Role of tiotropium in the treatment of COPD

Tiotropium is a potent, long-acting, selective anticholinergic bronchodilator. Treatment with tiotropium produces sustained improvements in lung function, particularly FEV₁ (peak, trough, average, and area under the curve) compared with either placebo or ipratropium in patients with moderate to severe COPD. Preliminary evidence suggests that treatment with tiotropium may slow the rate of decline in FEV₁, but this finding awaits confirmation. Tiotropium reduces lung hyperinflation, with associated improvements in exercise capacity. Tiotropium, compared with either placebo or ipratropium, improves a variety of patient-centered outcomes, including subjective dyspnea ratings and HRQL scores. Tiotropium reduces the frequency of COPD exacerbations and of hospitalizations due to exacerbations, but has not been shown to reduce all-cause mortality. Compared with the long-acting bronchodilators, tiotropium provides incrementally better bronchodilation, but it is not clearly superior in terms of patient-centered outcomes. Tiotropium has a good safety profile; however patients with severe cardiac disease, bladder outlet obstruction, or narrow angle glaucoma were excluded from all studies. Medico economic analyses suggest that treatment with tiotropium may also be cost-effective, primarily by reducing costs associated with hospitalizations.     

沙美特罗替卡松及噻托溴铵联合对COPD患者肺功能的的作用探究

目的探究沙美特罗替卡松及噻托溴铵联合治疗对COPD患者肺功能的的作用。方法将我院收治的COPD患者118例随机分为两组,实验组患者59例,联用噻托溴铵吸入剂18μg,1次/d,沙美特罗替卡松(50/250μg)吸入,2次/d。对照组患者59例,吸入沙美特罗替卡松(50/250μg),2次/d。疗程为6个月。观察比较两组患者治疗前后的疗效,FEV1、FEV1占预计值测量及进行呼吸困难分级。结果实验组患者总有效率89.8%(53/59),显著高于对照组患者总有效率76.3%(45/59),差异有统计学意义(P<0.05);治疗后实验组患者肺功能改善结果显著优于对照组患者,差异有统计学意义(P<0.05)。结论沙美特罗替卡松及噻托溴铵联合治疗COPD患者具有良好的临床疗效,可以显著改善患者的肺功能,提高患者的生活质量,值得临床应用。     

噻托溴胺治疗稳定期COPD

目的观察噻托嗅胺对稳定期慢性阻塞性肺疾病（COPD）患者的临床疗效。方法 40例稳定期COPD患者随机分成两组,实验组应用噻托嗅铵18 ug吸入,1次/天,对照组口服茶碱缓释片100 mg,2次/天.观察记录患者治疗前后肺功能、6min步行距离、生活质量评分。结果两组治疗后肺功能、临床症状等较治疗前均有好转,但实验组较对照组FEVl占预计值百分比明显增加,生活质量明显改善,6 min步行距离、临床症状明显改善。两组治疗前后各项指标比较,差异具有统计学意义（P〈0.05或P〈0.01）。结论长期规律吸入噻托溴胺可有效改善慢阻肺患者肺功能并缓解临床症状,提高患者的生活质量。     

Preoperative use of inhaled tiotropium in lung cancer patients with untreated COPD

Background and objective:   Lung cancer patients with COPD are at high risk during surgery. Tiotropium, a long-acting bronchodilator, is a preferred maintenance therapy for COPD, but its efficacy in the perioperative period has not been clarified.
Methods:   A retrospective review was performed of the medical records of 102 patients with primary lung cancer and COPD, who underwent scheduled surgery. Twenty-one lung cancer patients with untreated mild-to-severe COPD received tiotropium preoperatively. Spirometry was performed prior to and after 2 weeks of treatment with tiotropium, and at 3 months after surgery.
Results:   Two-week preoperative treatment with tiotropium significantly improved respiratory symptoms and pulmonary function as reflected by FVC (median 3.43 L pretreatment vs 3.52 L post-treatment), FEV₁ (median 2.06 L vs 2.32 L) and FEV₁% (73.2% vs 81.0%) (all P  < 0.001). Postoperative FEV₁% was significantly increased from a median of 56.0% (interquartile range 51.6–60.3) to 63.4% (60.8–66.0) ( P  < 0.001). The increase in FEV₁ was inversely associated with severity of COPD ( r  = −0.59, P  < 0.005). Lung resections were successfully accomplished without complications. The postoperative FEV₁ predicted prior to tiotropium treatment was underestimated (median predicted postoperative FEV₁ 1.65 L vs median measured postoperative FEV₁ 1.96 L, P  < 0.001).
Conclusions:   Preoperative treatment with tiotropium may facilitate surgical treatment for lung cancer patients with COPD. This is encouraging for COPD patients who may require curative lung resections.     

