吸入糖皮质激素联合氨茶碱治疗对支气管哮喘患者疗效及T淋巴细胞亚群的影响

发布时间：2018-05-14 03:01

本文选题：吸入性糖皮质激素 + 氨茶碱　；参考：《郑州大学》2012年博士论文

【摘要】：1 目的支气管哮喘是气道的慢性非特异性炎症反应。哮喘严重影响患者的生活、工作和学习,影响儿童及青少年的生长发育。严重哮喘急性发作,若未得到及时有效的治疗,可以致命。哮喘农村患病率高于城市,仅0.3%的患者按全球哮喘防治方案正规治疗[1],影响患者依从性不高的主要原因是经济困难。吸入性糖皮质激素是控制哮喘首选药物,其疗效好,副作用小,得到临床医生的肯定[2],但因价格较贵,难以普及。确定哮喘长期治疗方案,既要考虑药物的疗效及安全性,也要考虑患者的实际情况。贫困地区或低经济收入的患者,推荐使用ICS联合口服茶碱长期控制哮喘[2]。本研究的目的在于明确ICS(吸入糖皮质激素)联合口服茶碱的疗效及对呼吸道炎症的抑制作用,以及ICS(吸入糖皮质激素)联合口服茶碱治疗对体内T淋巴细胞亚群的影响,治疗过程中T淋巴细胞亚群与哮喘患者肺功能、气道炎症水平的相关性。本研究为哮喘的临床治疗提供参考,为广大中低收入哮喘人群寻找价廉、易接受的治疗方案。2 方法 2.1受试对象所有研究对象在实验前四周内未用全身糖皮质激素及其它抗过敏药,二周内未口服白三烯受体拮抗剂,一周内未吸入长效β2一受体激动剂口服β受体激动剂。1)吸入激素联合氨茶碱对中度持续哮喘患者的治疗作用。依据GINA诊断标准,选择我院呼吸科门诊2011年1月至2011年12月的中度哮喘患者25例,试验组患者每日吸入布地奈德(普米克都保,阿斯利康公司,批号:NC1219),每次200μg,每天2次;口服氨茶碱片0.1g每天3次。吸入激素联合口服氨茶碱或者长效β2受体激动剂控制中度持续哮喘的疗效观察及治疗前后体内T淋巴亚群的变化。依据《支气管哮喘防治指南》[2]哮喘诊断标准,选择郑州大学人民医院呼吸科门诊2011年1月至2011年12月的未控制哮喘患者280例。采用随机、开放、平行、对照的方法,将患者分为试验组(ICS+茶碱)和对照组(ICS+LABA)两组,每组140例。试验组每日吸入布地奈德(普米克都保,阿斯利康公司,批号:NC1219),每次200μg,每天2次;口服氨茶碱片(北京紫竹药业有限公司,批号:H11020445)0.1g,每天3次。对照组患者每日吸入布地奈德/福莫特罗(信必可都保,阿斯利康公司,批号:ML967),每吸(160/4.5)μg,每天2吸。研究期间给予舒喘灵气雾剂(上海信谊公司)用以必要时缓解症状。总疗程为3月。3)吸入糖皮质激素联合茶碱对未控制吸烟哮喘患者的疗效观察筛选门诊未控制支气管哮喘患者80例,随机分为试验组和对照组,试验组为吸烟患者,对照组为不吸烟患者。两组均每日吸入布地奈德,每次200μg,每天2次,联合口服氨茶碱片0.1g,每天3次。疗程3个月。2.2药物的选择及使用方法试验药物:普米克加茶碱组(普米克都保,阿斯利康公司,400ug/d分2次吸入,氨茶碱0.1,3次/日)。布地奈德/福莫特罗(信必可都保,阿斯利康公司,批号:ML967),每吸(160/4.5)μg,每天2吸。研究期间给以舒喘灵气雾剂(上海信谊公司)必要时用以缓解症状,疗程为6周。2.3观察指标1.不同药物治疗后哮喘控制水平;2.不同药物呼吸系统症状评分;3.不同药物治疗前后晨晚间峰流速((PEF);4.不同药物治疗前后FEV 1占预计值百分比(FEV}%);5.不同药物治疗前后诱导痰嗜酸粒细胞计数;6.不同药物治疗前后外周静脉血IL-4,Ig E;7.不同药物治疗前后外周血中Th1,Th2,Th17细胞的分布情况,以及血清中IL-4、IL-5、IL-17等细胞因子的水平。并分析其与以上临床指标的相关性。3 结果 3.1 ICS联合氨茶碱可以降低哮喘患者体内Th2、Th17细胞的比例,Th2、Th17细胞与哮喘患者肺功能、气道炎症水平有很好的相关性。3.2治疗哮喘1月时,ICS联合氨茶碱在改善PEF、ACT评分方面,明显不及ICS联合长效β2受体激动剂组(P均0.05),痰嗜酸粒细胞比例的改善优于ICS联合长效β2受体激动剂组(P0.05),Fe NO无明显区别(P0.05);治疗3月时,ICS联合氨茶碱对痰嗜酸粒细胞比例的改善优于ICS联合长效β2受体激动剂组(P0.05),对Fe NO、PEF、ACT评分的改善与对照组无明显区别(P均0.05)。两组均能降低哮喘患者体内Th2、Th17细胞的比例,降低外周血上清中IL-4、IL-5、IL-17、Ig E的水平,组间没有统计学差异。3.3吸烟患者用ICS联合氨茶碱治疗前、治疗3月后的ACT评分、PEF、FEV1%预计值、IL-4、IL-5、Ig E值分别为:(12.2±3.3)和(18.3±2.9),(255.9±99.7)L·min-1和(290.3±105.2)L·min-1,(66.5±4.7)和(72.9±5.4),(14.5±3.2)pg·m L-1和(12.3±3.4)pg·m L-1,(27.2±6.4)pg·m L-1和(24.2±5.8)pg·m L-1,(82.7±16.8)IU·m L-1和(67.1±14.3)IU·m L-1,非吸烟者分别为:(13.0±3.4)和(19.1±2.6),(279.1±103.3)L·min-1和(321.3±110.4)L·min-1,(68.8±5.8)和(74.8±5.5),(13.4±2.9)pg·m L-1和(11.4±2.8)pg·m L-1,(26.5±6.9)pg·m L-1和(22.8±6.2)pg·m L-1,(78.8±18.2)IU·m L-1和(66.4±17.8)IU·m L-1,两组组内比较差异有统计学意义(P0.05),组间比较差异无统计学意义(P0.05)。吸烟和非吸烟患者用ICS联合氨茶碱治疗后均能降低哮喘患者体内Th2、Th17细胞的比例,组间没有统计学差异。3.4统计学分析采用SPSS16.0统计软件进行数据分析。各项指标的变化值以x±s表示,采用多组比较的ANOVA检验,P0.05为差异有统计学意义。4 结论 4.1 ICS联合氨茶碱,可以降低哮喘患者体内Th2、Th17细胞的比例,Th2、Th17细胞与哮喘患者肺功能、气道炎症水平有很好的相关性。4.2 ICS(吸入糖皮质激素)联合氨茶碱,在改善哮喘患者肺功能、控制气道炎症方面与ICS联合长效β2受体激动剂有相似的疗效。4.3小剂量ICS(吸入糖皮质激素)联合小剂量氨茶碱,在改善吸烟哮喘患者症状、提高肺功能、控制气道炎症方面与不吸烟患者有相同的疗效。
[Abstract]:1 bronchial asthma is a chronic nonspecific inflammatory response in the airway. Asthma seriously affects the life, work and learning of the patients. It affects the growth and development of children and adolescents. The acute attack of severe asthma can be fatal if it is not given timely and effective treatment. The prevalence of asthma in rural areas is higher than that in the city, and only 0.3% of the patients are based on global asthma prevention. The main reason for the regular treatment of [1] is economic difficulty. Inhaled glucocorticoid is the first drug to control asthma. It has good curative effect and small side effect. It is difficult to be popularized by the clinician, but it is difficult to popularize the long-term treatment for asthma. The