Interaction and dose equivalence of salbutamol and salmeterol in patients with asthma.

OBJECTIVE--To examine the pharmacological interaction of salmeterol and salbutamol and to derive an estimate of dose equivalence of salmeterol for airway and systemic effects in patients with asthma. DESIGN--Randomised double blind crossover study. SUBJECTS--12 patients with mild asthma. INTERVENTION--Placebo or salmeterol 50, 100, 200 micrograms given on separate days followed two hours later by inhaled salbutamol in cumulative doses up to 3600 micrograms. MAIN OUTCOME MEASURES--Change in forced expiratory volume in one second (FEV1), heart rate, plasma potassium concentration, QTc interval, tremor amplitude, and creatine kinase myocardial isoenzyme concentration. RESULTS--Compared with placebo, the mean (95% confidence interval) changes in FEV1 and heart rate after salmeterol 200 micrograms were 0.61 (0.32 to 0.90) l and 7.0 (3.8 to 10.2) beats/min. Adding salbutamol caused a large increase in FEV1 after placebo (0.69 l) with progressively smaller changes after increasing doses of salmeterol (0.19 l after salmeterol 200 micrograms). Heart rate and QTc interval increased and plasma potassium concentration decreased roughly in parallel on the four study days with a suggestion of convergence at higher doses of salbutamol. Geometric mean dose equivalences for salmeterol 50 micrograms and 100 micrograms compared with salbutamol were 4.9 and 7.8 (mean 6.4) for FEV1 and ranged from 7.1 (2.9 to 17.0) to 12.6 (4.4 to 36.4) for heart rate, plasma potassium, and tremor (mean 9.5). CONCLUSIONS--The effect of adding salbutamol to salmeterol is largely additive. Weight for weight salmeterol may be up to 10 times more potent than salbutamol. Considering its longer duration of action salmeterol 50 micrograms twice daily could be equivalent to salbutamol in doses up to 500 micrograms four to six hourly.     

普米克都保联合沙丁胺醇对咳嗽变异性哮喘患儿的疗效分析

目的:探讨普米克都保联合沙丁胺醇对咳嗽变异性哮喘(CVA)患儿的疗效分析。方法:选取100例CVA患者,沙丁胺醇组(48例)给予沙丁胺醇联合用药组(52例)给予沙丁胺醇和普米克都保,观察并记录两组患者治疗后的疗效,咳嗽缓解及消失时间,治疗前后的用力肺活量(FVC),第1秒用力呼气容积(FEV1)、呼气峰流速(PEF)及最大呼气中段流速(MMEF)等肺功能指标及随访1个月期间的不良反应,评价普米克都保联合沙丁胺醇对咳嗽变异性哮喘的疗效。结果:治疗后联合用药组有效率明显高于沙丁胺醇组(P0.05),联合用药组中有92.3%患者,沙丁胺醇组有72.9%患者咳嗽症状在2周内消失,治疗后联合用药组咳嗽缓解时间和消失时间明显短于沙丁胺醇组(P0.05)。治疗前后,两组在FVC,FEVl,PEF上相比,差异没有统计学意义(P0.05),治疗前,两组MMEF水平均明显低于体检健康者(P0.05),其他肺功能指标与体检健康者相比,无统计学差异(P0.05)。治疗后联合用药组MMEF明显高于治疗前,且高于沙丁胺醇组(P0.05)。沙丁胺醇组治疗前后MMEF未出现明显变化(P0.05)。随访1个月期间,两组不良反应率相比,差异没有统计学意义(P0.05)。结论:普米克都保联合沙丁胺醇能对CVA具有较好的治疗作用,能缩短咳嗽症状消失时间,改善患儿肺功能,值得临床推广使用。     

布地奈德联合孟鲁司特钠对支气管哮喘患儿细胞因子、免疫功能影响

目的:探讨布地奈德联合孟鲁司特钠对支气管哮喘患儿细胞因子、免疫功能影响。方法:选自我院于2014年9月~2016年3月期间收治的支气管哮喘患儿96例,依据随机数字表法随机分为观察组与对照组,每组48例。对照组给予孟鲁司特钠治疗,观察组在对照组基础上结合布地奈德治疗。两组疗程均为4周。观察并比较两组的临床疗效、以及治疗前后患者血清细胞因子水平、免疫功能及肺功能的变化情况。结果:观察组治疗总有效率(95.83%)高于对照组(79.17%)(P0.05);观察组血清IL-5含量治疗后低于对照组,而IL-12含量高于对照组(P0.05);观察组血清Ig E含量治疗后低于对照组,而Ig A、Ig M含量高于对照组(P0.05);观察组FEV1和FVC治疗后高于对照组(P0.05);两组均未见明显不良反应。结论:布地奈德联合孟鲁司特钠治疗支气管哮喘患儿疗效显著,且作用可能与改善细胞因子、免疫功能及肺功能有关。     

