联合使用噻托溴铵和茶碱对慢性阻塞性肺疾病睡眠低氧的疗效及相关作用机制研究

发布时间：2018-08-10 18:17

【摘要】：目的:噻托溴铵和缓释茶碱是目前公认的对稳定期COPD患者夜间睡眠低氧既有效又安全的两种药,但二者单独治疗仍不能达到理想的效果。本研究通过对夜间睡眠血氧饱和度、血气分析、肺功能、呼吸中枢驱动、呼吸肌功能、肺动脉平均压及安全性指标的分析来评价联合使用噻托溴铵和缓释茶碱对稳定期COPD患者夜间睡眠低氧的疗效及安全性,并对二者的作用机制进行初步探讨,旨在为稳定期COPD患者夜间睡眠低氧寻找一更有效的药物治疗新途径。方法:依据入选标准和排除标准,严格筛选出存在夜间睡眠低氧的稳定期中重度COPD患者63例。受试者先进入1周的洗脱期,经洗脱期后合格者被随机分成3组进入4周的治疗期:噻托溴铵组(21例):每日下午吸入噻托溴铵干粉1粒(18μg);茶碱缓释片组(21例):每日早晚各口服茶碱缓释片2片(0.2g);联合治疗组(21例):联合应用噻托溴铵干粉和茶碱缓释片,用法同前。在洗脱期1周末(基线期)和治疗期4周末共随访2次,分别对各种疗效指标[夜间睡眠血氧饱和度(MSa O2、Mm Sa O2、T90)、血气分析(Pa O2、Pa CO2、Sa O2)、肺功能(FEV1、FVC、IC)、呼吸中枢驱动(P0.1)、吸气肌功能(PImax)、呼气肌功能(PEmax)、肺动脉平均压(m PAP)]及安全性指标进行检测。采用SPSS17.0软件进行统计学分析,计量资料以x±s表示,多组计量资料采用单因素方差分析,组内两两比较采用配对t检验,组间两两比较采用成组t检验,计数资料采用x2检验,以P0.05表示有显著性差异。结果:1最终纳入符合方案疗效统计分析的患者61例,其中噻托溴铵组21例、茶碱缓释片组20例、联合治疗组20例,三组在人口学和基线特征方面比较均无统计学差异(P0.05)。2各组治疗后与本组治疗前比较:(1)三组的MSa O2、Mm Sa O2、Pa O2、Sa O2、FEV1、FVC、IC、PImax均明显提高(P0.05或P0.01);(2)三组的T90、Pa CO2、m PAP均明显降低(P0.05或P0.01);(3)P0.1在噻托溴铵组明显降低(P0.05),在茶碱缓释片组明显提高(P0.05),而在联合治疗组则无明显变化(P0.05);(4)PEmax在联合治疗组明显提高(P0.05),在噻托溴铵组和茶碱缓释片组虽有增高趋势,但差异均无统计学意义(P0.05)。3联合治疗组治疗后与噻托溴铵组治疗后比较:(1)联合治疗组的MSa O2、Mm Sa O2、Pa O2、Sa O2、FEV1、IC、P0.1、PImax均明显提高(P0.05),T90、Pa CO2、m PAP均明显降低(P0.05);(2)联合治疗组的FVC、PEmax虽均有增高趋势,但差异均无统计学意义(P0.05)。4联合治疗组治疗后与茶碱缓释片组治疗后比较:(1)联合治疗组的MSa O2、Mm Sa O2、Pa O2、Sa O2、FEV1、FVC、IC、PImax均明显提高(P0.05或P0.01),T90、Pa CO2、P0.1、m PAP均明显降低(P0.05或P0.01);(2)联合治疗组的PEmax虽有增高趋势,但差异无统计学意义(P0.05)。结论:1噻托溴铵可通过改善肺通气和通气/血流比例失调、增强吸气肌肌力来明显改善COPD患者夜间睡眠低氧;2茶碱缓释片可通过改善肺通气和通气/血流比例失调、增强呼吸中枢驱动和吸气肌肌力来明显改善COPD患者夜间睡眠低氧;3噻托溴铵和茶碱缓释片联合优于各自单独治疗,具有协同增效的作用,可通过进一步改善肺通气和通气/血流比例失调、进一步增强吸气肌及呼气肌肌力来更加明显地改善COPD患者夜间睡眠低氧。
[Abstract]:OBJECTIVE: Tiotropium bromide and sustained-release theophylline are currently recognized as both effective and safe drugs for nocturnal hypoxia in patients with stable COPD, but they can not achieve ideal results by single treatment. To evaluate the efficacy and safety of tiotropium bromide combined with sustained-release theophylline in the treatment of nocturnal hypoxia in patients with stable COPD, and to explore the mechanism of action of the two drugs in order to find a more effective drug therapy for nocturnal hypoxia in patients with stable COPD. Sixty-three stable moderate to severe COPD patients with nocturnal sleep hypoxia were screened strictly according to the exclusion criteria. Subjects entered a one-week elution period and were randomly divided into three groups: the tiotropium bromide group (21 cases): one capsule of dry tiotropium bromide (18 ug) was inhaled in the afternoon every day; the theophylline sustained-release tablets group (21 cases): early daily. Two tablets of theophylline sustained-release tablets (0.2g) were taken orally at night in each group, and 21 tablets in the combined treatment group (21 cases) were given thiotropium bromide dry powder and theophylline sustained-release tablets in the same way. Function (FEV1, FVC, IC), respiratory center drive (P 0.1), inspiratory muscle function (PImax), expiratory muscle function (PEmax), mean pulmonary artery pressure (MPAP) and safety indicators were tested. SPSS17.0 software was used for statistical analysis, measurement data was expressed as X 65 Results: 1. 