白三烯抑制剂在哮喘治疗中的进展

目的:介绍白三烯抑制剂治疗哮喘的进展。方法:综述近年来国外有关文献,介绍和评价白三烯抑制剂的临床疗效,不良反应和用法用量。结果:白三烯抑制剂有效地治疗哮喘发作,且副作用较少。结论:白三烯抑制剂临床使用安全有效,是一类新的哮喘治疗药物。     

治疗哮喘的抗白三烯药物进展

本文综述近年来有关文献,介绍白三烯抑制剂的药理作用、临床疗效、不良反应和用法用量。认为白三烯抑制剂临床使用安全有效,是一类新型的哮喘治疗药物。     

白三烯受体拮抗剂治疗哮喘的进展和临床评价

目的:评价白三烯受体拮抗剂在治疗哮喘中的进展和临床应用.方法:检索国内外文献,对有关抗白三烯药物的文献进行分析、总结.结果:近年来,高选择性白三烯受体拮抗剂进展十分迅速,其通过抑制白三烯合成和白三烯受体而对抗哮喘.结论:该类药物为一类新型、安全和有效的抗炎和平喘药物,在防治成人和儿童的长期哮喘上展现了良好的治疗前景.     

白三烯及其调节剂在气道过敏性疾病中的应用

哮喘和过敏性鼻炎是最常见呼吸道疾病.过敏性鼻炎患者中约40%合并哮喘,而哮喘患者中30%～80%合并过敏性鼻炎.尽管吸入性激素是哮喘和过敏性鼻炎治疗的一线"金标准",但临床上仍有部分患者对吸入激素治疗无反应.白三烯在哮喘和过敏性鼻炎发病中发挥重要作用,白三烯调节剂通过拮抗白三烯受体或抑制白三烯合成而发挥抗炎等效果,并以...     

白三烯受体拮抗剂合理应用评价

目的：评价白三烯受体拮抗剂的临床应用概况。方法：收集国内外相关文献，从白三烯受体拮抗剂的作用机制、应用状况、不良反应等方面对常用的白三烯受体拮抗剂进行分析评价。结果及结论：白三烯受体拮抗剂成为哮喘临床治疗中最有效的介质拮抗剂，目前已普遍应用于临床。     

白三烯受体拮抗剂的作用与临床应用评价

目的 :介绍白三烯受体拮抗剂的作用进展和临床应用的评价。方法 :采用国内、外文献综述方法。结果和结论 :近年来 ,高选择性白三烯受体拮抗剂进展十分迅速 ,通过抑制白三烯合成和白三烯受体而对抗哮喘 ,对白三烯受体的选择性高 ,有良好的耐受性和药代动力学性质 ,成为一类新型、安全和有效的抗炎和平喘药物 ,在防治成人和 12岁以上儿童的长期哮喘上展现了良好的治疗前景     

白三烯受体拮抗剂及合成抑制剂与哮喘

哮喘是涉及多种炎性细胞和炎性介质的复杂疾病 ,白三烯是其重要的介质之一 ,研究显示抑制白三烯合成以及拮抗其作用有助于哮喘的控制。本文就白三烯受体拮抗剂及合成抑制剂与哮喘的关系作一综述     

白三烯调节剂在哮喘治疗中的应用

白三烯包括半胱氨酰白三烯（cysteinyl leukotrienes, CysLT）和白三烯B4（leukotriene B4, LTB4）等,是哮喘的主要炎症介质,参与哮喘发病的多种病理生理机制。白三烯调节剂已用于哮喘治疗,其中CysLT受体-1（CysLT receptor-1, CysLT1）拮抗剂可口服、单药治疗轻度持续性哮喘,但疗效通常不如吸入糖皮质激素。重症哮喘患者联合使用CysLT1拮抗剂和吸入糖皮质激素既能有效控制哮喘,又能减少吸入糖皮质激素的剂量。确定对CysLT1拮抗剂治疗反应良好的哮喘患者亚群有助于更好地发挥CysLT1拮抗剂的作用。CysLT1拮抗剂还有抗重塑作用,可防止哮喘患者的气道结构改变。本文主要就白三烯调节剂在哮喘治疗中的应用作一综述。     

