Asthma and Allergic Disease Center

哮喘及过敏性疾病中心

• 批准号: 7913906
• 负责人: THOMAS A. PLATTS-MILLS
• 金额: $ 77万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-12 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7913906
• 关键词: Asthma; Allergic; Disease; Center

DESCRIPTION (provided by applicant): The research program of the University of Virginia has focused on investigating the etiology of asthma, looking both at risk factors for the disease and the complex events surrounding an acute episode. These studies have provided extensive evidence about effects of chronic exposure to indoor allergens, as well as the relevance of viruses to acute episodes in the hospital; the role of chronic sinus disease; and most recently the effects of pH changes in the lung lining fluid. In addition, the studies have addressed the mechanisms by which T cells contribute as effector cells and regulatory cells in allergic disease. The four projects of the current proposal are presented as separate and distinct research plans, but they have developed from, and will continue to involve, strong interactions at multiple levels. Project 1: Allergen exposure, IgE responses, and total IgE in relation to asthma in at risk populations: The studies will investigate: a) the interaction between home exposure, sensitization, and inflammatory responses among adult patients presenting with acute asthma; b) lung symptoms and asthma among teenage children in rural and city schools, focusing on the interaction between physical fitness, obesity, and metabolic syndrome on the one hand, and allergic responses and inflammation on the other. Project 2: CD25+CD4+ T cells and IgE-mediated disease in humans: The phenotype and function of a novel CD25+CD4+ subset associated with IgE responses will be analyzed. Studies will include investigation of the link between these cells and IgE by monitoring circulating T cells in children with atopic dermatitis during the first years of life, and examining the effects of anti-lgE therapy on discrete T cell subsets in asthmatic subjects. Project 3: Impact of chronic hyperplastic eosinophilic sinusitis on asthma: Studies will investigate the hypothesis that the sinus tissue contributes to the systemic inflammatory response through the production of, and recirculation of, TH2-like lymphocytes, eosinophils, basophils, and fibrocytes; and that those cells in turn influence sinus associated lymphatic tissue, bone marrow, and the lungs. Project 4: Mechanisms of pH deviation in asthma and chronic cough: Using new methods of measuring exhaled breath pH, the studies will focus on distinguishing between patients with primary airway acidification and gastric acid aspiration. The studies will address cellular and biochemical pathology related to airway acidification in the setting of chronic cough or acute asthma exacerbations. PROJECT 1: Allergen Exposure, IgE Responses, and Total IgE in Relation to Asthma in at Risk Populations (PI Platts-Mills, T.) PROJECT 1 DESCRIPTION (provided by applicant): Over the last 40 years of the 20th century asthma has become epidemic in most of the Western World. In particular asthma has become an important cause of school absenteeism, hospitalization and mortality among populations living in poverty in the cities of the United States. Although many changes are thought to have contributed to the increase the real reasons for the time course (i.e. 1960-2000) are not clear. However it is clear that the majority of African American children and adults admitted to hospital with asthma are allergic to one or more indoor allergens, particularly those from dust mite or cockroach. Over this same time period there have been major changes in lifestyle leading to decreased time outdoors, more time sedentary and a rise in obesity. To further understand the interaction between different factors contributing to asthma, several different approaches will be employed. The first will use new techniques to measure allergen and endotoxin exposure in homes, and a novel approach to measuring IgE antibodies specific for airborne particles. The objective is to investigate the dose response relationship between exposure and immune responses to allergens for patients living in poverty. The second aim is to assess the relationships between IgE ab response and inflammation among the patients presenting to an emergency department with asthma. These patients are consistently -70% uninsured and 50% from a minority group. In this study the inflammation associated with asthma will be studied using both "traditional" markers such as eosinophilia, exhaled NO (eNO) and sinus CT score; as well as measurements of cytokines in serum and leukotrienes in urine. Finally teenagers aged 14-16 years will be studied to determine the independent effects of physical activity, obesity and allergic sensitization on asthmatic symptoms and airway inflammation. The participants will complete an exercise protocol with lung function and will be assessed for evidence of inflammation and allergic sensitization. The objective is to answer whether obesity, decreased fitness, or the metabolic syndrome influence the symptoms or the physiological effects of asthma. As in specific aim 2, inflammation will be assessed both by traditional markers and by assay of cytokines and leukotrienes. These studies will be applied to both rural and city school age children. The overall objective is to understand the effects of obesity, physical activity and allergic sensitization in relation to symptoms of breathlessness and airway obstruction.

