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糖皮质激素抵抗性哮喘:远不止表面所见。

Glucocorticoid-resistant asthma: more than meets the eye.

作者信息

Reddy Divya, Little Frederic F

机构信息

Department of Pulmonary, Allergy, Sleep and Critical Care Medicine, Pulmonary Center, Boston University School of Medicine , Boston, MA , USA.

出版信息

J Asthma. 2013 Dec;50(10):1036-44. doi: 10.3109/02770903.2013.831870. Epub 2013 Sep 25.

Abstract

INTRODUCTION

For decades glucocorticoids have been considered as the gold standard for the treatment of asthma. We present a case report of typical glucocorticoid-resistant asthma and current consensus in definitions of "severe refractory", "difficult" and "glucocorticoid-resistant" asthma.

METHODS

Full-text papers and abstracts were identified on the basis of a comprehensive literature search primarily in MEDLINE (1966 to June 2012) but also in the Cochrane Central Register of Controlled Trials database.

RESULTS

Glucocorticoid-resistant asthmatics are a small subset of patients who pose noteworthy diagnostic challenges while contributing disproportionately to health care costs. Recognition of various asthma phenotypes has aided in characterizing groups with severe asthma and given a better understanding of its pathophysiological process. The molecular mechanism of glucocorticoid action is complicated and several pathways have been identified to explain drug resistance, which in turn is crucial for drug development. Tobacco smoking appears to be the single most important contributor of glucocorticoid resistance. We present the emerging and promising concepts in the management of glucocorticoid-resistant asthma, which mainly include drugs targeting specific molecules, receptors, inflammatory cells or immune processes.

CONCLUSION

The challenges in making a diagnosis of glucocorticoid-resistant asthma may contribute to underestimating its prevalence and impact on patient care. Considerable progress has been made in identifying distinct phenotypes and mechanisms of glucocorticoid resistance; therefore the future of new drug development in management of asthma is promising.

摘要

引言

数十年来,糖皮质激素一直被视为治疗哮喘的金标准。我们报告一例典型的糖皮质激素抵抗性哮喘病例,并介绍目前关于“重度难治性”、“难治性”和“糖皮质激素抵抗性”哮喘定义的共识。

方法

通过全面的文献检索确定全文论文和摘要,主要检索MEDLINE数据库(1966年至2012年6月),同时也检索Cochrane对照试验中央注册数据库。

结果

糖皮质激素抵抗性哮喘患者是一小部分特殊患者,他们在诊断上存在显著挑战,同时对医疗费用的贡献不成比例。认识到各种哮喘表型有助于对重度哮喘患者群体进行特征描述,并更好地理解其病理生理过程。糖皮质激素作用的分子机制复杂,已确定多种途径来解释耐药性,这对药物研发至关重要。吸烟似乎是糖皮质激素抵抗的最重要单一因素。我们介绍了糖皮质激素抵抗性哮喘管理中新兴且有前景的概念,主要包括针对特定分子、受体、炎症细胞或免疫过程的药物。

结论

诊断糖皮质激素抵抗性哮喘面临的挑战可能导致低估其患病率及其对患者治疗的影响。在确定糖皮质激素抵抗的不同表型和机制方面已取得相当大的进展;因此,哮喘管理中新药研发的前景广阔。

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