噻托溴铵对COPD患者夜间低氧血症和炎症因子的影响观察

目的 探讨噻托溴铵对COPD患者夜间低氧血症的疗效,并观察其对患者炎症因子的影响.方法 选择100例稳定期COPD患者,随机分为对照组和实验组.对照组50例,采用原有治疗方案,实验组50例,在原有治疗方案的基础上,加服用噻托溴铵.分别比较两者患者治疗前后的夜间血压饱和度、晨起血气分析结果、肺功能和炎症因子的差异.结果 实验组治疗后MSaO2、MmSaO2和T90均高于对照组,P〈0.05.实验组治疗后PaO2、和SaO2均高于对照组,PaCO2低于对照组,P〈0.05.对照组治疗后IC为1.70±0.12L,实验组治疗后IC为1.86±0.2 L.实验组治疗后IC高于对照组,P〈0.05.实验组治疗后IL-8 、LTB4和MPO低于对照组,P〈0.05.结论 噻托溴铵可以显著改善COPD患者的夜间低氧血症,可以提高深吸气量,并具有显著的抗炎作用.     

Improvement in self-reported exercise participation with the combination of tiotropium and rehabilitative exercise training in COPD patients

Background

Improvements in ventilatory mechanics with tiotropium increases exercise tolerance during pulmonary rehabilitation. We wondered whether tiotropium also increased physical activities outside of pulmonary rehabilitation.

Methods

COPD patients participating in 8 weeks of pulmonary rehabilitation were studied in a randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily (tiotropium = 47, placebo = 44). Study drug was administered for 5 weeks prior to, 8 weeks during, and 12 weeks following pulmonary rehabilitation. Patients completed a questionnaire documenting participation in pre-defined activities outside of pulmonary rehabilitation during the 2 weeks prior to each visit. Patients who submitted an activity questionnaire at week 4 and on at least one subsequent visit were included in the analysis. For each patient, the number of sessions was multiplied with the duration of each activity and then summed to give overall activity duration.

Results

Patients (n = 46) had mean age of 67 years, mean baseline FEV₁ of 0.84 L (33% predicted). Mean (SE) increase in duration of activities (minutes during 2 weeks prior to each visit) from week 4 (prior to PR) to week 13 (end of PR) was 145 (84) minutes with tiotropium and 66 (96) minutes with placebo. The increase from week 4 to week 25 (end of follow-up) was 262 (96) and 60 (93) minutes for the respective groups. Increases in activity duration from week 4 to weeks 17, 21, and 25 were statistically significant with tiotropium. No statistical differences over time were observed within the placebo-treated group and differences between groups were not significant.

Conclusions

Tiotropium appears to amplify the effectiveness of pulmonary rehabilitation as seen by increases in patient self-reported participation in physical activities.     

Outcomes in COPD patients receiving tiotropium or salmeterol plus treatment with inhaled corticosteroids

Patients with COPD are frequently prescribed inhaled corticosteroids (ICS); however, it is unclear whether the treatment with ICS might modify responses to inhaled bronchodilators. Two 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies of tiotropium 18 μg once daily, compared with salmeterol, 50 μg bid, had been conducted in patients with moderate-to-severe COPD. Efficacy was assessed by spirometry, transition dyspnea index (TDI), St. George’s Respiratory Questionnaire (SGRQ), and exacerbations. Data from both studies were combined to form subgroups with regard to concurrent use of ICS. 796 patients receiving ICS were separately analyzed from 390 patients not receiving ICS. Mean age was 64 years, and pre-bronchodilator FEV₁ was 1.06 L (ICS group) and 1.13 L (non-ICS group). Both bronchodilators increased morning mean ± SE pre-dose FEV₁ compared with placebo (ICS groups: tiotropium 110 ± 20 mL, salmeterol 80 ± 20 mL; non-ICS groups: tiotropium 150 ± 30 mL, salmeterol 110 ± 30 mL; p > 0.05 for tiotropium vs salmeterol). Improvements in TDI and SGRQ and frequency of exacerbations also tended to be more profound for tiotropium. Treatment with tiotropium in patients with moderate-to-severe COPD was superior to salmeterol in lung function, irrespective of concurrent use of ICS.     

