抗胆碱药物在支气管哮喘治疗中的合理应用

异丙托溴铵(ipratropium bromide,爱全乐)是临床上常用的一种抗胆碱药物,噻托溴铵(tiotropium,思力华)是一种新型、强力和长效的选择性吸入型胆碱能受体拮抗剂。噻托溴铵与异丙托溴铵同M1、M2和M3受体的亲和力大致相等,但是,噻托溴铵从M1、M3胆碱受体复合物上解离的速度要比从M2胆碱受体复合物上解离的速度慢3.5和8倍。异丙托溴铵与β2受体激动剂联合应用具有叠加、互补作用,与单独应用β2受体激动剂,前者能显著提高肺功能,缩短住院时间,且副作用无明显增加,目前推荐两者联合应用治疗重症哮喘。噻托溴铵可以明显缓解患者呼吸困难症状,改善生活质量及日常体力活动,减少短效β2受体激动剂的使用次数,适用于哮喘等气道痉挛及气道高反应性患者的长期使用。     

噻托溴铵在慢性阻塞性肺病中的应用

噻托溴铵是新一代抗胆碱药，是异丙托溴铵（又名异丙托品，Ipratropium)的衍生物。它与M1及M3受体解离的速度明显慢于M2受体，故具有动力学选择性，从而发挥强大而持久的支气管扩张作用。不仅可明显而稳定地改善慢性阻塞性肺病（COPD）患者的肺功能，尚可改善其生活质量。使用方便，副作用极少，有望成为治疗COPD的首选药物。     

噻托溴铵联合布地奈德治疗轻中度哮喘的临床疗效评价

目的 观察噻托溴铵联合吸人糖皮质激素对轻中度哮喘患者的临床疗效.方法 60例轻中度哮喘患者随机分为两组:噻托溴铵组给予吸入噻托溴铵干粉剂(18μg,每日1次)与布地奈德干粉剂(200 μg,每日2次);福莫特罗组给予吸入布地奈德福莫特罗干粉剂(160/4.5 μg,每日2次).在治疗前及治疗后8 w测定两组症状体征及肺功能变化.结果 治疗后8w,噻托溴铵组及福莫特罗组患者症状体征评分和肺功能指标明显改善,两组间比较,差异无统计学意义(P＞0.05).结论 在吸入糖皮质激素的基础上加用噻托溴铵,可明显改善轻中度哮喘患者的症状和肺功能,其疗效和加用福莫特罗相当.     

老年人稳定期慢阻肺应用噻托溴铵的临床观察

目的探讨老年人COPD稳定期应用噻托溴铵治疗的疗效。方法选取58例慢性阻塞性肺疾病稳定期的患者,并随机分成两组即噻托溴铵组(30例)和异丙托溴铵组(28例),噻托溴铵组给予噻托溴铵治疗,异丙托溴铵组给予异丙托溴铵治疗,两组疗程均为60天,通过观察两组患者临床症状及肺功能改善情况等指标,分析对比两组疗效差别。结果噻托溴铵组的临床症状、肺功能改善情况明显优于异丙托溴铵组相关指标,P<0.05。结论噻托溴铵用于稳定期COPD的治疗效果优于异丙托溴铵。     

规律吸入噻托溴铵对慢性阻塞性肺疾病稳定期患者的长期疗效

噻托溴铵是一种长效的吸入型支气管扩张剂,通过选择性地拮抗M3受体发挥作用,吸入一次,疗效可维持24 h以上.目前已有的临床证据表明,规律使用该药对中、重度慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)具有良好疗效,除了改善肺功能参数外,它在改善呼吸困难、生活质量、减少急性加重次数和住院次数方面要优于安慰剂、异丙托溴胺和长效β2受体激动剂.本品用药方便,安全性好,可作为一线和基础药物长期用于稳定期COPD患者.噻托溴铵的远期疗效及其与其他药物联合治疗的作用还有待进一步研究.     

