Improved daytime spirometric efficacy of tiotropium compared with salmeterol in patients with COPD

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends long-acting bronchodilators as first-line maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). A study was conducted comparing the long-acting anticholinergic tiotropium with the long-acting beta-agonist salmeterol to confirm the significant improvements in daytime bronchodilator efficacy seen with tiotropium in previous studies. METHODS: Randomized, double-blind, double-dummy, parallel-group study, comparing daytime bronchodilator efficacy of tiotropium 18 mcg once daily with salmeterol 50 mcg twice daily in patients with COPD. Serial spirometry was performed over 12 h after 12 weeks of treatment. Co-primary endpoints were average (over 12 h) and peak FEV1 at 12 weeks. RESULTS: 653 patients were randomized (328 tiotropium, 325 salmeterol): mean age 64 years; 66% male; mean baseline FEV1 1.05 l (37.7% predicted). After 12 weeks, the average post-dose FEV1 over 12 h was significantly higher with tiotropium compared with salmeterol (167 vs. 130 mL, respectively, p=0.03), as was peak FEV1 (262 vs. 216 ml, respectively, p=0.01). The average FEV1 responses from 0-6 h and 6-12 h were higher in the tiotropium group compared with salmeterol (p<0.05). Peak and average FVC were significantly higher with tiotropium compared with salmeterol (p<0.01). Morning pre-dose FEV1 responses were not significantly different; however, tiotropium demonstrated a significantly higher pre-dose FVC than salmeterol (p<0.05). CONCLUSION: Tiotropium demonstrated significantly greater post-dose improvements in spirometric parameters compared with salmeterol. These improvements were sustained over 12 h.     

沙美特罗替卡松粉联合噻托溴铵治疗慢性阻塞性肺病稳定期C组患者的临床疗效观察

目的 观察吸入不同剂量沙美特罗替卡松粉（舒利迭）联合噻托溴铵治疗慢性阻塞性肺病（COPD）稳定期C组患者的疗效.方法 门诊选取72例COPD稳定期C组患者,随机分成3组,Ⅰ组单独吸入舒利迭（50μg沙美特罗/500 μg丙酸氟替卡松,2次/日）、Ⅱ组单独吸入噻托溴铵（18μg,1次/日）和Ⅲ组吸入舒利迭（50μg沙美特罗/250 μg丙酸氟替卡松,2次/日）＋噻托溴铵（18μg,1次/日）,共治疗12周.用药前后分别检测患者肺功能,应用改良的英国医学研究委员会呼吸困难量表（mMRC）进行评分、COPD评估测试（CAT）及6分钟步行试验（6MWT）.结果 Ⅰ、Ⅲ组患者肺功能指标、mMRC及CAT评分、6分钟步行距离均较治疗前明显改善（P＜0.05）;Ⅱ组患者肺功能指标改善不明显,6分钟步行距离、mMRC及CAT评分均较前改善（P＜0.05）.结论 沙美特罗替卡松粉（50 μg/250 μg,2次/日）联合噻托溴铵治疗COPD稳定期C组患者疗效确切,治疗风险未增加,值得临床推广.     

噻托溴铵联合沙美特罗替卡松对重度极重度慢性阻塞性肺疾病稳定期患者疗效分析

目的探讨联合吸人沙美特罗替卡松及噻托溴铵对重度极重度稳定期COPD患者肺通气功能指标、活动耐力及生活质量的疗效观察。方法选取2008年1月至2010年2月河间市人民医院门诊收治的102例稳定期重度极重度COPD患者,采用完全随机法分成A、B、C3组,A组给予噻托溴铵干粉剂,B组给予沙美特罗替卡松50／500μg,C组给予噻托溴铵干粉剂与沙美特罗替卡松联合吸人,共治疗6个月,在治疗3个月和6个月时分别进行肺通气功能评定、运动耐力评定、健康相关生活质量评价。结果3组患者治疗后肺通气功能评定、运动耐力评定、健康相关生活质量评价较治疗前均有改善,C组比A、B2组各指标改善明显,差异有统计学意义（P值均〈0．05）。结论联合使用噻托溴铵和沙美特罗替卡松可以更好地改善重度极重度稳定期COPD患者肺通气功能、提高运动耐力及生活质量,且不良反应发生率低,值得临床推广。     

