Longitudinal Observational Study of Severe Asthma

哮喘是一种常见疾病，也是一个重大的公共卫生问题，每10个人中就有1人受其影响，仅在美国就有近3000万人。大约5-10%的哮喘患者病情严重，难以用标准疗法控制。严重哮喘患者被认为对主要用于治疗哮喘的皮质类固醇具有相对抗性。此外，慢性皮质类固醇治疗通常会导致副作用，对结果产生不利影响。因此，严重哮喘患者需要更有效、安全、成本效益高且易于管理的治疗方案。更好地了解导致疾病严重程度和发病机制的不同因素，将有必要为严重哮喘患者确定新的、个性化的治疗和管理方法。我们的目标是更好地了解区分重度哮喘与轻度至中度哮喘的致病机制。在这样做的过程中，我们希望发现新的途径，可以有针对性地实现我们为严重哮喘患者开发新疗法的主要目标。

Asthma is a common disease and a significant public health problem, affecting one in every 10 individuals, nearly 30 million people in the US alone. About 5-10% of asthmatics have severe disease that is difficult to control with standard therapies. Severe asthmatics are considered to be relatively resistant to corticosteroids, a mainstay of therapy in asthma. Furthermore, chronic corticosteroid therapy often results in side effects that adversely affect outcomes. Thus, more effective treatment options, which are safe, cost-effective and easy to administer, are needed for severe asthmatics. A better understanding of the different factors that contribute to disease severity and pathogenesis will be necessary to identify new, personalized treatment and management approaches for severe asthmatics. Our goal is to gain a better understanding of the pathogenic mechanisms that differentiate severe asthma from mild to moderate asthma. In so doing, we hope to discover novel pathways that can be targeted to achieve our primary aim of developing new therapies for severe asthmatics. Progress achieved under this protocol is summarized as follows: 1. Serum levels of apolipoprotein A-I and large High Density Lipoprotein particles have been shown to be positively correlated with FEV1 in patients with atopic asthma. This demonstrates that circulating HDL particles are associated with less severe airflow obstruction in allergic asthma. A manuscript describing these finding has been published in the American Journal of Respiratory and Critical Care Medicine. 2. Serum levels of high-density lipoproteins have been shown to be negatively correlated with biomarkers of type 2 inflammation (e.g., blood eosinophil counts and serum periostin levels) in atopic asthmatics. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL-cholesterol and total HDL particles measured by NMR spectroscopy (HDLNMR). Serum periostin levels negatively correlated with total HDLNMR. In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This finding supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.