Szefler S J, Leung D Y
Dept of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Eur Respir J. 1997 Jul;10(7):1640-7. doi: 10.1183/09031936.97.10071640.
At the present time, emphasis is placed on viewing asthma as a manifestation of chronic airway inflammation, possibly secondary to allergen hypersensitivity. Consequently, one aspect of management is to institute measures of environmental control to minimize the inflammatory response related to allergen stimulation, and to administer anti-inflammatory therapy to resolve inflammation and prevent progression of disease. Most patients respond very favourably to conventional therapy, as recommended in recent guidelines for asthma management. Some cases, however, remain very difficult to control despite high-dose inhaled glucocorticoids, even combined with oral glucocorticoid therapy. Management of these patients raises questions about the conditions that alter response to glucocorticoid therapy. The patient with difficult to control asthma not only presents a challenge to clinical management but raises new questions concerning our ability to control the progression of disease. Is difficult to control asthma secondary to overwhelming or ongoing allergen exposure? Do anti-inflammatory medications, specifically inhaled glucocorticoids, really control the progression of the disease? Are these patients destined to become severe asthmatics at birth due to the inherent characteristics of their airways, or is this indeed a consequence of progressive inflammation? This review will summarize present concepts of glucocorticoid-resistant asthma, current knowledge of the mechanisms of persistent inflammation, and the implications for management. The gaps in information will also be addressed in order to stimulate interest in further research that could lead to better understanding of the disease and potential windows for therapeutic intervention.
目前，人们强调将哮喘视为慢性气道炎症的一种表现，可能继发于过敏原超敏反应。因此，治疗的一个方面是采取环境控制措施，以尽量减少与过敏原刺激相关的炎症反应，并进行抗炎治疗以消除炎症并预防疾病进展。大多数患者对近期哮喘管理指南中推荐的传统治疗反应良好。然而，一些病例尽管使用了高剂量吸入糖皮质激素，甚至联合口服糖皮质激素治疗，仍很难控制。这些患者的治疗引发了关于影响糖皮质激素治疗反应的因素的问题。难治性哮喘患者不仅给临床治疗带来挑战，还引发了关于我们控制疾病进展能力的新问题。难治性哮喘是由于大量或持续接触过敏原所致吗？抗炎药物，特别是吸入糖皮质激素，真的能控制疾病进展吗？这些患者是由于气道的固有特征在出生时就注定会成为重度哮喘患者，还是这确实是进行性炎症的结果？本综述将总结糖皮质激素抵抗性哮喘的当前概念、持续性炎症机制的现有知识以及对治疗的影响。还将讨论信息空白，以激发对进一步研究的兴趣，从而更好地理解该疾病并找到潜在的治疗干预窗口。
