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

在子宫内和儿童时期接触水中的砷会导致终生肺部疾病

• 批准号: 8118290
• 负责人: Craig M Steinmaus
• 金额: $ 41.14万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8118290
• 关键词: Adult; Age; Animals; Area; Arsenic; Biological Markers; Chemicals; Child; Childhood; Chile; Cities; Cross-Sectional Studies; Data; Defensins; Diet; Disease; Disease susceptibility; Environmental Epidemiology; Environmental Exposure; Exposure to; Future; Gender; Health; Health Hazards; Human; Individual Differences; Investigation; Laboratory Animals; Laws; Lead; Life; Link; Long-Term Effects; Longitudinal Studies; Lung; Lung diseases; Malignant neoplasm of lung; Measures; Metabolic; Metabolism; Non-Malignant; Peptides; Population; Predisposition; Pregnant Women; Prevalence; Proteomics; Public Health; Recording of previous events; Records; Recruitment Activity; Registries; Regulation; Relative Risks; Reporting; Research; Respiratory physiology; Risk; Sampling; Smoking; Source; Spirometry; Symptoms; Time; Tobacco smoke; Toxic Environmental Substances; Toxicant exposure; United States Environmental Protection Agency; Urine; Water; Water Supply; critical period; design; drinking water; early life exposure; environmental agent; epidemiology study; high risk; human data; in utero; lung development; prevent; pulmonary function; respiratory

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.

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砷等环境毒物的影响。此前来自智利北部的研究表明，儿童时期或在子宫内接触水中砷的人患肺癌的相对风险比成年人高 3-4 倍。一些研究也将水中的砷与非恶性肺部疾病的极高风险联系起来，但这些研究并未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影响。我们建议对来自智利北部的受试者进行一项肺功能（通过肺活量测定法测量）和呼吸系统健康的横断面研究，这些受试者在幼儿期或在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，该市从 1958 年到 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道症状患病率的测量结果将与 300 名年龄和性别匹配的终身居民进行比较阿里卡的居民是一个社会人口相似的邻近城市，没有高砷含量的历史。所有受试者将从智利选举登记处随机选出，该登记处包含智利人口的 94%。将收集尿液样本用于未来的敏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点是，该地区非常干燥，几乎每个人都生活在少数几个大城市之一，并从几个大型市政供水系统之一获取水。由于我们拥有过去 50 年所有这些来源的砷记录，因此有关终生接触砷的信息可能比世界其他任何地方都要准确得多。此外，大约 40 年前，安托法加斯塔发生了一段明显的高暴露时期，之前和之后的暴露水平较低，导致大量人口（约 250,000 人）在子宫内或幼儿时期受到高暴露，但成年后却没有受到高暴露。现在研究这些人的健康影响将使我们能够调查他们早年接触这些物质的长期影响。像这样的场景，具有明显的高暴露时期、大量人口、早年高暴露而不是成年期高暴露、以及过去暴露数据的准确数据，在环境流行病学中是没有先例的。该项目的科学重要性在于，关于人类肺部发育关键时期发生的环境暴露对终生影响的信息很少。公共卫生的重要性在于需要将生命早期暴露影响的信息纳入环境监管，并帮助评估是否需要采取更严格的公共卫生措施来识别和预防儿童和孕妇的有毒物质暴露。公共卫生相关性：饮用水中的砷暴露 是全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接触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（例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。