乙酰半胱氨酸泡腾片联合布地奈德福莫特罗吸入粉雾剂治疗中重度COPD患者的临床研究

Clinical trial of N-acetyl cysteine effervescent tablets combined with budesonide and formoterol fumarate powder for inhalation in the treatment of patients with moderate to severe COPD

目的探讨乙酰半胱氨酸(NAC)泡腾片联合布地奈德福莫特罗吸入粉雾剂对中重度慢性阻塞性肺病(COPD)患者的临床疗效及安全性。方法将中重度COPD患者随机分为NAC组、ST组和联合组,NAC组给予NAC泡腾片,将NAC泡腾片0.6 g溶于温开水(≤40℃)中服用,每次1片,qd,晚间顿服;ST组给予布地奈德福莫特罗吸入粉雾剂治疗,每次1吸,bid;联合组给予NAC泡腾片联合布地奈德福莫特罗吸入粉雾剂治疗,2种药物用法用量同NAC组和ST组。3组患者均治疗7 d。评估3组患者的临床疗效,比较3组患者的呼气峰流速(PEF)、第1秒用力呼气量(FEV1)、FEV1/用力肺活量(FVC)、血清CRP、PCT、SAA及6 min步行试验(6 MWT),并进行安全性评价。结果3组均入组40例患者。治疗7 d后,NAC组、ST组和联合组的总有效率分别为77.50%(31例/40例)、80.00%(32例/40例)和95.00%(38例/40例),NAC组、ST组与联合组,在统计学上差异均有统计学意义(均P<0.05);NAC组与ST组比较,在统计学上差异无统计学意义(P>0.05)。治疗7 d后,NAC组、ST组、联合组的FVC水平分别为(2.51±0.72)、(2.59±0.76)、(3.01±0.82)L,PaO_(2)水平分别为(2.24±0.61)、(2.29±0.64)、(2.87±0.72)L,FEV1/FVC水平分别为(89.24±4.28)%、(88.42±4.19)%、(95.35±4.27)%,血清CRP水平分别为(19.52±2.12)、(19.34±2.09)、(11.85±2.24)mg·L^(-1),血清PCT水平分别为(0.83±0.22)、(0.87±0.24)、(0.51±0.13)μg·L^(-1),血清SAA水平分别为(28.95±3.48)、(29.23±3.75)、(17.70±2.73)mg·L^(-1)。联合组上述指标与NAC组、ST组比较,在统计学上差异均有统计学意义(均P<0.05);NAC组上述指标与ST组比较,在统计学上差异均无统计学意义(均P>0.05)。3组患者的药物不良反应均以腹痛腹泻、头痛、恶心呕吐为主。NAC组、ST组和联合组的药物不良反应发生率分别为2.50%(1例/40例)、5.00%(2例/40例)和12.50%(5例/40例),在统计学上差异均无统计学意义(均P>0.05)。结论NAC泡腾片联合布地奈德福莫特罗吸入粉雾剂治疗中重度COPD患者,疗效显著,可有效改善肺功能,并降低血清CRP、PCT和SAA水平,且安全性较好。

Objective To explore clinical effect and safety of N-acetyl cysteine(NAC)effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation in the treatment of patients with moderate to severe chronic obstructive pulmonary disease(COPD).Methods Patients with moderate to severe COPD were randomly divided into NAC group,ST group and combination group.NAC group was treated with NAC effervescent tablets[NAC effervescent tablets 0.6 g was dissolved in warm water(≤4℃),one tab let/once,qd,take medicine at night],ST group was treated with budesonide and formoterol fumarate powder for inhalation(a inhalation/once,bid),combination group was treated with NAC effervescent tablets and budesonide and formoterol fumarate powder for inhalation.All patients were treated for 7 d.The clinical curative effect,peak expiratory flow(PEF),forced expiratory volume in 1 s(FEV_1),FEV_1/forced vital capacity(FVC),serum CRP,PCT,SAA,6 min walking test(6MWT)and safety in the three groups were evaluated.Results There were 40 cases in each group.After 7 d of treatment,total response rates of NAC group,ST group and combination group were 77.50%(31 cases/40 cases),80.00%(32 cases/40 cases)and 95.00%(38 cases/40 cases),the differences between combination group and NAC group or between combination group and ST group were statistically significant(P<0.05),but the difference between NAC group and ST group was not statistically significant(P>0.05).After 7 d of treatment,FVC levels in NAC group,ST group and combination group were(2.51±0.72),(2.59±0.76)and(3.01±0.82)L,PaO_(2) levels were(2.24±0.61),(2.29±0.64)and(2.87±0.72)L,FEV_1/FVC levels were(89.24±4.28)%,(88.42±4.19)%and(95.35±4.27)%,levels of serum CRP were(19.52±2.12),(19.34±2.09)and(11.85±2.24)mg·L^(-1),PCT levels were(0.83±0.22),(0.87±0.24)and(0.51±0.13)μg·L^(-1),SAA levels were(28.95±3.48),(29.23±3.75)and(17.70±2.73)mg·L^(-1),the differences between combination group and NAC group or between combination group and ST group were statistically significant(all P<0.05),but the difference between NAC group and ST group was not statistically significant(all P>0.05).The adverse drug reactions were mainly on abdominal pain,diarrhea,headache,nausea and vomiting in the three groups.The total incidence of adverse drug reactions in NAC group,ST group and combination group was2.50%,5.00%and 12.50%,the difference among the three groups was not statistically significant(all P>0.05).Conclusion The curative effect of NAC effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation is significant in patients with moderate to severe COPD,which can effectively improve pulmonary function,reduce levels of serum CRP,PCT and SAA,with good safety.