Pranlukast: a review of its use in the management of asthma

Pranlukast (Onon, Azlaire), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C(4), LTD(4) and LTE(4). It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225 mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. CONCLUSIONS: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting beta(2)-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.     

Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT(1) antagonist,pranlukast, in Japanese patients with moderate asthma

CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.     

沙美特罗丙酸氟替卡松联合孟鲁司特钠治疗咳嗽变异型哮喘的疗效观察

目的 观察沙美特罗丙酸氟替卡松联合孟鲁司特钠治疗成人咳嗽变异型哮喘的疗效.方法 采用完全随机对照试验方法将93例咳嗽变异型哮喘患者分为3组各31例,观察组吸入沙美特罗/丙酸氟替卡松(50 μg/250 μg)1吸,早晚各1次,孟鲁司特钠10 mg/次,顿服,共8周.沙美特罗/丙酸氟替卡松组吸入沙美特罗/丙酸氟替卡松(50 μg/250μg)1吸,早晚各1次,共8周.孟鲁司特钠组服用孟鲁司特钠10 mg/次,顿服,共8周.比较3组患者症状改善和肺功能变化情况.结果 治疗后症状积分均较治疗前低,差异有统计学意义(P＜0.05),3组组间差异有统计学意义(P＜0.05).8周治疗后观察组、沙美特罗/丙酸氟替卡松组和孟鲁司特钠组第1秒用力呼气容积(FEV1)、FEV1占预计值的百分比(FEV1％)、呼气峰流速(PEF)与治疗前比较差异均有统计学意义(均P＜0.05);治疗后观察组FEV1、FEV1％、PEF高于沙美特罗/丙酸氟替卡松组及孟鲁司特钠组,差异均有统计学意义[ FEV1:(1.65±0.52)L比(1.52±0.63)L,(1.46±0.53)L;FEV1％:(64.41±10.31)％比(62.81±11.03)％,(59.02±11.19)％; PEF:(5.24±1.15) L/min比(6.10±1.28) L/min,(6.62±1.00) L/min,均P＜0.05].结论 沙美特罗/丙酸氟替卡松与孟鲁司特钠联合应用治疗咳嗽变异型哮喘疗效优于单用沙美特罗/丙酸氟替卡松或孟鲁司特钠.     

Effects of pranlukast hydrate on serum eosinophil cationic protein levels in patients with adult bronchial asthma

Pranlukast hydrate (CAS 103177-37-3, ONO-1078) was administered to 20 patients with bronchial asthma, and examined the effects of this agent on serum eosinophil cationic protein (ECP) levels and peripheral blood eosinophil counts. The mean serum ECP level in the group comprised of patients with bronchial asthma was significantly higher than that in the control group comprised of healthy adults. In responders in whom improvement in asthmatic symptoms was observed, serum ECP levels were significantly decreased compared to the pretreatment values 4 weeks after commencement of pranlukast hydrate administration. However, there were no changes in non-responders. There was no correlation between serum ECP level and peripheral blood eosinophil count before administration of pranlukast hydrate. However, there was a correlation 4 weeks after administration was started. It is suggested that pranlukast hydrate inhibits eosinophilic activity in patients with bronchial asthma.     

Montelukast: a review of its therapeutic potential in persistent asthma

Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged > or = 6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed beta2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged > or = 15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged > or = 15 years with persistent asthma [forced expiratory volume in 1 second (FEV1) = 50 to 85% predicted] there was significantly (p < 0.05) greater improvement in FEV1, symptom scores, peak expiratory flow (PEF), as-needed beta2-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 microg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced > or = 11% improvement in FEV1, the median improvement in this parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV1, clinic PEF, as-needed beta2-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo. The combination of montelukast 10 mg/day plus inhaled beclomethasone 200 microg twice daily provided significantly better asthma control than inhaled beclomethasone 200 microg twice daily in adults with poorly controlled asthma (mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed beta2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study. Among adults (FEV1 > or = 70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study. During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients. In conclusion, montelukast is well tolerated and effective in adults and children aged > or = 6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.     

