孟鲁司特联合信必可都保治疗支气管哮喘的疗效观察

支气管哮喘是多种炎症细胞参与的气道慢性炎症性疾病,影响患者的劳动能力和生活质量。近年应用白三烯(LTS)受体拮抗剂治疗支气管哮喘越来越受到人们的关注,我科采用白三烯受体拮抗剂孟鲁司特联合信必可都保治疗支气管哮喘患者,取得较满意效果。     

白三烯支气管激发试验及其临床意义

半胱氨酰白三烯(简称白三烯,LT)是支气管哮喘(简称哮喘)炎症形成的重要介质,能够遏制白三烯炎症通路的白三烯受体拮抗剂,已被用于控制哮喘发作,但临床上发现部分患者的疗效不够理想.如何认识白三烯在气道炎症发展中的作用?使用白三烯作为激发剂进行支气管激发试验,能否更特异地衡量气道炎症,能否客观地评价白三烯受体拮抗剂(LTRA)的疗效,从而在本质上探索白三烯与哮喘的关系?现将国内外有关研究结果综述如下.     

顺尔宁治疗成人哮喘的有效性及安全性临床观察

顺尔宁(盂鲁司特钠)是第一个一天一次口服的白三烯受体拮抗剂。白三烯是支气管哮喘发病中一系列炎性细胞和炎性介质中的重要介质之一，它对支气管哮喘的发生、发展．在哮喘的病理生理中起着关键作用。有研究表明：在支气管哮喘患者病情发作期或稳定期体内白三烯水平均高于正常人。故白三烯合成抑制剂及受体阻断剂是临床治疗哮喘的最有效的介质拮抗剂．这类药物的临床使用可能实现哮喘治疗的重要突破。     

合理应用白三烯受体拮抗剂治疗支气管哮喘

白三烯受体拮抗剂在支气管哮喘治疗中占有重要地位,既可作单独治疗,也可作为辅助治疗。本文从《全球哮喘创议》（Global Initiative for Asthma,GINA）角度（治疗阶梯）出发,分析白三烯受体拮抗剂在支气管哮喘治疗中的合理应用。     

白三烯受体拮抗剂在支气管哮喘治疗中的合理应用

白三烯作为支气管哮喘(简称哮喘)气道炎症中的重要炎性介质,在哮喘的发病机制中发挥重要作用。本文结合2006年修订的《全球哮喘创议》(Global Initiative for Asthma,GINA)来分析白三烯受体拮抗剂在哮喘治疗中的地位和合理应用。     

支气管哮喘患者尿液白三烯E4测定及其临床意义

目前认为支气管哮喘是一种慢性气道炎症性疾病 ,炎症细胞在气道炎症过程中可以释放出许多炎性介质。近年来研究发现炎性介质中白三烯在哮喘慢性气道炎症过程中起了十分关键的作用。因此 ,白三烯受体拮抗剂和白三烯合成抑制剂在哮喘防治中的作用和地位也受到了重视。为了探讨白三烯在支气管哮喘发病中的作用以及白三烯受体拮抗剂治疗后的影响 ,我们对支气管哮喘患者作了尿液白三烯Ｅ4 (ＬＴＥ4 )的测定 ,以评价检测尿ＬＴＥ4 的临床意义。1　对象与方法1 1　对象　选择健康志愿者 15例 (正常对照组 ) ,男 7例 ,女 8例 ,平均年龄 (32 4± 4 6…     

白三烯受体拮抗剂在支气管哮喘中的应用进展

白三烯在哮喘炎症病变中起重要作用,白三烯受体拮抗剂和白三烯合成抑制剂对轻、中度支气管哮喘有良好疗效,并可作为吸入激素者的辅佐治疗。     

吸入脂氧素A4对支气管哮喘小鼠气道炎症调节Th1/Th2失衡的影响

白三烯(leukotriene)在支气管哮喘(简称哮喘)的病理发展过程中扮演着重要角色,应用白三烯受体拮抗剂或5-脂氧化酶抑制剂治疗哮喘,已取得公认的疗效[1].近年来已证明,脂氧素(lipoxins)是人体内拮抗白三烯的天然生理性物质,对于气道高反应性及炎症反应有多方面抑制作用[2].     

支气管哮喘患者尿液白三烯E4测定及其临床意义

目的探讨白三烯E4(LTE4)在支气管哮喘(简称哮喘)发病机制中的作用。方法用ELISA法对急性发作期和非急性发作期哮喘患者各20例及健康志愿者15名作尿液LTE4测定。结果哮喘急性发作组、非急性发作组尿液LTE4明显高于正常对照组(P<0.01)。哮喘急性发作组尿液LTE4值又明显高于非急性发作组(P<0.01)。哮喘非急性发作者用白三烯受体拮抗剂治疗后可使尿液LTE4水平明显降低。结论本研究结果表明白三烯在哮喘发病中起了重要的作用,检测尿液LTE4水平对于了解哮喘患者体内白三烯水平,以及评价白三烯受体拮抗剂的疗效具有一定的临床意义。     

白三烯受体及其拮抗剂与哮喘

白三烯受体及其拮抗剂正日益受到重视,一些白三烯拮抗剂已试用于哮喘的治疗。本文讨论了白三烯受体及其拮抗剂在哮喘治疗中的进展。     

Use of anti-inflammatory therapy and asthma mortality in Japan.

