Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations

OBJECTIVES: COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250/50 and salmeterol 50 microg twice daily on moderate to severe exacerbations. METHODS: Patients received standardized treatment with fluticasone propionate/salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/salmeterol 250/50 or salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization. RESULTS: In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with salmeterol (1.06 and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical improvements observed during run-in treatment with fluticasone propionate/salmeterol 250/50 were better maintained over 12 months with fluticasone propionate/salmeterol 250/50 than salmeterol. Adverse events were reported for a similar percentage of subjects across groups. A higher reporting of pneumonia was observed with fluticasone propionate/salmeterol 250/50 than salmeterol (7% vs. 4%). CONCLUSIONS: We conclude that fluticasone propionate/salmeterol 250/50 is more effective than salmeterol at reducing the rate of moderate to severe exacerbations over 1 year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.     

Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone

BACKGROUND: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide) plus a short-acting beta(2)-agonist (SABA). METHODS: Patients (N=2309) with symptomatic asthma (aged 12 years; forced expiratory volume in 1s 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 microg twice daily plus terbutaline as needed, for 6 months. RESULTS: Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 microg/day budesonide [1238 microg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 microg/day fluticasone [2000 microg/day BDP equivalent] with salmeterol/fluticasone therapy; P<0.0001). Both treatments were well tolerated. CONCLUSION: In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure.     

沙美特罗替卡松联合噻托溴铵吸入治疗中重度COPD 40例疗效观察

目的观察沙美特罗替卡松（舒利迭）联合噻托溴铵粉吸入剂（思力华）对中重度COPD的治疗效果。方法将40例临床诊断为中重度COPD的患者随机分为两组。A组：22例,舒利迭（50/500 ug）吸人,每天2次,加用思力华,使用吸入装置（HandiHaler）吸入,每次1粒胶囊（18 ug）,每天1次。B组：18例,单纯舒利迭（50/500 ug）吸人,每天2次.疗程3个月。观察两组患者治疗前后呼吸困难的评分、血气分析及肺功能情况。结果治疗3个月后,所有患者呼吸困难均减轻,但A组呼吸困难下降值明显高于B组（P〈0.001）。与B组比较,治疗后A组肺功能指标（FVC、FEV1及FEV1/FVC）及血气指标（SaO2、PaO2）明显升高,而PaCO2则明显下降（P〈0.01）。结论长效抗胆碱药噻托溴铵与舒利迭联合应用可明显改善中重度COPD患者的呼吸困难、血气和肺功能,优于单纯应用舒利迭,可使COPD得到良好的控制。     

Inhaled salmeterol/fluticasone propionate combination in chronic obstructive pulmonary disease

Salmeterol/fluticasone propionate is a fixed-dose combination of the long-acting beta2-adrenoceptor agonist salmeterol and the corticosteroid fluticasone propionate and is inhaled via the Diskus powder inhaler. In three randomized, double-blind, 24-week or 52-week studies in >2850 patients with chronic obstructive pulmonary disease (COPD), administration of salmeterol/fluticasone propionate 50/250 microg twice daily (in one study) and salmeterol/fluticasone propionate 50/500 microg twice daily (in the other studies) provided greater improvement in lung function than placebo or either component alone at the same nominal dosage. Both strengths of the combination product administered twice daily resulted in clinically meaningful increases in scores in health-related quality-of-life questionnaires that were specific for respiratory disease. Improvements in this and almost all other secondary measures of efficacy, including symptomatic outcomes, were significantly greater with the combination product than with placebo. Administration of salmeterol/fluticasone propionate as a combination product did not result in any untoward interactions that affected the pharmacodynamic, pharmacokinetic or tolerability profiles of the individual components. Candidiasis, hoarseness/dysphonia, throat irritation and headache occurred more frequently with salmeterol/fluticasone propionate than with placebo in patients with COPD.     

Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: a pilot study

BACKGROUND: International guidelines recommend the long-acting anticholinergic, tiotropium, or long-acting beta 2-agonists as maintenance therapy in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). The efficacy of long-acting beta(2)-agonists combined with inhaled corticosteroids (ICS) in the treatment of COPD has also been confirmed for severe and very severe COPD, but data comparing tiotropium with the combination of a long-acting beta 2-agonist and an ICS are lacking. METHODS: This 6-week multicentre, randomised, double-blind, triple-dummy pilot study compared the bronchodilator effects of tiotropium 18 microg once daily (n=56) vs. the combination of salmeterol 50 microg plus fluticasone 250 microg twice daily (n=51) in patients with moderate-to-very severe COPD. Serial spirometry was performed over 12h after 6 weeks of treatment. The primary endpoint was forced expiratory volume in 1s (FEV1) area under the curve from 0 to 12h (AUC0-12h) on Day 43. RESULTS: Randomization failed to provide treatment groups with comparable baseline characteristics for smoking history, current smokers, duration of COPD, FEV1, forced vital capacity (FVC) and reversibility. Mean+/-SD FEV1 was 1.31+/-0.47 l in the tiotropium group vs. 1.46+/-0.53 l in the salmeterol plus fluticasone group. Fewer patients in the tiotropium showed a 12% and 200 ml acute increase to short-acting bronchodilators at baseline. However, treatment with tiotropium alone resulted in comparable bronchodilation compared with salmeterol plus fluticasone, as measured by all the spirometric parameters at the end of the 6-week study period. FEV1 AUC0-12h was 1.55+/-0.03 l in the tiotropium group vs. 1.57+/-0.04 l in the salmeterol plus fluticasone groups (p=0.63). Trough (predose) FEV1 was 1.54+/-0.03 l in the tiotropium group vs. 1.46+/-0.03 l in the combination group (p=0.07), and peak FEV(1) was 1.68+/-0.04 l vs. 1.66+/-0.04 l, respectively, (p=0.77). FVC AUC0-12h, trough and peak were also comparable between groups at study end (p>0.05, for all). Further, rescue salbutamol use was similar in the tiotropium and combination groups and both treatment regimens were well tolerated. CONCLUSIONS: Six weeks of treatment with tiotropium resulted in comparable bronchodilation compared with salmeterol plus fluticasone in patients with moderate-to-very severe COPD, despite tiotropium patients having lower lung function and fewer patients considered reversible at baseline. The results of this pilot study will aid planning for further large-scale comparative studies.     

EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma

OBJECTIVES: This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids. METHODS: The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group. RESULTS: The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated. CONCLUSIONS: Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.     

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.     

The efficacy and safety of combination salmeterol (50 microg)/fluticasone propionate (500 microg) inhalation twice daily via accuhaler in Chinese patients with COPD

BACKGROUND: Few studies of the efficacy and safety of therapy with combinations of salmeterol/fluticasone propionate (SFCs) have been conducted in Chinese patients with COPD, and the benefits of combination therapy in nonsmoking patients with COPD are, to our knowledge, not known. STUDY OBJECTIVES: The aims were to establish the efficacy and tolerability of the therapy with SFC (salmeterol, 50 microg/fluticasone, 500 microg, twice daily) in the management of Chinese COPD patients and to investigate the effectiveness of SFC in nonsmokers with COPD. METHODS AND PATIENTS: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Changes in prebronchodilator and postbronchodilator FEV(1), quality of life determined by the St. George Respiratory Questionnaire (SGRQ) scores, relief bronchodilator use, nighttime awakenings, and frequency of exacerbations of COPD were measured in patients randomized to receive SFC (n = 297) or placebo (n = 148). Never-smokers, former smokers, and current smokers accounted for 11.7%, 66.7%, and 21.6%, respectively, of the study population. RESULTS: After 24 weeks, the mean changes in prebronchodilator and postbronchodilator FEV(1) were 180 mL (95% confidence interval [CI], approximately 91 to 268; p < 0.001) and 65 mL (95% CI, approximately 14 to 115; p = 0.012), respectively, greater for the SFC group than that for the placebo group. The differences in response to treatment were significant (all p < 0.0001) in former or current smokers but not in never-smokers (p > 0.05). The mean improvement in the total SGRQ score for the SFC group was 5.74 (p < 0.01) greater than that for the placebo group. SFC significantly reduced the frequency of nighttime awakenings and the use of relief bronchodilator. The adjusted ratio of exacerbations of COPD for the SFC group relative to the placebo group was 0.61 (95% CI, approximately 0.45 to 0.84; p < 0.01). There were no significant differences between the SFC and placebo groups in safety measures. CONCLUSIONS: SFC therapy achieved sustained improvement in lung function, quality of life, and control of symptoms, and was well tolerated in Chinese patients. Greater improvements in lung function were found only for COPD patients with a history of smoking. Trial registration: http://ctr.gsk.co.uk/Summary/fluticasone_salmeterol/studylist.asp Identifier: No. SCO100540.     

Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD

BACKGROUND: A 6-week, multicenter, randomized, double-blind, parallel-group study was conducted in patients with COPD to compare lung function improvements of tiotropium, 18 microg qd, plus formoterol, 12 microg bid, to salmeterol, 50 microg bid, plus fluticasone, 500 microg bid. METHODS: Following a screening visit, subjects entered a run-in period in which they received regular ipratropium. At randomization, patients were assigned to either tiotropium plus formoterol or salmeterol plus fluticasone. After 6 weeks of treatment, a 12-h lung function profile was obtained. The coprimary end points were FEV(1) area under the curve for the time period 0 to 12 h (AUC(0-12)) and peak FEV(1). RESULTS: A total of 729 patients were screened, and 605 patients were randomized and treated. A total of 592 patients (baseline FEV(1), 1.32 +/- 0.43 L/min [+/-SD]) were included in the analysis. After 6 weeks, the 12-h lung function profiles in the group receiving tiotropium plus formoterol were superior to those in the group receiving salmeterol plus fluticasone (mean difference in FEV(1) AUC(0-12), 78 mL [p = 0.0006]; mean difference in FVC AUC(0-12), 173 mL, p < 0.0001). Also, peak responses were in favor of tiotropium plus formoterol (difference in peak FEV(1), 103 mL [p < 0.0001]; difference in peak FVC, 214 mL [p < 0.0001]), as were FEV(1) and FVC at each individual time point after dose (p < 0.05). Predose FVC was significantly higher with the bronchodilator combination, while predose FEV(1) and rescue medication use did not differ significantly between groups. Both treatments were well tolerated. CONCLUSIONS: Tiotropium plus formoterol was superior in lung function over the day compared to salmeterol plus fluticasone in patients with moderate COPD. Long-term studies in patients with severe COPD are warranted to assess the relative efficacy of different treatment combinations. Trial registration: Clinicaltrials.gov Identifier: NCT00239421.     

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.     

Control of mild to moderate asthma over 1-year with the combination of salmeterol and fluticasone propionate

OBJECTIVE: The aim of this study was to assess asthma control using salmeterol plus fluticasone propionate (FP) in combination (SFC) versus salmeterol or FP as monotherapy in patients with mild to moderate asthma. METHODS: In this randomised, double-blind, parallel-group study, 322 symptomatic patients were recruited, of which 282 were randomised to receive either salmeterol (50 microg), FP (250 microg), or SFC (50 microg/250 microg), via a single Diskus inhaler twice daily for 12 months. Outcome variables included the number of patients requiring an increase in study medication and the number experiencing 2 exacerbations during the 12-month treatment period. Airway hyper-responsiveness (AHR) and lung function tests were performed at clinic visits. Peak expiratory flow, rescue medication use, symptom scores and adverse events were recorded in diary cards. RESULTS: Fewer patients required an increase in study medication with SFC (10.5%) than with either FP (34.8%) or salmeterol (61.1%) (P<0.001). Significantly fewer patients experienced 2 exacerbations with SFC (4.2%), compared with FP (17.4%; P<0.01) or salmeterol (40%; P<0.001). SFC improved AHR to a significantly greater extent than FP (methacholine PC20=1.8 mg/ml vs. 1.1 mg/ml; P<0.05) or salmeterol (methacholine PC20=1.8 mg/ml vs. 0.7 mg/ml; P<0.001). CONCLUSIONS: The protection against exacerbations may be attributed to better control of inflammation, AHR and lung function parameters achieved with salmeterol and FP in combination, compared with either treatment alone.     