Salmeterol decreases eosinophilic cationic protein and rescue medication in patients inhaling beclomethasone dipropionate: preliminary study in mild and moderate asthma in Trinidad, West Indies

Activated eosinophils play a critical role in asthma pathogenesis, and eosinophil cationic protein (ECP) is a useful indicator of inflammation. Inhaled corticosteroids and long-acting beta2-agonists (LABA) effectively control asthma symptoms and improve airway function. Salmeterol's anti-inflammatory efficacy as add-on therapy to inhaled corticosteroids has not been evaluated in Caribbean populations. We investigated nine non-smoking subjects (three men and six women; mean age: +/- SE, 50.7 +/- 3.82 years) with stable mild and moderate persistent asthma who were inhaling > or = 500 microg beclomethasone dipropionate (BDP) daily. This was a with-in-patient controlled laboratory blind study performed over 8 weeks. Patients received BDP for 2 weeks, add-on salmeterol 100 microg in weeks 3-6 and BDP alone in weeks 7-8. Patients recorded daily morning and night symptoms. Morning peak expiratory flow rate was measured on entry to the study and with sputum ECP at the end of weeks 2, 4, 6 and 8. Salmeterol together with BDP decreased sputum ECP from a pretreatment median value of 897.84 microg/l to 628.38 microg/l after 4 weeks, and ECP continued to decrease even after salmeterol withdrawal. Both drugs decreased the frequency of rescue medication use by approximately 50% and increased the median number of days per week without rescue salbutamol from 0 to 3 days. Salmeterol's bronchoprotective effect was maximal after 4 weeks and was sustained after its withdrawal. In conclusion, this study, performed in Trinidadian asthmatics, used ECP as a surrogate marker of bronchial inflammation and supports the recent Salmeterol Multi-center Asthma Research Trial (SMART) data recommending add-on salmeterol therapy to adequate anti-inflammatory medication such as inhaled corticosteroids for optimal asthma management. Further studies are required to evaluate the anti-inflammatory efficacy and possible tolerance to salmeterol in Caribbean patients.     

沙美特罗／丙酸氟替卡松治疗支气管哮喘的临床观察

目的观察沙美特罗／丙酸氟替卡松治疗支气管哮喘的临床疗效和安全性。方法将76例支气管哮喘患者随机分为治疗组和对照组,各38例。治疗组予沙美特罗／丙酸氟替卡松粉吸入剂（商品名：舒利迭）治疗,对照组予丙酸倍氯米松吸入剂（商品名：必可酮）治疗。结果治疗组的显效率为60．5％和总有效率94．7％分别高于对照组的34．2％和71．1％,差异均有统计学意义（P〈0．05）。2组治疗后第1秒用力呼气容积（FEV1）和呼气峰流量（PEF）均有显著改善,治疗组优于对照组,差异均有统计学意义（P〈0．01）。结论沙美特罗／丙酸氟替卡松粉吸入剂治疗支气管哮喘疗效肯定,且使用方便。     

T cell activation state in the induced sputum of asthmatics treated with budesonide

Bronchial hyperresponsiveness and airway infiltration with eosinophils and T lymphocytes are key features of asthma. In particular, CD4+ T cells are currently believed to play a pivotal role as initiators and coordinators of the asthmatic inflammatory response and, therefore, they represent a crucial target of corticosteroid treatment. The aim of the present investigation is thus to evaluate, in patients with mild asthma, the effects of inhaled corticosteroid therapy on the following parameters: (i) functional state of CD4+ T cells; (ii) airway eosinophilia; (iii) bronchial hyperresponsiveness to methacholine. The study was completed by twenty asthmatic, atopic subjects, subdivided into two groups of ten and treated for 12 weeks with either inhaled budesonide (200 microg twice daily) or terbutaline alone (500 microg twice daily), respectively. Expression of CD4+ T cell activation markers was measured in induced sputum at baseline and after 1, 4, 8 and 12 weeks of treatment by flow cytometry, which showed a down-regulation of HLA-DR and CD25 surface proteins in the budesonide group, compared with the control group; these differences resulted as being statistically significant through weeks 4-12. Budesonide also induced a quick, sharp reduction in the percentage of eosinophils detectable in induced sputum, as well as a more gradual progressive improvement in airway hyperresponsiveness to methacholine. Therefore, in addition to assessing various indices of bronchial inflammation, flow cytometry can be reliably applied to induced sputum in order to monitor, even in mildly symptomatic patients, the effects of anti-asthma treatments on T cell activation.     

