糖皮质激素难治性哮喘新疗法的治疗靶点
2009/11/16
背景：糖皮质激素是治疗轻-中度哮喘患者最强的抗炎药物。然而，仍有少部分哮喘患者（< 10%）对糖皮质激素治疗应答较差甚至无应答。由于目前缺少针对重度糖皮质激素难治性哮喘的合适药物治疗，因此其治疗花费占到全部哮喘患者医疗花费的约50％。
方法：若能揭示糖皮质激素不敏感的分子机制，则有助于深层次了解糖皮质激素作用的关键机制并合理制定治疗方案，以至恢复糖皮质激素的敏感性或采用其它方法替代激素治疗。本文主要综述了严重哮喘患者糖皮质激素不敏感的原因，讨论针对糖皮质激素难治性哮喘目前及将来治疗及预防策略。
结论：糖皮质激素难治性哮喘是一种异质性疾病，可以针对个体特异性，采用无糖皮质激素的药物或有效的新药进行联合治疗。对上述患者糖皮质激素不敏感原因的研究对其他疾病同样具有重要意义。
（林江涛 审校）
Expert Opin Ther Targets.2009 Sep;13(9):1053-1067.
Therapeutic targets for new therapy for corticosteroid refractory asthma.
Ito K, Mercado N.
National Heart and Lung Institute, Imperial College School of Medicine, Airways Disease Section, London SW3 6LY, UK. k.ito@imperial.ac.uk
BACKGROUND: Corticosteroids are the most potent anti-inflammatory agents for the treatment of mild to moderate asthma. However, a small percentage of the asthma population (< 10%) do not respond well, or at all, to corticosteroid therapy, and this severe corticosteroid-refractory asthma contributes to more than 50% of health care expenditure for all asthma because these is no appropriate pharmacological therapy.
METHODS: If the molecular mechanism of corticosteroid insensitivity is uncovered, it may in turn provide insights into the key mechanism of corticosteroid action and rational implementation of treatment regimens that restore corticosteroid sensitivity or replace corticosteroid therapy. This review focuses on why severe asthma patients are corticosteroid-insensitive, and discusses present and future therapeutic and preventative strategies for corticosteroid-refractory asthma.
CONCLUSIONS: Corticosteroid-refractory asthma is a heterogeneous disease and can be controlled by add-on treatment of corticosteroid-sparing agents or effective new drugs based on individual abnormalities. The elucidation of the cause of the relative lack of corticosteroid response in this subgroup of asthmatic individuals may have important implications for other diseases.
Ito K, et al. Expert Opin Ther Targets. 2009 Sep;13(9):1053-67.
方法：若能揭示糖皮质激素不敏感的分子机制，则有助于深层次了解糖皮质激素作用的关键机制并合理制定治疗方案，以至恢复糖皮质激素的敏感性或采用其它方法替代激素治疗。本文主要综述了严重哮喘患者糖皮质激素不敏感的原因，讨论针对糖皮质激素难治性哮喘目前及将来治疗及预防策略。
结论：糖皮质激素难治性哮喘是一种异质性疾病，可以针对个体特异性，采用无糖皮质激素的药物或有效的新药进行联合治疗。对上述患者糖皮质激素不敏感原因的研究对其他疾病同样具有重要意义。
（林江涛 审校）
Expert Opin Ther Targets.2009 Sep;13(9):1053-1067.
Therapeutic targets for new therapy for corticosteroid refractory asthma.
Ito K, Mercado N.
National Heart and Lung Institute, Imperial College School of Medicine, Airways Disease Section, London SW3 6LY, UK. k.ito@imperial.ac.uk
BACKGROUND: Corticosteroids are the most potent anti-inflammatory agents for the treatment of mild to moderate asthma. However, a small percentage of the asthma population (< 10%) do not respond well, or at all, to corticosteroid therapy, and this severe corticosteroid-refractory asthma contributes to more than 50% of health care expenditure for all asthma because these is no appropriate pharmacological therapy.
METHODS: If the molecular mechanism of corticosteroid insensitivity is uncovered, it may in turn provide insights into the key mechanism of corticosteroid action and rational implementation of treatment regimens that restore corticosteroid sensitivity or replace corticosteroid therapy. This review focuses on why severe asthma patients are corticosteroid-insensitive, and discusses present and future therapeutic and preventative strategies for corticosteroid-refractory asthma.
CONCLUSIONS: Corticosteroid-refractory asthma is a heterogeneous disease and can be controlled by add-on treatment of corticosteroid-sparing agents or effective new drugs based on individual abnormalities. The elucidation of the cause of the relative lack of corticosteroid response in this subgroup of asthmatic individuals may have important implications for other diseases.
Ito K, et al. Expert Opin Ther Targets. 2009 Sep;13(9):1053-67.
