D'Amato Gennaro, Piccolo Amedeo, Salzillo Antonello, Noschese Paolo, D'Amato Maria, Liccardi Gennaro
Division of Respiratory and Allergic Diseases, Department of Respiratory Diseases, High Speciality Hospital A. Cardarelli, Naples, Italy.
Recent Pat Inflamm Allergy Drug Discov. 2007 Nov;1(3):225-31. doi: 10.2174/187221307782418900.
The pathogenetic aspect of allergic bronchial asthma is characterized by airway inflammation with infiltration of mast cells, basophils, eosinophils, monocytes and T-helper (Th)2 lymphocytes. Most cases of asthma are atopic in nature and aeroallergens such as those released by pollens, Dermatophagoides, moulds etc, act as sensitizer and trigger agents which induce immune response through immunoglobulin E (IgE). IgE is the key mediator of allergic inflammatory reaction and plays a central role in the pathogenesis of atopic-allergic diseases such as those of respiratory tract: rhinitis and bronchial asthma. Currently antiinflammatory and bronchodilation treatments, with integration of other drugs such as antileucotrienes, are effective for most of asthma patients, but there are asthmatic subjects whose disease is incompletely controlled by inhaled or systemic corticosteroids and these patients account for about 50% of the healthcare costs of asthma. A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference in the action of IgE and IgE has been viewed as a target for novel immunological drug development in asthma. Monoclonal antibodies are a molecule able to interact with specific antigens and represent a very interesting options for asthma treatment and their patents. Omalizumab is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases and with clear efficacy in adolescent and adult patients with moderate-to-severe allergic asthma. This non-anaphylactogen anti-IgE antibody inhibits IgE functions blocking free serum IgE and inhibiting their binding to cellular receptors. By reducing serum IgE levels and IgE receptor expression on inflammatory cells in the context of allergic cascade. Omalizumab therapy is well tolerated and significantly improves symptoms, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids to control disease. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. In conclusion omalizumab represents a really new approach to the treatment of atopic asthma and may fulfil an important need in patients with moderate-to-severe asthma.
过敏性支气管哮喘的发病机制特点是气道炎症,伴有肥大细胞、嗜碱性粒细胞、嗜酸性粒细胞、单核细胞和辅助性T(Th)2淋巴细胞浸润。大多数哮喘病例本质上属于特应性,花粉、尘螨、霉菌等气传变应原作为致敏剂和触发剂,通过免疫球蛋白E(IgE)诱导免疫反应。IgE是过敏性炎症反应的关键介质,在呼吸道特应性过敏性疾病如鼻炎和支气管哮喘的发病机制中起核心作用。目前,抗炎和支气管扩张治疗,联合使用抗白三烯等其他药物,对大多数哮喘患者有效,但仍有一些哮喘患者,其病情无法通过吸入或全身使用皮质类固醇得到完全控制,这些患者占哮喘医疗费用的约50%。一种针对哮喘和其他过敏性呼吸道疾病的新型治疗方法涉及干扰IgE的作用,并且IgE已被视为哮喘新型免疫药物研发的靶点。单克隆抗体是一种能够与特定抗原相互作用的分子,是哮喘治疗及其专利方面非常有趣的选择。奥马珠单抗是一种人源化重组抗IgE单克隆抗体,用于治疗过敏性疾病,对中度至重度过敏性哮喘的青少年和成年患者有明确疗效。这种非过敏原性抗IgE抗体通过阻断游离血清IgE并抑制其与细胞受体的结合来抑制IgE功能。在过敏反应级联反应中,通过降低血清IgE水平和炎症细胞上IgE受体的表达来实现。奥马珠单抗治疗耐受性良好,能显著改善症状,减少哮喘发作以及使用高剂量吸入皮质类固醇来控制疾病的需求。此外,奥马珠单抗改善了严重持续性过敏性哮喘患者的生活质量,而目前可用的哮喘药物无法充分控制此类患者的病情。总之,奥马珠单抗代表了一种治疗特应性哮喘的全新方法,可能满足中度至重度哮喘患者的重要需求。