重症哮喘相关治疗一直无突破性进展的瓶颈，极大程度归结于重症哮喘的异质性和尚未完全明了且与轻、中度哮喘迥异的复杂病理机制。尽管应用临床表型（phenotype）对哮喘进行分类，可加深对哮喘异质性的认识，但这些临床表型，相对"孤立"，病理机制不明确，亦难以发现哮喘治疗新方法。本项目拟从重症哮喘异质性出发，从新近"哮喘内型（endotype）"假说入手，应用转录组学技术，诱导痰方法，从转化医学角度，采用分层聚类方法定义重症哮喘内型及其人口学、临床、病理和系统生物学特征，并分析重症哮喘内型间的转录组成分差异，及转录组信息与哮喘结局远期风险的关系，从转录组水平筛选具有预测和治疗前景的生物学标志物（biomarker）。若以上设想得以实施，（1）有望在西部建立重症哮喘诱导痰标本库/数据库，（2）为阐释重症哮喘病理新机制、规范重症哮喘教育和管理提供证据；（3）可望为发现重症哮喘治疗新方法提供科学证据。

The bottleneck problem that limits the big breakthrough of treatments for severe asthma, is attributed to heterogeneity and complicated pathogenic mechanisms, which differs from that in mild and moderate asthma. Until now, several clinical phenotypes of asthma have been defined which could improve our understanding of the heterogeneity of asthma, but these phenotypes, in isolation, do not identify the immunopathology that makes these clinical phenotypes distinct or makes it be difficult to search for a novel promising therapy. According to the recent hypothesis of asthma and "endotypes", we will use induced sputum-based transcriptomics, and hierarchical clustering analysis to define grouping of severe asthma endotypes, which are the integration of demographic, clinical, pathogenic, and transcriptome characteristics. Moreover, we will identify the differential components of the transcriptome between endotypes of severe asthma, explore the relationship between endotypes and the future risk of asthma outcomes, and screen for predictive and therapeutic biomarkers for severe asthma at translational level. Thus, we will establish a specimen bank of induced sputum and a database of severe asthma that could be the foundation for a severe asthma research program of China, provide evidence for elaborating pathogenic mechanisms, education and management of severe asthma, and screening novel therapies of severe asthma.