辛芩雾化剂对支气管哮喘患者肺功能及其生命质量的影响

目的 探讨辛芩雾化剂对支气管哮喘患者肺功能及其生命质量的影响.方法 124例支气管哮喘患者按随机数字表随机分为对照组(60例)和观察组(64例).2组均予同时配合抗炎、抗过敏、止咳、化痰等对症治疗.在此基础上,观察组加用辛芩雾化剂(3级:辛芩雾化剂30 ml;2级:辛芩雾化剂15 ml;1级:辛芩雾化剂15 ml)超声雾化吸入,对照组加用丙酸倍氯米松气雾剂(3级:200～300 μg;2级:100～200μg;1级:100～200 μg)吸入,2组中2、3级患者均加用β2受体激动剂吸入,于治疗3个月后评估临床症状、征候积分、疗效及生命质量评分.结果 观察组和对照组总有效率比较,差异无统计学意义[96.9％ (62/64)比100.0％ (60/60)] (P ＞0.05);观察组和对照组治疗后3个月测得的第1秒用力呼气容积占预计值百分比(FEV1％)、最大呼气流量(PEF)、最大呼气流速(PEFR)值均较治疗前明显改善[观察组:FEV1％为(87±4)％比(70±4)％,PEF为(350±40) L/min比(316±35) L/min,PEFR为(13.4±2.4)％比(18.3±3.0)％;对照组:FEV1％为(86±4)％比(71±4)％,PEF为(346±37) L/min比(326±37) L/min,PEFR为(14.3±2.1)％比(19.7±2.9)％](均P＜0.05).但2组治疗后3个月测得的FEV1％、PEF、PEFR值比较差异无统计学意义(P＞0.05).观察组生命质量评分总分[(62±6)分]明显优于对照组[(82±7)分](P＜0.05).结论 辛芩雾化剂吸入替代激素治疗能改善支气管哮喘患者肺功能及其生命质量,其治疗成人支气管哮喘安全、有效.     

吸入糖皮质激素对老年支气管哮喘患者血压和血糖的影响(附30例临床报告)

目的:探讨糖皮质激素吸入对老年性支气管哮喘的不良反应。方法:对30例老年性支气管哮喘患者在吸入糖皮质激素前和吸入后的每个月末的症状进行记分,测量峰流速(PEF)、PEF变异率、血压及血糖。选取30例健康老年人为对照组,比较血压、血糖的变化。结果:吸入激素后患者的症状明显缓解,PEF占个人预计值的百分比增加,PEF变异率下降,且血糖不增高,1例患者的血压升高,与对照组比较差异无统计学意义。结论:吸入糖皮质激素对老年性支气管哮喘患者的血糖无影响,对绝大多数患者的血压也无影响,但可能引起极个别患者血压升高。     

Zafirlukast versus budesonide on bronchial reactivity in subjects with mild-persistent asthma

Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better disease?s control when adding a second drug, than increasing the corticosteroid?s dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p<0.005), group B (p<0.001) and group C (p<0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids.     

