Wenzel Sally
National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Am J Respir Crit Care Med. 2005 Jul 15;172(2):149-60. doi: 10.1164/rccm.200409-1181PP. Epub 2005 Apr 22.
Severe asthma remains poorly understood and frustrating to care for, partly because it is a heterogeneous disease. Patients with severe asthma disproportionately consume health care resources related to asthma. Severe asthma may develop over time, or shortly after onset of the disease. The genetic and environmental elements that may be most important in the development of severe disease are poorly understood, but likely include both allergic and nonallergic elements. Physiologically, these patients often have air trapping, airway collapsibility, and a high degree of methacholine hyperresponsiveness. Specific phenotypes of severe asthma are only beginning to be defined. However, describing severe asthma by age at onset (early- vs. late-onset) appears to describe two phenotypes that differ at immunologic, physiologic, epidemiologic, and pathologic levels. In particular, early-onset severe asthma is a more allergic-associated disease than late-onset severe asthma. In addition, patients with severe asthma can be defined on the basis of presence and type of inflammation. Severe asthma with persistent eosinophilia (of either early or late onset) is more symptomatic and has more near-fatal events. However, at least 50% of patients with severe asthma have very little identifiable inflammation. Thus, "steroid resistance" may occur at numerous levels, not all of which are caused by a lack of effect of steroids on inflammation. Treatment remains problematic, with corticosteroids remaining the most effective therapy. However, 5-lipoxygenase inhibitors, anti-IgE, and immunomodulatory drugs are also likely to have a place in treatment. Improving therapy in this disease will require a better understanding of the phenotypes involved.
重度哮喘仍然难以被充分理解且治疗起来令人沮丧,部分原因在于它是一种异质性疾病。重度哮喘患者在哮喘相关医疗资源消耗方面占比过高。重度哮喘可能随时间逐渐发展,也可能在疾病发作后不久就出现。对于重度疾病发展过程中可能最为重要的遗传和环境因素,我们了解甚少,但可能包括过敏和非过敏因素。从生理角度来看,这些患者常常存在气体潴留、气道可塌陷性以及对乙酰甲胆碱的高度高反应性。重度哮喘的特定表型才刚刚开始被定义。然而,根据发病年龄(早发型与晚发型)来描述重度哮喘,似乎可以区分出在免疫、生理、流行病学和病理学层面存在差异的两种表型。特别是,早发型重度哮喘比晚发型重度哮喘更具过敏相关性。此外,重度哮喘患者可根据炎症的存在与否及类型来定义。伴有持续性嗜酸性粒细胞增多的重度哮喘(早发型或晚发型)症状更明显,且有更多濒死事件。然而,至少50%的重度哮喘患者几乎没有可识别的炎症。因此,“激素抵抗”可能在多个层面发生,并非所有情况都是由激素对炎症缺乏作用所致。治疗仍然存在问题,皮质类固醇仍然是最有效的治疗方法。然而,5-脂氧合酶抑制剂、抗IgE药物和免疫调节药物在治疗中也可能占有一席之地。改善这种疾病的治疗需要更好地了解其中涉及的表型。
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