白三烯受体拮抗剂治疗咳嗽变异性哮喘临床疗效观察

目的：分析研究白三烯（LTs）受体拮抗剂治疗咳嗽变异性哮喘的临床价值。方法：按照随机分组方法将来本院就诊的80例咳嗽变异性哮喘患者分为治疗组和对照组各40例,对照组采用基础治疗,治疗组在基础治疗的基础上采用白三烯（LTs）受体拮抗剂孟鲁司特钠（商品名为顺尔宁）进行治疗。结果：治疗组有效率为95.0%（38/40）,其中有效27例,好转11例;对照组有效率为87.5%（35/40）;治疗组治疗效果明显优于对照组（P〈0.05）。结论：白三烯受体拮抗剂治疗咳嗽变异性哮喘临床效果较好,顺应性好,无明显副作用,可以作为治疗咳嗽变异性哮喘的临床用药加以推广使用。     

白三烯拮抗剂在治疗支气管哮喘中的作用

白三烯,特别是半胱氨酸白三烯在支气管哮喘的发病中起着关键作用,目前有关支气管哮喘治疗的最新进展主要集中在白三烯拮抗剂。现已批准应用于临床的白三烯拮抗剂主要有白三烯受体拮抗剂和５－脂氧酶抑制剂。本文综述了这两类药物的体内外效应,药物动力学,以及近年来白三烯拮抗剂在各类型哮喘中的应用经验。推荐白三烯拮抗剂作为一种控制剂,可应用于轻中度持续性哮喘病人。     

Cost effectiveness of leukotriene modifiers in adults with asthma

Asthma is the most common chronic disorder in industrialised nations, with over 100 million people worldwide affected. Leukotrienes are chemical mediators released from mast cells, eosinophils and basophils. They cause bronchoconstriction, an increase in mucous secretions and activation of inflammatory cells. Leukotriene modifiers are a long-term controller medication used to treat asthma. They function by selectively competing for the leukotriene receptor sites, thereby blocking their action, or by inhibiting 5-lipoxygenase and thus preventing leukotriene formation. Both current US and Global Initiative for Asthma treatment guidelines have clarified the role of leukotriene modifiers in the management of asthma in adults and children. Leukotriene modifiers have two distinct roles: to replace inhaled corticosteroids in milder asthma and as an add-on therapy to inhaled corticosteroids in more severe asthma.While efficacy is certainly an important issue, economic considerations are also important in a disease such as asthma where there are a variety of treatment options and the severity of the disease varies widely. This review examined published studies to better understand the cost effectiveness of leukotriene modifiers in adults with asthma. Fifteen articles were found that analysed the cost effectiveness of leukotriene modifiers, with almost all performed in the US. The vast majority of the studies were retrospective claims analyses, but three randomised controlled trials incorporating economic outcomes have been reported. The majority of the articles found that for both monotherapy in mild persistent asthma and add-on therapy in moderate persistent asthma, leukotriene modifiers were less cost effective than inhaled corticosteroids with or without a long-acting beta2-adrenoceptor agonist. However, these results must be viewed cautiously as in several studies there were methodological issues such as comparisons of unequal treatment groups or inappropriate use of leukotriene modifiers in stepwise treatment.     

Leukotriene modifiers: novel therapeutic opportunities in asthma

Cysteinyl leukotrienes (Cys-LT) are powerful proinflammatory autacoids that cause long-lasting bronchoconstriction, plasma leakage, increased mucus production; their biological activity suggests a prominent role in the etiopathology of asthma and several Cys-LT receptor antagonists and synthetase inhibitors have been developed as new antiasthmatic drugs. Zafirlukast was discovered by a mechanism-based approach to drug discovery; early structure-activity relationship analyses of the prototype SRS-A antagonist FPL-55712, lead to the identification of an indole-containing lead compound that was more specific than FPL-55712. Modifications were made on the lipid-like tail, indole backbone and acidic head region of this lead compound, resulting in potent and selective leukotriene receptor antagonists such as ICI-198615 and 204219 (zafirlukast). On the basis of successful results in preclinical asthma models, zafirlukast was recommended for clinical development and became the first leukotriene-modifier to be approved for the treatment of asthma. Leukotriene biosynthesis inhibitors (LSI) also represent a promising approach to the treatment of asthma and may theoretically provide a broader protection than Cys-LT receptor antagonists by inhibition of the synthesis of the two major leukotrienes, the Cys-LT and the chemotactic LTB4. The LSI BAY X-1005 is the result of a broad chemistry program that identified 15-HETE as an endogenous inhibitor of leukotriene synthesis and REV 5901 as a lead prototypic quinoline-based 5-lipoxygenase (5-LO) inhibitor. Clinical studies demonstrated the effectiveness of BAY X-1005 in experimental conditions such as allergen provocation and cold-air induced asthma. However, no consistent treatment effect in the overall asthma population (mild to moderately severe asthmatics) lead to discontinuation of its development.     

