噻托溴铵联合茶碱缓释片治疗稳定期慢性阻塞性肺疾病疗效观察

目的观察联合噻托溴铵、茶碱缓释片对COPD稳定期的治疗作用。方法 33例COPD稳定期患者随机分为试验组17例和对照组16例。在未给予其它治疗的情况下,两组采用噻托溴铵吸入18μg日1次,试验组在此基础上给予茶碱缓释片0.2日二次口服,疗程为6个月。在试验前后分别测定肺功能,并比较开始试验前、后6个月两组COPD患者急性发作次数。结果在试验组FEV1、FEV1/FVC和FEV1/预计值较试验前均有显著提高（P〈0.01）。开始试验后6个月较试验前6个月COPD急性发作次数减少（P〈0.01）。对照组FEV1/FVC和FEV1/预计值与试验前差异无显著性（P均〉0.05）。开始试验后6个月较试验前6个月COPD急性发作次数的差异无显著性（P〉0.05）。结论噻托溴铵联合茶碱缓释片能够改善稳定期COPD的肺功能及急性发作次数。     

无创通气联合噻托溴铵在老年COPD伴Ⅱ型呼吸衰竭的临床应用

目的评价无创通气联合噻托溴铵在COPD伴Ⅱ型呼吸衰竭的临床疗效。方法将126例老年COPD合并Ⅱ型呼吸衰竭患者随机分入对照组与观察组,对照组患者接受常规治疗,观察组患者在常规治疗基础上给予无创通气联合噻托溴铵吸入,疗程4周。比较两组治疗后4周血气分析指标及肺功能的改变。结果治疗后4周观察组血气分析指标PaO2、PaCO2及pH值均显著优于对照组,差别具有统计学意义（P〈0.05）;与对照组相比,治疗后观察组肺功能指标FEV1、FVC和FEV1/FVC显著提高（P〈0.05）。结论无创通气联合噻托溴铵治疗老年COPD合并Ⅱ型呼吸衰竭可显著改善血气分析指标及肺功能,提高生活质量。     

国产噻托溴铵粉雾剂与沙美特罗替卡松治疗COPD的肺功能观察

目的分析国产噻托溴铵粉雾剂与沙美特罗替卡松治疗COPD的肺功能变化。方法选取48例门诊Ⅱ级中度COPD患者,男28例,女20例,其中单一吸入国产噻托溴铵粉雾剂(天晴速乐,18μg)14例,单一吸入沙美特罗替卡松(舒利迭,50/250μg)34例。用药前、用药后第4周、第8周记录肺功能。结果所有入选患者在用药4周及8周后肺功能均较前改善,噻托溴铵组的第4周FEV1增加值为133.5±11.8 ml,第8周为68.8±22.0 ml,第4周FVC增加值为151.1±55.8 ml,第8周为55.9±19.6 ml;沙美特罗替卡松组第4周FEV1增加值100.6±24.0 ml,第8周为60.1±17.6 ml,第4周FVC增加值为137.5±41.3 ml,第8周为55±22.4 ml。两组FEV1、FVC增加值无统计学差异。结论国产噻托溴铵粉雾剂与沙美特罗替卡松均可在短期内改善COPD患者肺功能,两组各自的FEV1、FVC增加值差异无统计学意义,噻托溴铵组患者依从性逊于沙美特罗替卡松组。     

噻托溴铵与缓释茶碱对COPD稳定期患者生存质量及肺功能研究

目的观察长期吸入噻托溴铵及应用缓释茶碱对慢性阻塞性肺疾病(COPD)稳定期生存质量及肺功能的影响。方法对96例确诊为COPD稳定期患者随机分为两组,噻托溴铵组给予常规治疗加用长期吸入噻托溴铵,缓释茶碱组为常规治疗加用茶碱缓释片,对两组的生存质量及肺功能进行对比,评价噻托溴铵与缓释茶碱对COPD稳定期患者生存质量及肺功能的影响。结果噻托溴铵较缓释茶碱能提高生存质量及肺功能,有明显的差异性;噻托溴铵组用药1个月肺功能较治疗前无明显改善,3个月后能明显改善肺功能。结论长期吸入噻托溴铵较缓释茶碱能更好的改善患者生存质量及肺功能。     

