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个人中就有一个患有哮喘，仅在美国就有近3000万人。大约5%-10%的哮喘患者患有严重的疾病，这些疾病很难用标准的治疗方法来控制。重症哮喘患者被认为对皮质类固醇类药物相对耐受，皮质类固醇是哮喘的主要治疗方法。此外，慢性皮质类固醇治疗经常会导致副作用，对预后产生不利影响。因此，对严重哮喘患者来说，需要更有效的治疗方案，这些方案安全、经济、易于管理。更好地了解影响疾病严重程度和发病机制的不同因素将是确定重症哮喘患者新的、个性化的治疗和管理方法所必需的。我们的目标是更好地了解区分重度哮喘和轻度至中度哮喘的发病机制。通过这样做，我们希望发现新的途径，可以有针对性地实现我们的主要目标，即为严重哮喘患者开发新的治疗方法。 在该议定书下取得的进展概述如下： 1.特应性哮喘患者血清载脂蛋白A-I和大颗粒高密度脂蛋白水平与FEV1呈正相关。这表明，在过敏性哮喘中，循环中的高密度脂蛋白颗粒与较轻的气流阻塞有关。一份描述这些发现的手稿已经发表在《美国呼吸与重症护理医学杂志》上。 2.在特应性哮喘患者中，血清高密度脂蛋白水平与2型炎症的生物标志物(如血嗜酸粒细胞计数和血清Periostin水平)呈负相关。在特应性哮喘患者中，血中嗜酸性粒细胞与血清高密度脂蛋白-胆固醇和核磁共振波谱测定的总高密度脂蛋白颗粒呈负相关。血清Periostin水平与总高密度脂蛋白核磁共振呈负相关。相比之下，血中嗜酸性粒细胞计数与血清甘油三酯水平呈正相关。这项研究首次证明，在特应性哮喘患者中，高密度脂蛋白颗粒与血中嗜酸性粒细胞呈负相关，而血清甘油三酯与其呈正相关。这一发现支持了血清高密度脂蛋白和甘油三酯水平可能与特应性哮喘的系统性2型炎症有关的概念。

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.