Therapeutic conversion of the combination of ipratropium and albuterol to tiotropium in patients with chronic obstructive pulmonary disease

BackgroundIpratropium and albuterol, combined in a single formulation, is widely used as three to four times daily maintenance therapy in COPD. This trial compared tiotropium, once daily, as a potential alternative to patients already taking the ipratropium/albuterol combination.Methods676 patients with moderate to very severe stable COPD (mean FEV₁ = 39% of predicted) maintained on ipratropium/albuterol were randomized to receive over an 84 day period either tiotropium (18 mcg) each morning, or continue with ipratropium (26 mcg)/albuterol (206 mcg), 2 actuations 4 times daily, using a parallel group, double-blind, double-dummy design. Six-hour spirometry was assessed on study days 1, 22, and 84, along with safety assessments and other efficacy measures.ResultsIn terms of primary outcomes, mean trough FEV₁ at 84 days was larger in the tiotropium arm, as compared with the ipratropium/albuterol arm (difference = 86 ml; 95% CI, 49 to 123 ml, p < 0.0001). The mean FEV₁ AUC_0–6 at 84 days was also larger in the tiotropium arm (difference = 17 ml; 95% CI, ?21 to 56 ml), this difference being statistically non-inferior to the ipratropium/albuterol arm (p < 0.001), but not statistically superior (p = 0.37). Other efficacy measures were similar in the two groups. Lower respiratory adverse events were reported in 40 tiotropium patients vs. 52 ipratropium/albuterol patients. Safety reporting was otherwise similar.ConclusionPatients previously maintained on the ipratropium/albuterol combination taken four times daily can be switched to tiotropium once daily with the reasonable expectation of at least equivalent bronchodilation during daytime hours and superior bronchodilation during early morning hours.     

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.     

噻托溴铵对稳定期COPD患者夜间睡眠低氧的临床疗效

目的观察噻托溴铵对慢性阻塞性肺疾病(COPD)患者夜间睡眠低氧和睡眠质量的疗效。方法 40例存在夜间睡眠低氧的稳定期COPD患者随机分为两组,治疗组吸入噻托溴铵,对照组吸入安慰剂,治疗前后检测夜间血氧饱和度、血气分析、肺功能和匹兹堡睡眠质量指数(PSQI)评分。结果治疗后治疗组夜间平均血氧饱和度、夜间最低血氧饱和度、动脉血氧分压和动脉血氧饱和度较对照组明显升高(均P<0.05),夜间血氧饱和度小于90%的时间占总睡眠时间的百分比和PSQI总分较对照组显著降低(均P<0.01),第1秒用力呼气容积、用力肺活量和深吸气量较对照组显著增加(均P<0.01)。结论噻托溴铵能改善COPD患者夜间睡眠低氧和睡眠质量。     

吸入噻托溴铵对慢性阻塞性肺疾病患者运动耐量的影响

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者呼气气流受限导致气体陷闭和肺过度充气,从而导致COPD患者特征性的临床症状.每天一次噻托溴铵18μg,通过长效的抗胆碱能作用维持24 h气道通畅,已显示出能持续减轻COPD患者呼吸困难症状,提高运动耐量和健康相关性生活质量.     

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.     

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。     

噻托溴铵对稳定期重度慢性阻塞性肺疾病肺动态过度充气的影响

目的 探讨每日一次吸入噻托溴铵对稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)肺动态过度充气的影响.方法 实验对象使用信封法COPD稳定期患者40例被随机分入治疗组(噻托溴铵,18 μg,1次/d)和对照组(未吸入噻托溴铵),在接受实验药物治疗的当天、治疗后的第48天及第56天分别进行肺功能测定,测定最大深吸气量(IC)和功能残气量(FRC)值各3次,取其最高值以供数据分析;用食道气囊法检测动态内源性呼气末正压(PEEPidyn),取8个连续呼吸计算结果的均值作为测定值,在接受实验药物治疗的当天、治疗后的第48天及第56天分别进行测定.结果 随机分组的患者人口统计学和基线特征各项指标差异无统计学意义,有可比性;治疗开始两组FRC、IC、PEEPidyn值差异无统计学意义(P＞0.05),治疗第28天噻托溴铵组FRC、PEEPidyn值较治疗第0天及对照组下降,IC值增加.但差异无统计学意义(P＞0.05);治疗的第56天噻托溴铵组FRC、PEEPidyn值较治疗第0天及对照组进一步下降,IC值进一步增加,且差异有统计学意义(P＜0.01).结论 每日一次吸入噻托溴铵一定疗程可一定程度改善稳定期重度COPD肺动态过度充气.     