噻托溴铵治疗稳定期慢性阻塞性肺疾病疗效观察

目的评价噻托溴铵治疗稳定期慢性阻塞性肺疾病(COPD)的疗效和安全性。方法将50例年龄40～75岁稳定期Ⅰ、Ⅱ级COPD患者随机分为治疗组和对照组。治疗组吸入噻托溴铵干粉剂(18μg,每日1次)治疗13周。在治疗前,治疗4周及12周分别测定肺功能。结果治疗组第一秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC、FEV1占预计值的百分比上升值较对照组有有显著性差异(P<0.05)。噻托溴铵的常见不良反应为口干(2例,8%),无心血管系统异常和心电图异常报告。结论噻托溴铵对于稳定期Ⅰ、Ⅱ级COPD患者疗效显著且安全可靠。     

噻托溴铵和氨茶碱对稳定期慢性阻塞性肺疾病的干预作用

目的评价噻托溴铵干粉剂对中、重度稳定期慢性阻塞性肺疾病(COPD)患者肺功能和气道重塑的影响。方法采用随机对照研究140例COPD患者,噻托溴铵组使用噻托溴铵干粉剂,对照组使用氨茶碱片,总观察时间12 w,治疗前后测定肺功能,酶联免疫吸附测定痰中转化生长因子(TGF)-β1。结果治疗后徵托溴铵组深吸气量(OIC)、第1秒用力肺活量(FEV1)和用力肺活量(FVC)明显改善,分别增加了102、256、154 ml,TGF-β1阳性率为37.5%,对照组肺功能改善不明显,TGF-β1阳性率为65.0%。噻托溴铵组TGF-β1阳性率低于对照组。FEV1与TGF-β1阳性率呈负相关。结论噻托溴铵能改善中、重度稳定期COPD患者的肺功能和气道重塑,FEV1与TGF-β1阳性率呈负相关。     

国产噻托溴铵粉雾剂治疗慢性阻塞性肺疾病的多中心临床研究

目的 评价国产噻托溴铵粉雾剂治疗COPD的临床疗效和安全性.方法 采用多中心、随机、双盲、安慰剂平行对照的研究方法,对205例筛选合格的I、Ⅱ级COPD稳定期患者,采用随机数字表法给予国产噻托溴铵粉雾剂18μg,每日1次,或用安慰剂治疗12周.在筛选期、用药后6和12周分别测定肺功能.结果 103例入选噻托溴铵组,用药后12周临床症状的控制率为25.2%(26/103),有效率为65.1%(67/103);102例入选对照组,用药后12周临床控制率为5.1%(5/99),有效率为30.3%(30/99).噻托溴铵组用药后12周FEV1增加值和增加率[(0.2±0.3)L和(19.2±29.1)%]明显高于对照组[(0.0±0.2)L和(0.8±18.2)%],FVC增加值和增加率(0.2 L和11.6%)明显高于对照组(0.0 L和2.2%).噻托溴铵组不良反应主要为口干和咽喉不适等,发生率(7.8%,8/103)略低于对照组(12.8%,13/102),差异无统计学意义(X2=1.381,P>0.05).结论 国产噻托溴铵粉雾剂可显著改善COPD患者的临床症状和肺功能,临床应用有效、安全.     

噻托溴铵粉吸入剂对稳定期中、重度COPD的疗效以及安全性评价

目的探讨噻托溴铵粉吸入剂治疗中重度COPD稳定期的临床疗效以及安全性。方法将本院收治的126例稳定期中重度COPD患者随机分为实验组和对照组,实验组患者给予噻托溴铵粉吸入剂治疗,对照组患者给予异丙托溴铵气雾剂治疗,治疗前后比较两组患者的临床症状评分、6 min步行距离(6MWD),并进行肺功能测定、动脉血气分析,治疗期间记录两组患者不良反应的发生情况。结果两组患者各项指标较治疗前均显著改善(P<0.05),实验组FEV1%、FEV1/FVC、PaO2、6MWD显著高于对照组(P<0.05),症状评分、PaCO2显著低于对照组(P<0.05),两组均无严重不良反应发生。结论噻托溴铵粉对于稳定期中、重度COPD疗效确切,且安全性较高。     