噻托溴铵联合沙美特罗/氟替卡松治疗重度以上COPD稳定期的临床分析

目的探讨噻托溴铵(思力华)联合沙美特罗/氟替卡松(舒利迭)对COPD稳定期患者的肺功能、生活质量和急性发作次数等的改变。方法基础治疗为吸入舒利迭50/500 ug、Q 12 h,对照组加予复方异丙托溴铵(可必特)气雾剂2喷、Bid,治疗组加予思力华18 ug、Qd。每月复诊一次,观察6月。结果治疗6月后,治疗组FEV1增加0.20 L(1.24±0.15 vs 1.04±0.13),症状评分平均下降7.1分;对照组FEV1增加0.11 L(1.12±0.11 vs 1.01±0.15),症状评分平均下降4.1分;同组间前后有统计学差异(P<0.05);两组之间有统计学差异(P<0.05)。而不良反应相似且较轻。结论两种治疗均能改善重度及以上COPD患者的肺功能和临床症状;但噻托溴铵组更为优越,应在临床中推广。     

噻托溴铵联合大剂量沙美特罗/氟替卡松治疗重度支气管哮喘合并COPD稳定期的临床观察

目的 为了探讨更好的治疗重度支气管哮喘(简称哮喘)合并慢性阻塞性肺疾病(COPD)的方法,提高重度哮喘合并COPD患者的生活质量.为重度哮喘合并COPD防治积累更多临床经验.方法对于临床确诊的重度哮喘合并COPD的患者,随机分为两组,一组为对照组,给予复方异丙托溴铵气雾剂(可必特)联合中等剂量沙美特罗/氟替卡松(舒利迭...     

噻托溴铵联合大剂量沙美特罗/氟替卡松治疗重度支气管哮喘合并COPD稳定期的临床观察

目的 为了探讨更好的治疗重度支气管哮喘（简称哮喘）合并慢性阻塞性肺疾病（COPD）的方法,提高重度哮喘合并COPD患者的生活质量.为重度哮喘合并COPD防治积累更多临床经验.方法 对于临床确诊的霞度哮喘合并COPD的患者,随机分为两组,一组为对照组,给予复方异丙托溴铵气雾剂（可必特）联合中等剂量沙美特罗/氟替卡松（舒利迭50/250μg）治疗,一组为治疗组,给予噻托溴铵下粉吸入剂（思力华）联合大剂量沙美特罗/氟替卡松（舒利迭50/500μg）粉吸入剂治疗.采取随机、开放、自身对照和组间对照的方法,每月复诊一次,详细记录每例患者的肺功能变化、生活质量、急性发作次数、下次急性发作的间隔时间、住院次数、经济费用和不良反应.分析对比二者对重度哮喘合并COPD的综合疗效,为期一年.结果 治疗前两组患者FEV1分别为对照组（1.14±0.13）L、治疗组（1.11±0.15）L,两组之间差异无统计学意义.治疗一年后FEV1对照组为（1.30±0.14）L,治疗组（1.39±0.15）L,两组之间差异无统计学意义.同组之间治疗前后差异均有统计学意义（P〈0.05）.治疗前两组的临床症状评分分别为对照组（43.3±1.11）分、治疗组（44.7±0.97）分,两组之间差异无统计学意义.治疗～年后两组的临床症状评分分别为对照组（38.9±1.07）分、治疗组（38.24±0.96）分,两组之间差异无统计学意义.对照组治疗前后临床症状评分平均下降4.4分,治疗组治疗前后临床症状评分平均下降6.5分,治疗前后差异均有统计学意义（P〈0.001）,两组相比差异有统计学意义（P〈0.05）.治疗一年中两组的平均急性发作次数分别为对照组（1.24±0.21）次/年人、治疗组（0.79±0.13）次/年人,治疗组平均减少（0.45±0.15）次/年人,两组差异有统计学意义（P〈0.01）.治疗一年中两组患者下次急性发作的平均间隔时间分别为对照组（162±27）d、治疗组（187±32）d,差异无统计学意义.两组的住院次数分别为对照组（0.22±0.04）次,治疗组（0.12±0.06）次,治疗组与对照组相比差异有统计学意义（P〈0.05）.治疗一年两组的经济费用分别为对照组（4 212±383）元、治疗组（12 382±475）元,治疗组明显增加,与对照组相比差异有统计学意义（P＜0.001）.两组不良反应相似,但均较轻微.结论 噻托溴铵联合大剂量沙美特罗/氟替卡松吸人治疗和复方异丙托溴铵气雾剂联合中等剂量沙美特罗/氟替卡松治疗均能够改善霞度哮喘合并COPD患者的肺功能和临床症状、提高生活质量、减少急性发作次数、延长下次急性发作的间隔时间、减少住院次数,不良反应轻微,适合于重度哮喘合并COPD的治疗.噻托溴铵联合大剂量沙美特罗/氟替卡松吸人治疗在提高生活质量、减少急性发作次数、减少住院次数方面优于中等剂量沙美特罗/氟替卡松联合复方异丙托溴铵气雾剂治疗,但费用昂贵,限制了其在临床的推广.     

