Longitudinal Observational Study of Severe Asthma

严重哮喘的纵向观察研究

• 批准号: 9550561
• 负责人: Stewart Levine
• 金额: $ 66.52万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9550561
• 关键词: Adrenal Cortex Hormones; Adverse effects; Affect; American; Apolipoprotein A-I; Asthma; Biological Markers; Chronic; Clinical; Clinical Data; Collection; Critical Care; Data; Disease; Extrinsic asthma; Goals; HDL-triglyceride; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Individual; Inflammation; Journals; Link; Longitudinal observational study; Manuscripts; Measures; Medicine; NMR Spectroscopy; Natural History; Obstruction; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Phenotype; Physiological; Protocols documentation; Public Health; Publishing; Pulmonary Function Test/Forced Expiratory Volume 1; Resistance; Serum; Severity of illness; Specimen; Steroids; Testing; Time; Triglycerides; asthmatic; base; cohort; cost effective; disorder control; effective therapy; eosinophil; novel; novel therapeutics; particle; periostin; personalized management; personalized medicine; respiratory

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.

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人受到影响，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，难以用标准疗法控制。 重度哮喘患者被认为对皮质类固醇激素（哮喘治疗的主要药物）相对耐药。 此外，慢性皮质类固醇治疗经常导致对结果产生不利影响的副作用。 因此，严重哮喘患者需要更有效的治疗选择，这些选择是安全的、具有成本效益的和易于管理的。更好地了解不同的因素，有助于疾病的严重程度和发病机制将是必要的，以确定新的，个性化的治疗和管理方法，为严重哮喘。 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的主要目标，为严重哮喘患者开发新的治疗方法。 根据该议定书取得的进展概述如下： 1. 在特应性哮喘患者中，载脂蛋白A-I和大高密度脂蛋白颗粒的血清水平已被证明与FEV 1呈正相关。 这表明循环HDL颗粒与过敏性哮喘中不太严重的气流阻塞有关。 描述这些发现的手稿已发表在美国呼吸和重症监护医学杂志上。 2. 高密度脂蛋白的血清水平已显示与2型炎症的生物标志物（例如，血液嗜酸性粒细胞计数和血清骨膜蛋白水平）。 在特应性哮喘患者中，血液嗜酸性粒细胞与血清HDL-胆固醇和总HDL颗粒呈负相关，通过NMR光谱（HDLNMR）测量。血清骨膜蛋白水平与总HDLNMR呈负相关。 相反，血嗜酸性粒细胞计数与血清甘油三酯水平呈正相关。 本研究首次证明，高密度脂蛋白颗粒呈负相关，而血清甘油三酯呈正相关，与血液嗜酸性粒细胞在特应性哮喘。 这一发现支持了血清HDL和甘油三酯水平可能与特应性哮喘中的全身性2型炎症有关的概念。