Does Low-Dose Seretide Reverse Chronic Obstructive Pulmonary Disease and Are the Benefits Sustained Over Time? An Open-Label Swedish Crossover Cohort Study Between 1999 and 2005

Chronic obstructive pulmonary disease (COPD) still poses a formidable challenge to patients and clinicians alike. A fixed-dose dry powder combination inhaler, Seretide/Advair, containing salmeterol and fluticasone, is licensed in the European Community for the treatment of moderate to severe COPD in the strength of 50/500 μg twice daily (BID). Several studies have investigated the effects of this combination and show improved forced expiratory volume in 1 s (FEV₁), quality of life, and a decrease of exacerbations. Most of the studies have run for less than 1 year. The aim of this investigator-initiated, independent study was to elucidate if the combination containing 50 μg of salmeterol and 250 μg of fluticasone BID could be shown to have the same beneficial effect as the higher dosage, and if the effect could be sustained over time.     

The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma

The aim of this study was to compare the efficacy and safety of salmeterol/fluticasone propionate combination product (SFC) with fluticasone propionate (FP) plus oral montelukast (M) over 12 weeks in symptomatic asthma patients. The study was a multinational, randomised, double-blind, double-dummy, parallel-group design in patients aged > or = 15 years. After a 4-week run-in during which all patients received FP 100 microg twice daily, patients were randomised to inhaled SFC (50/100 microg) twice daily or inhaled FP 100 microg twice daily and oral M 10 mg once daily. Patients kept daily records of their peak expiratory flow (PEF) symptom scores and use of rescue medication. Over the 12-week treatment period, the adjusted increase in mean morning PEF was significantly greater in the SFC group (36 l/min) than the FP/M group (19 l/min; P < 0.001).The improvement in FEV1 was also significantly greater in the SFC group (mean treatment difference 0.11 l; P < 0.001). SFC provided significantly better control of daytime and night-time symptoms and there were fewer exacerbations. Patients in the SFC group were also significantly more likely to have a rescue-free day. Both treatments were equally well tolerated. Combination therapy with FP plus salmeterol (SFC) produced significantly greater improvements in lung function and asthma control than the addition of montelukastto FP.     

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。     

Changes in lung function and health status in patients with COPD treated with tiotropium or salmeterol plus fluticasone

Background and objective: The effects of tiotropium, a long‐acting anticholinergic drug, were compared with those of the combination of salmeterol, a long‐acting β₂‐agonist, and fluticasone, an inhaled corticosteroid, in patients with COPD. Methods: A 4‐month, randomized, open cross‐over study of tiotropium, 18 µg once daily, versus salmeterol, 50 µg, plus fluticasone, 200 µg, twice daily, was conducted in patients with COPD. Efficacy was assessed by spirometry and responses to the St George's Respiratory Questionnaire (SGRQ). After 4 months, patients were asked to select their subsequent therapy and indicate the reasons for their selection. Results: A total of 78 patients completed the study. There were no significant differences in the improvements in FEV₁ or SGRQ scores between the therapies. Similar numbers of patients selected tiotropium (42.3%) and salmeterol plus fluticasone (57.7%). However, those who preferred one of the therapies demonstrated greater improvements in SGRQ scores with that therapy. One subgroup of patients (30.8%) showed greater improvements in dyspnoea and FEV₁ in response to tiotropium, and the other subgroup of patients (35.9%) showed greater improvements in dyspnoea and FEV₁ in response to salmeterol plus fluticasone. Some patients (14.1%) selected salmeterol plus fluticasone because of positive effects on sputum expectoration. Conclusions: The study was unblinded and the results need to be interpreted with caution. However, tiotropium and salmeterol plus fluticasone had similar overall effects on pulmonary function and SGRQ scores in patients with COPD. Responses to the two therapies were heterogeneous, and the patients who showed greater improvements in FEV₁ or SGRQ scores with one of the therapies preferred it for their subsequent treatment.     

Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.     

噻托溴铵联合大剂量沙美特罗/氟替卡松治疗重度支气管哮喘合并COPD稳定期的临床观察

目的 为了探讨更好的治疗重度支气管哮喘（简称哮喘）合并慢性阻塞性肺疾病（COPD）的方法,提高重度哮喘合并COPD患者的生活质量.为重度哮喘合并COPD防治积累更多临床经验.方法 对于临床确诊的霞度哮喘合并COPD的患者,随机分为两组,一组为对照组,给予复方异丙托溴铵气雾剂（可必特）联合中等剂量沙美特罗/氟替卡松（舒利迭50/250μg）治疗,一组为治疗组,给予噻托溴铵下粉吸入剂（思力华）联合大剂量沙美特罗/氟替卡松（舒利迭50/500μg）粉吸入剂治疗.采取随机、开放、自身对照和组间对照的方法,每月复诊一次,详细记录每例患者的肺功能变化、生活质量、急性发作次数、下次急性发作的间隔时间、住院次数、经济费用和不良反应.分析对比二者对重度哮喘合并COPD的综合疗效,为期一年.结果 治疗前两组患者FEV1分别为对照组（1.14±0.13）L、治疗组（1.11±0.15）L,两组之间差异无统计学意义.治疗一年后FEV1对照组为（1.30±0.14）L,治疗组（1.39±0.15）L,两组之间差异无统计学意义.同组之间治疗前后差异均有统计学意义（P〈0.05）.治疗前两组的临床症状评分分别为对照组（43.3±1.11）分、治疗组（44.7±0.97）分,两组之间差异无统计学意义.治疗～年后两组的临床症状评分分别为对照组（38.9±1.07）分、治疗组（38.24±0.96）分,两组之间差异无统计学意义.对照组治疗前后临床症状评分平均下降4.4分,治疗组治疗前后临床症状评分平均下降6.5分,治疗前后差异均有统计学意义（P〈0.001）,两组相比差异有统计学意义（P〈0.05）.治疗一年中两组的平均急性发作次数分别为对照组（1.24±0.21）次/年人、治疗组（0.79±0.13）次/年人,治疗组平均减少（0.45±0.15）次/年人,两组差异有统计学意义（P〈0.01）.治疗一年中两组患者下次急性发作的平均间隔时间分别为对照组（162±27）d、治疗组（187±32）d,差异无统计学意义.两组的住院次数分别为对照组（0.22±0.04）次,治疗组（0.12±0.06）次,治疗组与对照组相比差异有统计学意义（P〈0.05）.治疗一年两组的经济费用分别为对照组（4 212±383）元、治疗组（12 382±475）元,治疗组明显增加,与对照组相比差异有统计学意义（P＜0.001）.两组不良反应相似,但均较轻微.结论 噻托溴铵联合大剂量沙美特罗/氟替卡松吸人治疗和复方异丙托溴铵气雾剂联合中等剂量沙美特罗/氟替卡松治疗均能够改善霞度哮喘合并COPD患者的肺功能和临床症状、提高生活质量、减少急性发作次数、延长下次急性发作的间隔时间、减少住院次数,不良反应轻微,适合于重度哮喘合并COPD的治疗.噻托溴铵联合大剂量沙美特罗/氟替卡松吸人治疗在提高生活质量、减少急性发作次数、减少住院次数方面优于中等剂量沙美特罗/氟替卡松联合复方异丙托溴铵气雾剂治疗,但费用昂贵,限制了其在临床的推广.     

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。     

Efficacy of salmeterol xinafoate in the treatment of COPD

STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. Interventions: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.