Inhaled salmeterol/fluticasone propionate: a review of its use in chronic obstructive pulmonary disease

The salmeterol/fluticasone propionate dry powder inhaler (DPI) [Advair Diskus, Seretide Accuhaler] contains the long-acting beta2-adrenoceptor agonist salmeterol and the inhaled corticosteroid fluticasone propionate. In the US, twice-daily salmeterol/fluticasone propionate 50/250 microg is approved for use in adults with chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis, and in the EU, the twice-daily 50/500 microg dosage is approved for use in patients with severe COPD, repeat exacerbations and significant symptoms despite bronchodilator therapy. In patients with moderate-to-severe COPD, twice-daily inhaled salmeterol/fluticasone propionate 50/250 or 50/500 microg for 24-52 weeks improves predose forced expiratory volume in 1 second (FEV1) significantly more than salmeterol monotherapy, improves postdose or postbronchodilator FEV1 significantly more than fluticasone propionate monotherapy and results in clinically significant improvements in health-related quality of life. Salmeterol/fluticasone propionate 50/500 microg significantly reduced annual COPD exacerbations, especially in severe COPD. Some corticosteroid-related adverse events were increased in recipients of fluticasone propionate with or without salmeterol versus salmeterol monotherapy or placebo; withdrawal from fluticasone propionate, including combination therapy, needs careful management to minimise COPD exacerbations. The DPI combining a corticosteroid and long-acting beta2-agonist provides benefits over monotherapy and may encourage patient compliance in COPD.     

血清和诱导痰嗜酸粒细胞阳离子蛋白在评价普米克治疗哮喘气道炎症中的作用

目的 :探讨血清、诱导痰嗜酸粒细胞阳离子蛋白 (ECP)与哮喘气道炎症及哮喘严重程度的关系。方法 :40例哮喘患者 (轻度 1 6例 ,中、重度 2 4例 )经普米克治疗前后分别行血清、诱导痰ECP以及肺功能第一秒用力呼气容量 (FEV1 )检测 ,并同时与正常人群血清、诱导痰ECP比较。结果 :哮喘患者治疗后血清、诱导痰ECP明显下降 (P <0 .0 1 ) ,肺功能FEV1 明显上升 (P <0 .0 1 ) ;哮喘患者治疗前 (发作期)血清、诱导痰ECP均明显高于正常人群 (P <0 .0 1 ) ,治疗后 (缓解期 )诱导痰ECP仍明显高于正常人群 (P <0 .0 1 ) ,血清ECP则稍高于正常人群 (P >0 .0 5 ) ;中、重度哮喘血清、诱导痰ECP明显高于轻度哮喘 (P <0 .0 5 ) ;血清、诱导痰ECP与FEV1 呈显著负相关 (r=-0 .48、-0 .5 0 ,P <0 .0 5 )。结论 :血清、诱导痰ECP可反映哮喘气道炎症以及严重程度 ,可用于哮喘气道炎症的研究以及指导治疗 ,诱导痰ECP比血清ECP更敏感。     

沙美特罗联合氟替卡松治疗支气管哮喘临床观察

目的观察沙美特罗联合氟替卡松治疗支气管哮喘的临床效果。方法90例支气管哮喘患者随机分为治疗组和对照组各45例。对照组予以抗感染、吸氧、止咳化痰等综合治疗,治疗组在对照组基础上联合应用丙酸氟替卡松和沙美特罗吸入治疗,分别在治疗前和治疗3个月后进行1s用力呼气容积（FEV1）、用力肺活量（FVC）和呼气峰流量（PEF）测定。并对哮喘症状进行评分。结果2组治疗后FEV1、FVC、PEF均升高,差异均有统计学意义（P〈0.05）,且治疗组改善情况优于对照组,差异均有统计学意义（P〈0.05）;2组治疗后哮喘症状评分均降低,差异均有统计学意义（P〈0.05）,且治疗组改善情况优于对照组,差异有统计学意义（P〈0.05）。结论联合吸入沙美特罗和氟替卡松治疗支气管哮喘能够达到哮喘控制,具有良好的疗效。     

Inhaled salmeterol/fluticasone propionate combination: a review of its use in persistent asthma