Effect of tiotropium on health-related quality of life as a primary efficacy endpoint in COPD

Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL). This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD. HRQoL was assessed using the St. George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated. The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9). Mean ± SD baseline SGRQ total score was 47.4 ± 18.1. Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029). Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV₁]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo. Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ.     

沙美特罗替卡松联合噻托溴铵治疗稳定期COPD的临床观察

目的 观察吸入不同剂量沙美特罗替卡松联合噻托溴铵治疗稳定期COPD患者的疗效.方法 门诊选取90例稳定期中-重度度COPD患者,随机分成3组,A组单独吸入噻托溴铵（18 μg 1/日）,B组吸入沙美特罗替卡松（50/250 μg 2/日）＋噻托溴铵（18 μg 1/日）和C组吸入沙美特罗替卡松（50/500 μg 2/日）＋噻托溴铵（18 μg 1/日）,共治疗12周.用药前后分别检测患者肺功能,6分钟步行试验（6MWT）,MMRC评分.结果 A组患者治疗后肺功能、6MWD及MMRC评分均有所好转,但无统计学差异（P＞0.05）;B组中度COPD患者治疗后的肺功能显著改善,6MWT力增加,MMRC评分降低（P＜0.05）;重度患者的疗效均无统计学差异（P＞0.05）;C组患者疗效显著（P＜0.05）,中度患者较B组无更大获益.结论 沙美特罗替卡松（50/250 μg 2/日）联合噻托溴铵（18 μg 1/日）治疗稳定期中度COPD患者疗效确切,且减少患者经济负担和药物副作用.     

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。     

Efficacy of tiotropium in COPD patients from Asia: a subgroup analysis from the UPLIFT trial

Background and objective: Studies in respiratory diseases other than chronic obstructive pulmonary disease suggest potentially differing responses to medications among patients from different regions. We report a subgroup analysis of patients recruited to Asian centres from a previously reported 4‐year COPD trial. Methods: Subgroup analysis from a randomized, double‐blinded, placebo‐controlled trial of tiotropium 18 µg daily in COPD. Primary end‐point was rate of decline in FEV₁. Secondary end‐points included spirometry at individual time points, health‐related quality of life (St George's Respiratory Questionnaire), exacerbations and mortality. Results: Of 5992 patients, 362 were from Asian centres (100 from Japan). Mean age 66 years, 95% men, 13% current smokers, BMI: 21 kg/m²; post‐bronchodilator FEV₁: 44% predicted; St George's Respiratory Questionnaire total score: 44 units. No treatment effect was observed for rate of decline in FEV₁ although annual decline was less in Asian patients. Morning pre‐bronchodilator FEV₁ and forced vital capacity improved in Asian patients (P < 0.05). Tiotropium reduced number of exacerbations (rate ratio (95% confidence interval (CI)): 0.73 (0.57–0.94)). Hazard ratios (95%CI) for exacerbations and hospitalized exacerbations (tiotropium/control) were 0.81 (0.62–1.05) and 0.85 (0.61–1.19), respectively. St George's Respiratory Questionnaire total score improved by 1.5–6.1 units (P < 0.05 for months 18, 24, 30 and 36) with tiotropium. Fatal events occurred in 34 tiotropium (18.5%) and 42 control (23.6%) patients. Conclusions: In COPD patients from Asia, tiotropium improves lung function, improves health‐related quality of life and reduces exacerbations over 4 years of treatment.     