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.     

噻托溴胺粉雾剂对稳定期慢性阻塞性肺疾病患者深吸气量的改善作用

目的观察噻托溴胺对稳定期慢性阻塞性肺疾病(COPD)患者深吸气量的影响,探讨深吸气量(IC)对评价支气管扩张剂疗效评估的价值。方法将2003年8月至2005年3月南京医科大学附属南京第一医院呼吸内科收治的60例稳定期COPD患者,随机分成观察组(A组)噻托溴胺粉雾剂吸入;对照组(B组)安慰剂吸入。于研究第1天、第43天(约6周)、第85天(约12周)检测1秒钟用力呼气量(FEV1)、FEV1占预计值的百分比[FEV1(%)]、用力呼气量(FVC)、FEV1/FVC、IC等指标。结果观察组FEV1在第6周与对照组比较显著升高(t=2.018,P=0.048),12周差异无显著性(t=1.723,P=0.090);FEV1(%)在第6周、12周与对照组比较差异无显著性(t分别为1.761、1.387,P分别为0.083、0.171);FVC在第6周、12周与对照组比较,均有显著升高(t分别为2.762、2.255,P分别为0.008、0.029);FEV1/FVC在第6周、12周与对照组比较,差异无显著性(t分别为0.370、0.668,P分别为0.713、0.507);IC在第6周、12周较对照组显著增高(t分别为3.204、3.109,P分别为0.002、0.003)。结论噻托溴胺可使稳定期COPD患者IC增大。对于判断COPD气流受限的指标FEV1/FVC、FEV1(%),用于判断支气管扩张剂的疗效方面则不够敏感。IC是评价支气管扩张剂疗效的可靠指标。     

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。     

The efficacy of continuous nursing care for patients with chronic obstructive pulmonary disease: A randomized controlled trial protocol

Background:Chronic obstructive pulmonary disease (COPD) is a kind of disease that can be prevented and treated. It is characterized by the progressive limitation of airflow and is one of the most familiar human health barriers worldwide. For our program, the objective is to evaluate the impact of continuous care on the life quality of the COPD patients.Methods:This study will be implemented from June 2021 to March 2022 at Shandong Chest Hospital. The experiment was granted through the Research Ethics Committee of Shandong Chest Hospital (0029-4651). The criteria for inclusion involves:

• (1)patients diagnosed with COPD;
• (2)patients with expectorant, chronic cough, dyspnea, and other symptoms;
• (3)patients who volunteered to take part in our study;
• (4)have the cognitive ability to take part in interviews and fill in questionnaires.

The criteria for exclusion contains:

• (1)patients with unstable physical conditions, for instance, congestive heart failure, recent myocardial infarction, acute cerebrovascular diseases, and malignant tumor;
• (2)suffering from bronchial asthma or bronchiectasis;
• (3)patients with serious physical dysfunction;
• (4)patients who are unwilling to offer the informed consent to take part in this experiment.

For our research, the result measure is St. George''s Respiratory Questionnaire (SGRQ).Results:Table 1 reflects the comparison results of 2 groups after the intervention.Conclusion:The continuous care on the basis of the theory of Information, Knowledge, Attitude, and Practice (IKAP) can promote the improvement of life quality in the COPD patients.Trial registration number: researchregistry 6266.     

