雾化吸入布地奈德对慢性阻塞性肺疾病合并呼吸衰竭机械通气的影响

Effectiveness of nebulised budesonide therapy for chronic obstructive pulmonary disease with respiratory failure requiring mechanical ventilation for an exacerbation

目的观察雾化吸入布地奈德在慢性阻塞性肺疾病（COPD）急性加重期的治疗作用。方法将2009年11月至2011年1月COPD合并呼吸衰竭需要机械通气治疗的住院患者随机分为三组：对照组给予雾化沙丁胺醇（2ml，Q6h）和异丙托溴铵（0．5mg，q．i．d．）；甲泼尼龙组在沙丁胺醇和异丙托溴铵（剂量及用法同对照组）治疗基础上加用甲泼尼龙静脉注射，40mg／d，使用5d停药；布地奈德组在沙丁胺醇和异丙托溴铵（剂量及用法同对照组）治疗基础上加用布地奈德混悬液雾化吸入（2mg，Q8h），使用5d后停用。分别记录上机1h、上机72h、上机5d、上机7d痰Ib8水平、TNF-α水平、C反应蛋白（CRP）水平、随机血糖水平。结果共有48例符合本研究标准，其中对照组15例、甲泼尼龙组17例、布奈德组16例。上机72h甲泼尼龙组和布地奈德组痰IL-8、TNF-α、CRP水平与本组上机1h比较明显降低，差异均具有统计学意义（P〈0．05），而对照组直到上机5d，痰IL-8、TNF-α、CRP水平才较本组上机1h明显降低，差异具有统计学意义（P〈0．05）；上机7d，甲泼尼龙组和布地奈德组痰Ib8、TNF-α、CRP水平均明显低于对照组，差异具有统计学意义（P〈0．05）;在上机72h、上机5d、上机7d，甲泼尼龙组和布地奈德组痰Ib8、TNF-α、CRP水平比较差异均无统计学意义（P〉0．05）。上机7d，甲泼尼龙组随机血糖水平较对照组及布地奈德组明显升高，三组比较差异有统计学意义（F=18．2，P=0．025）。结论在COPD急性加重期，应用布地奈德雾化吸人治疗具有与全身应用糖皮质激素相似的治疗效果，而布地奈德全身不良反应少，使用更加安全。

Objective To evaluate the safety and efficacy of nebulised budesonide suspension compared with systemic corticosteroid in the treatment of chronic obstructive pulmonary disease （COPD） patients with respiratory failure requiring mechanical ventilation for an exacerbation. Methods COPD patients for an exacerbation were prospectively enrolled in the study. Informed consent was obtained from all the participants. The patients from November, 2009 to December, 2011 were randomly sorted into three groups. The treatment groups were as follows. Control group received bronchodilator treatment with nebulised salbutamol （2 ml,Q6h） and nebulised ipratropium bromide （0.5 mg q. i. d. ） in separate sessions. Methylprednisolone group received systemic corticosteroids with methylprednisolone （i. v. 40 mg q. i. d. ） for 5 days beside the same bronchodilator treatments as control group. Budesonide group received nebulised corticosteroids with nebulised budesonide （2 rag, Q8h） for 5 days beside the same bronchodilator treatments as control group. All patients were given mechanical ventilation and antibiotics that were used according to patientts condition. IL-8 of induced sputum and absolute blood glucose level were detected at 1 h,72 h,5 d,7 d for mechanical ventilation. Results 48 patients completed the study （15in control group, 17 in methylprednisolone group, 16 in budesonide group）. At 1 h for mechanical ventilation, there is no statistical difference for sputum IL-8,TNF-α and CRP in three groups. At 72 h for mechanical ventilation, Sputum IL-8,TNF-α and CRP in methylprednisolone group and budesonide group were lower than those at 1 h （ P〈0.05）. At 5 d for mechanical ventilation, Sputum IL-8, TNF-α and CRP in control group was lower than those at 1 h （ P =0. 023）. At 7 d sputum IL-8,TNF-α and CRP in methylprednisolone group and budesonide group were lower than those in control group （ P〈0.05）. There is no statistical difference for sputum IL-8, TNF-αand CRP levels at 72 h, 5 d, 7 d between methylprednisolone group and budesonide group （ P〈0.05）. Blood glucose exhibited an upward trend only in methylprednisolone group. Conclusions Nebulised budesonide exerted less systemic activity than systemic corticosteroid administration, as indicated by serial blood glucose measurements. In conclusion, the data suggest that high-dose nebulised budesonide may be an alternative to systemic corticosteroids in the treatment of exacerbations of COPD.