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: 7440227
• 负责人: Robert S. Tepper
• 金额: $ 33.07万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7440227
• 关键词: Acute; Adrenal Cortex Hormones; Adult; Age; Age-Years; Agonist; Air; Allergens; Allergic; Allergic rhinitis; Alveolar; Anti-Inflammatory Agents; Anti-inflammatory; Asthma; Atopic Dermatitis; Australia; B-Lymphocytes; Biopsy; Biopsy Specimen; Blood Cells; Breathing; Bronchial Provocation Tests; Bronchiolitis; Cells; Characteristics; Chemokine, Other; Child; Childhood; Clinical; Complex; Dependence; Development; Diffuse; Diffusion; Disease; Disease remission; Dose; Early Intervention; Eczema; Effectiveness; Environment; Environmental Risk Factor; Epithelial Cells; Exhalation; Exhibits; Extrinsic asthma; Family history of; Food; Functional Residual Capacity; Gastrointestinal tract structure; Genetic; Genetic Predisposition to Disease; Glucocorticoids; Growth; Histamine; Human; Hypersensitivity; IgE; Immune; Individual; Infant; Inflammation; Inflammatory; Inflammatory Response; Insulin; Interleukin-13; Interleukin-4; Interleukin-5; Intestines; Invasive; Irrigation; Kinetics; Laboratories; Life; Lung; Lung Inflammation; Lung Lavage Fluid; Macrophage Inflammatory Proteins; Measures; Modeling; Mononuclear; Mus; Nature; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; Nose; Organ; Patients; Peripheral; Peripheral Blood Mononuclear Cell; Population; Procedures; Process; Production; Rate; Recording of previous events; Recurrence; Relative (related person); Research Personnel; Risk; Risk Factors; Secondary to; Serum; Skin; Small Inducible Cytokine A18; Sputum; Steroids; Surface; Symptoms; T-Cell Activation; Testing; Time; Toddler; Transcriptional Activation; Up-Regulation; Wheezing; age group; airborne allergen; airway hyperresponsiveness; airway inflammation; airway obstruction; asthmatic airway; atopy; chemokine; cohort; cytokine; design; disorder prevention; early childhood; early onset; eosinophil; human CCL17 protein; infancy; insight; macrophage-derived chemokine; methacholine; peripheral blood; respiratory; response

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）：哮喘是一种以气道阻塞、气道高反应性和气道炎症反复发作为特征的疾病。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续性密切相关。患有早期持续性哮喘的儿童也更可能是特应性个体，他们在婴儿期发生湿疹，然后进展为具有特定食物不耐受的胃肠道症状，然后具有呼吸道症状。在特应性婴儿中，超过50%的婴儿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“过敏性进展”，其由遗传易感性和环境因素之间的复杂相互作用引起。在多个靶器官如皮肤、胃肠道和气道中存在炎症过程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的Th 2应答增强先于临床哮喘的发生;然而，我们目前不知道特应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，而且可能有助于其发展。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这种疾病的策略，关键是要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。具体目标#1：评估特应性皮炎婴儿是否表现出哮喘气道的表型特征。将在患有特应性皮炎的婴儿和健康对照组中测量气道反应性和呼出的一氧化氮动力学。使用培养的鼻气道上皮细胞从这些婴儿，我们也将评估生产的Th 2趋化因子的细胞与IL-4和IL-13刺激后。 具体目标2：评估哮喘气道表型特征的存在是否可识别5岁时发生临床哮喘的婴幼儿。

项目成果

Evaluation of airway reactivity and immune characteristics as risk factors for wheezing early in life.

• DOI: 10.1016/j.jaci.2010.06.028
• 发表时间: 2010-09
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Yao, Weiguo;Barbe-Tuana, Florencia M.;Llapur, Conrado J.;Jones, Marcus H.;Tiller, Christina;Kimmel, Risa;Kisling, Jeffrey;Nguyen, Evelyn T.;Nguyen, James;Yu, Zhangsheng;Kaplan, Mark H.;Tepper, Robert S.
• 通讯作者: Tepper, Robert S.

Altered cytokine production by dendritic cells from infants with atopic dermatitis.

患有特应性皮炎的婴儿的树突状细胞产生的细胞因子发生改变。

• DOI: 10.1016/j.clim.2010.09.001
• 发表时间: 2010
• 期刊: Clinical immunology (Orlando, Fla.)
• 作者: Yao,Weiguo;Chang,JiHoon;Sehra,Sarita;Travers,JeffreyB;Chang,Cheong-Hee;Tepper,RobertS;Kaplan,MarkH
• 通讯作者: Kaplan,MarkH