描述（由申请人提供）： 弗吉尼亚大学的研究计划的重点是研究哮喘的病因，既着眼于疾病的危险因素，也是围绕急性发作的复杂事件。这些研究提供了有关长期暴露于室内过敏原的影响以及病毒与医院急性发作的相关性的广泛证据。慢性鼻窦病的作用；最近，肺部内膜流体变化的影响。此外，这些研究已经解决了T细胞在过敏性疾病中作为效应细胞和调节细胞贡献的机制。当前提案的四个项目作为独立而独特的研究计划提出，但它们已经从多个层面上发展并将继续涉及强烈的互动。项目1：与哮喘患者相关的过敏原暴露，IgE反应和总IgE：研究将调查：a）在患有急性哮喘的成年患者中，家庭暴露，致敏和炎症反应之间的相互作用； b）农村和城市学校的少年儿童的肺症状和哮喘，一方面着重于身体健康，肥胖和代谢综合征之间的相互作用，另一方面是过敏反应和炎症。项目2：CD25+ CD4+ T细胞和人类IgE介导的疾病：将分析与IgE响应相关的新型CD25+ CD4+子集的表型和功能。研究将包括研究这些细胞与IgE之间的联系，通过监测生命的头几年中特应性皮炎儿童的循环T细胞，并检查抗LGE疗法对哮喘受试者离散T细胞子集的影响。项目3：慢性增生性嗜酸性鼻窦炎对哮喘的影响：研究将调查窦组织通过产生和再循环Th2样淋巴细胞，嗜酸性嗜酸性粒细胞，碱性粒细胞和纤维细胞来有助于全身性炎症反应的假设；这些细胞又会影响鼻窦相关的淋巴组织，骨髓和肺。项目4：哮喘和慢性咳嗽中pH偏差的机制：使用测量呼气呼吸pH值的新方法，研究将重点在于区分原发性气道酸化和胃酸抽吸的患者。这些研究将针对与气道酸化有关的细胞和生化病理学，在慢性咳嗽或急性哮喘患者的情况下。 项目1：与AT风险种群中的哮喘有关的过敏原暴露，IgE反应和总IgE（Pi Platts-Mills，T。） 项目1描述（申请人提供）： 在20世纪的过去40年中，哮喘在大多数西方世界的流行病已经成为流行病。尤其是哮喘已成为居住在美国城市贫困人口中的学校缺勤，住院和死亡率的重要原因。尽管人们认为许多变化导致了时间课程的实际原因增加（即1960-2000）。但是，很明显，大多数非洲裔美国儿童和成人哮喘住院医院对一个或多个室内过敏原过敏，尤其是那些来自尘螨或蟑螂的过敏原。在同一时期，生活方式发生了重大变化，导致户外时间的减少，久坐的时间和肥胖症的增加。为了进一步了解导致哮喘的不同因素之间的相互作用，将采用几种不同的方法。第一个将使用新技术来测量房屋中的过敏原和内毒素暴露，并采用一种新型的测量对空气颗粒特异性的IgE抗体的方法。目的是研究生活在贫困患者中的暴露与对过敏原的免疫反应之间的剂量反应关系。第二个目的是评估出现在患有哮喘的急诊科的患者中IgE AB反应与炎症之间的关系。这些患者始终未投保 - 少数群体的未保险和50％。在这项研究中，将使用“传统”标记（例如嗜酸性粒细胞，呼出NO（ENO）和Sinus CT评分）研究与哮喘相关的炎症。以及尿液中血清和白三烯中细胞因子的测量。最终，将研究14-16岁的青少年，以确定体育活动，肥胖和过敏敏化对哮喘症状和气道炎症的独立影响。参与者将完成具有肺功能的运动方案，并将评估以证明炎症和过敏反应的证据。目的是回答肥胖，健身降低或代谢综合征是否会影响哮喘的症状或生理影响。与特定目标2一样，炎症将通过传统标记和细胞因子和白三烯的测定进行评估。这些研究将应用于农村和城市学龄儿童。总体目的是了解肥胖，体育活动和过敏反应与呼吸困难和气道阻塞有关的影响。