Antileukotriene drugs in childhood asthma: what is their place in therapy?

Leukotriene antagonists are a new class of anti-inflammatory drugs which have shown clinical efficacy in the management of asthma. However, their role in paediatric asthma is still unclear. In essence, while there are theoretical reasons as to why leukotriene antagonists would be of use in the management of childhood asthma, there is little clinical data on their use in this patient group. Studies with leukotriene antagonists to date have been performed in children with chronic 'undertreated' asthma which, under current recommendations, should be treated with inhaled corticosteroids. Furthermore, the magnitude of effect of leukotriene antagonists on lung function (forced expiratory volume in one second of less than 5% better than placebo) and daily symptoms (0.23 puffs per day of B2 agonist less than placebo), while reaching statistical significance, is unlikely to be of clinical significance in children with chronic undertreated asthma. There is, however, good evidence for leukotriene antagonist use in exercise induced asthma in children. We conclude that although leukotriene antagonists may play an important role in the management of childhood asthma in the future, particularly as corticosteroid sparing agents and in exercise induced asthma, clinical data in paediatric asthma is poor.     

白三烯受体拮抗剂治疗哮喘后血清白细胞介素-5及支气管肺泡灌洗液嗜酸性粒细胞凋亡的变化

目的　探讨白三烯受体拮抗剂对嗜酸性粒细胞 (EOS)凋亡的诱导作用及其机制。方法　支气管哮喘患者 5 0例 (哮喘组 ,其中 30例急性发作期 ,2 0例非急性发作期 )采用酶联免疫吸附试验 (EL ISA)法测定经白三烯受体拮抗剂治疗前后血清白细胞介素 (IL) - 5水平。分离 5 0例支气管哮喘患者支气管肺泡灌洗液 EOS,测定经白三烯受体拮抗剂治疗前后 EOS的凋亡率。结果　白三烯受体拮抗剂对 IL - 5介导的 EOS存活有抑制作用。哮喘组在白三烯受体拮抗剂治疗后的血清 IL - 5水平比治疗前显著降低 (P<0 .0 1)。治疗后的 EOS凋亡率与治疗前比较差异有显著性 (P<0 .0 1)。结论　白三烯受体拮抗剂能有效诱导 EOS凋亡 ,凋亡 EOS通过拮抗 IL - 5机制获得     

支气管哮喘、慢阻肺患者应用白三烯受体拮抗剂的疗效观察

目的：探讨白三烯受体拮抗剂治疗支气管哮喘、慢阻肺（COPD）患者的疗效。方法：选择上述疾病各20例患者,服用 同样测量安可来,观察治疗前后以血中白三烯C4、嗜伊红细胞、肺功能PET数值变化,判断疗效。结果：哮喘组治疗前血中LTC4、EOS浓度高于正常,PEF低于正常。治疗,血中LTC4、EOS浓度下降,肺功能PEF上升（P＜0．01）。COPD组发作期治疗前血中LTC4、EOS浓度高于正常,肺功能PEF低于正常。治疗后LTC4、EOS血中浓度无明显变化,PEF无明显上升（P＞0．05）,两组间疗效比较差异有显著性（P＜0．01）。结论：哮喘与COPD由于发病机理不同,对白三烯体拮抗剂的疗效也不同,因灰哮喘是涉及气道一系列炎性细胞和介质复杂的病理过程,白三烯是主要介质之一。     

