Study of Soy Isoflavones in Asthma (SOYA)

大豆异黄酮治疗哮喘的研究 (SOYA)

• 批准号: 8089559
• 负责人: Lewis J Smith
• 金额: $ 33.25万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089559
• 关键词: 12 year old; Adrenal Cortex Hormones; Animals; Antioxidants; Asthma; Biological Markers; Breathing; C-reactive protein; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Complex; Data Coordinating Center; Diet; Dietary Practices; Dietary Supplementation; Dietary intake; Disease; Drug usage; Effectiveness; Environmental Risk Factor; Epidemiology; Exhalation; Forced expiratory volume function; Genetic; Genistein; Goals; Health Care Costs; Health Services Accessibility; Healthcare; Human; In Vitro; Individual; Inflammation; Intake; Interleukin-6; Lead; Leukotriene C4; Leukotriene E4; Leukotrienes; Link; Masks; Measures; Morbidity - disease rate; Myofibroblast; Nitric Oxide; Nutrient; Outcome; Outcome Measure; Participant; Pathway interactions; Patients; Peak Expiratory Flow; Pharmaceutical Preparations; Placebo Control; Placebos; Plasma; Prevalence; Public Health; Public Health Schools; Pulmonary Function Test/Forced Expiratory Volume 1; Quality of life; Randomized; Randomized Controlled Clinical Trials; Reporting; Research Design; Respiratory physiology; Role; Severities; Severity of illness; Symptoms; Testing; United States; Vitamins; airway inflammation; cost; daidzein; dietary supplements; effective therapy; eosinophil; glycitein; health related quality of life; human study; improved; isoprostaglandin F2alpha type-III; novel; peripheral blood; primary outcome; public health relevance; research study; secondary outcome; soy; soy protein isolate; treatment response; urinary

DESCRIPTION (provided by applicant): This is the application for the Lead Clinical Center for the Study of Soy Isoflavones in Asthma (SOYA). It is linked to the Data Coordinating Center (DCC) application submitted by Dr. Robert Wise from the Johns Hopkins Bloomberg School of Public Health. Asthma is a common disease that has a major impact on morbidity and health care costs. Although the prevalence and severity of asthma have increased over the last several decades, the specific causes remain unknown. One possible mechanism is a change in diet. Yet, epidemiological and interventional studies designed to identify key nutrients or antioxidant vitamins that may be responsible for the increase in disease severity have produced inconsistent results. We recently reported and have since confirmed an association between low soy genistein intake and more severe asthma. We subsequently found that (1) the soy isoflavone genistein inhibits two key pathways that may contribute to asthma severity, human peripheral blood eosinophil leukotriene (LT) C4 synthesis and myofibroblast differentiation, and (2) a soy isoflavone supplement reduces exhaled nitric oxide (FeNO) and ex vivo LTC4 synthesis in patients with inadequately controlled asthma. We now propose a clinical trial to test the novel hypothesis that dietary supplementation with soy isoflavones is an effective treatment in patients with poorly controlled asthma. The study will include 380 patients with low dietary soy intake, 12 years of age or older, who are taking inhaled corticosteroids, leukotriene modifiers, or both and have inadequately controlled asthma. Participants will be randomly assigned to treatment with either a soy isoflavone supplement (containing genistein, daidzein and glycitein) 100 mg daily or placebo for six months. The primary outcome measure is forced expiratory volume in one second (FEV1), an objective measure of lung function. Secondary outcomes include biomarkers of airway inflammation (FeNO, exhaled breath condensate 8-isoprostane), measures of asthma symptoms (e.g., asthma control scores, unscheduled health care contacts, quality of life), and asthma exacerbations. Tertiary outcomes include biomarkers of systemic inflammation (peripheral blood eosinophil counts, C-reactive protein and interleukin-6 levels). Treatment response will be correlated with plasma genistein concentrations. The results of this trial will increase understanding of the role of diet in asthma; may identify a novel, safe and relatively inexpensive treatment for patients with asthma; and potentially have a major impact on public health in the United States. Public Health Relevance: The impact of this study is potentially large because diet may influence asthma severity and asthma is a common disease. Preliminary studies from our group have shown that low intake of soy is associated with more severe asthma and also suggest that soy isoflavone supplements can improve asthma. The major soy isoflavones (genistein and daidzein) can be safely given as supplements for prolonged periods, and their cost is substantially lower than most currently used drug treatments for asthma.

描述（由申请人提供）： 这是哮喘（大豆）大豆异黄酮研究铅临床中心的应用。它与约翰·霍普金斯彭博公共卫生学院的罗伯特·怀斯（Robert Wise）博士提交的数据协调中心（DCC）申请有关。哮喘是一种对发病率和医疗保健成本产生重大影响的常见疾病。尽管在过去的几十年中，哮喘的患病率和严重程度有所增加，但具体原因仍然未知。一种可能的机制是饮食的变化。然而，旨在鉴定可能导致疾病严重程度增加的关键营养素或抗氧化维生素的流行病学和介入研究导致了不一致的结果。我们最近报告并已经证实了低大豆染料木黄酮摄入量与更严重的哮喘之间的关联。 We subsequently found that (1) the soy isoflavone genistein inhibits two key pathways that may contribute to asthma severity, human peripheral blood eosinophil leukotriene (LT) C4 synthesis and myofibroblast differentiation, and (2) a soy isoflavone supplement reduces exhaled nitric oxide (FeNO) and ex vivo LTC4 synthesis in patients哮喘控制不足。现在，我们提出了一项临床试验，以检验新的假设，即用大豆异黄酮补充饮食是对哮喘控制良好的患者的有效治疗方法。该研究将包括380例饮食中摄入量低的患者，12岁或以上的患者，他们正在服用吸入的皮质类固醇，白细胞修饰剂或两者兼而有之，并且没有充分控制的哮喘。参与者将每天用大豆异黄酮补充剂（含有染料木黄酮，大豆蛋白酶和糖素）随机分配给参与者六个月。主要结局度量是在一秒钟内强制呼气量（FEV1），这是肺功能的客观度量。次要结果包括气道炎症的生物标志物（FENO，呼出的呼吸冷凝物8-异丙烷），哮喘症状的度量（例如，哮喘控制评分，未完成的医疗保健接触，生活质量）和哮喘患者。第三结局包括全身炎症的生物标志物（外周血嗜酸性粒细胞计数，C反应蛋白和白介素-6水平）。治疗反应将与血浆染料木黄酮浓度相关。该试验的结果将增加对饮食在哮喘中作用的理解。可以鉴定针对哮喘患者的新颖，安全且相对廉价的治疗；并有可能对美国的公共卫生产生重大影响。公共卫生相关性：这项研究的影响可能很大，因为饮食可能影响哮喘的严重程度和哮喘是一种常见疾病。我们小组的初步研究表明，大豆摄入量的摄入量与更严重的哮喘有关，也表明大豆异黄酮补充剂可以改善哮喘。可以将主要的大豆异黄酮（染料木黄酮和大豆）安全地作为延长时期的补充，并且它们的成本大大低于大多数当前使用的药物治疗哮喘的药物。