Genetic And Environmental Factors In Childhood Respirato

我们开发了一种方便和廉价的方法，收集颊细胞作为学龄儿童研究的DNA来源。该方法产生大量高质量的DNA。我们在中国武汉和南加州的研究中使用了这种方法。我们在去年发表了一篇关于这种方法的论文。 在武汉的研究中，我们发现生活在燃煤做饭或取暖的家庭中的儿童喘息的患病率增加。与吸烟者生活在一起的儿童咳嗽和产生痰的风险增加。这一中国人群对于研究环境烟草烟雾对健康的影响特别感兴趣，因为吸烟的母亲很少。大部分的接触来自吸烟的父亲。我们还发现，在这项研究中，霉菌暴露是哮喘、咳嗽和痰的最强危险因素。 我们还开始与Darryl Zeldin博士合作，在国家过敏原调查中研究Alternaria暴露的决定因素以及Alternaria水平与哮喘之间的关系，这是NIEHS对家庭过敏原的研究。这项工作是论文工作的一部分，沿着武汉的研究，为一个新的环境健康科学研究，Paivi萨洛，NIEHS博士前IRTA。 该项目的目的是研究影响儿童呼吸道疾病风险的遗传和环境因素，并评估基因-环境相互作用。为此，我们对来自三个不同哮喘患病率人群的学龄儿童进行了一组三项国际研究：中国武汉（低）、墨西哥城（中等）和美国南加州（高）。这三个地点提供了一系列可能与遗传易感性相互作用的环境因素。这些因素包括臭氧、内毒素和环境烟草烟雾。中国武汉人群的显著暴露是室内燃煤、环境烟草烟雾的高流行率和环境空气污染。墨西哥城工厂是北美臭氧水平最高的工厂，内毒素水平也很高。南加州的研究提供了一系列暴露于空气污染的良好特征。 本项目中的三项研究在学龄儿童中进行，设计略有不同。武汉的这项研究是一项以学校为基础的研究，研究对象是1999年入学的22所学校的5,051名七年级学生。我们收集了环境暴露和呼吸结果数据、肺功能和口腔细胞DNA。目前，我们正在跟踪学生的第三年。 墨西哥城的研究采用了案例-父母三元组设计。我们在市中心的一家医院招募了7 - 17岁的哮喘儿童，他们的父母作为对照。病例-父母三联体设计使得能够检查候选基因协会的偏见，由于种族分层，一个潜在的问题，在两个人口混合的墨西哥城。病例-父母三联体设计还允许辨别胎儿与母体的遗传效应。墨西哥城的人口经历了北美最高的臭氧水平。环境内毒素也升高。我们正在根据人类和动物的证据，研究与臭氧呼吸反应有关的候选基因。 南加州的研究是一项以学校为基础的空气污染队列研究，我在来NIEHS之前帮助建立了这项研究。从1998年春天开始，我开始收集这群人的遗传物质，以检查哮喘和肺功能受损的候选基因。该系列非常成功，已纳入NIEHS/EPA儿童中心赠款，现在获得了壁外资助。 在南加州的研究中，我们今年的主要发现是，户外运动水平最高的儿童如果生活在高臭氧社区，患哮喘的风险会增加。这是第一个前瞻性研究表明，臭氧暴露可能是哮喘的危险因素之一。我们还发现臭氧暴露与更高水平的缺课有关。在另一种类型的分析中，我们发现，从PM10较低的社区搬迁到PM10较高的社区的儿童肺功能增长下降。这些研究有助于确定空气污染对成长中的儿童的不利影响。 我们已经建立了一个有效和高效的方法来收集大量的高质量的遗传材料的儿童在学校为基础的研究。这篇发表的文章对计划进行类似研究的研究人员应该是有用的。 我们正在继续在墨西哥城进行的哮喘病例-父母队列研究中招募受试者。到目前为止，我们已经登记了超过250个完整的三合会。DNA提取完成这些样本，我们已经检查了样本的基因多态性，可能参与响应臭氧。我们选择的基因的基础上，从小鼠模型的臭氧效应，以及臭氧效应的机理研究的结果。基因包括IL-13、IL-6、IL-8、TNF-α、GSTP1、NQ01和髓过氧化物酶。我们正在继续进行受试者招募和遗传分析，并希望在2004财年早期完成数据收集。在对IL-13的初步分析中，发现两个连接的启动子变体的风险增加。结果是在基于这些多态性的功能效应预测的方向上。 在武汉的研究中，我们确定了中国青少年呼吸道疾病的几个危险因素-环境烟草烟雾，室内燃煤和暴露于霉菌。关于这一人群呼吸道疾病的危险因素的数据很少。这个群体很有趣，因为大部分的烟草烟雾暴露是通过父亲。很少有母亲吸烟。尽管如此，环境烟草烟雾对健康的影响是显而易见的。这一人群也值得关注，因为燃煤仍然是一种常见的暴露。

We developed a convenient and inexpensive method for the collection of buccal cells as a source of DNA in studies of school aged children. The method yields a large amount of high quality DNA. We used the method in our studies in Wuhan China and Southern California. We published a paper on this method in the past year. In the Wuhan study, we found that children living in homes were coal was burned for cooking or heating have an increased prevalence of wheezing. Children living with smokers are at increased risk of cough and phlegm production. This Chinese population is of special interest for the study of health effects of environmental tobacco smoke because there are very few mothers who smoke. Most of the exposure comes from smoking fathers. We have also found that mold exposure is the strongest risk factor in this study of wheezing, cough and phlegm. We are also beginning a collaboration with Dr. Darryl Zeldin to look at determinants of Alternaria exposure and the relation between Alternaria levels and asthma in the National Allergen Survey, an NIEHS study of home allergens. This work is part of the thesis work, along with the Wuhan study, for a UNC environmental health sciences study, Paivi Salo, an NIEHS predoctoral IRTA. The aim of this project is to examine genetic and environmental factors that influence the risk of childhood respiratory illnesses and to evaluate gene-environment interactions. To this end, we have assembled a set of three international studies of school aged children from populations with three different asthma prevalences: Wuhan China (low), Mexico City (intermediate) and Southern California, US (high). The three sites provide a range of exposures to environmental factors that are likely to interact with genetic susceptibility. These include ozone, endotoxin and environmental tobacco smoke. Notable exposures in the Wuhan China population are indoor coal burning, high prevalence of environmental tobacco smoke, and ambient air pollution. The Mexico City site is notable for the highest levels of ozone in