Department of Translational Medical Sciences (DISMET), University of Naples Federico II, Naples, Italy.
Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Curr Med Chem. 2019;26(16):2801-2822. doi: 10.2174/0929867325666180110094542.
Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments. Although in most patients the disease can be controlled by some combination of pharmacologic agents, in some 5-10% of patients the disease remains uncontrolled. Several monoclonal antibodies (mAbs) targeting pathogenetic molecules (e.g., IgE, IL-5, IL- 5Rα, IL-4, IL-13, TSLP) are currently available or under development for the treatment of different forms of severe type 2 asthma. The identification of diagnostic and predictive biomarkers (e.g., IgE, blood eosinophil count, FeNO, periostin, etc.) has revolutioned the field of targeted therapy in severe asthma. Monoclonal antibodies targeting Th2-driven inflammation are generally safe in adult patients with moderate-to-severe asthma. The long-term safety of these biologics is a relevant issue that should be addressed. Unfortunately, little is known about non-type 2 asthma. Further studies are needed to identify biomarkers to guide targeted therapies of different forms of non-type 2 asthma.
哮喘是一种异质性疾病,其特征为慢性气道炎症,导致广泛的临床表现。重度哮喘患者代表了大量医疗资源的消耗和住院治疗。此外,这些患者存在发病率和死亡率增加的风险。最近,已经确定了几种哮喘表型和内型。确定哮喘的特定亚型对于优化新型治疗的临床获益至关重要。尽管在大多数患者中,疾病可以通过某些药物组合控制,但在大约 5-10%的患者中,疾病仍然无法控制。目前有几种针对致病分子(例如 IgE、IL-5、IL-5Rα、IL-4、IL-13、TSLP)的单克隆抗体 (mAb) 可用于或正在开发中,用于治疗不同形式的重度 2 型哮喘。诊断和预测生物标志物(例如 IgE、血嗜酸性粒细胞计数、FeNO、骨膜蛋白等)的鉴定彻底改变了重度哮喘的靶向治疗领域。针对 Th2 驱动炎症的单克隆抗体在中重度哮喘的成年患者中通常是安全的。这些生物制剂的长期安全性是一个需要解决的相关问题。不幸的是,对于非 2 型哮喘知之甚少。需要进一步的研究来确定生物标志物,以指导不同形式的非 2 型哮喘的靶向治疗。