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预防运动诱发哮喘的单剂量药物:描述性综述

Single-dose agents in the prevention of exercise-induced asthma: a descriptive review.

作者信息

Anderson Sandra D

机构信息

Department of Respiratory Medicine, 11 West, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia.

出版信息

Treat Respir Med. 2004;3(6):365-79. doi: 10.2165/00151829-200403060-00004.

Abstract

Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that occurs after vigorous exercise in 50-60% of patients with asthma. The need to condition the air inspired during exercise causes water to be lost from the airway surface, and this is thought to cause the release of inflammatory mediators (histamine, leukotrienes, and prostaglandins) from mast cells. EIA is associated with airway inflammation and its severity is markedly reduced following treatment with inhaled corticosteroids. Drugs that inhibit the release of mediators and drugs that inhibit their contractile effects are the most successful in inhibiting EIA. Single doses of short-acting beta(2)-adrenoceptor agonists, given as aerosols immediately before exercise, are very effective in the majority of patients with asthma, providing about 80% protection for up to 2 hours. Long-acting beta(2)-adrenoceptor agonists (LABAs) given in single doses can be effective for up to 12 hours when used intermittently, but tolerance to the protective effect occurs if they are taken daily. Drugs such as cromolyn sodium (sodium cromoglicate) and nedocromil given as aerosols are less effective than beta(2)-adrenoceptor agonists (beta(2)-agonists), providing 50-60% protection for only 1-2 hours, but they have some advantages. They do not induce tolerance, the aerosol dosage can be easily titrated for the individual, and the protective effect is immediate. Because they cause no significant adverse effects, multiple doses can be used in a day. Leukotriene receptor antagonists, such as montelukast and zafirlukast, are also used for the prevention of EIA and provide 50-60% protection for up to 24 hours when given as tablets. Tolerance to the protective effect does not develop with regular use. If breakthrough EIA occurs, a beta(2)-agonist can be used effectively for rescue medication. For those patients with more persistent symptoms, the use of a LABA in combination with an inhaled corticosteroid has raised a number of issues with respect to the choice of prophylactic treatment for EIA. The most important issue is the development of tolerance to the protective effect of a LABA such that extra treatment may be needed in the middle of a treatment period. Recommending extra doses of a beta(2)-agonist to control EIA is not advisable on the basis that multiple doses can enhance the severity of EIA, delay spontaneous recovery from bronchoconstriction, and enhance responses to other contractile stimuli. It is time to take into account the advantages and disadvantages of the different drugs available to prevent EIA and to recognize that there are some myths related to their use in EIA.

摘要

运动诱发性哮喘(EIA)是指50%-60%的哮喘患者在剧烈运动后出现的气道短暂性狭窄。运动时吸入空气的调节需求会导致气道表面水分流失,这被认为会促使肥大细胞释放炎症介质(组胺、白三烯和前列腺素)。EIA与气道炎症相关,吸入糖皮质激素治疗后其严重程度会显著降低。抑制介质释放的药物和抑制其收缩作用的药物在抑制EIA方面最为成功。在运动前即刻以气雾剂形式给予单剂量短效β₂肾上腺素受体激动剂,对大多数哮喘患者非常有效,可提供约80%的保护,持续长达2小时。单剂量长效β₂肾上腺素受体激动剂(LABA)间歇使用时,其保护作用可持续长达12小时,但如果每日服用,会产生保护作用耐受性。色甘酸钠和奈多罗米等药物以气雾剂形式使用时,效果不如β₂肾上腺素受体激动剂(β₂激动剂),仅能提供50%-60%的保护,持续1-2小时,但它们有一些优点。它们不会产生耐受性,气雾剂剂量可根据个体情况轻松调整,且保护作用即刻起效。由于它们不会引起明显的不良反应,一天可使用多剂量。白三烯受体拮抗剂,如孟鲁司特和扎鲁司特,也用于预防EIA,以片剂形式给药时,可提供50%-60%的保护,持续长达24小时。长期使用不会产生保护作用耐受性。如果发生突破性EIA,β₂激动剂可有效用于急救药物。对于那些症状更持续的患者,LABA与吸入糖皮质激素联合使用在EIA预防性治疗的选择方面引发了一些问题。最重要的问题是对LABA保护作用产生耐受性,以至于在治疗期间可能需要额外治疗。基于多剂量会加重EIA严重程度、延迟支气管收缩的自发恢复以及增强对其他收缩刺激的反应,不建议推荐额外剂量的β₂激动剂来控制EIA。现在是时候考虑现有预防EIA的不同药物的优缺点,并认识到在EIA治疗中使用这些药物存在一些误区了。

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