小剂量阿奇霉素联合噻托溴铵治疗稳定期慢性阻塞性肺疾病的临床研究

Clinical observation for low-dose azithromycin with tiotropium bromide in the treatment of stable chronic obstructive pulmonary disease

目的观察小剂量阿奇霉素联合噻托溴铵粉吸入剂治疗稳定期慢性阻塞性肺疾病（COPD）患者的临床疗效及安全性。方法110例稳定期COPD患者随机分为噻托溴铵单药组（A组）36例、阿奇霉素联合噻托溴铵组（B组）38例、常规治疗对照组（C组）36例3组。A组在常规治疗基础上给予吸入噻托溴铵粉吸入剂18恤g，每日1吸；B组吸入噻托溴铵并同时予阿奇霉素片每次250mg口服，2次／周；C组仅接受常规治疗。疗程均为6个月。结果3组治疗6个月后咳嗽、咳痰、气促评分及急性加重情况、6min步行距离及生活质量评分比较，差异有统计学意义（F值分别为29．37、62．56、7．59、148．35、317．68、16．60，P均〈0．01）。与c组治疗后比较，B组治疗后病例急性加重次数明显减少[（2．1＋0．6）次与（4．9±0．7）次，P〈0．05]；临床症状评分咳嗽[（1．3±0．5）分与（2．2±0．6）分，19〈0．05]、咳痰[（1．0±0．2）分与（1．7±0．3）分，P〈0．05]、气促[（1．5±0．8）分与（2．1±0．6）分，P〈0．05]、运动耐力[6min步行距离（370．00±14．26）m与（290．00±12．85）m，P〈0．05]及生活质量[SGRQ总分：（293-8）分与（42±11）分，P〈0．05]明显改善。B组与A组治疗后比较，急性加重次数[（2．1±0．6）次与（3．2±0．8）次，P〈0．05]、临床症状评分咳嗽[（1．3±0．5）分与（1．8±0．4）分，P〈0．05]、咳痰[（1．0±0．2）与（1．3±0．3）分，P〈0．05]、气促[（1．5±0．8）分与（1．9±0．6）分，P〈0．05）]、运动耐力[6min步行距离（370．00±14．26）m与（330．00±13．76）m，P〈0．05]及生活质量[（SGRQ总分：（29±8）分与（36±10）分，P〈0．05]改善优于A组，差异均有统计学意义。结论小剂量阿奇霉素联合噻托溴铵治疗稳定期COPD，疗效佳，优于噻托溴铵单药治疗，且安全性高。

Objective To study the efficacy and safety of low-dose azithromycin with tiotropium bromide in the treatment of stable chronic obstructive pulmonary disease. Methods A hundred and ten patients were randomized into three groups ： tiotropium bromide group （ 36 cases, group A ）, azithromycin with tiotropium bromide group（38 cases, group B）and control group （36 cases, group C）. Patients in group A were given tiotropium bromide （18 μg,q. d ）in addition to conventional treatment. The patients in group B were given low- dose azithromycin （250 mg.twice a week）in combined with tiotropium bromide. The patients in control group were given the conventional treatment only. The courses of treatment lasted for six months. Results Compared with the control group,the frequency of acute exacerbation in patients treated with azithromycin and tiotropium bromide was reduced remarkably （ 2. 1 ± 0. 6 and 4. 9 ± 0. 7, t = 18. 5061, P 〈 0. 05 ）. The severity of clinic symptoms （ Cough 1.3 ± 0. 5 vs. 2. 2 ± 0. 6, P 〈 0. 05 ）, expectoration （ 1.0 ± 0. 2 vs. 1.7 ± 0. 3, P 〈 0. 05 ）, anhelation （ 1.5 ± 0. 8 vs. 2. 1 ± 0. 6, t = 3. 6342, P 〈 0. 001 ） ], life quality （ 29 ± 8 vs. 42 ~ 11, P 〈 0. 05 ） and six-minutes walking distance（ [ 370. 00 ± 14. 26 ] m vs. [ 290.00 ± 12. 85 ] m, P 〈 0. 05 ） of the azithromycin with tiotropium bromide group were improved significantly when compared with control. Compared with the tiotropium bromide group, the frequency of acute exacerbation （ 2. 1 ± 0. 6 vs. 3.2± 0. 8, P 〈 0. 05 ）, the severity of clinic symptoms （ Cough 1.3± 0. 5 vs. 1.8 ± 0. 4,P 〈 0.05 ）, expectoration （ 1.0 ± 0. 2 vs. 1.3±0. 3, P 〈 0.05 ） and anhelation（ 1.5 ± 0. 8 vs. 1.9 ± 0. 6, P 〈 0. 05 ） ]; life quality （ 29 ± 8 vs. 36 ± 10, P 〈 0. 05 ） and six-minutes walking distance （ [ 370. 00 ± 14. 26 ] m vs. [ 330. 00 ± 13.76 ] m, P 〈 0. 05 ） were improved over those of tiotropium bromide group. Conclusion The long-term low-dose azithromycin in combined with tiotropium bromide is good and safe in treating stable COPD. Therefore,it is worth of further clinical evaluation.