布地奈德溶液治疗哮喘急性发作的疗效评价

目的：评价吸入布地奈德溶液治疗哮喘急性发作的有效性和安全性。方法：选择54例哮喘急性发作的中重度患者接受1周的吸入布地奈德溶液治疗,随访2周,比较用药前、用药后第24小时,48小时,停药2周时FEVI值,PEF值。FVC值及患者对疗效的自我评价。结果：治疗后各项指标均有明显改善。在肺功能改善方面优于症状改善。无明显不良反应。结论：吸入布地奈德溶液临床疗效显著,安全性好,是目前治疗哮喘急性发作的最佳的吸入激素制剂之一。     

孟鲁司特钠联合布地奈德混悬液对哮喘急性发作患儿血清EOS、ECP水平和肺功能的影响

目的:探索孟鲁司特钠联合布地奈德混悬液对哮喘急性发作患儿血清嗜酸性粒细胞(EOS)、嗜酸性粒细胞阳离子蛋白(ECP)水平和肺功能的影响。方法:选择自2015年10月至2016年10月我院收治的200例支气管哮喘急性发作患儿,按照随机数表法分成观察组和对照组各100例。对照组患儿口服孟鲁司特钠,观察组患儿在对照组基础上给予布地奈德气雾剂进行雾化治疗,两组均治疗1周。统计分析两组患儿的临床有效率,肺功能指标,包括第1秒用力呼气容积(FEV1)、用力肺活量(FVC)及FEV1/FVC,对比治疗前后两组患儿血清中EOS、ECP水平的变化。结果:治疗后,观察组的总有效率为97.00%,显著高于对照组的81.00%(P0.05);经治疗后两组患儿肺功能指标均较治疗前明显改善,且观察组患儿优于对照组(P0.05);两组患儿治疗后EOS、ECP水平均低于治疗前,而观察组患儿低于对照组,差异均有统计学意义(P0.05)。结论:孟鲁司特钠联合布地奈德对于小儿哮喘的急性发作具有良好的临床疗效,能显著改善患儿肺功能和血清中炎症因子的水平,减轻患儿体内的炎症反应,值得在临床上推广应用。     

Comparison of salbutamol given intravenously and by intermittent positive-pressure breathing in life-threatening asthma.

A double-blind crossover trial was carried out during 22 episodes of life-threatening asthma in 19 patients to compare salbutamol given as a 500 microgram intravenous injection and as a 0 . 5% solution administered by intermittent positive-pressure breathing (IPPB) for three minutes. Relief of pulsus paradoxus was significantly better after IPPB than the intravenous treatment. Both treatments significantly improved the peak expiratory flow rate. Salbutamol given intravenously produced a mean increase in heart rate of over 20 beats/min five minutes after treatment compared with the relief of tachycardia that occurred after administration by IPPB. Four patients had noticeable cardiovascular side effects after salbutamol given intravenously, but no such effects were noticed after administration by IPPB. Two patients withdrawn shortly after entry into the trial because of a worsening clinical condition had received intravenous salbutamol. It is concluded that salbutamol given by IPPB is better than that given by slow intravenous injection in severe acute asthma.     

Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.

OBJECTIVE--To compare safety of salmeterol and salbutamol in treating asthma. DESIGN--Double blind, randomised clinical trial in parallel groups over 16 weeks. SETTING--General practices throughout the United Kingdom. SUBJECTS--25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516). INTERVENTIONS--Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study. MAIN OUTCOME MEASURES--All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs. RESULTS--Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event. CONCLUSIONS--Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.     