咳嗽变异性哮喘患儿尿白三烯E_4测定的意义

目的探讨咳嗽变异性哮喘(CVA)患儿尿白三烯E4(LTE4)测定的临床意义。方法收集咳嗽变异性哮喘46例作为病例组,并随机分成孟鲁司特治疗组(n=24)和常规治疗组(n=22);选取同期门诊健康体检儿童20例为对照组。检测两组急性发作期和缓解期尿LTE4水平和外周血嗜酸性粒细胞计数,并进行比较;对病例组患儿尿LTE4与外周血嗜酸性粒细胞计数进行相关性分析。结果孟鲁司特组、常规治疗组缓解期较急性期尿LTE4明显降低,P<0.01;缓解期孟鲁司特治疗组儿童尿LTE4水平显著低于常规治疗组,差异有统计学意义(P<0.01);两组与健康对照组比较,差异均有统计学意义;且孟鲁司特组、常规治疗组尿LTE4下降值有显著性差异(P<0.05)。急性期咳嗽变异哮喘儿童尿LTE4水平与外周血嗜酸性粒细胞计数无相关性(P>0.05)。结论白三烯在咳嗽变异性哮喘的发病机制中有重要作用,白三烯受体拮抗剂在咳嗽变异性哮喘治疗上的作用是显著的。测定CVA患儿尿LTE4水平可以为CVA的临床诊断和治疗监测提供依据。     

孟鲁司特对支气管哮喘儿血、尿白三烯水平的影响

目的:探讨孟鲁司特对支气管哮喘儿血、尿白三烯水平的影响. 方法:选取本院2012年1月~2013年6月支气管哮喘患儿162例,随机分为两组,81例患儿实施常规治疗为对照组,81例患儿在常规治疗基础上口服孟鲁司特为观察组,疗程3个月,分析两组患儿血、尿白三烯的改变情况,比较两组患儿的病症改善情况及治疗效果. 结果:两组患儿治疗后血、尿白三烯均较治疗前显著降低.观察组患儿血白三烯(5.0±1.8ng/mL)、尿白三烯(128.5±49.7ng/mL)均明显低于对照组(9.4±2.1ng/mL)、(182.9±47.6ng/mL),观察组患儿肺部湿啰音消失时间(4.7±0.9d)、咳嗽消失时间(6.7±1.1d)、住院时间(7.1±1.4d)均明显小于对照组(6.3±1.2d)、(8.2± 1.7d)、(9.7±2.0d),观察组患儿治疗总有效率(98.8%)明显高于对照组(87.7%),(P<0.05).结论:孟鲁司特可明显降低支气管哮喘患儿血、尿白三烯水平,有效改善患儿的临床病症,明显缩短治疗时间,显著提高治疗效果.     

Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part II: clinical studies with leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma.

The demonstration that leukotrienes, mainly cysteinyl leukotrienes, have biological properties relevant to the pathogenesis of asthma has stimulated the development of many therapeutic compounds to block these deleterious effects. Two main classes of leukotriene modulators have been developed: CysLT1 receptor antagonists and leukotriene synthesis inhibitors. This article reviews the pharmacodynamics, the effects on baseline airway function, the protective effects in airway challenges as well as the results in chronic asthma of the different leukotriene modulators. In addition, the complementary anti-inflammatory effect of leukotriene modulators to that of corticosteroids and H1-histamine receptor antagonists is reviewed. Finally, a concise overview of the clinical responsiveness to this new class of drug, the safety and the drug interactions as well as the place in the strategies of treatment for asthmatic patients of the leukotriene modulators is also provided.     

顺尔宁联合雾化吸入治疗儿童哮喘急性发作100 例临床分析

目的 观察顺尔宁联合雾化(普米克令舒和万托林)治疗儿童哮喘急性发作的临床疗效.方法 选取2009年1月至2010年12月符合儿童哮喘诊断标准的哮喘急性发作患儿100例(轻、中度), 随机分为两组: 对照组50例,予普米克令舒1.0 mg/次和万托林2.5 mg/次混合后加生理盐水至3～ 4 ml,2次/d,经氧气驱动雾化吸入;治疗组50例,在对照组用药的基础上加口服顺尔宁,疗程为10 d.比较两组临床症状、体征消失时间及肺功能测定(FEV1 、PEF).结果 治疗组的临床症状消失时间比对照组明显缩短(P<0.05),两组治疗前、治疗后10 d比较肺功能各项指标差异有统计学意义(P<0.01).结论 顺尔宁联合雾化吸入治疗儿童哮喘急性发作,能迅速缓解临床症状,改善肺功能,具有协同作用,且用药安全性高,值得临床推广应用.