沙美特罗替卡松联合噻托溴铵吸入治疗中重度COPD 40例疗效观察

目的观察沙美特罗替卡松（舒利迭）联合噻托溴铵粉吸入剂（思力华）对中重度COPD的治疗效果。方法将40例临床诊断为中重度COPD的患者随机分为两组。A组：22例,舒利迭（50/500 ug）吸人,每天2次,加用思力华,使用吸入装置（HandiHaler）吸入,每次1粒胶囊（18 ug）,每天1次。B组：18例,单纯舒利迭（50/500 ug）吸人,每天2次.疗程3个月。观察两组患者治疗前后呼吸困难的评分、血气分析及肺功能情况。结果治疗3个月后,所有患者呼吸困难均减轻,但A组呼吸困难下降值明显高于B组（P〈0.001）。与B组比较,治疗后A组肺功能指标（FVC、FEV1及FEV1/FVC）及血气指标（SaO2、PaO2）明显升高,而PaCO2则明显下降（P〈0.01）。结论长效抗胆碱药噻托溴铵与舒利迭联合应用可明显改善中重度COPD患者的呼吸困难、血气和肺功能,优于单纯应用舒利迭,可使COPD得到良好的控制。     

噻托溴铵和沙美特罗/氟替卡松及二者联合吸入治疗慢性阻塞性肺疾病临床观察

目的 观察联合吸入噻托溴铵和沙美特罗/氟替卡松治疗稳定期中重度慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的疗效.方法 216例符合条件的中重度COPD患者纳入试验(男1 78例,女38例),按照随机数字表法分为4组:①联合治疗组56例(男46例,女10例),吸入沙美特罗/氟替卡松50/500 μg每日2次,同时吸入噻托溴铵干粉胶囊1粒(18 μg),每日1次;②沙美特罗/氟替卡松组54例(男46例,女8例),吸入沙美特罗/氟替卡松50/500 μg,每日2次;③噻托溴铵组54例(男44例,女10例),吸入噻托溴铵干粉胶囊1粒(18 μg),每日1次;④空白对照组52例(男42例,女10例),未应用胆碱能受体抑制剂、长效β2受体激动剂及糖皮质激素治疗.分别对四组患者治疗前和治疗后12个月肺功能指标、BODE (The Body-Mass Index,Airflow Obstruction,Dyspnea,and Exercise Capacity)指数、生活质量、药物不良反应进行观察对比,评价药物的疗效和安全性.结果 共有176例患者完成了试验,其中联合治疗组48例(男40例,女8例),沙美特罗/氟替卡松组40例(男32例,女8例),噻托溴铵组46例(男36例,女10例),空白对照组42例(男32例,女10例).治疗结束时各试验组FEV1明显高于试验前对应组(P＜0.01).联合治疗组的FEV1(1.19±0.03)L,较沙美特罗/氟替卡松组(1.13±0.01)L、噻托溴铵组(1.15±0.01)L、空白对照组(1.07±0.02)L明显升高(P＜0.01).急性发作次数和应用缓解药次数:联合治疗组的急性发作次数和应用缓解药次数中位数(四分位数间距)分别是[1.0(0-1)]、[1.0(0-1)]次,明显低于沙美特罗/氟替卡松组[1.0(0-2)]、[1.0(0-2)]次,噻托溴铵组[1.5(0-2)]、[1.0(0-2)]次,空白对照组[2.0(0-3)]、[2.0(0-4)]次,差异有统计学意义(P＜0.05).联合治疗组试验后BODE指数(6.10±1.30)明显低于沙美特罗/氟替卡松组(6.51±1.32)、噻托溴铵组(6.61±1.23)、空白对照组(7.11±1.35),差异有统计学意义(P＜0.01).结论 噻托溴铵联合沙美特罗/氟替卡松治疗稳定期中重度COPD,疗效优于单独使用其中一种药物.     

