Cytokine Dysregulation, Virus Infections, And Asthma

细胞因子失调、病毒感染和哮喘

• 批准号: 7485955
• 负责人: Robert F Lemanske
• 金额: $ 70.39万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7485955
• 关键词: Acute; Address; Adolescence; Age; Allergic; Allergic rhinitis; Aspirate substance; Asthma; Atopic Dermatitis; Birth; Blood; Childhood; Childhood Asthma; Clinical; Data; Dendritic Cells; Development; Disease remission; Environmental Tobacco Smoke; Etiology; Evaluation; Event; Exhalation; Fibrinogen; Frequencies; Gender; Grant; Image; Immune; Immune response; Immunity; In Vitro; Infection; Interferons; Interleukin-10; Interleukin-13; Interleukin-5; Irrigation; Learning; Life; Ligands; Lower Respiratory Tract Infection; Lower respiratory tract structure; Lung; Nature; Nitric Oxide; Nose; Numbers; Oscillometry; Outcome; Pathway interactions; Pattern; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phenotype; Physiological; Physiology; Plethysmography; Population; Predisposition; Primary Prevention; Production; Puberty; Recording of previous events; Respiratory Tract Diseases; Respiratory Tract Infections; Rhinovirus; Severities; Sex Characteristics; Specimen; Spirometry; Sputum; Testing; Time; Tissues; Translating; Vaccines; Viral; Viral Respiratory Tract Infection; Virulence; Virus; Virus Diseases; Wheezing; airway hyperresponsiveness; base; cohort; cytokine; design; disease phenotype; early childhood; gene environment interaction; in vivo; infancy; methacholine; novel; pathogen; peripheral blood; pet animal; receptor; respiratory; respiratory virus; response; therapy development

Abnormalities in immune response to viral infections and the virulence patterns of certain respiratory viruses have been felt to contribute significantly to the inception, progression, and severity of childhood asthma through unknown mechanisms. Using a birth cohort to study these relationships, we have made a number of novel and important observations pertaining to immune response profiles and virus infections during early life, and more recently with continued maturation of the cohort, we have placed these findings in the context of gene-environment interactions, developmental aspects, and gender differences. The most novel finding thus far has been that moderate to severe rhinovirus (RV)-induced wheezing illnesses during infancy are the most significant event in early life that predicts the subsequent development of childhood asthma. Moreover, these outcomes appear to be related to deficiencies in the production of interferons in response to these infections. Thus, the overall hypothesis of this project is that susceptibility to, and the clinical severity and manifestations of RV infections throughout childhood and early adolescence, is related to a deficiency in interferon responses to viral infection. We therefore propose to continue evaluation of cytokine response profiles from three tissue compartments (blood, nasal aspirates, and induced sputum) that have been previously stored and prospectively obtained as they relate to the development and physiological consequences of wheezing illnesses with specific viral pathogens, the development of various atopic phenotypes, and the expression and remission of asthma through infancy, childhood and early adolescence. This project comprises the entire COAST cohort that, in addition to its own specific aims and objectives, provides all of the phenotypic characterization and biologic specimens and DMA for the remaining projects in this application. Defining mechanisms by which viral infections impact on the clinical expression of childhood asthma is clearly relevant to the development of therapies aimed at both acute treatment in the form of medications and primary prevention in the form of vaccines.

对病毒感染的免疫反应减弱和某些呼吸道疾病的毒力模式 已经感觉到病毒显著地促进了 儿童哮喘通过未知的机制使用出生队列来研究这些关系， 我们已经对免疫反应谱进行了一些新的重要观察， 和病毒感染，最近随着队列的不断成熟，我们 将这些发现置于基因-环境相互作用，发育方面， 和性别差异。迄今为止最新的发现是中度到重度鼻病毒 婴儿期由RV引起的喘息性疾病是生命早期最重要的事件， 预测儿童哮喘的后续发展。此外，这些结果似乎是 与这些感染引起的干扰素产生不足有关。因此 本项目的总体假设是， RV感染贯穿儿童期和青春期早期，与干扰素缺乏有关 对病毒感染的反应。因此，我们建议继续评估细胞因子反应 来自三个组织隔室（血液、鼻吸出物和诱导痰）的特征， 先前存储并预期获得，因为它们与发育和生理相关， 特定病毒病原体引起的喘息性疾病的后果， 表型，以及婴儿期、儿童期和早期哮喘的表达和缓解 青春期该项目包括整个海岸队列，除了自己的具体目标， 和目标，提供了所有的表型表征和生物标本和DMA， 其余项目在此申请。定义病毒感染影响 儿童哮喘的临床表现显然与治疗方法的发展有关， 包括药物形式的急性治疗和疫苗形式的初级预防。