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 个人中就有一人患有哮喘，仅在美国就有近 3000 万人患有哮喘。 大约 5-10% 的哮喘患者患有标准疗法难以控制的严重疾病。 严重哮喘患者被认为对皮质类固醇具有相对抵抗力，而皮质类固醇是哮喘的主要治疗方法。 此外，长期皮质类固醇治疗常常会产生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、安全、具有成本效益且易于管理的治疗方案。有必要更好地了解导致疾病严重程度和发病机制的不同因素，以确定针对严重哮喘患者的新的个性化治疗和管理方法。 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。 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为严重哮喘患者开发新疗法的主要目标。 该议定书所取得的进展总结如下： 1. 特应性哮喘患者血清载脂蛋白 A-I 和高密度脂蛋白大颗粒水平与 FEV1 呈正相关。 这表明循环中的高密度脂蛋白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《美国呼吸与重症监护医学杂志》上。 2. 特应性哮喘患者的血清高密度脂蛋白水平已被证明与 2 型炎症生物标志物（例如血液嗜酸性粒细胞计数和血清骨膜素水平）呈负相关。 在特应性哮喘患者中，血液嗜酸性粒细胞与核磁共振波谱 (HDLNMR) 测量的血清 HDL 胆固醇和总 HDL 颗粒呈负相关。血清骨膜素水平与总 HDLNMR 呈负相关。 相反，血液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，HDL 颗粒与血液嗜酸性粒细胞呈负相关，而血清甘油三酯则呈正相关。 这一发现支持了这样的观点：HDL 和甘油三酯的血清水平可能与特应性哮喘的全身 2 型炎症有关。