Evaluating the pharmacoeconomic effect of adding tiotropium bromide to the management of chronic obstructive pulmonary disease patients in Singapore

OBJECTIVE: To perform a pharmacoeconomic analysis on the treatment of chronic obstructive pulmonary disease (COPD) with the addition of tiotropium bromide. METHODS: Pharmacoeconomic modeling was performed utilizing the efficacy of tiotropium bromide from the literature on different settings and severity of COPD. Reductions in exacerbations, hospitalizations, and number of exacerbation days per year were derived from these studies. Cost of drug treatment, exacerbations, hospitalization, and loss of income were derived from local data in Singapore and reported in Singapore dollars (US$1=S$1.71). A model was constructed to calculate the impact of one-year treatment with tiotropium bromide, and the results were reported for the total incremental cost per year, cost per year needed to reduce one hospitalization in one year, and cost-savings from hospitalizations in one year. Sensitivity analysis were performed for different number of patients treated per year, differing cost of hospitalization, different cost for tiotropium bromide, different impact of tiotropium bromide on clinical outcomes, and the different amount of substitution drug utilized in the comparator group. RESULTS: Using the different clinical effects and looking at the impact on treating 1000, 2000, and 10,000 patients per year, most of the results showed a high level of decrease in overall cost per year that ranged from S$145.40 to S$840.37 per patient treated. Cost per year needed to reduce one hospitalization in one year ranged from S$3217.31 to S$18,148.92. Cost-savings from hospitalizations in one year per patient treated ranged from $57.16 to $322.49. This may contribute as high as 83% of the overall cost saving. Sensitivity analysis supports the cost savings finding. CONCLUSION: Adding tiotropium bromide for severe COPD patients would lead to a significant cost savings for the economy.     

噻托溴铵联合沙美特罗/丙酸氟替卡松治疗慢性阻塞性肺疾病稳定期患者的疗效观察

目的 观察沙美特罗/丙酸氟替卡松(舒利迭)联合噻托溴铵粉吸入剂(思力华)对慢性阻塞性肺疾病(COPD)缓解期的治疗效果.方法 采用随机、双肓的方法将85例COPD患者分为观察组和对照组,观察组A组给予噻托溴铵和沙美特罗/丙酸氟替卡松治疗,对照组B组给予沙美特罗/内酸氟替卡松治疗.分别对两组患者治疗前后的呼吸困难的评分、...     

Changes in lung function and health status in patients with COPD treated with tiotropium or salmeterol plus fluticasone

