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）：哮喘是一种以反复发作的气道阻塞、气道高反应性和气道炎症为特征的疾病。哮喘有很强的遗传因素；哮喘和过敏家族史与婴儿患哮喘的风险和哮喘症状的持续存在密切相关。早期出现持续性哮喘的儿童也更有可能是特应性个体，他们在婴儿期出现湿疹，然后发展为出现特定食物不耐受的胃肠道症状，然后出现呼吸道症状。在特应性婴儿中，超过 50% 随后出现反复呼吸道症状和哮喘。特应性症状的这种进展被称为“过敏进行曲”，是遗传易感性和环境因素之间复杂相互作用的结果。皮肤、胃肠道和气道等多个靶器官中炎症过程的存在支持了特应性的全身性质。对于患有特应性皮炎的婴儿，过敏原致敏和外周血细胞Th2反应增强先于临床哮喘的发生；然而，我们目前还不知道特应性婴儿的气道何时成为具有炎症和高反应性（哮喘的表型特征）的靶器官。在小鼠中，表皮过敏原致敏会导致特应性皮炎以及气道反应性升高。这一发现表明，特应性皮炎不仅可能先于哮喘发生，而且还可能促进其发展。如果这种情况也发生在人类身上，那么对婴儿特应性皮炎进行更积极的治疗可能会最大限度地减少哮喘的发生。我们对哮喘起源的了解是有限的。为了设计早期干预和预防该疾病的策略，确定气道何时成为靶器官以及特应性婴儿在生命早期是否具有哮喘气道的表型特征至关重要。具体目标#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。将测量患有特应性皮炎的婴儿和健康对照组的气道反应性和呼出一氧化氮动力学。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。 具体目标#2：评估哮喘气道表型特征的存在是否可以识别 5 岁时出现临床哮喘的婴儿和幼儿。