噻托溴铵对轻到中度COPD患者疗效观察

目的评价噻托溴铵对轻中度COPD患者的疗效。方法在12周时间内,轻中度COPD患者接受治疗后分别测定其1 d,15 d,85 d噻溴托按组（18 ug qd）和安慰剂组的肺功能（以给药前1 d测定值为基线）。结果两组用药前平均FEV1预计值%为73.4±12.5。试验结束时噻托溴铵组FEV1用药前及用药后2 h曲线下面积（AUC0~2 h）与安慰剂组对照,都有显著提高（P〈0.0001）。两组不良反应相似。结论噻托溴铵较安慰剂显著改善轻度COPD患者肺功能。     

Comparison of tiotropium plus formoterol to tiotropium alone in stable chronic obstructive pulmonary disease: a meta-analysis

Background and objective: It is not clear whether combination therapy with tiotropium plus formoterol has greater efficacy, without increasing the burden of adverse events, compared with tiotropium alone. This meta‐analysis was performed to evaluate the differences in efficacy and adverse events associated with combination therapy compared with tiotropium alone, in patients with stable COPD. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for this analysis. Randomized controlled trials of 2 or more weeks of treatment with tiotropium plus formoterol or arformoterol, compared with tiotropium alone, were reviewed. Studies were pooled to yield odds ratio (OR) or weighted mean differences (WMD), with 95% confidence interval (CI). Results: Eight trials, involving 1868 randomized patients, met the inclusion criteria. Treatment with tiotropium plus formoterol significantly improved the average FEV₁ (WMD 105 mL, 95% CI: 69–142), average FVC (WMD 135 mL, 95% CI: 96–174) and trough FEV₁ (WMD 53 mL, 95% CI: 30–76), compared with tiotropium alone, although the difference was not statistically significant for trough FVC. The mean change in transitional dyspnoea index (TDI) was markedly greater with tiotropium plus formoterol (WMD 1.50, 95% CI: 1.01–1.99) than with tiotropium alone, and there was a similar difference in the proportion of patients with a clinically significant change in TDI (OR 2.34, 95% CI: 1.58–3.46). There tended to be fewer adverse events and COPD exacerbations with tiotropium plus formoterol, compared with tiotropium alone, but the differences were not statistically significant. Conclusions: Tiotropium plus formoterol significantly improved lung function and symptom scores compared with tiotropium alone. There was a trend towards a reduction in adverse events, although the difference was not statistically significant. Long‐term trials are necessary to evaluate the effects of tiotropium plus formoterol and to clarify the role of combination therapy, compared with tiotropium alone.     

A rational approach to single,dual and triple therapy in COPD

The complexity of COPD treatment has increased over the last 5 years mainly because of the proliferation of drugs and delivery devices. In this paper, we will focus on currently available therapy used for maintaining patient well‐being rather than acute relief of symptoms. We propose a series of principles for rational therapy, and following a review of how currently available treatments perform in isolation and when compared with each other, we suggest an approach to aid the rational selection of the most appropriate treatment based on current evidence.     

低剂量茶碱治疗慢性阻塞性肺疾病疗效观察

目的观察口服低剂量茶碱治疗中重度慢性阻塞性肺疾病（COPD）的效果。方法采用随机、单盲、安稳剂对照方法,选择中重度稳定期COPD患者61例,随机分为两组,观察组31例,对照组30例。观察组口服茶碱缓释片,对照组服用安慰剂,进行3个月实验,观察肺功能、生活质量的改善和不良反应发生的情况。结果观察组治疗后生活质量评分有改善（P〈0．002）、肺功能有轻到中度的改善（P〈0．05）,不良反应少,对照组上述指标无改善。结论口服低剂量茶碱治疗中重稳定期COPD患者有较好的疗效,短期可改善肺功能。     