噻托溴铵吸入治疗AECOPD的临床观察

目的探讨噻托溴铵治疗AECOPD患者的临床疗效。方法选择78例AECOPD患者,随机分为常规治疗组(对照组)37例和噻托溴铵治疗组(治疗组)41例,治疗组应用噻托嗅铵18μg吸入,1次/天,观察两组患者治疗前后症状、呼吸困难评分及肺功能变化。结果两组有效率达100%,且治疗组较对照组改善更明显,治疗后两组临床症状、呼吸困难评分和肺功能等比较,差异有统计学意义(P<0.05)。结论噻托溴铵吸入治疗AECOPD,能明显缓解患者症状,改善肺功能,是治疗AECO-PD的有效选择。     

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。     

吸入噻托溴铵对老年稳定期COPD患者的治疗

迷走神经介导的支气管痉挛是COPD患者气流受阻塞的主要不利因素，抑制支配支气管平滑肌的迷走神经可以使痉挛的支气管平滑肌舒张。COPD患者气道胆碱能神经张力是增高的，因此使用M受体阻滞剂可改善患者的气流受限。噻托溴铵作为一种新型干粉吸入制剂，具有强大、特异的抗胆碱能作用，作用持久，每日仅需一次用药，临床应用方便，因此得到较广泛应用。本文就噻托溴铵对老年稳定期中重度COPD患者的疗效以及安全性进行初步评价。     

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。     

噻托溴铵治疗慢性阻塞性肺疾病研究进展

噻托溴铵是一种新型的胆碱能M3受体阻断剂,长期每天吸入1次(18 μg)可有效地改善稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者的肺功能,减少呼气末气体陷闭,减少动态肺过度充气,缓解呼吸困难,从而可以进一步改善其生存和生活质量,减少急性发作的次数,推迟急性发作出现的时间,减少患者的住院天数.噻托溴铵为稳定期COPD患者的治疗提供了新的手段.     

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)     

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.     

Tiotropium bromide

Tiotropium bromide is a novel, inhaled, once-daily anticholinergic bronchodilator that has recently been approved in the United States for use in patients with COPD. Its unique feature is the persistence of bronchodilation for > 24 h due to prolonged M(3) muscarinic receptor blockade. Tiotropium provides significant improvement in spirometry and lung volumes. Clinically relevant outcomes such as the relief of dyspnea, improvement in the quality of life (health status), and reductions in the frequency and severity of acute exacerbations have been consistently obtained with tiotropium in clinical trials. In head-to-head trials, tiotropium administered once daily resulted in bronchodilation (peak, trough, and area under the curve) that was statistically superior to ipratropium administered four times daily and salmeterol administered twice daily. Clinical outcomes (dyspnea, quality of life, exacerbation frequency) were numerically but not always statistically better with tiotropium than salmeterol. Long-term studies of the combination of tiotropium with adrenergic agents, methylxanthines, or inhaled corticosteroids have not been reported in full. Several 1-year studies demonstrate that the only significant side effect of tiotropium was dryness of the mouth, which occurred in approximately 10 to 16% of patients; it is well tolerated by patients and safe.     

The Role of Tiotropium Bromide,a Long-Acting Anticholinergic Bronchodilator,in the Management of COPD

Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a new long-acting inhaled anticholinergic agent with superior pharmacodynamic properties compared with the short-acting anticholinergic, ipratropium bromide. Tiotropium bromide has been consistently shown to have a greater impact than ipratropium bromide on clinically important outcome measures such as health status. The mechanisms of clinical benefit with tiotropium bromide are multifactorial, but improved airway function, which enhances lung emptying and allows sustained deflation of over-inflated lungs, appears to explain improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium bromide therapy has also been associated with reduction in acute exacerbations of COPD as well as reduced hospitalizations. The safety profile of tiotropium bromide is impressive: dry mouth is the most common adverse event and rarely necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has been demonstrated in clinical trials lasting up to 1 year. There is preliminary information that the combination of long-acting anticholinergics and long-acting beta2-adrenoceptor agonists provides additive physiological and clinical benefits. According to recent international guidelines, long-acting bronchodilators should be considered early in the management of symptomatic patients with COPD in order to achieve effective symptom alleviation and reduction in activity limitation. Tiotropium bromide, because of its once-daily administration and its established efficacy and tolerability profile, has emerged as an attractive therapeutic option for this condition.     

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.     

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.     