purpose of the study was to identify the efficacy of the combination of ICS (inhaled glucocorticoids) combined with oral theophylline and the inhibitory effect on respiratory inflammation, as well as the combination of ICS (inhaled glucocorticoid) and oral theophylline treatment, in poor or low income patients. The purpose of the study is to use ICS combined with oral theophylline for long-term control of asthma [2].. The effect of therapy on the T lymphocyte subsets in the body, the correlation between the T lymphocyte subsets and the lung function and airway inflammation in the patients with asthma. This study provides a reference for the clinical treatment of asthma, and for the majority of the middle and low income asthma people to find the inexpensive and acceptable treatment program.2 method, all the subjects of the subjects are in the actual study. No systemic glucocorticoid and other antiallergic drugs were used in the four weeks before the test. No oral leukotriene receptor antagonist was taken within two weeks. The therapeutic effect of inhaled hormone combined with aminophylline on moderate persistent asthmatic patients was not inhaled during one week. The effect of inhaled hormone and aminophylline on moderate persistent asthmatic patients was not inhaled within one week. According to GINA diagnostic criteria, 2 Department of respiration outpatients in our hospital were selected. 2 In 25 cases of moderate asthma from January to December 2011, patients in the test group inhaled budesonide daily (general Mick, AstraZeneca, batch number: NC1219), 200 mu g each time, 2 times a day, 3 times a day for oral Aminophylline Tablets 0.1g. Inhaled hormone combined oral aminophylline or long effect beta 2 receptor agonists to control the efficacy of moderate persistent asthma The changes of T lymphatic subgroup in the body before and after treatment were observed and 280 cases of uncontrolled asthma in the Department of respiration of the Department of respiration, Zhengzhou University from January 2011 to December 2011 were selected according to the diagnostic criteria of asthma prevention and control guidelines of the people's Hospital of Zhengzhou University. The patients were randomly, open, parallel, and controlled. The patients were divided into the experimental group (ICS+ theophylline) and the control group (I CS+LABA) two groups, each group of 140 cases. The test group inhaled budesonide daily (Mick Du Bao, AstraZeneca, batch number: NC1219), 200 mu g each time, 2 times a day; oral Aminophylline Tablets (Beijing zizuzhu Pharmaceutical Co., H11020445) 0.1g, 3 times a day. The control group inhaled budesonide / formoterol daily (sure, Ashley) "Kang company, batch number: ML967), each inhalation (160/4.5) mu g, 2 inhalation per day. During the study period, the sulbactin aerosol (Shanghai Xinyi company) was used to relieve symptoms when necessary. The total course was March.3) inhaled corticosteroids combined theophylline for uncontrolled smoking patients, 80 cases of uncontrolled bronchial asthma were selected and randomly divided into a trial. The two groups were inhaled budesonide daily, 200 g each time, 2 times a day, combined oral Aminophylline Tablets 0.1g, 3 times a day. The course of treatment for 3 months.2.2 drugs and the use of a test drug: Pulmicort and theophylline group (general Mick, AstraZeneca, 400ug/d, 2) Inhalation, aminophylline 0.1,3 times / day). Budionide / formoterol (sure, AstraZeneca, batch number: ML967), each inhalation (160/4.5) mu g, 2 inhalation per day. During the study