾病急性加重期患者肺功能、6MWT、mMRC、咳嗽、咳痰、气短、CAT评分,提高PaO2,降低FeNO、hs-CRP、E0%、IL-6等炎性标志物水平,对高风险AECOPD患者疗效优于低剂量。

Objective To investigate the clinical efficacy of different doses of budesonide/formoterol in the treatment of an acute exacerbation of chronic obstructive pulmonary disease in patients.Methods A total of 200 inpatients with an acute exacerbation of chronic obstructive pulmonary disease graded C/D by global initiative for chronic obstructive lung disease(GOLD)staging system who received treatment in Jiuquan City People's Hospital,China from January to December in 2019 were included in this study.They were randomly divided into a control group and a treatment group(n=100/group).Based on anti-infection and expectorant treatment,the treatment group was given inhalation therapy(higher dose budesonide/formoterol,320μg/9μg),while the control group was identically given inhalation therapy(lower dose budesonide/formoterol,160μg/4.5μg),with a total course of 9 days in each group.Before treatment and at 5 and 9 days of treatment,procalcitonin(PCT),high-sensitivity C-reactive protein(hs-CRP),fractional exhaled nitric oxide(FeNO),percentage of eosinophils(EO%),partial pressure of oxygen(PaO2),lactic acid,interleulin-6(IL-6),forced expiratory volume in 1 second(FEV1),the ratio of FEV1/forced vital capacity(FVC)were monitored in each group.COPD assessment test(CAT)score,modified Medical Research Council(mMRC)dyspnea score,6-minute walking test(6MWT),and symptom improvement were determined in each group.Results Before treatment,there were no significant differences in PCT and PaO2 between the control and treatment groups(both P>0.05).There were significant differences in PCT,PaO2,FeNO,hs-CRP,E0(%),IL-6,FEV1,FEV1/FVC,6MWT,mMRC,cough,expectoration,shortness of breath and CAT score measured at 5 days of treatment between the treatment and control groups(t=2.416,3.289,3.982,4.871,3.332,4.098,5.253,6.214,3.843,7.268,5.387,7.392,5.398,6.349,all P<0.05).There were significant differences in PCT,PaO2,FeNO,hs-CRP,E0(%),IL-6,FEV1/FVC,FEV1,6MWT,mMRC,cough,expectoration,shortness of breath and CAT score measured at 9 days of treatment between the treatment and control groups(t=2.508,4.032,2.948,3.527,3.118,5.251,5.325,6.338,2.907,6.289,3.246,2.084,2.151,2.527,all P<0.05).At 5 days of treatment,lactic acid level in the observation group was significantly lower than that in the control group(t=4.341,P<0.05).At 9 days of treatment,there was no significant difference in lactic acid level between the control and observation groups(t=1.173,P>0.05).There was no significant difference in the incidence of adverse reactions between the control and treatment groups[4%(4/100)vs.5%(5/100),P>0.05].Conclusion Inhalation of high doses of budesonide/formoterol can greatly improve pulmonary function,6MWT performance,decrease mMRC and CAT scores,alleviate cough,expectoration,shortness of breath,and decrease serum levels of FeNO,hs-CRP,E0(%),IL-6 and other inflammatory factors.Inhalation of higher doses of budesonide/formoterol exhibits better efficacy in the treatment of an acute exacerbation of chronic obstructive pulmonary disease in patients than inhalation of lower doses of budesonide/formoterol.