Tiotropium (Spiriva) - a long-acting inhaled anticholinergic for the treatment of chronic obstructive pulmonary disease (COPD)

Anticholinergics are agents of first choice for the symptomatic treatment of patients with COPD. Tiotropium (Ba 679 BR, Spiriva) is a long-acting inhaled anticholinergic designed for once-daily bronchodilator treatment of COPD. Tiotropium is a selective antagonist of pulmonary M1 and M3 muscarinic receptor subtypes, that produces a long-lasting (24 hours), dose-dependent bronchodilation and bronchoprotection against constrictive stimuli, e. g. methacholine, following inhalation of single doses. Clinical trials with tiotropium in COPD patients over a maximum treatment duration of one year have confirmed a persisting bronchodilator effect of tiotropium compared with placebo and ipratropium, as well as meaningful clinical improvements in lung function, hyperinflation, exercise tolerance, symptom control and quality of life. Moreover, recent trials indicate that treatment with tiotropium also reduces the frequency of COPD exacerbations and hospitalizations. Comparative trials further suggest that the bronchodilator potency of tiotropium may be superior to those of available COPD treatments. Besides a higher incidence of dry mouth, the side effect profile was comparable to ipratropium bromide. In conclusion, present clinical data suggest that tiotropium has the potential of a first-line treatment for patients with COPD.     

肺康复联合噻托溴铵对慢性阻塞性肺疾病稳定期患者BODE指数的影响

目的 观察肺康复联合吸入噻托溴铵粉剂对中-重度COPD稳定期患者BODE指数的影响.方法 选择我院呼吸科门诊2013年10月至2015年7月确诊COPD稳定期患者60例,分为联合组(肺康复联合噻托溴铵)和对照组.对照组给予常规COPD药物基础上吸入单一噻托溴铵粉吸入剂治疗.联合组指在常规药物治疗基础上给予肺康复(包括呼吸功能锻炼、长期家庭氧疗、营养支持、心理疏导等综合治疗),联合每日吸入噻托溴铵粉吸入剂.对比2组治疗后3个月、6个月的BODE指标及BODE指数变化.结果 联合组与对照组比较治疗3个月后BODE指标(BMI、呼吸困难程度、6MWD、FEV1％ pred)、BODE指数有改善,差异有统计学意义(t=2.23,P＞0.05;t=2.44、7.78、4.36、2.61,P＜0.05),治疗6个月后BODE指标(BMI、呼吸困难程度、6MWD、FEV2％ pred)、BODE指数有显著改善,差异有统计学意义(t=4.26、3.25、23.74、9.73、4.78,P＜0.05).结论 中-重度COPD稳定期患者实施肺康复联合吸入噻托溴铵粉剂治疗后,BODE相关指标及BODE指数显著改善,长期的肺康复及噻托溴铵使用有更大获益.     

NVA237, a long-acting muscarinic antagonist, as an emerging therapy for chronic obstructive pulmonary disease

Bronchodilation with a long-acting muscarinic antagonist (LAMA) or long-acting β(2)-agonist is central to the management of chronic obstructive pulmonary disease (COPD). Tiotropium, the first LAMA available for use in COPD, has been shown to be an effective bronchodilator and is generally safe and well tolerated. However, tiotropium has limitations that include a high incidence of dry mouth, slow onset of action and, in some studies, a part of the patient population did not achieve clinically significant bronchodilation. It also remains unclear whether tiotropium reduces progressive deterioration of lung function in patients with COPD. An ideal LAMA would provide clinically meaningful bronchodilation, deliver symptom relief, prevent disease progression, improve exercise tolerance and health status, prevent and treat complications and exacerbations and reduce mortality risk. A 24-h duration of action, rapid onset of action and a good safety and tolerability profile are also desirable. The once-daily LAMA, NVA237 (glycopyrronium bromide), may meet some of these characteristics. NVA237 has high selectivity for the muscarinic type-3 (M(3)) receptor which might potentially result in a higher therapeutic index than tiotropium, which is less selective for M(3). Phase II studies showed that NVA237 once daily provides clinically significant 24-h bronchodilation with a rapid onset of action and a favourable safety and tolerability profile. Phase III studies are ongoing that will assess the long-term safety and efficacy of NVA237.