Miller Christopher Wt, Krishnaswamy Narayanaswamy, Johnston Chambless, Krishnaswamy Guha
Division of Allergy and Clinical Immunology, Quillen College of Medicine, Johnson City, TN, USA.
Clin Mol Allergy. 2008 May 20;6:4. doi: 10.1186/1476-7961-6-4.
Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).
特应性疾病和哮喘在全球范围内正以惊人的速度增长。现在人们已经充分认识到,哮喘是一种气道慢性炎症性疾病。许多患者的炎症过程是由免疫球蛋白E(IgE)依赖性过程驱动的。肥大细胞在过敏原和IgE的作用下被激活并释放介质,导致一系列反应,最终导致B淋巴细胞、T淋巴细胞、嗜酸性粒细胞、成纤维细胞、平滑肌细胞和内皮细胞激活。这种复杂的细胞相互作用、细胞因子、趋化因子和生长因子的释放以及气道的炎症重塑导致慢性哮喘。一部分患者会发展为严重的气道疾病,这可能极其病态甚至致命。虽然有许多治疗哮喘的方法,但它仍然是一种慢性且无法治愈的疾病,其特征是病情加重、住院以及药物相关的不良反应。奥马珠单抗是慢性哮喘的一种新选择,它通过结合并抑制IgE的作用来发挥作用,从而干扰前面所述的哮喘级联反应的一个环节。这是一种针对IgE的人源化单克隆抗体,已被证明在哮喘中有许多有益作用。奥马珠单抗的使用可能会受到药物成本以及一些报道的不良反应的影响,包括罕见的过敏反应可能性。在特定病例中谨慎使用时,奥马珠单抗为疾病管理提供了一个非常重要的工具。它已被证明在荨麻疹、血管性水肿、乳胶过敏和食物过敏中还有其他作用,但数据有限且适应证远未明确。除了减少病情加重外,它还有节省类固醇的作用,因此可能会减少一些高剂量糖皮质激素治疗患者的不良反应。研究表明,使用奥马珠单抗后哮喘患者的生活质量指标有所改善,但对肺功能的影响出人意料地小,这表明肺功能、病情加重和生活质量之间存在脱节。使用这种药物可能很少发生过敏反应,美国食品药品监督管理局(FDA)已推荐了适当的预防措施。按照目前的做法以及新的哮喘指南的建议,这种生物制剂适用于中度或重度持续性过敏性哮喘(第5和6步)。