North America and endotoxin levels are also high. The Southern California study offers a range of well characterized exposures to air pollution. The three studies in this project are conducted among school aged children with slightly different designs. The Wuhan study is a school-based study of 5,051 seventh graders at 22 schools enrolled in 1999. We collected environmental exposure and respiratory outcome data, pulmonary function and DNA from buccal cells. We are currently following the students for the third year. The Mexico City study uses the case-parent triad design. We are enrolling asthmatic children aged 7-17 at an inner city hospital along with their parents as controls. The case-parent triad design enables the examination of candidate gene associations from bias due to ethnic stratification, a potential problem in the two population mix of Mexico City. The case-parent triad design also allows the discernment of fetal versus maternal genetic effects. This Mexico City population experiences the highest ozone levels in North America. Ambient endotoxin is also elevated. We are examining candidate genes involved in respiratory responses to ozone, based on human and animal evidence. The Southern California study is a school-based air pollution cohort study that I helped establish before coming to NIEHS. Beginning in the spring of 1998, I initiated a collection of genetic material on the cohort to examine candidate genes for asthma and impaired growth of pulmonary function. This collection was so successful that it was incorporated into an NIEHS/EPA Children's Center grant and is now extramurally funded. In the Southern California study, out main finding this year was that children with the highest levels of outdoor exercise were at increased risk of developing asthma if they lived in high ozone communities. This is one of the first prospective studies to suggest that ozone exposure may be a risk factor for asthma. We also found ozone exposure was related to higher levels of school absence. In another type of analysis we found that children relocating from communities with lower PM10 to those with higher PM10 experienced decreased growth in lung function. Together these studies help to establish adverse effects of air pollution in growing children. We have established an effective and efficient means of collecting a large amount of high quality genetic material on children in school based studies. This published work should be useful to investigators planning similar studies. We are continuing subject enrollment in our case-parent traid study of asthma in Mexico City. To date, we have enrolled over 250 complete triads. DNA extraction is complete on these samples and we have examined samples for polymorphisms in genes that are plausibly involved in response to ozone. We have selected genes based on results from mouse models of ozone effects as well as mechanistic studies of ozone effects. Genes include IL-13, IL-6, IL-8, tnf-alpha, GSTP1, NQ01 and myeloperoxidase. We are continuing with subject enrollment and genetic analyses and hope to complete data collection by early FY 2004. In preliminary analyses on IL-13, an increased risk was seen for two linked promoter variants. The results are in the direction predicted based on functional effects of these polymorphisms. In the Wuhan study, we have identified several risk factors for respiratory illness among Chinese adolescents -- enviromental tobacco smoke, indoor coal burning and exposure to molds. There are few data on risk factors for respiratory illness in this population. The population is interesting because most of the environmnental tobacco smoke exposure is via the fathers. Few mothers smoke. Nonetheless, health effects of environmental tobacco smoke were clearly seen. This population is also of interest because coal burning remains a common exposure.