Esteban-Gorgojo Ignacio, Antolín-Amérigo Darío, Domínguez-Ortega Javier, Quirce Santiago
Department of Allergy, Hospital General de Villalba, Madrid, Spain,
Department of Allergy, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain.
J Asthma Allergy. 2018 Oct 29;11:267-281. doi: 10.2147/JAA.S153097. eCollection 2018.
Although non-eosinophilic asthma (NEA) is not the best known and most prevalent asthma phenotype, its importance cannot be underestimated. NEA is characterized by airway inflammation with the absence of eosinophils, subsequent to activation of non-predominant type 2 immunologic pathways. This phenotype, which possibly includes several not well-defined subphenotypes, is defined by an eosinophil count <2% in sputum. NEA has been associated with environmental and/or host factors, such as smoking cigarettes, pollution, work-related agents, infections, and obesity. These risk factors, alone or in conjunction, can activate specific cellular and molecular pathways leading to non-type 2 inflammation. The most relevant clinical trait of NEA is its poor response to standard asthma treatments, especially to inhaled corticosteroids, leading to a higher severity of disease and to difficult-to-control asthma. Indeed, NEA constitutes about 50% of severe asthma cases. Since most current and forthcoming biologic therapies specifically target type 2 asthma phenotypes, such as uncontrolled severe eosinophilic or allergic asthma, there is a dramatic lack of effective treatments for uncontrolled non-type 2 asthma. Research efforts are now focusing on elucidating the phenotypes underlying the non-type 2 asthma, and several studies are being conducted with new drugs and biologics aiming to develop effective strategies for this type of asthma, and various immunologic pathways are being scrutinized to optimize efficacy and to abolish possible adverse effects.
尽管非嗜酸性粒细胞性哮喘（NEA）并非最广为人知且最常见的哮喘表型，但其重要性不可低估。NEA的特征是在非主导性2型免疫途径激活后出现无嗜酸性粒细胞的气道炎症。这种表型可能包括几种定义不明确的亚表型，其定义为痰液中嗜酸性粒细胞计数<2%。NEA与环境和/或宿主因素有关，如吸烟、污染、工作相关因素、感染和肥胖。这些危险因素单独或共同作用，可激活特定的细胞和分子途径，导致非2型炎症。NEA最相关的临床特征是其对标准哮喘治疗反应不佳，尤其是对吸入性糖皮质激素反应不佳，导致疾病严重程度更高且哮喘难以控制。事实上，NEA约占严重哮喘病例的50%。由于目前和即将推出的大多数生物疗法专门针对2型哮喘表型，如未控制的严重嗜酸性粒细胞性或过敏性哮喘，因此对于未控制的非2型哮喘，严重缺乏有效的治疗方法。目前的研究工作正集中在阐明非2型哮喘的潜在表型，并且正在对新药和生物制剂进行多项研究，旨在为这类哮喘开发有效的策略，同时正在仔细研究各种免疫途径，以优化疗效并消除可能的不良反应。