Asthma treatment guidelines were introduced in Japan in the 1990s, insisting as elsewhere, on the importance of anti-inflammatory therapy. The present study assessed whether use of anti-inflammatory medications was associated with a decrease in asthma mortality in Japan, the first country to use leukotriene receptor antagonists. A population-based ecological study was conducted, spanning the period 1987-1999, among people aged 5-34 yrs in Japan. The association between the yearly rate of asthma death and sales of inhaled corticosteroids and leukotriene receptor antagonists was estimated using Poisson regression. The yearly asthma death rate was stable at 6-7 deaths per million before the introduction of leukotriene receptor antagonists in 1995 and decreased by 23% thereafter, reaching 3.5 per million in 1999. The rate of asthma death was found to decrease with increasing use of both leukotriene receptor antagonists and inhaled corticosteroids. The rate ratio of asthma death was 0.96 per 1 million 25-day treatment courses of inhaled corticosteroids and 0.80 for every 1 million 25-day treatment courses of leukotriene receptor antagonists, consumed per year in Japan. The increasing use of inhaled corticosteroids and leukotriene receptor antagonists may have contributed to the significant reduction in asthma mortality among young asthmatics in Japan.     

Tolerability Profiles of Leukotriene Receptor Antagonists and Long-Acting β2-Adrenoceptor Agonists in Combination with Inhaled Corticosteroids for Treatment of Asthma: A Review

Inhaled corticosteroids, long-acting β₂-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting β₂-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting β₂-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.     

Tolerability Profiles of Leukotriene Receptor Antagonists and Long-Acting β2-Adrenoceptor Agonists in Combination with Inhaled Corticosteroids for Treatment of Asthma: A Review

Inhaled corticosteroids, long-acting β₂-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting β₂-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting β₂-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.     

The anti-inflammatory effects of leukotriene-modifying drugs and their use in asthma

Asthma is a chronic inflammatory disease of the airways. Anti-inflammatory drug therapy, primarily using corticosteroids, is now considered the first-line treatment in the management of all grades of asthma severity. Although corticosteroids are believed to be the most potent anti-inflammatory agents available, they do not suppress all inflammatory mediators involved in the asthmatic response. Leukotrienes, which are lipid mediators generated from the metabolism of arachidonic acid, play an important role in the pathogenesis of asthma. They produce bronchospasm, increase bronchial hyperresponsiveness, mucus production, and mucosal edema, and enhance airway smooth muscle cell proliferation and eosinophil recruitment into the airways, and their synthesis or release is unaffected by corticosteroid administration. The use of leukotriene synthesis inhibitors or leukotriene receptor antagonists as anti-inflammatory therapies in asthma has therefore been investigated. Beneficial effects of leukotriene-modifying drugs have been demonstrated in the management of all grades of asthma severity, and there is evidence that certain patient groups (such as those with exercise-induced asthma or aspirin-induced asthma) may be particularly suitable for such therapy.     

Thromboxane A2 inhibition: therapeutic potential in bronchial asthma

Bronchial asthma is a disease defined by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. In addition to histamine and acetylcholine, recent studies have emphasized the role of arachidonic acid metabolites (leukotrienes, prostaglandins and thromboxane A(2)) in the pathogenesis of asthma. Among these mediators, thromboxane A(2) (TXA(2)) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A(2) is believed to be involved not only in late asthmatic responses but also in bronchial hyperresponsiveness, a typical feature of asthma. Strategies for inhibition of TXA(2) include TXA(2) receptor antagonism and thromboxane synthase inhibition. Results of double-blind, placebo-controlled clinical trials have proven the efficacies of the thromboxane receptor antagonist seratrodast and the thromboxane synthase inhibitor ozagrel in the treatment of patients with asthma. Seratrodast and ozagrel are available in Japan for the treatment of asthma. Ramatroban, another thromboxane receptor antagonist, is currently under phase III clinical evaluation in Europe and Japan for the treatment of asthma. The pharmacological profiles of the thromboxane modulators may be improved by combination with leukotriene D(4) receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D(4) and thromboxane A(2 )receptors, may have potent therapeutic effects in the treatment of bronchial asthma. Large scale clinical trials are necessary to further define the role of thromboxane modulators in the treatment of patients with asthma.     