噻托溴铵对稳定期慢性阻塞性肺疾病患者血清细胞因子水平及肺功能的影响

目的探讨噻托溴铵对稳定期慢性阻塞性肺疾病(简称慢阻肺)患者肺功能的影响及气道炎症的改善作用。方法选择符合病例选择标准的患者81例,采用随机数字表法分为观察组40例和对照组41例,对照组口服茶碱缓释片,观察组给予噻托溴铵干粉剂,疗程均为16周。治疗前后观察第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC、FEV1/预计值以及血清超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-12(IL-12)变化。结果两组患者治疗前FEV1/FVC、FEV1/预计值比较,差异无统计学意义(P0.05)。治疗16周时,两组患者FEV1/FVC、FEV1/预计值较本组治疗前均明显提高,差异有统计学意义(P0.05),且观察组提高幅度明显大于对照组(P0.05)。两组患者治疗前血清hs-CRP、TNF-α、IL-6及IL-12水平相似,差异无统计学意义(P0.05);治疗16周时,两组血清hs-CRP、TNF-α、IL-6及IL-12水平较本组治疗前均明显降低,差异有统计学意义(P0.05),且观察组降低幅度明显大于对照组(P0.05)。观察组患者不良反应发生率10.00%,对照组不良反应发生率14.63%,差异无统计学意义(P0.05)。结论噻托溴铵治疗善稳定期慢阻肺可显著改善患者肺功能、下调血清hs-CRP、TNF-α、IL-6及IL-12表达,抑制慢性炎性反应,延缓肺功能的减退。     

克拉霉素联合噻托溴胺治疗慢性阻塞性肺疾病（COPD）疗效

目的观察克拉霉素联合噻托溴胺治疗COPD患者的临床疗效和肺功能变化。方法符合入选条件的COPD 101例患者中, 61例病人感染过肺炎衣原体(Cpn)。所有患者随机分成Tio组(用噻托溴胺治疗)和CT组(用克拉霉素+噻托溴胺治疗)。用微量免疫荧光技术(MIF)检测抗Cpn抗体,胶体金法(DIGFA)快速定量测定C 反应蛋白(CRP)。结果治疗后两组病人的临床症状均有显著改善：Tio组P<0.05, CT组P<0.001;FEV1/FVC(%)CT组明显增强：Tio组P<0.05;CT组P<0.01; 两组的CRP含量均下降, 但CT组比Tio组更显著(分别为P=0.0000和P=0.0134); 但CT组Cpn IgM的阳性率显著下降(P=0.001)。结论克拉霉素联合噻托溴胺治疗COPD,二药合用可加强两种药物的协同疗效作用,使疗效更佳,因此CT方案值得临床推荐。     

思力华与舒利迭联合应用治疗稳定期COPD的疗效观察

目的探讨思力华联合舒利迭治疗稳定期慢性阻塞性肺病(chronic obstructive pulmonary diseases,COPD)的疗效及安全性。方法研究对象为2010年11月~2011年12月我院收治的258例稳定期COPD患者,随机分为治疗组(129例)、对照组(129例)。治疗组吸入舒利迭50μg/250μg/次,2次/d,思力华18μg/次,1次/d;对照组仅吸入舒利迭50μg/250μg/次,2次/d,用药12周,比较分析两组疗效。结果治疗组显效率(65.9%)及总有效率(93.8%)均显著高于对照组(27.9%,62.8%)(P0.05),治疗后肺功能指标FEV1、FEV1/FVC及动脉血气PaO2均明显升高(P0.05),且治疗组显著高于对照组(P0.05),而动脉血气PaCO2明显降低(P0.05),且治疗组显著低于对照组(P0.05),两组不良反应发生率比较差异无统计学意义(P0.05)。结论舒利迭联合思力华治疗稳定期COPD的临床疗效显著,优于单用舒利迭,可明显改善患者动脉血气及肺功能,是稳定期COPD患者的理想治疗方案。     

噻托溴铵粉雾剂治疗慢性阻塞性肺病的有效性及安全性

目的观察噻托溴铵粉雾剂治疗慢性阻塞性肺病（COPD）的有效性及安全性。方法采用随机、双盲、双模拟阳性药平行对照、多中心临床研究的方法。对223例COPD稳定期Ⅰ、Ⅱ和Ⅲ级患者,分别吸入噻托溴铵粉雾剂（试验组）和异丙托溴铵定量气雾剂（对照组）,治疗28 d,测定患者用药前后不同时间的肺功能。结果 1.治疗28 d,对照组和试验组的临床改善率分别为47.71%（P〈0.05）和59.46%（P〈0.05）。2.各组给药后30、60、120 m in、28 d,FEV1与基线相比,差别均有统计学意义（P〈0.05）。治疗后28 d,试验组FEV1、FVC与对照组相比,差别有统计学意义（P〈0.01）。结论规律吸入噻托溴铵粉雾剂可显著改善COPD患者的临床症状,无严重药物不良反应。