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。     

噻托溴铵在治疗慢性阻塞性肺疾病中的非支气管扩张作用

慢性阻塞性肺疾病是一种以气流受限不完全可逆为特征的气道炎症性疾病.非神经源性的胆碱能系统在炎症的发生发展和气道重塑中发挥了重要作用.噻托溴铵作为一种新型的抗胆碱能药物,其作用不仅仅局限于扩张气道,它在调节气道炎症和重塑方面也起到了作用.     

戒烟对稳定期慢性阻塞性肺疾病的治疗作用

目的探讨戒烟对稳定期COPD的治疗作用。方法纳入2011年7月-2013年7月经福建医科大学附属泉州第一医院肺功能室检查确诊的稳定期COPD患者193例,按是否采用戒烟治疗及最终完成情况分为戒烟成功组、戒烟失败组及非戒烟组：戒烟成功亚组62例,均为男性,平均年龄为（60．82±5．63）岁,平均吸烟指数为（852±100）年·支;戒烟失败亚组36例,均为男性,平均年龄为（60．61±4．91）岁,平均吸烟指数为（812±139）年·支;非戒烟组95例,均为男性,平均年龄为（60．49±8．77）岁,平均吸烟指数为（833土143）年·支。采用FEV。为肺功能评价指标,CAT评分为COPD病情评价指标。进行为期半年的随访。结果各试验组患者在年龄、体质量指数及吸烟指数等方面差异无统计学意义。戒烟成功组患者治疗后体质量增加（2．85±1．27）kg,CAT评分下降（6．05±2．60）分,戒烟前后对比差异有统计学意义（t值分别为17．763、18．351,P值均d0．01）;FEV,增加（O．04±0．18）L,戒烟前后对比差异无统计学意义（t=1．900,P=0．062）。而戒烟失败组及未戒烟组治疗前后体质量、CAT评分及FEV,变化差异均无统计学意义（P值均〉0．05）。结论戒烟半年即对稳定期COPD具有=定的治疗作用,主要表现在体质量增加、临床症状减轻,而肺功能则无明显改善。     

吸入噻托溴铵干粉与异丙托溴铵定量气雾剂治疗慢性阻塞性肺疾病的疗效与安全性比较

目的比较噻托溴铵干粉吸入剂与异丙托溴铵定量气雾剂治疗慢性阻塞性肺疾病(COPD)4周的疗效与安全性。方法采用多中心、随机、双盲、双模拟、平行对照研究方法,对221例筛选合格的稳定期中重度COPD患者给予吸入噻托溴铵干粉剂(18μg,每日1次)或异丙托溴铵定量气雾剂(2喷/次,每日4次)治疗4周。在治疗前,治疗后2周及4周,给药前5min,给药后30、60、120及180min分别测定肺功能。结果首要疗效指标第一秒用力呼气容积(FEV1)谷值反应。治疗4周后噻托溴铵组FEV1谷值反应显著优于异丙托溴铵组[(0.063±0.024)L,95%CI为0.016～0.111L,t=2.63,P=0.009],显示噻托溴铵组患者的通气功能得到持续改善;噻托溴铵组的用力肺活量(FVC)谷值反应在治疗4周时较异丙托溴铵组增高(0.133±0.047)L,t=2.83,P=0.005;与基线相比,给药后0～3h平均FEV1的变化(FEV1AUC0～3h)及平均FVC变化(FVCAUC0～3h)在两组比较差异均无统计学意义;缓解喘息应急药物的使用量在两组间比较差异无统计学意义(t=0.60,P=0.548)。本研究中噻托溴铵组有12例(10.9%)、异丙托溴铵组有18例(16.2%)发生不良事件,两组比较差异无统计学意义(χ2=1.326,P=0.249)。噻托溴铵的常见不良反应为口干(5例,4.5%),无心血管系统异常和心电图异常报告。结论每日1次吸入噻托溴铵18μg较每日4次异丙托溴铵治疗,对COPD患者具有更强的支气管扩张作用。噻托溴铵耐受性良好,与异丙托溴铵具有相似的安全性。     

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.