Corticosteroid-sparing effect of chromoglycate sodium and nedocromil

The most appropiate management for bronchial asthma is the control of airway inflammation. Corticosteroids are the most effective anti-inflammatory drugs available, but they have a number of side effects; most of these are dose-dependent. In children, asthma control should be accomplished with low steroid doses possibly given by inhalation. In a double-bind placebo-controlled crossover study a group of children with mild to moderate asthma received NED 16 mg/day or BDP 400 mug/day. Values for FEV(1), PEF, symptoms use ofbronchodilators overlapped, whereas bronchial hyper-responsiveness assessed by histamine bronchoprovocation challenge was better with BDP than NED. In another case, one boy with high bronchial hyper-reactivity assessed by provocation test with hypertonic solution, experienced a significant improvement only after 2 weeks of therapy with Deflazacort (2 mg/Kg/day) followed by 4 months on combined treatment with NED (16 mg/day) and BDP (300 mu/day). Authors conclude that NED could have a steroidsparing effect over long-term use.     

Effect on beta adrenergic receptors of tachyphylaxis on the sensitivity of smooth muscle in the bronchi to beta adrenergic receptor agonists in bronchial asthma

The study involved 30 subjects: 15 healthy individuals and 15 patients with atopic bronchial asthma of the moderate degree. Salbutamol was administered to asthmatic patients in the intravenous infusion for 7 days. beta-adrenergic receptor density in the lymphocytes and FEV1 were evaluated before and after therapy. Moreover, isoprenaline test was carried out to evaluate the sensitivity of the bronchial smooth muscle to beta-agonist. The test was performed prior to and after salbutamol therapy. It was found that beta-receptor agonist statistically significantly decreases beta-adrenergic receptor density. Equivalently, bronchial smooth muscle is less sensitive to beta-agonist in the same degree as a decrease in beta-adrenergic receptor density in the peripheral blood lymphocytes.     

孟鲁司特联合信必可治疗支气管哮喘的疗效及对患者肺功能和血嗜酸细胞、C反应蛋白水平的影响

目的:探讨孟鲁司特联合信必可治疗支气管哮喘的疗效及对患者肺功能和血嗜酸细胞(EOS)、C反应蛋白(CRP)水平的影响。方法:选取我院2016年1月～2017年4月收治的136例支气管哮喘患者,按照随机数字表法均分为两组。对照组(68例)采取信必可治疗,观察组(68例)在此基础上加用孟鲁司特治疗。治疗12周后,评价两组的临床疗效,对比两组治疗前后哮喘症状评分、肺功能、外周血EOS计数及血清CRP水平变化的情况。结果:经12周治疗后,观察组总有效率为95.59%(65/68),与对照组[79.41%(54/68)]相比显著上升(P0.01)。与治疗前对比,两组治疗12周后日间与夜间哮喘评分、外周血EOS计数、血清CRP水平均显著下降(P0.01),且观察组以上指标均显著低于对照组(P0.01)。与治疗前相比,两组治疗12周后肺功能指标FVC、FEV1、PEF值均有明显升高(P0.01);且观察组以上指标均显著高于对照组(P0.01)。结论:孟鲁司特联合信必可治疗支气管哮喘可有效改善患者的肺功能,减轻气道炎症反应,促进哮喘症状缓解,疗效确切。     

Bronchodilator Effect of Oral Salbutamol in Asthmatics Treated with Corticosteroids

In a double-blind trial the effect on ventilatory function of oral salbutamol (in two different doses) and a placebo were studied in 12 patients with chronic asthma receiving regular maintenance treatment with prednisolone. Salbutamol in a dose of 4 mg four times daily, given for a period of four weeks, produced a sustained and statistically significant increase in peak expiratory flow rate over the pretreatment recordings. This effect was not observed with a lower dose of salbutamol (2 mg four times daily) or with a placebo. Salbutamol in the higher dose would seem to be an effective and safe oral bronchodilator that can be recommended for the treatment of mild or moderate asthma. The duration of treatment in this study was, however, limited to four weeks, and it is not known whether effective bronchodilatation would be maintained if the drug were given for longer periods.     

