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

描述（由申请人提供）：据估计，美国有2000万人的饮用水中砷含量接近或高于现行监管标准。发育中的肺部可能特别容易受到包括砷在内的环境毒物的影响。先前在智利北部进行的研究表明，儿童或子宫内接触水中砷的人患肺癌的相对风险是成年接触者的3-4倍。几项研究也将水中的砷与非恶性肺病的极高风险联系起来，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。我们建议对来自智利北部的受试者进行肺功能（通过肺活量测定法测量）和呼吸健康的横断面研究，这些受试者在幼年或子宫内暴露于高砷水平，现在已成年。我们将招募300名安托法加斯塔市的终身居民，该城市在1958年至1970年的市政供水中砷浓度非常高。这些受试者的肺功能和呼吸系统症状的患病率将与非洲300名年龄和性别匹配的终身居民进行比较，非洲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随机选择，该登记处包含智利94%的人口。尿液样本将用于未来易感性和早期影响的生物标志物研究。在智利北部进行这项研究的优势在于，该地区非常干燥，几乎每个人都生活在为数不多的大城市中，从为数不多的几个大型市政供水系统中取水。因为我们有过去50年所有这些来源的砷记录，所以一生接触砷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，安托法加斯塔出现了一段明显的高暴露期，前后暴露量都很低，这造成了大量（约25万人）在子宫内或幼儿时期就受到高度暴露，但成年后却没有。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，具有明显的高暴露期，人口众多，早年高暴露但成年后不高暴露，以及过去暴露的准确数据，这在环境流行病学中是没有先例的。这个项目的科学重要性在于，在人体肺部发育的关键时期，很少有关于环境暴露对终生影响的信息。在公共卫生方面的重要性在于，需要将关于生命早期接触影响的信息纳入环境法规，并有助于评估是否需要采取更严格的公共卫生措施，以查明和防止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

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.