聯(lián)合使用噻托溴銨和茶堿對(duì)慢性阻塞性肺疾病睡眠低氧的療效及相關(guān)作用機(jī)制研究
發(fā)布時(shí)間：2018-08-10 18:17
【摘要】：目的:噻托溴銨和緩釋茶堿是目前公認(rèn)的對(duì)穩(wěn)定期COPD患者夜間睡眠低氧既有效又安全的兩種藥,但二者單獨(dú)治療仍不能達(dá)到理想的效果。本研究通過(guò)對(duì)夜間睡眠血氧飽和度、血?dú)夥治�、肺功能、呼吸中樞�?qū)動(dòng)、呼吸肌功能、肺動(dòng)脈平均壓及安全性指標(biāo)的分析來(lái)評(píng)價(jià)聯(lián)合使用噻托溴銨和緩釋茶堿對(duì)穩(wěn)定期COPD患者夜間睡眠低氧的療效及安全性,并對(duì)二者的作用機(jī)制進(jìn)行初步探討,旨在為穩(wěn)定期COPD患者夜間睡眠低氧尋找一更有效的藥物治療新途徑。方法:依據(jù)入選標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn),嚴(yán)格篩選出存在夜間睡眠低氧的穩(wěn)定期中重度COPD患者63例。受試者先進(jìn)入1周的洗脫期,經(jīng)洗脫期后合格者被隨機(jī)分成3組進(jìn)入4周的治療期:噻托溴銨組(21例):每日下午吸入噻托溴銨干粉1粒(18μg);茶堿緩釋片組(21例):每日早晚各口服茶堿緩釋片2片(0.2g);聯(lián)合治療組(21例):聯(lián)合應(yīng)用噻托溴銨干粉和茶堿緩釋片,用法同前。在洗脫期1周末(基線期)和治療期4周末共隨訪2次,分別對(duì)各種療效指標(biāo)[夜間睡眠血氧飽和度(MSa O2、Mm Sa O2、T90)、血?dú)夥治?Pa O2、Pa CO2、Sa O2)、肺功能(FEV1、FVC、IC)、呼吸中樞驅(qū)動(dòng)(P0.1)、吸氣肌功能(PImax)、呼氣肌功能(PEmax)、肺動(dòng)脈平均壓(m PAP)]及安全性指標(biāo)進(jìn)行檢測(cè)。采用SPSS17.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)量資料以x±s表示,多組計(jì)量資料采用單因素方差分析,組內(nèi)兩兩比較采用配對(duì)t檢驗(yàn),組間兩兩比較采用成組t檢驗(yàn),計(jì)數(shù)資料采用x2檢驗(yàn),以P0.05表示有顯著性差異。結(jié)果:1最終納入符合方案療效統(tǒng)計(jì)分析的患者61例,其中噻托溴銨組21例、茶堿緩釋片組20例、聯(lián)合治療組20例,三組在人口學(xué)和基線特征方面比較均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。2各組治療后與本組治療前比較:(1)三組的MSa O2、Mm Sa O2、Pa O2、Sa O2、FEV1、FVC、IC、PImax均明顯提高(P0.05或P0.01);(2)三組的T90、Pa CO2、m PAP均明顯降低(P0.05或P0.01);(3)P0.1在噻托溴銨組明顯降低(P0.05),在茶堿緩釋片組明顯提高(P0.05),而在聯(lián)合治療組則無(wú)明顯變化(P0.05);(4)PEmax在聯(lián)合治療組明顯提高(P0.05),在噻托溴銨組和茶堿緩釋片組雖有增高趨勢(shì),但差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。3聯(lián)合治療組治療后與噻托溴銨組治療后比較:(1)聯(lián)合治療組的MSa O2、Mm Sa O2、Pa O2、Sa O2、FEV1、IC、P0.1、PImax均明顯提高(P0.05),T90、Pa CO2、m PAP均明顯降低(P0.05);(2)聯(lián)合治療組的FVC、PEmax雖均有增高趨勢(shì),但差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。4聯(lián)合治療組治療后與茶堿緩釋片組治療后比較:(1)聯(lián)合治療組的MSa O2、Mm Sa O2、Pa O2、Sa O2、FEV1、FVC、IC、PImax均明顯提高(P0.05或P0.01),T90、Pa CO2、P0.1、m PAP均明顯降低(P0.05或P0.01);(2)聯(lián)合治療組的PEmax雖有增高趨勢(shì),但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1噻托溴銨可通過(guò)改善肺通氣和通氣/血流比例失調(diào)、增強(qiáng)吸氣肌肌力來(lái)明顯改善COPD患者夜間睡眠低氧;2茶堿緩釋片可通過(guò)改善肺通氣和通氣/血流比例失調(diào)、增強(qiáng)呼吸中樞驅(qū)動(dòng)和吸氣肌肌力來(lái)明顯改善COPD患者夜間睡眠低氧;3噻托溴銨和茶堿緩釋片聯(lián)合優(yōu)于各自單獨(dú)治療,具有協(xié)同增效的作用,可通過(guò)進(jìn)一步改善肺通氣和通氣/血流比例失調(diào)、進(jìn)一步增強(qiáng)吸氣肌及呼氣肌肌力來(lái)更加明顯地改善COPD患者夜間睡眠低氧。
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R563.9
本文編號(hào)：2175809
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R563.9
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