Therapeutic targets for new therapy for corticosteroid refractory asthma

被引:16
作者
Ito, Kazuhiro [1 ]
Mercado, Nicolas [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Sch Med, Natl Heart & Lung Inst, Airways Dis Sect, London SW3 6LY, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
bio-agent; corticosteroid refractory; future therapies; molecular mechanism; restoration; severe asthma; NECROSIS-FACTOR-ALPHA; GLUCOCORTICOID-RECEPTOR PHOSPHORYLATION; HISTONE DEACETYLASE ACTIVITY; SEVERE ULCERATIVE-COLITIS; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; TNF-ALPHA; AIRWAY INFLAMMATION; TREATMENT REGIMENS; OXIDATIVE STRESS;
D O I
10.1517/14728220903078431
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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-spa ring 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.
引用
收藏
页码:1053 / 1067
页数:15
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