Department of Respiratory Medicine, Airways Disease, National Heart & Lung Institute, Imperial College London, United Kingdom.
Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom.
Semin Respir Crit Care Med. 2018 Feb;39(1):91-99. doi: 10.1055/s-0037-1607391. Epub 2018 Feb 10.
Severe therapy-resistant asthma has been defined as "asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy". Patients who usually present with 'difficult-to-treat asthma' should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.
重度治疗抵抗性哮喘被定义为“需要高剂量吸入皮质类固醇（ICSs）加第二种控制器（和/或全身皮质类固醇）治疗才能防止其变得‘不受控制’或尽管进行这种治疗仍保持‘不受控制’的哮喘”。通常表现为“难治性哮喘”的患者应首先进行评估，以确定他/她是否患有排除其他诊断的哮喘，如果是，哮喘是否可以归类为重度治疗抵抗性。这需要评估对药物的依从性、混杂因素和合并症。随着确定表型以优化对现有和新疗法的反应，越来越多的重度治疗抵抗性哮喘的管理将得到帮助。重度哮喘患者通常使用高剂量 ICS 和长效β-激动剂（LABA）的联合治疗，此外，还经常服用维持剂量的口服皮质类固醇。表型可以通过测量血液嗜酸性粒细胞计数和呼气中一氧化氮水平以及痰液粒细胞计数来确定。对于目前有有效靶向生物疗法的重度过敏性哮喘和重度嗜酸性粒细胞性哮喘这两种已定义的表型，可以分别使用抗免疫球蛋白 E（IgE）和抗白细胞介素（IL）-5 抗体。通过定义非嗜酸性粒细胞或非 T2 表型，将取得进一步进展。对于重度哮喘患者，最终在专门的重度哮喘中心进行调查和管理非常重要。