The long-acting beta2-agonist salmeterol and the corticosteroid fluticasone propionate are available as a combination inhalation device for the treatment of persistent asthma. Well designed studies in adults, adolescents and children aged > or =4 years, demonstrate that combined salmetero/fluticasone propionate 50/100, 50/250 and 50/500 microg administered via a dry powder inhaler (DPI) is clinically equivalent to concurrent delivery of the same dosages of the 2 drugs via separate DPIs. In adults and adolescents, combined salmeterol/fluticasone 50/100 and 50/250 microg twice daily produced rapid improvements in lung function that were consistently greater than those in patients receiving monotherapy twice daily salmeterol 50 microg, fluticasone propionate 100 or 250 microg or placebo in 2 well designed studies. Recipients of the combination had a significantly greater probability of completing 12 weeks of treatment than patients receiving monotherapy or placebo. The combination also produced significant improvements between baseline and end-point in all secondary outcome variables (morning and evening peak expiratory flow, daytime symptom scores, days and nights without asthma symptoms and requirements for as-needed beta-agonists) and health-related quality of life (QOL). Combination therapy was superior to monotherapy with salmeterol and placebo for all outcomes in both studies, and was superior to fluticasone propionate 100 microg for all but 1 outcome (nights without awakenings) in 1 study. Similar results were obtained in patients who had previously been using short acting beta2-agonists alone. Combined twice daily salmeterolfluticasone propionate 50/100 and 50/250 microg produced greater improvements in lung function than inhaled budesonide at higher dosages than fluticasone propionate in the combination. Combined salmeterol/fluticasone propionate 50/250 microg produced similar improvements in lung function to concurrent budesonide 800 microg plus formoterol 12 microg when given twice daily for 12 weeks. In another 12-week trial, combined salmeterol/fluticasone propionate 50/100 microg was more effective than oral montelukast 10 mg/day plus fluticasone propionate 100 microg twice daily in patients with suboptimally controlled asthma. Salmeterol/fluticasone is more cost effective than monotherapy with fluticasone propionate or budesonide. The most frequent adverse events associated with salmeterol/fluticasone propionate are headache, throat irritation, hoarseness and candidiasis. CONCLUSION: Combined salmeterol/fluticasone propionate is as effective as the 2 drugs given concurrently via separate inhalers and significantly more effective than either drug given alone at the same nominal dosage. The combination is also significantly more effective than montelukast plus fluticasone propionate or monotherapy with inhaled budesonide. Furthermore, the combination is more cost effective than inhaled corticosteroid monotherapy.     

氨茶碱联合糖皮质激素吸入治疗轻中度支气管哮喘临床疗效分析

目的 了解氨茶碱联合糖皮质激素吸入治疗轻中度支气管哮喘患者的临床疗效.方法 回顾性分析2013年6月—2015年6月期间收治的118例轻中度支气管哮喘患者的临床特征及治疗资料,按治疗方法分为3组,A组为氨茶碱口服和糖皮质激素吸入联合使用,B组单纯口服氨茶碱,C组单纯吸入糖皮质激素.疗程为3个月.观察3组治疗前后呼出气一氧化氮(FeNO)、最大呼气流速峰值(PEF)、第一秒用力呼气容积占预测值的百分比(FEV1%)和哮喘控制测试评分表(ACT)评分变化情况,临床疗效及不良反应发生情况.结果 3组治疗后PEF、FEV1%和ACT评分均高于治疗前(P<0.05);A和C组治疗后FeNO水平低于治疗前(P<0.05).治疗后3组FeNO、FEV1%预计值和ACT评分比较差异有统计学意义(P均<0.001).3组治疗总有效率比较差异无统计学意义(P>0.05).3组临床疗效程度分布和不良反应发生率差异均有统计学意义(P<0.001,P<0.05).结论 氨茶碱与糖皮质吸入联合治疗支气管哮喘安全有效.     