噻托溴铵治疗COPD的临床疗效观察

目的研究老年性吸烟稳定期COPD应用噻托溴铵的临床疗效。方法分析2009年1月～2011年9月我院收治的90例老年性吸烟稳定期COPD患者,随机分成治疗组和对照组个45例:治疗组(每日给予患者18μg噻托溴铵吸入剂+沙丁胺醇气雾剂);对照组(每隔12小时给予患者口服0.1 g氨茶碱+沙丁胺醇气雾剂),治疗后对患者进行2个月的随访观察,比较两组患者治疗后肺功能的改善情况。结果治疗组经过治疗后St George评分显著降低,优于对照组,并且相对于治疗前FEV1/Pred、FEV1、FEV1/FVC的评分值均有显著提高(P<0.01),对照组治疗效果不明显(P>0.05)。结论噻托溴铵吸入剂联合沙丁胺醇气雾剂可以显著改善老年性吸烟稳定期COPD患者的肺功能。     

老年中重度稳定期慢性阻塞性肺疾病患者应用噻托溴铵的疗效与安全性

目的探讨老年中重度稳定期慢性阻塞性肺疾病(COPD)患者应用噻托溴铵(吸入剂量18μg,1次/d)的疗效和安全性。方法在中重度稳定期96例COPD患者,连续3年应用噻托溴铵,每3个月检测肺功能第1秒用力呼吸气量占预计值的百分比(FEV1)和用力肺活量(FVC),圣·乔治呼吸问卷计分(SGRQ)评估生活质量,观察急性加重的发生率及用药的不良反应。结果经连续3年的治疗观察,与对照组比较,噻托溴铵治疗组用药后的FEV1较基线值显著增加,FEV1增加0.26 L(P0.01),并且重度COPD患者肺功能改善明显,治疗组在6个月后肺功能下降趋势明显变缓。噻托溴铵组患者SGRQ评分低于对照组,在重度治疗后的第3个月,噻托溴铵治疗组SGRQ总评分较基线低了6.85,对照组SGRQ总评分较基线低了1.14,SGRQ总评分治疗组较对照组明显改善(P0.01);在中度患者中治疗6个月后SGRQ总评分治疗组较对照组比较有明显改善。COPD急性加重率治疗组与对照组之比为0.75(95%CI 0.58~0.96;P0.05)。在安全指标方面治疗组与对照组没有显著差异。结论噻托溴胺对于改善肺通气功能、健康状态及降低急性发作频率等方面显示出了独特的长处,且耐受性良好,是目前稳定期COPD患者的有效药物。     

Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.

AIMS: Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted). METHODS: In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1). RESULTS: Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar. CONCLUSION: Compared with placebo, tiotropium improved lung function in patients with mild COPD.     

吸入噻托溴铵联合舒利迭治疗稳定期中重度COPD的临床研究

目的研究吸入噻托溴铵联合舒利迭治疗稳定期中重度慢性阻塞性肺疾病(COPD)的治疗效果。方法 45例稳定期中重度COPD患者(完成实验43例,因病情加重退出实验2例)随机分成两组,治疗组给予噻托溴铵(商品名:思力华)及舒利迭(沙美特罗/氟替卡松)吸入治疗12周,对照组给予舒利迭吸入治疗12周,比较两组治疗前后临床症状、体征、血氧饱和度及肺功能主要指标。结果与对照组比较,治疗组FEV1/FVC以及FEV1占预计值百分比显著提高,临床症状体征及血氧饱和度明显改善(P0.05)。结论吸入噻托溴铵联合舒利迭可有效改善肺功能并缓解临床症状。     

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.     

噻托溴铵联合沙美特罗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 观察噻托溴铵联合沙美特罗替卡松对慢性阻塞性肺疾病(COPD)稳定期的治疗效果.方法 采用随机、双盲的方法将62例COPD患者分为观察组和对照组,观察组给予噻托溴铵和沙美特罗替卡松治疗,对照组给予沙美特罗替卡松治疗,分别对两组患者治疗前后呼吸困难评分和肺功能检测进行比较.结果 治疗两个月后,与对照组比较观察组肺功能FEV1、FVC、FEV1/FVC%,呼吸困难评分改善差异有统计学意义(P＜0.05).结论 噻托溴铵与沙美特罗替卡松联合吸入治疗COPD,疗效优于沙美特罗替卡松单药治疗.     