period, the schuterol aerosol (Shanghai Xinyi) was given to relieve symptoms when necessary, and the treatment course was 6 weeks.2.3 observation index 1. different medication after treatment of asthma control level; 2. no The same drug respiratory system symptom score; 3. morning and evening peak flow rate (PEF) before and after treatment with different drugs; 4. FEV 1 before and after treatment of different drugs (FEV}%); 5. induced phlegm eosinophil count before and after treatment of different drugs; 6. IL-4, Ig E before and after treatment of different drugs; 7. Th1, Th2 in peripheral blood before and after treatment of different drugs. The distribution of Th17 cells, the level of IL-4, IL-5, IL-17 and other cytokines in the serum, and analyze the correlation with the above clinical indicators,.3 results 3.1 ICS combined with aminophylline can reduce the proportion of Th2, Th17 cells in the patients with asthma, Th2, Th17 cells have a good correlation with the lung function of the asthmatic patients and the level of airway inflammation. In January, ICS combined with aminophylline was less than ICS combined with long effect beta 2 receptor agonist (P 0.05) in improving PEF and ACT score. The improvement of phlegm eosinophil ratio was better than ICS combined with long-acting beta 2 receptor agonist group (P0.05), Fe NO had no significant difference (P0.05); ICS combined with aminophylline was used to modify phlegm eosinophil ratio in March. Better than ICS combined with long effect beta 2 receptor agonist group (P0.05), the improvement of Fe NO, PEF, ACT score was not significantly different from the control group (P 0.05). The two groups could reduce the proportion of Th2 and Th17 cells in the patients with asthma, and reduce the level of IL-4, IL-5, IL-17, and IL-17, and there was no statistical difference between the groups. Before the treatment, the ACT scores after March, PEF, FEV1% predicted values, IL-4, IL-5 and Ig E values were respectively (12.2 + 3.3) and (18.3 + 2.9), (255.9 + 99.7) L min-1 and (290.3 + 105.2) L. Min-1, (66.5 + 4.7) and (72.9 + 5.4). .1 + 14.3) IU. M L-1, non smokers were (13 + 3.4) and (19.1 + 2.6), (279.1 + 103.3) L / min-1 and (321.3 + 110.4) L. Min-1, (68.8 + 5.8) and (74.8 + 5.5). There was statistical significance (P0.05), there was no statistical difference between groups (P0.05). Smoking and non smoking patients with ICS combined with aminophylline could reduce the proportion of Th2 and Th17 cells in the patients with asthma. There was no statistical difference between groups and.3.4 statistical analysis was analyzed by SPSS16.0 meter software. The change values of each index were x +. S indicated that using multiple comparison ANOVA tests, P0.05 was statistically significant.4 conclusion 4.1 ICS combined aminophylline, which could reduce the proportion of Th2, Th17 cells in asthmatic patients, Th2, Th17 cells and lung function in asthmatic patients, and a good correlation between the airway inflammation level and the.4.2 ICS (inhaled corticosteroids) combined with aminophylline, in improving asthma. Pulmonary function and control of airway inflammation in asthmatic patients are similar to ICS combined with long effect beta 2 receptor agonists..4.3 small dose of ICS (inhaled corticosteroids) combined with small dose aminophylline has the same effect in improving the symptoms of asthma, improving lung function, and controlling airway inflammation.

【学位授予单位】：郑州大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R562.25

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