重症哮喘患者糖皮质激素反应性及其机制的研究进展

摘要

重症哮喘的特点是即使予以高剂量的吸入糖皮质激素(GC)甚至口服GC仍很难达到疾病控制的目的.重症哮喘占哮喘患者的5%~10%,虽不常见,但因这部分患者常需消耗特殊医疗资源、反复住院、误工/误学等,所导致的直接及间接经济负担很大.恢复GC敏感性是重症哮喘患者治疗研究的一个重要方向.GC反应性降低的机制有p38丝裂原活化蛋白激酶活性增加、丝裂原活化蛋白激酶磷酸化酶1表达下降、组蛋白去乙酰化酶2活性降低、糖皮质激素受体β上调等,影响GC反应性的相关因素有遗传因素、炎症因素、吸烟、肥胖、维生素D水平等.%Severe asthma is characterized by difficulty to achieve disease control despite high -dose inhaled glucocorticoids plus long-acting β2 -agonists or oral corticosteroids.Severe asthma is not a frequent condition because its prevalence lies within 5% to 10% of the general asthma population.However,there are substantial direct and indirect costs associated with the treatment of severe asthma due to extensive use of specialized medical care ,frequent hospitalization,and missed school/workdays.Restoring corticosteroid sensitivity in severe asthma is an important direction for solving this problem .Various mechanisms explaining corticosteroid insensitivity have been proposed ,including increased activity of p38 mitogenactivated protein kinase, lower expression of mitogen-activated protein kinase phosphatase-1, lower activity of histone deacetylase 2,increased expressio n of glucocorticoid receptor -βand so on.Corticosteroid insensitivity has been associated with different comorbid conditions such as gene ,inflamation,smoking,obesity,and low vitamin D level.