噻托溴铵治疗老年慢性阻塞性肺疾病稳定期患者的临床观察

目的探讨噻托溴铵治疗老年慢性阻塞性肺疾病（COPD）稳定期患者的临床疗效。方法 90例老年COPD稳定期患者均吸入噻托溴铵每日1粒,疗程3月,比较患者治疗前后肺功能、血气分析指标、慢性阻塞性肺疾病评估测试（CAT）评分。结果噻托溴铵治疗后血氧分压显著改善（P〈0.05）,二氧化碳分压明显降低（P〈0.05）;治疗前后CAT评分差异有统计学意义（P〈0.05）。结论噻托溴铵吸入治疗老年COPD稳定期患者,能明显改善肺功能、改善氧合,缓解症状,提高生活质量,是治疗老年COPD稳定期患者的有效选择。     

噻托溴铵治疗COPD稳定期的疗效观察

目的探讨噻托溴铵治疗COPD稳定期的临床疗效。方法选取我院COPD稳定期的患者64例,分为观察组与对照组,各32例,观察组使用噻托溴铵治疗,对照组使用常规治疗,观察比较两组患者的治疗效果、不良反应发生率,并比较治疗前后急性加重次数,治疗前和治疗后2周末、4周末、8周末、16周末、24周末的FEV1和FEV1/FVC的值。结果观察组治疗总有效率为90.6%(29/32),不良反应发生率为6.3%(2/32),对照组治疗总有效率为68.8%(22/32),不良反应发生率为3.1%(1/32),两组治疗总有效率比较有明显差异(P<0.05),具有统计学意义。结论噻托溴铵在治疗COPD稳定期的临床疗效显著,明显优于常规治疗。     

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、...     

