Airway as Target Organ in Infants with Atopic Dermatitis

气道作为特应性皮炎婴儿的靶器官

• 批准号: 7101917
• 负责人: Robert S. Tepper
• 金额: $ 27.19万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7101917
• 关键词: allergens; atopic dermatitis; atopy; clinical research; human subject; infant human (0-1 year); interleukin 13; interleukin 4; nitric oxide; preschool child (1-5); respiratory epithelium; respiratory system; skin hypersensitivity

DESCRIPTION (provided by applicant): Asthma is a disease characterized by recurrent episodes of airway obstruction, by airway hyperresponsiveness, and airway inflammation. There is a strong genetic component to asthma; family history of asthma and allergy are strongly associated with the risk of an infant developing asthma and the persistence of asthma symptoms. Children with early onset of persistent asthma are also more likely to be atopic individuals, who develop eczema during infancy and then progress to having gastro-intestinal symptoms of specific food intolerance and then to having respiratory symptoms. Of atopic infants, more than 50% subsequently develop recurrent respiratory symptoms and asthma. This progression of atopic symptoms has been referred to as "the allergic march", which results from complex interactions between genetic susceptibility and environmental factors. The presence of an inflammatory process in multiple target organs such as the skin, gastrointestinal tract, and the airways supports the systemic nature of atopy. For infants with atopic dermatitis, allergen sensitization and the heightened Th2 response of the peripheral blood cells precedes the occurrence of clinical asthma; however, we currently do not know when the airway of the atopic infant becomes a target organ with inflammation and hyperresponsiveness, the phenotypic characteristics of asthma. In mice, epicutaneous allergen sensitization produces atopic dermatitis, as well as heightened airway reactivity. This finding has suggested that atopic dermatitis may not only precede asthma, but may also contribute to its development. If this also occurs in humans, then more aggressive treatment of atopic dermatitis in infants might minimize the development of asthma. Our understanding of the origins of asthma is limited. In order to design strategies for early intervention and prevention of this disease, it is critical to determine when the airway becomes a target organ and whether atopic infants have phenotypic characteristics of the asthmatic airway early in life. Specific Aim # 1: Evaluate whether infants with atopic dermatitis exhibit the phenotypic characteristics of the asthmatic airway. Airway reactivity and exhaled nitric oxide kinetics will be measured in infants with atopic dermatitis and healthy controls. Using cultured nasal airway epithelial cells from these infants, we will also evaluate the production of Th2 chemokines following stimulation of the cells with IL-4 and IL-13. Specific Aim # 2: Evaluate whether the presence of phenotypic characteristics of the asthmatic airway identifies infants and toddlers that develop clinical asthma by 5 years of age.

描述（由申请人提供）：哮喘是一种疾病，其特征是气道阻塞，气道高反应性和气道炎症。哮喘有很强的遗传成分。哮喘和过敏的家族史与婴儿患哮喘的风险和哮喘症状的持久性密切相关。早期发作持续性哮喘的儿童也更有可能是特有的个体，他们在婴儿期间患湿疹，然后发展为患有特定食物不耐受的胃肠道症状，然后患有呼吸道症状。特应性婴儿，超过50％随后出现复发性呼吸道症状和哮喘。特应症状的这种进展被称为“过敏游行”，这是由于遗传敏感性和环境因素之间的复杂相互作用而引起的。在皮肤，胃肠道和气道等多个靶器官中存在炎症过程，支持了特应性的系统性。对于特征性皮炎的婴儿，过敏原敏化和外周血细胞的TH2反应增强，先于临床哮喘的发生。但是，我们目前不知道何时炎症和反应性（哮喘的表型特征）何时成为具有炎症和过度反应性的靶器官。在小鼠中，表皮过敏原敏化会产生特应性皮炎，并提高气道反应性。这一发现表明，特应性皮炎可能不仅先于哮喘，而且可能有助于其发育。如果这也发生在人类中，那么对婴儿特应性皮炎的更具积极性治疗可能会最大程度地减少哮喘的发展。我们对哮喘起源的理解是有限的。为了设计早期干预和预防这种疾病的策略，必须确定气道何时成为靶器官，以及特应性婴儿早期是否具有哮喘气道的表型特征。特定目的＃1：评估患有特应性皮炎的婴儿是否表现出哮喘气道的表型特征。气道反应性和呼出的一氧化氮动力学将在患有特应性皮炎和健康对照的婴儿中测量。使用这些婴儿培养的鼻气道上皮细胞，我们还将评估用IL-4和IL-13刺激细胞后Th2趋化因子的产生。 具体目的＃2：评估哮喘气道的表型特征是否会识别出在5岁之前发展临床哮喘的婴儿和幼儿。