Inhaled Corticosteroids versus Leukotriene Antagonists as First-Line Therapy for Asthma

Inhaled corticosteroids are the most effective anti-inflammatory drugs for asthma. Leukotriene receptor antagonists are a new class of anti-inflammatory drugs that have the advantage of oral administration and the potential for better compliance compared with inhaled corticosteroids. This article summarizes evidence from randomized controlled trials, comparing the efficacy and tolerability of inhaled corticosteroids with those of leukotriene receptor antagonists in patients with persistent asthma. The evidence derived from a systematic review of randomized controlled trials confirms that patients treated with inhaled corticosteroids of chlorofluorocarbon-propelled beclomethasone 400 mug/day or fluticasone propionate 200 mug/day have better asthma control than those treated with oral leukotriene receptor antagonists. More specifically, treatment with inhaled corticosteroids is associated with 65% fewer exacerbations requiring systemic corticosteroids, greater improvement in spirometry and symptoms, fewer night-time awakenings and less use of rescue beta(2)-adrenoceptor agonists. This review does not identify any difference in short-term safety between inhaled corticosteroids and leukotriene receptor antagonists. Although adverse effects typically associated with inhaled corticosteroids (such as growth suppression, osteopenia, and adrenal suppression) were not measured, preventing a fair comparison of the safety profile on long-term use.In conclusion, the scientific evidence does not support the substitution of leukotriene receptor antagonists for low doses of inhaled corticosteroids, which should remain first-line therapy for asthma control.     

Thromboxane A<Subscript>2</Subscript> Inhibition

Bronchial asthma is a disease defined by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. In addition to histamine and acetylcholine, recent studies have emphasized the role of arachidonic acid metabolites (leukotrienes, prostaglandins and thromboxane A₂) in the pathogenesis of asthma. Among these mediators, thromboxane A₂ (TXA₂) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A₂ is believed to be involved not only in late asthmatic responses but also in bronchial hyperresponsiveness, a typical feature of asthma.Strategies for inhibition of TXA₂ include TXA₂ receptor antagonism and thromboxane synthase inhibition. Results of double-blind, placebo-controlled clinical trials have proven the efficacies of the thromboxane receptor antagonist seratrodast and the thromboxane synthase inhibitor ozagrel in the treatment of patients with asthma. Seratrodast and ozagrel are available in Japan for the treatment of asthma. Ramatroban, another thromboxane receptor antagonist, is currently under phase III clinical evaluation in Europe and Japan for the treatment of asthma.The pharmacological profiles of the thromboxane modulators may be improved by combination with leukotriene D₄ receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D₄ and thromboxane A₂ receptors, may have potent therapeutic effects in the treatment of bronchial asthma. Large scale clinical trials are necessary to further define the role of thromboxane modulators in the treatment of patients with asthma.     

Japanese Guideline for Adult Asthma 2014

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting 02-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled 02-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and coughvariant asthma are also important issues that need to be considered.     

Churg Strauss syndrome after introducing oral steroid to inhaler: a report of three cases

The tetrad of bronchial asthma, severe sinusitis, nasal polyp, eosinophilia, and systemic vasculitis is the main feature of allergic granulomatosis and angitis (Churg- Strauss Syndrome). This vasculitis is usually seen idiopathic in patients with a long history of asthma; oral steroids using steroid inhalers, vaccination and desensitization might be triggering factors. Drugs such as leukotriene receptor antagonists (LTRAS), penicillin, sulphonamides, anticonvulsants and thiazides have also been implicated. By presenting the cases in this article, the authors suggest that some cases of CSS may be partially or totally suppressed by corticosteroid therapy of asthma for long periods and replacing oral steroid by inhaler will reveal a pathologic condition of CSS, called frustes CSS forms. We report three subjects with asthma who had been receiving previously multiple corticosteroid courses for control, but when systemic corticosteroids were discontinued or switched over to steroid inhaler, the patients developed a similar syndrome.     

Japanese Guideline for Adult Asthma

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause an intractable asthma. The number of patients with asthma has increased, while the number of patients who die from asthma has decreased (1.7 per 100,000 patients in 2009). The aim of asthma treatment is to enable patients with asthma to lead a healthy life without any symptoms. A partnership between physicians and patients is indispensable for appropriate treatment. Long-term management with agents and elimination of causes and risk factors are fundamental to asthma treatment. Four steps in pharmacotherapy differentiate mild to intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid (ICS), varying from low to high doses. Long-acting β₂ agonists (LABA), leukotriene receptor antagonists, and theophylline sustained-release preparation are recommended as concomitant drugs, while anti-IgE antibody therapy is a new choice for the most severe and persistent asthma. Inhaled β₂ agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, etc., are used as needed against acute exacerbations. Allergic rhinitis, chronic obstructive pulmonary disease (COPD), aspirin induced asthma, pregnancy, and cough variant asthma are also important factors that need to be considered.