In utero and childhood exposure to arsenic in water and lifelong lung disease

描述（由申请人提供）：美国估计有2000万人暴露于接近或高于现行监管标准的饮用水中的砷水平。发育中的肺可能特别容易受到包括砷在内的环境毒物的影响。以前在智利北方的研究表明，儿童时期或子宫内接触砷的人患肺癌的相对风险比成年人高3-4倍。有几项研究也将水中的砷与非恶性肺病的高风险联系起来，但这些研究没有评估在肺部发育的关键时期接触砷可能产生的长期或永久性影响。我们提出了一个横断面研究的肺功能（肺量计测量）和呼吸系统健康的科目从北方智利谁暴露于高砷水平的幼儿或在子宫内，现在是成年人。我们将招募安托法加斯塔市的300名终身居民，该城市在1958年至1970年期间的市政供水中砷浓度非常高。将这些受试者的肺功能和呼吸道症状患病率的测量结果与300名年龄和性别匹配的阿里卡终身居民进行比较，阿里卡是一个邻近的社会人口统计学相似的城市，没有高砷水平的历史。所有受试者将从智利选举登记处（包含94%的智利人口）中随机选择。将采集尿液样本用于未来的敏感性和早期效应生物标志物研究。在智利北方进行这项研究的好处是，这一地区非常干燥，几乎每个人都住在少数几个大城市中，并从少数几个大型市政供水系统中获得水。因为我们有过去50年所有这些来源的砷记录，所以关于终生暴露的信息比世界上任何其他地方都要准确得多。此外，大约40年前安托法加斯塔发生了一个明显的高暴露时期，前后暴露量都很低，造成了大量人口（约250，000人）在子宫内或幼儿时期就受到高暴露，但成年后则没有。现在研究这些人的健康影响将使我们能够调查他们早期生活暴露的长期影响。像这样的情况，其独特的高暴露期，人口众多，早期生活中的高暴露，而不是成年期，以及过去暴露的准确数据，在环境流行病学中没有先例。这一项目的科学重要性在于，关于在肺部发育的关键时期发生的环境暴露的终身影响，人类几乎没有任何信息。公共卫生的重要性在于需要将关于生命早期接触影响的信息纳入环境法规，并帮助评估是否需要采取更严格的公共卫生措施，以确定和预防儿童和孕妇接触有毒物质。公共卫生相关性：饮用水中的砷暴露 是一种在世界范围内广泛存在的健康危害。这项研究将有助于揭示有关儿童暴露于砷对健康的长期影响的重要新信息。它还将有助于确定其他因素，如饮食或烟草烟雾暴露是否会与砷相互作用，导致长期肺部疾病。

DESCRIPTION (provided by applicant): An estimated 20 million people in the US are exposed to levels of arsenic in their drinking water near or above the current regulatory standard. The developing lung may be particularly susceptible to environmental toxicants including arsenic. Previous studies from northern Chile suggest that people exposed to arsenic in water as young children or in utero have relative risks of lung cancer that are 3-4 times higher than those exposed as adults. Several studies have also linked arsenic in water to very high risks of non-malignant lung disease, but these have not assessed the possible long-lasting or permanent effects of exposure during the critical periods of lung development. We propose a cross-sectional study of pulmonary function (measured by spirometry) and respiratory health in subjects from northern Chile who were exposed to high arsenic levels as young children or in utero and who are now adults. We will recruit 300 lifelong residents of the city of Antofagasta which had very high arsenic concentrations in municipal water supplies from 1958 to 1970. Measures of pulmonary function and prevalence of respiratory symptoms in these subjects will be compared to 300 age- and gender-matched lifelong residents of Arica, a neighboring sociodemographically similar city with no history of high arsenic levels. All subjects will be randomly selected from the Chile Electoral Registry which contains 94% of the Chilean population. Urine samples will be collected for future biomarker studies of susceptibility and early effects. The advantage of doing this study in northern Chile is that this area is incredibly dry and almost everyone lives in one the few large cities and obtains water from one of a few large municipal water supplies. Because we have arsenic records for all these sources for the last 50 years, information on lifetime exposure can be much more accurate than anywhere else in the world. Also, a distinct period of high exposure occurring in Antofagasta about 40 years ago, with low exposure before and after, has created a large population (about 250,000) who were highly exposed in utero or as young children but not as adults. Studying health effects in these people now will allow us to investigate the long-term impacts of their early life exposure. A scenario like this, with its distinct period of high exposure, large population, high exposure in early life but not in adulthood, and accurate data on past exposure, is without precedent in environmental epidemiology. The scientific importance of this project lies in the fact that little information is available in humans on the lifelong effects of environmental exposures that occur during critical periods of lung development. The public health importance lies in the need to incorporate information on early life exposure effects into environmental regulation, and in helping to assess whether more rigorous public health measures are needed to identify and prevent toxic exposures in children and pregnant women. PUBLIC HEALTH RELEVANCE: Arsenic exposure from drinking water is a widespread health hazard throughout the world. This study will help reveal important new information concerning the long term health impact of childhood exposure to arsenic. It will also help determine whether other factors such as diet or tobacco smoke exposure can interact with arsenic to cause long term lung disease.