Background and objective: The effects of tiotropium, a long‐acting anticholinergic drug, were compared with those of the combination of salmeterol, a long‐acting β₂‐agonist, and fluticasone, an inhaled corticosteroid, in patients with COPD. Methods: A 4‐month, randomized, open cross‐over study of tiotropium, 18 µg once daily, versus salmeterol, 50 µg, plus fluticasone, 200 µg, twice daily, was conducted in patients with COPD. Efficacy was assessed by spirometry and responses to the St George's Respiratory Questionnaire (SGRQ). After 4 months, patients were asked to select their subsequent therapy and indicate the reasons for their selection. Results: A total of 78 patients completed the study. There were no significant differences in the improvements in FEV₁ or SGRQ scores between the therapies. Similar numbers of patients selected tiotropium (42.3%) and salmeterol plus fluticasone (57.7%). However, those who preferred one of the therapies demonstrated greater improvements in SGRQ scores with that therapy. One subgroup of patients (30.8%) showed greater improvements in dyspnoea and FEV₁ in response to tiotropium, and the other subgroup of patients (35.9%) showed greater improvements in dyspnoea and FEV₁ in response to salmeterol plus fluticasone. Some patients (14.1%) selected salmeterol plus fluticasone because of positive effects on sputum expectoration. Conclusions: The study was unblinded and the results need to be interpreted with caution. However, tiotropium and salmeterol plus fluticasone had similar overall effects on pulmonary function and SGRQ scores in patients with COPD. Responses to the two therapies were heterogeneous, and the patients who showed greater improvements in FEV₁ or SGRQ scores with one of the therapies preferred it for their subsequent treatment.     

噻托溴胺粉吸入剂对稳定期COPD患者运动耐量及肺功能的疗效

目的探讨稳定期COPD患者予噻托溴胺粉吸入剂治疗后运动耐量及肺功能的改善作用。方法 60例稳定期COPD患者,随机分成治疗组、对照组以及空白对照组。观察三组治疗不同时期肺功能的变化和St Georges呼吸问卷(SGRQ)情况,进行6 min步行试验观察运动耐力的变化。结果用药6个月后治疗组患者咳嗽、咳痰、气促等症状明显好转,前后比较(P<0.05),用药6个月后治疗组FEV1、FVC、FEV1/FVC及FEV1占预计值(%)、运动耐力较对照组及空白对照组改善,三组比较差异有显著性(P<0.05)。治疗组运动耐力(6MWT)增加,SGRQ评分比较治疗组明显下降(P<0.05)。结论吸入噻托溴胺粉吸入剂对稳定期COPD患者运动耐量及肺功能有改善作用,并可以减少急性发作次数,改善患者生活质量,且副反应少。     

噻托溴铵联合低流量吸氧治疗COPD稳定期合并Ⅱ型呼吸衰竭患者疗效分析

目的探讨噻托溴铵联合低流量吸氧治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期合并呼吸衰竭的疗效。方法将72例COPD稳定期合并呼吸衰竭的患者随机分成两组,联合治疗组给予噻托溴铵联合低流量吸氧治疗(2L/min)。对照组单纯采用低流量吸氧(2L/min)治疗,在治疗3个月后观察两组治疗前后肺功能情况、同期采用6min步行距离评价运动能力(6MWD/m)及生活质量评分(St Georae's respiratory questionaire,SGRQ)。结果治疗3个月后,所有患者肺功能指标(FVC、FEV1及FEV1/FVC%)、同期采用6min步行距离评价运动能力及生活质量评分均有所改善,但联合治疗组各项指标的改善,与对照组比较,差异有显著性(P0.05)。结论长效抗胆碱药噻托溴铵联合低流量吸氧治疗可明显改善COPD稳定期患者的呼吸困难及肺功能,优于单纯低流量吸氧治疗。     

吸入舒利迭对重度稳定期慢性阻塞性肺疾病的肺功能临床分析

目的探讨沙美特罗/氟替卡松治疗是否能改善慢性阻塞性肺疾病(chronicobstructive pulmonary disease,COPD)缓解期患者的肺通气功能。方法重度COPD稳定期患者64例随机分为治疗组和对照组。对照组给予常规治疗,应用氨茶碱、异丙托溴铵等。治疗组在常规治疗的基础上吸入沙美特罗/氟替卡松(50/250μg)。在治疗前,治疗后24周测定肺功能,评价肺功能改善状况。结果治疗组在治疗后24周肺功能有明显改善,和对照组相比有显著差异(P0.05)。结论沙美特罗/氟替卡松是改善稳定期重度COPD患者肺功能的一种有效治疗方法。