Tiotropium Bromide

Tiotropium bromide (Spiriva) is a long-acting anticholinergic bronchodilator that maintains bronchodilation for at least 24 hours, allowing once-daily administration. The active moiety is the tiotropium cation (tiotropium); tiotropium bromide 22.5 micrograms is equivalent to 18 micrograms of tiotropium cation. Greater improvements in lung function from baseline (primary endpoint mean trough FEV(1)) were observed with inhaled tiotropium 18 micrograms once daily than with placebo in 6-month and 1-year randomized, double-blind trials in patients with COPD. Tiotropium improved lung function (trough FEV(1) response) more effectively than ipratropium bromide (ipratropium) 40 micrograms four times daily in 1-year clinical trials, and was at least as effective as salmeterol 50 micrograms 12-hourly in 6-month trials. Preliminary data suggest that tiotropium alone or in combination with once-daily formoterol has a greater bronchodilator effect than twice-daily formoterol in patients with COPD. Improvements in patients' perception of health-related quality of life (HR-QOL) or dyspnea were greater with tiotropium than with placebo or ipratropium, and were similar to those with salmeterol. Reductions in the frequency and severity of acute exacerbations and in the use of rescue medication were also greater with tiotropium than with ipratropium or placebo. There was no evidence of tachyphylaxis with tiotropium during 1-year clinical trials. Inhaled tiotropium was generally well tolerated in clinical trials. Apart from dry mouth, the type and incidence of adverse events with tiotropium were similar to those with ipratropium, salmeterol or placebo in patients with COPD. In conclusion, inhaled tiotropium 18 micrograms once daily improved lung function, dyspnea, and HR-QOL, and decreased the incidence of acute COPD exacerbations and the use of rescue medication relative to placebo or ipratropium in clinical trials in patients with COPD. Tiotropium was at least as effective as salmeterol in terms of bronchodilator efficacy and improvements in dyspnea or HR-QOL. With the exception of dry mouth, the tolerability profile of tiotropium was similar to that with placebo, ipratropium, or salmeterol. Consequently, inhaled tiotropium is likely to be a valuable option for first-line, long-term maintenance therapy in the management of bronchoconstriction in patients with symptomatic COPD. Tiotropium bromide has a quaternary ammonium structure and acts as an anticholinergic bronchodilator; the active moiety is the tiotropium cation (tiotropium). A 22.5 micrograms dose of tiotropium bromide provides 18 micrograms of tiotropium. Orally inhaled tiotropium bromide antagonizes the muscarinic M(1), M(2), and M(3) receptors located in airway smooth muscle, reversing vagally mediated bronchoconstriction. Receptor binding assays and in vitro tests indicate that tiotropium bromide is kinetically selective for M(1) and M(3) receptors over the M(2) receptor, unlike ipratropium bromide, which is nonselective. Animal and in vitro studies showed that tiotropium bromide was more potent ( approximate, equals 20-fold) than ipratropium bromide in displacing [(3)H]N-methylscopolamine (NMS) from muscarinic receptors, and had a more sustained protective effect (>70% inhibition) against NMS binding. Tiotropium bromide was a more potent inhibitor of bronchial contraction than atropine ( approximate, equals 23-fold), and had a slower onset and markedly longer duration of action than atropine or an equipotent dose of ipratropium bromide. Aerosol particle penetration is improved with tiotropium, without delaying mucus clearance from the lungs. Tiotropium 4.5-36 micrograms once daily for 4 weeks increased mean trough and average FEV(1) and FVC and mean PEFR values from baseline compared with placebo, with no evidence of tachyphylaxis. Improvements in trough FEV(1) from baseline with tiotropium 4.5-36 micrograms were not dose dependent. Based on a lack of dose response, the optimal once-daily tiotropium dosage is 18 micrograms. Steady-state trough FEV(1) values are achieved within 48 hours of commencing tiotrochodilation (for >/=24 hours) and an attenuation of the nocturnal decline in FEV(1) that were unaffected by timing of the daily tiotropium dose were seen in randomized, double-blind, placebo-controlled studies in patients with stable COPD. The drug improved static and dynamic lung hyperinflation (evidenced by reduced trapped air volume and increased tidal volume and end-of-exercise inspiratory capacity), and improved exertional dyspnea (during activities of daily living and exertion) and exercise tolerance compared with placebo in randomized, double-blind studies. In patients with stable COPD, improved sleep-related oxygen desaturation that was unaffected by the timing of the daily dose was seen with tiotropium but not with placebo. Clinically significant treatment-related disorders of conduction or rhythm, or changes in heart rate were not observed with tiotropium in this patient group. Mean maximal plasma concentrations (C(max)) were observed within 5 minutes of inhalation of a single dose of tiotropium 18 micrograms in patients with COPD. Plasma drug levels declined to minimum concentrations (C(min)) within 1 hour of treatment in healthy volunteers. Mean steady-state C(max) concentrations (16 ng/L) were achieved after 2-3 weeks of once-daily inhaled tiotropium 18 micrograms in elderly patients with COPD; tiotropium does not appear to accumulate once steady-state has been achieved.The estimated absolute bioavailability of tiotropium at steady state in healthy volunteers was approximately 20-25%, and approximately 72% of the drug is bound to plasma proteins. Excretion of tiotropium is predominantly renal (through active secretion by the kidneys), although in vitro studies suggest that cytochrome P450 (CYP) oxidation (possibly involving CYP2D6 and CYP3A4 enzymes) may have a minor role. In patients with COPD, renal excretion of the unchanged drug at 24 hours (Ae(24)) was approximately 7%. The mean plasma elimination half-life after single or multiple doses in healthy volunteers and elderly patients with COPD was approximately 5-6 days. The renal clearance and urinary excretion of tiotropium decrease with increasing age; however, these changes are not considered to be clinically significant. Because of altered steady-state C(max), C(min), area under the concentration-time curve, and Ae(24) values, caution is required with tiotropium administration in patients with moderate-to-severe renal impairment. The pharmacokinetics of tiotropium in patients with severe renal or hepatic impairment have not been studied. Tiotropium does not interact with drugs such as cimetidine or ranitidine, which are also eliminated by active renal secretion. Orally inhaled tiotropium bromide has been evaluated as a bronchodilator for the management of patients with COPD in randomized, double-blind 6-month and 1-year trials, and in several shorter studies. In clinical trials, COPD was diagnosed according to the American Thoracic Society guidelines. The bronchodilator effect was expressed as the trough FEV(1) response (the mean change in FEV(1) from baseline measured 1 hour prior to and immediately before a scheduled dose), and was the primary endpoint in all but two clinical trials. The bronchodilator effect with tiotropium 18 micrograms once daily was superior to that with placebo in several well designed trials in patients with COPD. Moreover, greater improvements in mean peak and average FEV(1) responses occurred with tiotropium but not with placebo. Mean trough, peak, and average FVC responses, and weekly mean morning and evening PEFR values were also improved to a greater extent with tiotropium than with placebo. Tiotropium demonstrated a greater bronchodilator effect than ipratropium bromide (hereafter referred to as ipratropium when used at approved dosages) 40 micrograms four times daily in two 1-year trials in patients with COPD. Mean peak and average FEV(1), mean trough FVC responses, and weekly mean morning and evening PEFR values were also increased to a greater extent with tiotropium than with ipratropium. In one of the two 6-month trials that compared the efficacy of tiotropium with that of inhaled salmeterol 50 micrograms twice daily, greater improvements from baseline in mean trough, peak, and average FEV(1) and FVC responses were seen with tiotropium than with salmeterol. Increases in weekly mean evening, but not morning, PEFR values were generally greater with tiotropium than salmeterol. In the second trial, improvement in the primary endpoint (mean trough FEV(1) response from baseline) with tiotropium or salmeterol was similar, although peak and average responses were superior with tiotropium. Preliminary results from a 6-week crossover study in patients with COPD suggested that tiotropium alone or in combination with once-daily formoterol improved mean trough and average FEV(1) and trough FVC values from baseline to a greater extent than twice-daily formoterol. More patients achieved a clinically important improvement (increase of >/=1 unit) in the transitional dyspnea index focal score (a measure of dyspnea-related impairment) with tiotropium than with placebo in the 1-year trials. Tiotropium was superior to ipratropium in 1-year trials, and was at least as effective as salmeterol in 6-month trials, in achieving a clinically important improvement in focal scores. Tiotropium recipients experienced fewer COPD exacerbations than placebo or ipratropium recipients and had fewer and shorter COPD-related hospitalizations compared with placebo recipients. Unlike salmeterol, tiotropium lengthened the time to onset of the first exacerbation and decreased the number of exacerbations compared with placebo in two 6-month trials. Similar proportions of tiotropium, salmeterol, and placebo recipients required COPD-related hospitalizations. (ABSTRACT TRUNCATED)     

