噻托溴铵联合布地奈德福莫特罗吸入对高海拔慢性肺心病气道炎症和呼吸功能的影响

Effects of tiotropium bromide combined budesonide and formoterol by airway suction on airway inflammation and respiratory function in patients with chronic cor pulmonale at high altitude

目的探讨噻托溴铵联合布地奈德福莫特罗吸入对高海拔慢性肺心病(HACCP)患者气道炎症和呼吸功能的影响。方法 128例HACCP患者随机分为观察组和对照组,每组64例。2组在抗感染、祛痰、茶碱、氧疗常规治疗的基础上,观察组给予噻托溴铵(18μg/次,每日1次)联合布地奈德福莫特罗吸入(160μg/4.5μg/次,每日2次);对照组仅给予噻托溴铵吸入,剂量同观察组。治疗前、治疗6周后进行肺功能、动脉血气、诱导痰TNF-α、IL-6、运动耐力测定及BODE指数评估。结果治疗后,观察组和对照组的FEV1%pred、FEV1/FVC、Pa O2、6MWD[分别为(45.3±6.7)%、(47.8±7.1)%、(51.5±5.8)mm Hg、(421.5±52.8)m和(40.1±6.5)%、(43.4±6.7)%、(47.7±5.4)mm Hg、(378.7±50.4)m]较治疗前[分别为(35.4±6.6)%、(39.3±7.1)%、(42.6±5.5)mm Hg、(342.6±55.5)m和(34.9±6.4)%、(38.6±7.0)%、(42.0±5.5)mm Hg、(340.5±52.4)m]显著升高(均P<0.01),Pa CO2、诱导痰TNF-α、IL-6水平、BODE指数[分别为(47.8±5.8)mm Hg、(35.7±6.7)ng/L、(27.5±5.4)ng/L、(4.4±0.8)和(51.2±5.6)mm Hg、(40.3±6.4)ng/L、(31.2±5.6)ng/L、(5.2±0.8)]较治疗前[分别为(56.8±6.1)mm Hg、(48.6±6.6)ng/L、(35.5±6.2)ng/L、(6.1±0.9)和(56.1±5.9)mm Hg、(47.9±6.2)ng/L、(34.9±6.6)ng/L、(6.0±0.8)]显著降低(均P<0.01)。观察组与对照组比较差异非常显著(均P<0.01)。6MWD与TNF-α、IL-6显著负相关,与FEV1%pred、Pa O2显著正相关(均P<0.001);BODE指数与TNF-α、IL-6显著正相关,与FEV1%pred、Pa O2显著负相关(均P<0.001)。结论噻托溴铵联合LABA+ICS或单纯噻托溴铵气道吸入均能显著地改善HACCP患者的气道炎症、呼吸功能,提高运动耐力和生活质量,噻托溴铵联合LABA+ICS的疗效优于单纯噻托溴铵。

Objective To explore the Effects of tiotropium bromide combined budesonide and formoterol by airway suction on airway inflammation and respiratory function in patients with chronic cot pulmonale at high altitude （HACCP）. Methods 128 patients with HACCP were randomly divided into the observation group and control group, each group with 64 cases. The all patients in 2 groups received routine treatment of anti-infection, expectorant, theophylline, and oxygen therapy. The observation group received tiotropium bromide powder for inhalation （18μg, once a day） combined budesonide/formoterol （160/5.4 μg, twice a day） , and control group received alone tiotropium bromide powder for inhalation （ 18 μg, once a day） All patients were examined for pulmonary function, arterial blood gas, level of induced sputum TNF-α, IL-6, 6MWD, and BODE index before and after 6 weeks treatment. Results after treatment, FEV1% pred, FEV1/ FVC, PaO2, 6 MWD in observation group and control group were both significantly higher [ （ 45.3± 6.7 ） %, （47.8±7.1）%, （51.5±5.8）mmHg, （421.5±52.8）m and（40.1±6.5）%, （43.4±6.7）%, （47.7±5.4）mmHg, （378.7±50.4）m, respectively] than those before treatment [ （35.4±6.6）%, （39.3±7.1）%, （42.6±5.5） mmHg, （342.6±55.5）m and（34.9±6.4）, （38.6±7.0）%, （42.0±5.5）mmHg）, （340.5±52.4）m, respectively] （all P〈0. 01）. PaCO2, level of induced sputum TNF-a, IL-6, and BODE index were both significantly lower[（47.8±5.8）mmHg, （35.7±6.7） ng/L, （27.5±5.4） ng/L, （4.4±0.8） and （51.2±5.6） mmHg, （40.3±6.4）ng/L, （31.2±5.6）ng/L, （5.2±0.8）, respectively] than those before treatment [ （56.8± 6.1）mmHg, （48.6±6.6） ng/L, （35.5±6.2） ng/L, （ 6.1 ±0.9） and（56.1 ±5.9） mmHg, （47.9±6.2） ng/L, （34.9±6.6） ng/L, （ 6.0±0.8）, respectively] （ all P〈0.01 ）, all parameters in observation group were different significantly Compared with those control group after treatment （all P〈0.01）. After treatment, 6 MWD in 128 patients was negative correlated with TNF-α and IL-6, positive correlated with FEV1% pred, PaO2（ all P〈 0.001 ）, BODE index was positive correlated with TNF-α and IL-6, and negative correlated with FEV] % pred and PaO2 （all P〈 0.001 ）. Conclusions The tiotropium bromide combined LABA ＋ ICS or pure tiotropium bromide by airway suction can significantly improve the airway inflammation, respiratory function, exercise endurance, and heath related quality of life in patients with HACCP. The effect of tiotropium bromide combined LABA＋ICS is more effective than pure tiotropium bromide.