Cost-effectiveness of fluticasone propionate in the treatment of chronic obstructive pulmonary disease: a double-blind randomized,placebo-controlled trial

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating disease and places a large financial burden on health-care systems and society.We prospectively evaluated the cost-effectiveness offluticasone propionate (FP) treatment in patients with moderate-to-severe COPD, who were symptomatic on regular bronchodilator therapy. METHODS: An economic analysis was performed in a 6-month, randomized, double-blind clinical trial comparing FP 1,000 microg/day with placebo in 281 patients aged 45-79 years with symptomatic moderate-to-severe COPD. Data on clinical efficacy, health-care resource use and productivity loss associated with the management of COPD were prospectively collected. The main outcome measures were the incremental cost-effectiveness of achieving a > or = 10% improvement in FEV1 and of remaining exacerbation-free throughout the study.The economic evaluation was costed from the perspective of the NHS (direct costs) and of society (direct and indirect costs). RESULTS: FP was significantly more effective than placebo in terms of the proportions of patients demonstrating a > or = 10% improvement in FEV1 (32 vs. 19%; P = 0.02) and remaining free of moderate/severe exacerbations (75 vs. 63%; P = 0.02).The difference between the groups in total costs was not significantly different. Incremental cost-effectiveness analyses showed that the additional clinical benefits of FP relativeto placebo, in terms of a > or = 10% improvement in FEV1 or an increased number of patients free of moderate/severe exacerbations, were achieved at minimal additional costs from an NHS perspective (additional 0.25 pounds per day for bath) or at a net saving from a societal perspective. Sensitivity analysis showed that these results were robust to changes in the underlying assumptions. CONCLUSIONS: Treatment with FP was associated with statistically significant clinical benefits in patients with moderate-to-severe COPD currently symptomatic on regular bronchodilator therapy. As the differences in direct and total costs compared with placebo were small and non-significant, this treatment can be considered cost-effective in this patient population.     

Plant-based formulation in the management of chronic obstructive pulmonary disease: a randomized double-blind study

BACKGROUND: A randomized double-blind placebo controlled clinical study was undertaken to investigate the safety and efficacy of a plant-based formulation (DCBT1234-Lung KR), which earlier through 2 trials was found to improve FEV1 and the quality of life of COPD patients. OBJECTIVE: The efficacy of DCBT1234-Lung KR was assessed using pulmonary function tests, arterial blood gas (ABG) analyses and the clinical symptoms of COPD in a 6-month study period against a matching placebo and a biomedical drug combination (salbutamol+theophylline+bromhexine). METHODS: One hundred and five subjects aged between 35 and 85 years with a smoking history of more than 20 pack years, showing little or no improvement in FEV1 upon a bronchial challenge of 200 microg of inhaled salbutamol and exhibiting ABG percentage of less than 85% of oxygen saturation were taken up for the study. The study had 3 arms viz., the plant-based formulation (DCBT1234-Lung KR), placebo and salbutamol (12 mg/day) plus theophylline (300 mg/day) plus bromhexine (24 mg/day). The end point of the study was determined as an improvement of FEV1 by 200 mL and/or increased ABG values (>90% PaO2) and clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, and sleep disturbances. RESULTS: DCBT1234-Lung KR patients showed statistically significant (95% level) improvement in FEV1 and PaO2 in comparison with salbutamol+theophylline+bromhexine and placebo patients. Twenty-three per cent of DCBT1234-Lung KR patients, 19% of salbutamol+theophylline+bromhexine group and 12% of placebo group patients showed the desired 200 mL improvement in FEV1 values in comparison with the other 2 arms. Improved PaO2 was observed in 15.4% of the DCBT1234-Lung KR patients while no improvement was seen with patients in any other arms. Symptoms like dyspnoea, wheezing, cough, expectoration, disability and sleep disturbances also significantly reduced in DCBT1234-Lung KR and the biomedical group patients, but not in the placebo arm. CONCLUSIONS: DCBT1234-Lung KR was equivalent, if not better than the present day treatment with salbutamol, theophylline and bromhexine combination in COPD patients and this was ascertained using FEV1 and ABG values.     

Human diaphragm remodeling associated with chronic obstructive pulmonary disease: clinical implications

Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.     