61 patients were included in the final statistical analysis of the efficacy of the scheme, including 21 cases in the tiotropium group, 20 cases in the theophylline sustained-release tablet group, 20 cases in the combined treatment group, and 20 cases in the combined treatment group. Difference (P 0.05). 2 After treatment, the MSa O 2, Mm Sa O 2, Pa O 2, Sa O 2, FEV1, FVC, IC and PImax in the three groups were significantly increased (P 0.05 or P 0.01); (2) T90, Pa CO 2, and m PAP in the three groups were significantly decreased (P 0.05 or P 0.01); (3) P 0.1 was significantly decreased in the tiotropium bromide group (P 0.05), and significantly increased in the theophylline sustained-release tablet group (P 0.05), but significantly decreased in the combined group (P 0.05). There was no significant change in the treatment group (P 0.05); (4) PEmax in the combined treatment group significantly increased (P 0.05), in the tiotropium bromide group and theophylline sustained-release tablets group although there was an increasing trend, but the difference was not statistically significant (P 0.05). 3 After treatment, the combined treatment group compared with tiotropium bromide group after treatment: (1) combined treatment group MSA O 2, Mm SaO 2, PaO 2, SaO 2, FEV1, IC, P 0.1, P Imax were significantly increased (P 0.05), T90, Pa CO2, m PAP were significantly decreased (P 0.05); (2) FVC, PEmax in the combined treatment group were increased, but the difference was not statistically significant (P 0.05). 4 After treatment, the combined treatment group and theophylline sustained-release tablet group were compared: (1) The combined treatment group MSO 2, Mm SaO 2, PaO 2, SaO 2, FEV1, FVC, IC, PImax were significantly increased. (P 0.05 or P 0.01), T90, PaCO 2, P 0.1, and m PAP were significantly decreased (P 0.05 or P 0.01); (2) Although PEMAX in the combined treatment group increased, there was no significant difference (P 0.05). Conclusion: 1-tiotropium bromide can significantly improve nocturnal sleep hypoxia in COPD patients by improving pulmonary ventilation and ventilation/blood flow imbalance, enhancing inspiratory muscle strength; 2-theophylline slow-release therapy group. Tablets can significantly improve nocturnal sleep hypoxia in patients with COPD by improving pulmonary ventilation and ventilation/blood flow imbalance, enhancing respiratory central drive and inspiratory muscle strength; 3-tiotropium bromide and theophylline sustained-release tablets are superior to their respective treatment alone, with synergistic effect, and can be improved by further improving pulmonary ventilation and ventilation/blood flow imbalance. Increasing the strength of inspiratory and expiratory muscles one step can improve the sleep hypoxia of COPD patients more obviously.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R563.9

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