Genetic And Environmental Factors In Childhood Respirato

长期以来，哮喘一直被认为是家族性的。最近，进行了连锁研究，以确定涉及的特定基因。然而，随着多个联系区域的确定，这项工作进展缓慢。很明显，基因-环境的相互作用在决定谁会患哮喘方面很重要。到目前为止，进行的联系研究还没有被设计成适当地探索相互作用。鉴于哮喘的复杂性质，显然有必要进行候选基因关联研究，以确定疾病基因及其与环境因素的相互作用。 长期以来，空气污染在哮喘恶化中的作用一直受到重视。臭氧是一种氧化性空气污染物，是会加重现有哮喘的因素之一。最近的数据表明，臭氧和其他空气污染物可能在哮喘病因中发挥作用，但数据很少。最近在动物身上进行的关联研究开始确定与臭氧和其他吸入污染物的特定生理反应有关的基因。 该项目包括几项研究，包括遗传多态、环境因素及其相互作用在儿童呼吸系统疾病病因学中的作用。主要项目是对墨西哥城臭氧暴露程度较高的人群进行哮喘遗传易感性的家庭研究。本研究采用个案-父母三合会设计。虽然学科招生仍在进行中，但我们已经开始发表这项研究的手稿。 另一项成分研究是对武汉市中学生呼吸道疾病危险因素的横断面调查，中国。在过去的一年里，我们发现，与西方人口中的一些报告相反，早年在家中接触动物的儿童患哮喘的风险并没有降低。然而，在武汉这一人群中，暴露在内毒素和其他细菌产品中的比例很高，这种暴露并不具有保护性。 在另一项研究中，我正在与泽尔丁博士、北卡罗来纳大学的调查人员以及当地一家名为Advanced Energy的公司的工程师合作，对他们将于2004财年开始的一项研究进行补充。我的补充将描述安装了降低湿度水平的功能的新住宅、按照现有建筑规范建造的新住宅以及主体正在搬出的旧住宅中暴露在空气中的霉菌的特征。这项工作将提供重要的先导数据，证明北卡罗来纳州早期接触真菌对健康影响的新研究是合理的。 我还在继续开发墨西哥城呼吸系统疾病早期生命因素的研究，并正在进行规划工作，将这项研究扩展到当地人口。这项工作是2003财年(ES 44010)的一个单独的ZO1项目。为了简单起见，我将那个项目折叠到这个项目中。

Asthma has long been known to run in families. More recently, linkage studies have been conducted to identify specific genes involved. However, this work has gone slowly with multiple regions of linkage being identified. It is clear that gene-environment interactions are important in determining who develops asthma. Linkage studies conducted to date have not been designed to properly explore interactions. Given the complex nature of asthma, it is clear that candidate gene association studies will be necessary to identify disease genes and interactions with environmental factors. The role of air pollution in asthma exacerbation has long been appreciated. Ozone, an oxidant air pollutant, is one of the agents that can worsen existing asthma. Recent data suggest that ozone and other air pollutants may play a role in asthma etiology, but there are few data. Recent linkage studies in animals are beginning to identify genes that are involved in specific physiologic responses to ozone and other inhaled pollutants. This project includes several studies the role of genetic polymorphisms, environmental factors and their interaction in the etiology of childhood respiratory disease. The primary project is a family study of genetic susceptibility to asthma in a highly ozone exposed population, Mexico City. This study uses the case-parent triad design. Although subject enrollment is still ongoing, we are starting to publish manuscripts from this study. Another component study is a cross-sectional examination of risk factors for respiratory disease among middle school students in Wuhan, China. In the past year, we have found that children with early life exposure to animals in the home are not at reduced risk of asthma, contrary to some reports in Western populations. However, in this Wuhan population, in which exposure to endotoxin and other bacterial products is high from other sources, this exposure is not protective. In another study, I am collaborating with Dr. Zeldin, investigators at UNC and engineers at a local company, Advanced Energy, to add onto a study that they will be beginning in FY2004. My addition will characterize airborne mold exposure in new homes fitted with features to reduce moisture levels and new homes built to existing building codes as well as older homes that subjects are moving out of. This work will provide important pilot data to justify a new study of health effects of fungal exposure in early life in North Carolina. I am also continuing development work on studies of early life factors in respiratory disease in Mexico City and am doing planning work to extend this study to local populations. This work was a separate ZO1 project in FY2003 (ES 44010). I am folding that project into this one for simplicity.