酮替芬联合沙丁胺醇气雾剂喷吸对咳嗽变异性哮喘患者嗜酸性粒细胞趋化因子与肺功能的影响

目的:探讨酮替芬联合沙丁胺醇气雾剂喷吸对咳嗽变异性哮喘患者嗜酸性粒细胞趋化因子与肺功能的影响。方法:选择2015年3月到2016年4月我院接诊的98例咳嗽变异性哮喘患者研究,按抽签法将其随机分为观察组和对照组,每组49例。对照组患者给予沙丁胺醇气雾剂、氨茶碱治疗,观察组在对照组基础上给予酮替芬治疗。观察比较治疗前后两组临床疗效;白天及夜间咳嗽症状评分;嗜酸性粒细胞(EOS)计数和嗜酸性粒细胞趋化因子(Eotaxin)水平;肺功能相关评价指标(FVC、FEV1、PEF)。结果:治疗后,观察组有效率(93.88%)高于对照组(79.59%),差异有统计学意义(P0.05)。两组白天及夜间咳嗽症状评分均显著下降,观察组下降更为明显[(0.77±0.39)VS(0.99±0.52)、(0.87±0.32)VS(1.07±0.34)],差异有统计学意义(P0.05);两组EOS计数和Eotaxin水平均明显下降,观察组下降更为显著[(188.47±30.39)VS (232.59±30.52)、(169.44±27.79)VS (191.07±34.34)],差异具有统计学意义(P0.05);两组相关评价指标(FVC、FEV1、PEF)均明显提高,观察组相关指标值提高更为显著[(3.99±0.39)VS(3.87±0.12)、(3.87±0.79)VS(3.52±0.39)、(7.99±1.98)VS(7.34±1.01)],差异有统计学意义(P0.05)。结论:酮替芬联合沙丁胺醇气雾剂喷吸对咳嗽变异性哮喘的疗效显著,能明显降低患者嗜酸性粒细胞趋化因子的水平,显著改善患者的肺功能,值得临床推广运用。     

Value of ambroxol in treatment of bronchial asthma and spastic bronchitis]

Ambroxol (Bronchopront-Mack) was administered to 73 patients with the bronchial asthma and spastic bronchitis with expectoration disorders. The drug was given in the dosage forms of slow release capsules, syrup, drops, intramuscular injections and inhalations for about 14 days. All patients have been carefully examined clinically, PEF has been measured, and sputum physico-chemical properties have been tested prior to and 10 days after treatment. Complete disappearance of cough, liquefaction of sputum and clearance of airways have been achieved in 47% of patients. A significant improvement has been noted in 38.4% of cases. The treatment failed in 2.7% of patients. Ambroxol has been well tolerated. No adverse effects on laboratory findings have been noted. Results suggest, that ambroxol is valuable drug in the combined treatment of patients with the bronchial asthma and spastic bronchitis.     

The effect of interval training in children with exercise-induced asthma competing in soccer

A lot of emphasis has been placed in screening individuals with exercise-induced bronchospasm in order to avoid persistence bronchial hyperactivity and consequent chronic silent inflammation of the respiratory tract. The purpose of this study was to evaluate the effect of interval training on the respiratory function and endurance in children with exercise-induced asthma (EIA) participating in the sport of soccer. Twenty-nine boys ages 10-14, who developed EIA after a 6-minute free running test (decline in forced expiratory volume in 1 second: FEV(1)10%), participated in the study. They were divided into 2 groups (experimental: n = 18, and control: n = 11), fulfilling the same criteria (i.e., age, body height and weight, and severity of asthma). The experimental group exercised with the interval training method for a period of 8 weeks, (3 sessions per week), whereas the control group exercised with the usual football program. Measurements were made for FEV(1) and endurance in both groups, before and after the application of training (8 weeks). Following the implementation of the training program, a significant improvement in FEV(1) and endurance was documented in the experimental group, as well as significant differences between the 2 groups. In conclusion, duration and aerobic training via the interval method seems to be beneficial to soccer players with EIA.     

顺尔宁对变应性鼻炎患者血清肺表面活性蛋白A、D动态水平影响及近 期疗效观察

目的:探讨顺尔宁对变应性鼻炎患者体内肺表面活性蛋白A、D水平的影响及近期疗效观察。方法:纳入的变应性鼻炎患者分成单纯变应性鼻炎患者组不伴哮喘组106例,变应性鼻炎伴哮喘患者组75例,健康成人组20例作为实验对照组。连续应用顺尔宁8周后,统计患者鼻部总体症状评分,以及血清SP-A、SP-D水平的动态变化情况。结果:单纯变应性鼻炎组、变应性鼻炎伴哮喘组患者治疗4周后、8周后与治疗前比较,鼻部总体症状评分均明显降低,差异均有统计学意义(均P0.05)。治疗4周后,单纯变应性鼻炎组、变应性鼻炎伴哮喘组患者血清SP-A、D水平较治疗前,差异无统计学意义(均P0.05);治疗8周后,单纯变应性鼻炎组、变应性鼻炎伴哮喘组患者血清SP-A、D水平较治疗前明显下降(均P0.05)。结论:顺尔宁可影响变应性鼻炎患者体内SP-A、SP-D水平,改善鼻部不适的症状。     

Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year,double blind,randomised, comparative trial

Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone.Design and setting A 52 week, two period, double blind, multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol.Participants Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for ≥ 1 year, a baseline forced expiratory volume in one second (FEV₁) value 50-90% predicted, and a β agonist improvement of ≥ 12% in FEV₁.Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation.Results 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19.1% in the group receiving salmeterol and fluticasone; the difference was 1% (95% confidence interval -3.1% to 5.0%). With a risk ratio (montelukast-fluticasone/salmeterol-fluticasone) of 1.05 (0.86 to 1.29), treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone. Salmeterol and fluticasone significantly increased FEV₁ before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone (P ≤ 0.001), whereas FEV₁ after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups. Montelukast and fluticasone significantly (P = 0.011) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone. Both treatments were generally well tolerated.Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol.     

Mechanism of bronchodilator effect in chronic airflow limitation.

OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities. METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined. RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001). CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance.     

Response to disodium cromoglycate in children with chronic asthma

Twenty-three children with chronic severe perennial asthma received randomly-allocated disodium cromoglycate or placebo four times a day for 12 weeks, and the alternative regimen for the subsequent 12 weeks. More than half the patients improved while on DSCG according to clinical assessment. There was a significant increase in the mean FEV_{0·75 second} during the drug period, largely owing to dramatic improvement in nine patients. No reduction in the mean decrease of FEV after exercise was demonstrated. Response, when it occurred, was evident within four weeks. The effect of the medication was consistent in individual patients throughout the 12-week period. No evidence of toxicity was discovered during the period of study.     

信必可对咳嗽变异性哮喘的辅助治疗

目的探讨信必可对咳嗽变异性哮喘患者的辅助治疗。方法选择2016年1月至2017年1月于宁波市第九医院就诊的117例咳嗽变异性哮喘患者,按照随机数字表将患者分为观察组(59例)和对照组(58例)。对照组患者采用常规治疗,观察组在对照组基础上结合信必可治疗。两组患者疗程均为8周。比较两组患者治疗效果,治疗前后患者第1秒用力呼气容积(FEV1)与FEV1/用力肺活量(FVC)变化,白介素-5(IL-5)和白介素-10(IL-10)变化,以及不良反应发生情况。结果观察组患者总有效率(94.92%)高于对照组(75.86%),差异有统计学意义(χ~2=8.550,P0.05)。两组患者治疗后FEV1和FEV1/FVC增加(P0.05),且治疗后观察组患者FEV1和FEV1/FVC高于对照组(P0.05)。两组患者治疗后血清IL-5水平降低而IL-10水平增加(P0.05),且治疗后观察组患者血清IL-5水平低于对照组,血清IL-10水平高于对照组(P0.05)。两组患者用药期间均未出现明显不良反应。结论信必可对咳嗽变异性哮喘患者辅助治疗的临床疗效显著,可改善患者肺功能,降低炎性介质IL-5水平和提高IL-10水平,患者无明显不良反应,安全可靠,值得进一步研究。     

噻托溴铵治疗老年稳定期COPD 临床观察

目的:探讨噻托溴铵吸入剂对老年吸烟稳定期慢性阻塞性肺疾病(COPD)的临床疗效。方法:入选稳定期COPD老年患者92例,随机分为2组各46例,观察组予噻托溴铵吸入剂18微克每日一次,对照组予缓释茶碱0.1克每12小时口服,两组均按需使用沙丁胺醇气雾剂,随访2月,比较两组治疗前后的肺功能与生活质量改善情况。结果:观察组治疗后St George评分明显下降(P<0.01),显著低于对照组(P<0.01),FEV1/FVC、FEV1/Pred、FEV1均较治疗前明显升高(P<0.01),而对照组治疗前后无显著差异(P>0.05)。结论:吸入噻托溴铵能显著改善老年吸烟COPD稳定期患者的肺功能与生活质量。