MATERNAL INFLUENCES ON CHILDHOOD ASTHMA

该项目旨在研究产妇 妊娠期过敏状态和婴儿免疫特征， 在生命早期，与随后的标记物发展有关 儿童哮喘的风险。该项目的具体目标是：（1） 研究过敏母亲可能增加 发生哮喘相关过敏倾向的可能性 2）在他们的孩子中; 2）描述以下免疫反应 病毒性下呼吸道疾病（LRI）与过敏性 （3）确定婴儿的关系; 婴儿出生时过敏体质与LRIs免疫应答 哮喘风险的免疫系统标志物的后续发展。 本申请假设T辅助细胞（Th2）偏斜（如 由刺激的IL-4和IL-5的产生升高指示 外周血单核细胞（PBMC）将至少通过 3岁以下儿童：a）母亲患有活动性过敏症 妊娠期鼻炎或Th2细胞因子谱; B）具有Th2谱 在生命早期并发展为喘息性LRI;或c）发展为早期 致敏的霉菌链格孢。 该项目将招收四名 100名妇女，其中一半患有医生诊断的过敏性鼻炎， 怀孕的第三个三个月，并跟踪他们的婴儿从出生到 生命的前五年。 审议的主要成果将 是免疫系统功能的指标（来自有丝分裂原的细胞因子谱， 刺激的PBMC、总血清IgE水平、过敏原特异性IgE水平， 皮肤试验反应性）在儿童出生时，一年，三年 还有五年 类似的免疫系统功能测试将在 在母亲和父亲身上进行，并获得关于 呼吸道症状 血液将在第一次 医生诊断的LRI，以评估细胞因子反应。血清学， 呼吸道合胞病毒（RSV）将在12个月时获得， 年龄 免疫系统标志物对免疫缺陷风险的综合评估 哮喘将在五岁时进行。这是他项目的目的 提供免疫学根源的知识， 儿童哮喘，从这些个体中可以识别出谁 干预可能是至关重要的;此外， 信息将有助于制定有效和具体的 哮喘的一级预防策略。

This project is designed to investigate the mechanisms whereby maternal allergic status during pregnancy and infant immune characteristics, early in life, are associated with the subsequent development of markers of asthma risk in children. The Specific Aims of the project are 1) to investigate mechanisms by which allergic mothers may increase the likelihood of development of an asthma-related allergic predisposition in their children; 2) to characterize the immunologic response following viral lower respiratory tract illnesses (LRIs) in relation to allergic predisposition of the infant; and 3) to determine the relation of the infant's allergic predisposition at birth and immune response with LRIs to the subsequent development of immune system markers of asthma risk. The application hypothesize that a T helper cell (Th2) skew (as indicated by elevated production of IL-4 and IL-5 from stimulated peripheral blood mononuclear cells PBMCs) will be observed at least by age three years in children who: a) have mothers with active allergic rhinitis or Th2 cytokine profiles in pregnancy; b) have Th2 profiles early in life and develop wheezing LRIs; or c) develop early sensitization to the mold Alternaria. The project will enroll four hundred women, half with physician-diagnosed allergic rhinitis, in the third trimester of pregnancy and follow their infants from birth through the first five years of life. The principal outcomes considered will be indicators of immune system function (cytokine profiles from mitogen- stimulated PBMCs, total serum IgE levels, allergen-specific IgE levels, skin test reactivity) in the children at birth, one year, three years and five years. Similar tests of immune system function will be conducted on both the mother and father, and data obtained regarding respiratory symptoms. Blood will be obtained at the time of the first physician-diagnosed LRI, to assess the cytokine response. Serologies to respiratory syncytial virus (RSV) will be obtained at twelve months of age. A comprehensive evaluation of immune system markers for risk of asthma will be conducted at age five. It is the intent of his project to provide knowledge of the immunological roots for the development of asthma in childhood, from which individuals might be identified for whom intervention might be critical; furthermore, it is intended that this information will assist in the development of effective and specific strategies for primary prevention of asthma.