Bagnasco Diego, Ferrando Matteo, Varricchi Gilda, Puggioni Francesca, Passalacqua Giovanni, Canonica Giorgio Walter
Allergy and Respiratory Diseases, DIMI Department of Internal Medicine, University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy.
Department of Translational Medical Sciences, Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy.
Front Med (Lausanne). 2017 Aug 31;4:135. doi: 10.3389/fmed.2017.00135. eCollection 2017.
The definition of asthma has changed considerably in recent years, to the extent that asthma is no longer considered a single disease but a heterogeneous disorder that includes several phenotypes and, possibly, endotypes. A more detailed analysis of the immunological mechanisms underlying the pathogenesis of asthma shows interleukin 5 (IL-5) to be a crucial cytokine in several asthma phenotypes. In fact, IL-5 exerts selective action on eosinophils, which, in turn, sustain airway inflammation and worsen asthma symptoms and control. Clinical trials have shown drugs targeting IL-5 or its receptor alpha subunit (IL-5Ra) to be a promising therapeutic approach to severe asthma, whose characteristics render standard therapy of little use: systemic corticosteroids only partially control the disease and have well-known adverse effects, and omalizumab is used for allergic subtypes. Analysis of the design process of clinical trials reveals the importance of patient selection, taking into account both clinical data (e.g., exacerbations, lung function, and quality of life) and biomarkers (e.g., eosinophils, which are predictive of therapeutic response).
近年来，哮喘的定义发生了很大变化，以至于哮喘不再被视为单一疾病，而是一种异质性疾病，包括几种表型，甚至可能包括几种内型。对哮喘发病机制背后免疫机制的更详细分析表明，白细胞介素5（IL-5）是几种哮喘表型中的关键细胞因子。事实上，IL-5对嗜酸性粒细胞发挥选择性作用，而嗜酸性粒细胞反过来又会维持气道炎症并加重哮喘症状及病情控制难度。临床试验表明，针对IL-5或其受体α亚基（IL-5Ra）的药物是治疗重度哮喘的一种有前景的治疗方法，重度哮喘的特点使得标准治疗几乎无效：全身用糖皮质激素只能部分控制疾病，且有众所周知的不良反应，而奥马珠单抗用于过敏性亚型。对临床试验设计过程的分析揭示了患者选择的重要性，要同时考虑临床数据（如急性加重、肺功能和生活质量）和生物标志物（如嗜酸性粒细胞，其可预测治疗反应）。