丙卡特罗联合孟鲁司特治疗儿童支气管哮喘的疗效观察

目的:探讨丙卡特罗联合孟鲁司特治疗儿童支气管哮喘的疗效及其对趋化素样因子-1(CKLF-1)、嗜酸粒细胞阳离子蛋白(ECP)、白细胞介素-12(IL-12)、IL-13水平及肺功能的影响。方法:选取我院2017年8月至2019年4月收治的支气管哮喘患儿94例,按随机数表法分为对照组和观察组各47例,两组患儿均接受抗炎、平喘、扩张支气管等常规治疗,对照组给予孟鲁司特钠片,观察组在对照组治疗基础上给予丙卡特罗治疗,比较两组患儿治疗后的临床疗效,分析治疗前后两组CKLF-1、ECP、IL-12、IL-13水平及肺功能变化情况。结果:观察组总有效率高于对照组(P<0.05),不良反应发生率(8.51%)与对照组(4.26%)比较差异无统计学意义(P>0.05)。治疗前,两组患儿CKLF-1、ECP、IL-12、IL-13水平及肺功能指标比较差异无统计学意义(P>0.05);治疗后观察组IL-12、第1秒用力呼气容积(FEV1)、第1秒用力呼气容积占用力肺活量百分比(FEV1/FVC)、呼气峰流速值(PEF)、呼气高峰流量(PEFR)水平高于对照组,CKLF-1、ECP、IL-13水平低于对照组(P<0.05)。结论:丙卡特罗联合孟鲁司特治疗儿童支气管哮喘可改善肺功能,调节CKLF-1、ECP、IL-12、IL-13表达水平,提高临床疗效,且不增加不良反应。     

射干煎剂对支气管哮喘患者肺功能、EOS与ECP的影响

目的:研究射干煎剂对支气管哮喘患者肺功能、外周血嗜酸性粒细胞(EOS)计数与嗜酸性粒细胞阳离子蛋白(ECP)水平的影响。方法:48例支气管哮喘患者随机分为治疗组24例,对照组24例。对照组采用常规治疗方法,治疗组在常规治疗基础上加用射干煎剂每次30mL,每天3次。疗程均为4周。观察2组治疗后的临床疗效、肺功能指标、治疗前后外周血EOS计数、ECP水平。结果:治疗组总有效率(95.8%)高于对照组(83.3%);治疗组第1秒用力呼气流速(FEV1)下降率和呼气峰流速(PEF)下降率均显著高于对照组(P<0.05)。2组治疗后外周血EOS计数、ECP水平较治疗前均显著降低(P<0.05),且治疗组外周血ECP水平显著低于对照组(P<0.05)。结论:射干煎剂能明显改善支气管哮喘患者肺功能,降低外周血EOS计数与ECP水平。     

Inhaled salmeterol/fluticasone propionate combination: a pharmacoeconomic review of its use in the management of asthma

