Arsenic and child respiratory health in Bangladesh

描述（由申请人提供）：肺是摄入饮用水中无机砷的长期健康影响的一个令人惊讶的重要目标，但儿童期暴露的影响在很大程度上是未知的。儿童可能特别容易受到影响，因为肺部的发育一直持续到儿童时期。在智利，我们发现，儿童时期接触饮用水中砷的人，成年后患肺癌和慢性呼吸道疾病的风险增加了10倍。在印度的西孟加拉，我们发现患有砷引起的皮肤损伤和高砷饮用水暴露的成年人肺功能受损，慢性呼吸道疾病的发病率增加。然而，迄今为止，砷摄入对肺功能和呼吸系统健康的影响尚未在儿童中进行过研究。我们在孟加拉国的合作者已经检查了167，000人的皮肤病变，并测量了他们饮用水中的砷浓度。我们计划研究300名6-16岁的儿童，他们生活在管井水砷浓度大多超过300 μ g/L的家庭中，其中至少有一名家庭成员发生了与砷有关的皮肤病变。将从没有皮肤损伤的家庭中选出300名儿童作为未接触的对照组，这些儿童的饮水中含有低于50微克/升的汞。肺功能和呼吸道症状，包括慢性咳嗽和呼吸急促，将评估与整个儿童期所有饮用水来源（包括子宫内暴露）中当前和过去砷浓度的关系。将研究与室内空气污染、饮食和营养状况相关的潜在易感性和相互作用。还将评估由于儿童将砷代谢为尿样中鉴定的高毒性甲基化化合物的程度的个体差异而导致的易感性差异。这些暴露和未暴露家庭的儿童提供了一个独特的机会，以确定在肺生长和发育的关键时期砷暴露的影响。鉴于全世界大量儿童暴露于饮用水中的砷，以及这些结果与未来人口发病率和死亡率的相关性，生命早期砷暴露造成的不良呼吸影响可能对公共卫生产生重大影响。

DESCRIPTION (provided by applicant): The lung is a surprisingly important target for the long term health effects of ingestion of inorganic arsenic in drinking water, but the impact of exposure during childhood is largely unknown. Children are likely to be especially susceptible since the development of the lung continues into childhood. In Chile, we have found that people who were exposed to arsenic in drinking water as children have 10-fold increased risks of lung cancer and chronic respiratory disease mortality when they become adults. In West Bengal, India we have found that adults with arsenic-caused skin lesions and high arsenic drinking water exposures have impaired lung function and increased rates of chronic respiratory disease. To date however, the impact of arsenic ingestion on lung function and respiratory health has not so far been studied in children. This application takes advantage of the fact that our collaborators in Bangladesh have examined 167,000 people for skin lesions and measured the arsenic concentrations in their drinking water. We plan to study 300 children aged 6-16 years living in the families having tube well water arsenic concentration mostly over 300 ug/L, and in which at least one member of the family has developed arsenic-related skin lesions. An unexposed comparison group of 300 children will be selected from families with no skin lesions, and whose water contains less than 50 ug/L. Lung function and respiratory symptoms, including chronic cough and shortness of breath, will be assessed in relation to current and past arsenic concentrations in all sources of drinking water throughout childhood, including in utero exposure. Potential susceptibility and interactions associated with indoor air pollution, diet, and nutritional status, will be investigated. Differences in susceptibility due to individual variability in the degree to which children metabolize arsenic to highly toxic methylated compounds identified in urine samples will also be assessed. The children in these exposed and unexposed families provide a unique opportunity to identify the effects of arsenic exposure during critical time periods of lung growth and development. The public health impact of adverse respiratory effects due to arsenic exposure in early life could be substantial given the large number of children exposed to arsenic in drinking water worldwide and the relevance of these outcomes for future population morbidity and mortality.