Nimmagadda S R, Spahn J D, Leung D Y, Szefler S J
Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, University of Colorado Health Sciences Center, Denver, USA.
Ann Allergy Asthma Immunol. 1996 Nov;77(5):345-55; quiz 355-6. doi: 10.1016/S1081-1206(10)63332-7.
Reading this article will reinforce the reader's knowledge of the definition, pathophysiology, differential diagnosis, and treatment of the steroid-resistant asthmatic patient.
Prospective and retrospective data from the authors' experience were evaluated. In addition, a Medline database was searched from 1981, using the key words "asthma," "glucocorticoids," and "glucocorticoid resistance" with the restrictions of English language and human subjects. Relevant articles referenced in retrieved sources and current texts on severe asthma were also utilized.
Data source abstracts, pertinent articles, and book chapters meeting the objectives were critically reviewed.
Although rare, individuals with steroid-resistant asthma are often the most difficult-to-manage asthmatic patients in that they have severe disease yet fail to respond to glucocorticoids. To make the diagnosis of steroid-resistant asthma, the patient must fail to respond to a 7 to 14-day course of daily prednisone as measured by less than a 15% improvement in morning prebronchodilator FEV1 following the glucocorticoid course. Ongoing inflammation is thought to play a major role in the pathogenesis of steroid-resistant asthma, and recent studies have demonstrated diminished glucocorticoid receptor to glucocorticoid, or diminished glucocorticoid receptor to DNA binding as possible mechanisms for diminished glucocorticoid responsiveness. Alternative asthma therapies such as methotrexate, cyclosporine, and intravenous gammaglobulin are often used in this group of asthmatic patients.
The patient with steroid-resistant asthma presents several challenges. These individuals often display many of the sequelae of long-term systemic glucocorticoid use while achieving little therapeutic benefit. Prior to making the diagnosis of steroid-resistant asthma, diseases that can contribute to poor control of asthma must be ruled out, and noncompliance issues addressed. Alternative asthma therapies are often used; however, they also carry the potential for adverse effects, and have not been thoroughly studied in this population of asthmatic patients.
阅读本文将增强读者对激素抵抗型哮喘患者的定义、病理生理学、鉴别诊断及治疗的认识。
对作者经验中的前瞻性和回顾性数据进行了评估。此外，检索了1981年以来的Medline数据库，使用关键词“哮喘”“糖皮质激素”和“糖皮质激素抵抗”，限定语言为英语且研究对象为人类。还利用了检索来源中引用的相关文章以及当前关于重度哮喘的文献。
对符合目标的数据源摘要、相关文章及书籍章节进行了严格审查。
尽管激素抵抗型哮喘患者较为罕见，但他们往往是最难管理的哮喘患者，因为他们患有严重疾病却对糖皮质激素无反应。要诊断为激素抵抗型哮喘，患者在接受每日泼尼松治疗7至14天后，若晨间支气管扩张剂使用前第一秒用力呼气容积（FEV1）改善不足15%，则判定为对糖皮质激素无反应。持续炎症被认为在激素抵抗型哮喘的发病机制中起主要作用，最近的研究表明，糖皮质激素受体与糖皮质激素结合减少，或糖皮质激素受体与DNA结合减少，可能是糖皮质激素反应性降低的机制。这类哮喘患者常使用甲氨蝶呤、环孢素和静脉注射丙种球蛋白等替代哮喘疗法。
激素抵抗型哮喘患者面临诸多挑战。这些患者常常表现出长期全身使用糖皮质激素的诸多后遗症，却几乎未获得治疗益处。在诊断激素抵抗型哮喘之前，必须排除可能导致哮喘控制不佳的疾病，并解决不依从问题。常使用替代哮喘疗法；然而，这些疗法也有产生不良反应的可能性，且尚未在这类哮喘患者中进行充分研究。
