Airway as Target Organ in Infants with Atopic Dermatitis

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。哮喘有很强的遗传成分；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。早发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%的婴儿随后出现反复的呼吸道症状和哮喘。这种特应性症状的进展被称为“过敏行军”，是遗传易感性和环境因素之间复杂相互作用的结果。炎症过程在多个目标器官如皮肤、胃肠道和气道的存在支持了特应性的全身性。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，我们目前尚不清楚过敏性婴儿的气道何时成为具有炎症和高反应性的靶器官，这是哮喘的表型特征。在小鼠中，表皮过敏原致敏产生特应性皮炎，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，而且可能促进哮喘的发展。如果这也发生在人类身上，那么对婴儿特应性皮炎进行更积极的治疗可能会将哮喘的发展降到最低。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。气道反应性和呼出一氧化氮动力学将测量婴儿特应性皮炎和健康对照。使用这些婴儿培养的鼻气道上皮细胞，我们还将评估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能识别5岁前出现临床哮喘的婴幼儿。

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.