The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial. The US Tiotropium Study Group

STUDY OBJECTIVE: To compare the bronchodilator efficacy and safety of tiotropium and placebo. DESIGN: A 3-month, randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Outpatient. PATIENTS: Four hundred seventy patients with stable COPD (mean FEV(1) = 38.6% predicted). INTERVENTIONS: Tiotropium 18 microg (N = 279) or placebo (N = 191) given once daily via a lactose-based dry-powder inhaler device. Measurements and results: Spirometry was evaluated on days 1, 8, 50, and 92. Data were expressed as the mean trough (ie, before morning dose; 23 to 24 h after previous dose) and average response observed in the 3 h after the dose was received. Tiotropium produced significant improvement in trough FEV(1) and FVC, averaging 12% greater than baseline on day 8; these improvements were maintained on days 50 and 92. The average postdose FEV(1) was 16% greater than baseline on day 1 and 20% greater than baseline on day 92; FVC was 17% greater than baseline on day 1 and 19% greater than baseline on day 92. Tiotropium was significantly more effective than placebo in both trough and average FEV(1) and FVC response (p < 0.001). These spirometric effects were corroborated by significant improvements in daily morning and evening peak expiratory flow rate, as well as a reduction in "as-needed" albuterol use. Symptoms of wheezing and shortness of breath were significantly less in patients receiving tiotropium, and the physician global assessment noted overall improvements with those treated with tiotropium relative to placebo. The most common reported adverse event after tiotropium was dry mouth (9.3% vs 1.6% relative to placebo; p < 0.05). CONCLUSIONS: These data demonstrate that tiotropium is a safe and effective once-daily anticholinergic bronchodilator and should prove useful as first-line maintenance therapy in COPD.     

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.