茶碱治疗慢性阻塞性肺疾病的随机双盲平行对照研究

目的观察长期口服小剂量缓释茶碱治疗稳定期慢性阻塞性肺疾病(COPD)的疗效和安全性。方法采用随机双盲安慰剂平行对照研究方法,对2002至2003年广东韶关农村地区流行调查中筛选出符合入选标准的110例稳定期 COPD 患者进行简单随机分组,分别予缓释茶碱(每次100 mg,每天2次)和安慰剂口服治疗1年。评估肺功能、慢性阻塞性肺疾病急性发作(AECOPD)情况、生活质量、气促分数、治疗满意度和不良反应等。疗效比较采用优势检验。结果 85例(缓释茶碱组42例,对照组43例)完成1年随访。目标治疗(ITT)人群分析结果显示,缓释茶碱组 AECOPD总次数[(0.8±1.2)次/年]较安慰剂组[(1.7±2.6)次/年]减少(Z=-1.674,P=0.047),AECOPD总时间[(4.6±7.9)d]较安慰剂组[(12.5±22.8)d]减少(Z=-1.699,P=0.045);中度及以上AECOPD 次数[(0.4±1.0)次/年]较安慰剂组[(1.0±1.8)次/年]显著减少(Z=-2.136,P=0.017),扩张前的第一秒用力呼气容积(FEV_1)递减值[(0.006±0.180)L]较安慰剂组[(-0.503±0.169)L]显著减少(t=1.789,P=0.038),疗效总满意度(其中对疗效很满意的患者16例)较安慰剂组(对疗效很满意患者3例)高(Z=-2.198,P=0.014),首次 AECOPD 时间(中位数表示,365 d)较安慰剂组(276 d)延迟(X~2=3.880,P=0.049),但两组支气管扩张试验后的 FEV_1递减值(t=-0.012,P=0.495)和不良反应(P=0.076)比较差异均无统计学意义。符合方案(PP)人群分析结果显示类似的结果,缓释茶碱组的生活质量[(-28±20)分]较安慰剂组[(-20±23)分]显著改善(F=2.893,P=0.047)。结论小剂量缓释茶碱长期治疗稳定期 COPD 安全有效。     

The effects of counseling on smoking cessation among patients hospitalized with chronic obstructive pulmonary disease: a randomized clinical trial

Seventy-four cigarette-smoking patients admitted with COPD to the Chest Unit of a 600-bed teaching hospital served as subjects for a randomized trial of smoking cessation counseling. All patients were advised to quit smoking and smoking in the unit was not allowed. One-half of the patients were, in addition, provided with a self-help manual and three to eight 15- to 20-min counseling sessions on alternate days while in hospital. Self-reports of smoking status were obtained at 3 and 6 months, a sample of which were validated with serum COHb. The results were disappointing. Differences between the counseled group and the controls both in rates of cessation at 6 months (33.3% vs 21.4%) and, for patients still smoking, reductions in amount smoked would have lacked practical significance even if statistical significance had been obtained. Some alternative treatment approaches are suggested for this group of patients.     

Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial

PURPOSE: Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease (COPD) in the short term, but their long-term effects are not known. We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD. SUBJECTS AND METHODS: One hundred patients were randomly assigned to receive either an exercise training program that included cycling, walking, and strength training (n = 50) or usual medical care (n = 50). Thirty-four patients in the training group were evaluated after 6 months (end of training), and 26 were evaluated after 18 months of follow-up. In the control group, 28 patients were evaluated at 6 months and 23 after 18 months. We measured pulmonary function, 6-minute walking distance, maximal exercise capacity, peripheral and respiratory muscle strength, and quality of life (on a 20 to 140-point scale), and estimated the cost-effectiveness of the program. RESULTS: At 6 months, the training group showed improvement in 6-minute walking distance [mean difference (training - control) of 52 m; 95% confidence interval (CI), 15 to 89 m], maximal work load (12 W; 95% CI, 6 to 19 W), maximal oxygen uptake (0.26 liters/min; 95% CI, 0.07 to 0.45 liters/min), quadriceps force (18 Nm; 95% CI, 7 to 29 Nm), inspiratory muscle force (11 cm H(2)O; 95% CI, 3 to 20 cm H(2)O), and quality of life (14 points; 95% CI, 6 to 21 points; all P <0.05). At 18 months all these differences persisted (P <0.05), except for inspiratory muscle strength. For 6-minute walking distance and quality of life, the differences between the training group and controls at 18 months exceeded the minimal clinically-important difference. CONCLUSION: Among patients who completed the 6-month program, outpatient training resulted in significant and clinically relevant changes in 6-minute walking distance, maximal exercise performance, peripheral and respiratory muscle strength, and quality of life. Most of these effects persisted 18 months after starting the program.     

Effectiveness of thoracic kinesio taping on respiratory function and muscle strength in patients with chronic obstructive pulmonary disease: A protocol of randomized,double-blind placebo-controlled trial

Background:To our knowledge, only 1 study has investigated the effects of kinesio taping (KT) on pulmonary function and functional capacity of patients with chronic obstructive pulmonary disease (COPD). Therefore, there is still a lack of high-quality evidence to prove the effectiveness of KT for COPD patients. Our purpose was to investigate the effect of KT on respiratory function and muscle strength in the COPD patients who were in stable condition.Methods:This research project has been received ethical approval from the Medical Research and Ethics Committee in Affiliated Nanhua Hospital, University of South China. This work is a part of a comprehensive research project to assess and provide intervention that potentially improves respiratory function and quality of life among patients with COPD. Participants recruited into the study need to fulfill the following criteria: clinical diagnosis of COPD and symptoms indicative of exacerbation; spontaneous breathing on hospital admission; and physiotherapy since the first day of hospitalization. Patients will be assigned at random to the COPD medical treatment + KT (Group 1), or the COPD medical treatment alone (Group 2). The outcome measures are pulmonary function and respiratory muscle strength. The level of statistical significance is set as P < .05.Results:This protocol will provide a reliable theoretical basis for the following research.Conclusions:It was hypothesized that thoracic KT could significantly change pulmonary function and functional capacity in patients with COPD.Trial registration:This study protocol was registered in Research Registry (researchregistry6632).