National Heart and Lung Institute, Imperial College and NIHR Biomedical Research Unit, Royal Brompton Hospital, London, UK.
Curr Opin Pulm Med. 2012 Jan;18(1):35-41. doi: 10.1097/MCP.0b013e32834d09a5.
Severe asthma remains a condition in search of deeper understanding and of newer effective therapies. Risk factors for developing severe asthma, phenotyping of disease, characterizing the inflammatory response and understanding of poor therapeutic responses to corticosteroids are important areas of research. The development of biomarkers for phenotypic diagnosis and prognostic reasons is important.
Severe asthma has been defined as asthma that does not respond adequately to asthma medications, particularly corticosteroids, with continuing loss of control of asthma and future risk of exacerbations and side effects from corticosteroid therapy. This is a heterogeneous condition and cluster analyses have yielded phenotypes on the basis of age of onset of disease, sex, lung function, atopy and questionnaire data. Use of sputum eosinophil counts has further defined a group with persistent eosinophilic inflammation despite corticosteroid therapy, and a noneosinophilic group with uncontrolled asthma.
Use of a single biomarker provides value in phenotyping and in predicting response to treatment but many more biomarkers such as those derived from -omic approaches remain to be used in the analysis. A systems biology approach to finding novel biomarkers is the way forward to stratify severe asthma so that appropriate and distinct therapies can be selected for each subtype.
重度哮喘仍然是一种需要深入了解和更有效治疗方法的疾病。发展为重度哮喘的风险因素、疾病表型分析、炎症反应特征以及对皮质类固醇治疗反应不佳的理解，都是重要的研究领域。生物标志物的开发对于表型诊断和预后原因非常重要。
重度哮喘被定义为对哮喘药物（尤其是皮质类固醇）反应不足的哮喘，表现为哮喘控制持续不佳，未来有加重和皮质类固醇治疗副作用的风险。这是一种异质性疾病，聚类分析根据疾病的发病年龄、性别、肺功能、过敏和问卷调查数据得出了不同的表型。痰嗜酸性粒细胞计数的使用进一步定义了一组患者，尽管接受了皮质类固醇治疗，但仍存在持续的嗜酸性粒细胞炎症，另一组则是非嗜酸性粒细胞性哮喘，控制不佳。
单一生物标志物的使用在表型分析和预测治疗反应方面具有价值，但还有许多其他生物标志物，如基于组学方法的生物标志物，有待在分析中使用。寻找新的生物标志物的系统生物学方法是为重度哮喘分层的前进方向，以便为每种亚型选择合适和独特的治疗方法。