Asthma guidelines recommend an inhaled corticosteroid plus a long-acting inhaled beta(2)-agonist (beta(2)-adrenoceptor agonist) as the preferred maintenance therapy for moderate and severe persistent asthma. Advair/Seretide Diskus also registered as Accuhaler is fixed-dose salmeterol (a long-acting inhaled beta(2)-agonist) and fluticasone propionate (a corticosteroid) administered via a single powder inhalation device. The clinical effectiveness of salmeterol/fluticasone propionate in patients with persistent asthma symptoms has been established in comparative clinical trials. Pharmacoeconomic analyses, based on data from these clinical trials, have been conducted from a healthcare payer perspective in various countries. In patients with asthma not controlled with inhaled corticosteroids, salmeterol/fluticasone propionate was associated with more favourable (lower) cost-effectiveness ratios than fluticasone propionate monotherapy, oral montelukast plus inhaled fluticasone propionate, inhaled budesonide, and inhaled formoterol plus budesonide. As the initial maintenance therapy in patients with persistent asthma symptoms while receiving short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate was cost effective relative to montelukast monotherapy. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with fluticasone propionate or montelukast monotherapy, salmeterol/fluticasone propionate consistently had a more favourable cost-effectiveness ratio in terms of per successfully treated week or symptom-free day and/or was associated with small incremental costs to achieve significant additional clinical benefits. In clinical practice, salmeterol plus fluticasone propionate was associated with lower asthma-related costs than treatment with other maintenance therapies.In patients with asthma symptoms despite treatment with inhaled corticosteroids, salmeterol/fluticasone propionate produced clinically meaningful improvements in overall Asthma Quality of Life Questionnaire (AQLQ) scores relative to salmeterol or placebo monotherapy, in emotional function domain scores relative to fluticasone propionate or budesonide, and in asthma symptoms domain scores relative to budesonide. In patients with persistent asthma symptoms while receiving short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate produced clinically meaningful improvements in overall AQLQ scores compared with fluticasone propionate or montelukast. CONCLUSIONS: Pharmacoeconomic analyses indicate that salmeterol/fluticasone propionate administered via a single inhaler represents a cost-effective treatment option (relative to fluticasone propionate at the same nominal dosage, budesonide, formoterol plus budesonide and montelukast plus fluticasone propionate) in patients with asthma not controlled with inhaled corticosteroid therapy. In patients with asthma not controlled with short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate is a cost effective treatment relative to monotherapy with montelukast. Importantly, salmeterol/fluticasone propionate is also associated with improvements in health-related quality of life.     

Zafirlukast: an update of its pharmacology and therapeutic efficacy in asthma

Zafirlukast is a selective and competitive orally administered inhibitor of the cysteinyl leukotrienes LTC4, LTD4 and LTE4. The drug is indicated for the prophylaxis and treatment of chronic asthma, and has been developed in response to mounting evidence indicating the importance of the cysteinyl leukotrienes in the pathogenesis of this disorder. The efficacy of zafirlukast 20 mg twice daily has been shown in double-blind placebo-controlled studies of up to 13 weeks' duration in patients aged > or = 12 years. Zafirlukast was consistently superior to placebo in improving objective measures of lung function and subjective measures such as symptom scores and use of as-required bronchodilator therapy. This dosage is also as effective when added to low-dosage inhaled corticosteroid therapy as doubling of corticosteroid dosages. Recent studies indicate superior efficacy over zafirlukast of twice-daily inhaled fluticasone propionate 88 microg or salmeterol 42 microg, although zafirlukast was nevertheless associated with clinical improvement. Data also show zafirlukast 40 mg to be of similar efficacy to pranlukast 225 mg (both twice daily). Overall, preliminary pharmacoeconomic data suggest that healthcare costs are reduced by zafirlukast therapy, although superior cost effectiveness has been reported with inhaled fluticasone propionate. and further studies are needed. Data are available to show improvements in patient-rated quality of life, and preference for and high rates of compliance with zafirlukast. In clinical trials, zafirlukast has shown an adverse event profile similar to that of placebo. Isolated reports of hepatic dysfunction in a small number of individuals receiving the drug have been received, and recommendations for monitoring of patients are in place. Although no causal relationship has been established between zafirlukast and Churg-Strauss Syndrome, patients undergoing corticosteroid dosage reductions require careful surveillance. Conclusions: zafirlukast is an effective and well tolerated agent for preventive monotherapy in mild to moderate persistent asthma. Emerging data indicate benefit of the drug when added to low-dosage inhaled corticosteroids and show that it may be a viable alternative to inhaled adjunctive treatments and increased corticosteroid dosages in some patients. Although inhaled fluticasone propionate and salmeterol have been associated with greater clinical improvement than zafirlukast in clinical studies, compliance considerations and the confirmed clinical efficacy relative to placebo of the drug denote zafirlukast as an effective alternative in treatment programmes based on individualised therapy. As experience with zafirlukast accumulates, it is expected that the drug will be positioned more definitively in national and international treatment guidelines.