Division of Asthma, Allergy and Lung Biology, King’s College London, London, England, UK; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London London, England, UK.
Ther Clin Risk Manag. 2007 Oct;3(5):771-87.
This paper is an overview of the diagnosis, differential diagnosis and cellular and molecular mechanisms of glucocorticoid resistant asthma. It addresses the clinical definition and rationale for the diagnosis of therapy resistant asthma. It purports that, since glucocorticoid resistant asthmatics are not globally physiologically glucocorticoid resistant, then the phenomenon is most likely acquired, probably in immune cells (and most probably in T cells and monocyte/macrophages), as a result of local inflammatory and environmental influences. The molecular mechanisms which have been uncovered to date which could account for glucocorticoid resistance are discussed, in particular the roles of AP-1 and p38 MAP kinase signaling, the role of the beta-isoform of the glucocorticoid receptor and the role of histone proteins and DNA folding. Finally, there are suggestions for clinical management of these patients based on accumulated evidence.
本文是对糖皮质激素抵抗性哮喘的诊断、鉴别诊断及细胞和分子机制的综述。文中涉及了治疗抵抗性哮喘的临床定义和诊断原理。由于糖皮质激素抵抗性哮喘患者并非在整体生理学上抵抗糖皮质激素，因此该现象很可能是获得性的，可能发生在免疫细胞（最有可能是 T 细胞和单核细胞/巨噬细胞）中，是局部炎症和环境影响的结果。文中讨论了迄今为止发现的可能导致糖皮质激素抵抗的分子机制，特别是 AP-1 和 p38 MAP 激酶信号转导、糖皮质激素受体β亚型的作用以及组蛋白蛋白和 DNA 折叠的作用。最后，根据现有证据，提出了针对这些患者的临床管理建议。
