Prenatal Low Level Tobacco & Phthalate Exposure & Childhood Respiratory Health

描述(由申请人提供) 哮喘和呼吸道感染是儿童健康的主要负担。产前烟草暴露是幼儿喘息的一个关键危险因素，但关于产前低水平烟草暴露(如不吸烟的孕妇被动暴露)与儿童喘息或呼吸道感染风险的关系的数据很少。有新的、但有限的证据表明，邻苯二甲酸盐等新的环境风险因素会导致喘息。生物标记物的进步提供了直接量化内部剂量指标的能力，减少了暴露的错误分类，并增强了我们将暴露与疾病联系起来的能力。这项K23提案的主要目标是使用暴露的一系列生物标志物，严格描述常见环境暴露与儿童早期喘息和呼吸道感染风险的关系。具体目的是：1)测试产前吸烟暴露的哪一项指标(不同的生物标记物，家长报告)与出生前三年的喘息、呼吸道感染和肺部炎症(呼出的一氧化氮的部分，FeNO)风险最密切相关；2)调查怀孕期间母亲低水平被动烟草暴露与出生前三年喘息、呼吸道感染和肺部炎症(FeNO)风险的关系；以及3)调查产前邻苯二甲酸酯暴露与出生前三年喘息、呼吸道感染和肺部炎症的风险的关系。这一建议是新颖的，因为它使用了一系列生物标记物来客观地衡量个人在怀孕和儿童早期的暴露负担和低水平的暴露。此外，我们将首次使用生物标记物探索产前邻苯二甲酸盐暴露与儿童喘息、呼吸道感染和肺部炎症风险的作用。通过这个K23，申请人将发展儿科环境流行病学方面的专业知识，使他能够帮助拓宽儿童环境毒理学和呼吸道流行病学的模型。它还将提供在临床儿科发展独立研究事业所需的背景和培训，并加强我们对环境风险因素如何影响儿童哮喘和呼吸系统疾病的发展和恶化的了解，并将这些知识纳入预防和治疗工作。

DESCRIPTION (provided by applicant) Asthma and respiratory infection pose major burdens to child health. Prenatal tobacco exposure is a key risk factor for wheeze in young children, but there is little data about the relationship of prenatal low level exposures to tobacco (e.g. passive exposure of nonsmoking pregnant women) with risk of childhood wheeze or respiratory infection. There is emerging, yet limited evidence for novel environmental risk factors for wheeze such as phthalates. Advances in biomarkers offer an ability to quantify indicators of internal dose directly, reduce exposure misclassification, and enhance our ability to link exposures with disease. The primary objective for this K23 proposal is to rigorously characterize the relationship of common environmental exposures with risk of wheeze and respiratory infection in early childhood using serial biomarkers of exposure. The specific aims are to: 1) Test which measure of prenatal tobacco smoke exposure (different biomarkers, parent-report) is most strongly associated with risk of wheeze, respiratory infection, and pulmonary inflammation (fraction of exhaled nitric oxide, FeNO) in the first three years of life; 2) Investigate the association of low levels of maternal passive tobacco smoke exposure during pregnancy with risk of wheeze, respiratory infection, and pulmonary inflammation (FeNO) in children of nonsmoking mothers in the first three years of life; and 3) Investigate the association of prenatal phthalate exposure with risk of wheeze, respiratory infection, and pulmonary inflammation in the first three years of life. This proposal is novel because it uses serial biomarkers to measure individual exposure burden and low levels of exposure objectively throughout pregnancy and early childhood. Additionally, we will be the first to explore the role of prenatal phthalate exposure with the risk of childhood wheeze, respiratory infection, and pulmonary inflammation using biomarkers. Through this K23, the applicant will develop expertise in pediatric environmental epidemiology to position him to help broaden the model of environmental toxicology and respiratory epidemiology in children. It will also provide the background and training needed to develop an independent research career in clinical pediatrics and enhance our understanding of how environmental risk factors affect the development and exacerbation of pediatric asthma and respiratory disease and integrate this knowledge into prevention and treatment efforts.