Arsenic Exposure, Impaired Respiratory Function, and Immunosuppression

 描述(申请人提供)：饮用水中的砷(As)是一个主要的公共健康问题，影响着全球超过2亿人。流行病学研究，包括我们自己的研究，已经证明AS与包括肺功能受损在内的非恶性呼吸道结果以及与肺部感染有关。虽然AS导致非恶性肺部疾病的生理机制仍然很大程度上尚不清楚，但来自动物研究的新证据表明，免疫系统紊乱是一种合理的作用模式。AS在导致呼吸功能障碍的免疫机制中的作用尚未在人类中得到评估。在这项研究中，我们建议通过测量630名在Heals队列中特征良好的成年人的肺功能和激活的T细胞功能，来检验长期接触饮用水对呼吸结果和相关免疫功能的影响。此外，我们还将探索免疫调节剂维生素D对同一人群肺功能的可能保护作用。通过设计，我们从我们的人群队列中仔细选择了以下三组人(每组210人)，根据他们在2000年基线和在3-10年内的三次随访中测量的水和尿砷水平。第1组包括基线以来持续暴露于低水AS(&lt；10微克/L)的受试者；第2组包括基线时暴露于高水位AS(&gt；50微克/L)的受试者，然后切换到低水位AS；以及第3组包括持续暴露于高水位AS的受试者。我们将比较第一组、第二组和第三组的研究结果(肺功能和T细胞功能)，并评估这些组的趋势。我们将把水、尿砷和尿砷作为AS暴露的标志物。我们还将构建一个累积砷指数(CAI)作为砷暴露的衡量标准。这项极具可行性和成本效益的研究结果将第一次提供重要的数据 时间，来自一项关于低到中等剂量砷暴露对肺部和免疫影响的前瞻性人群研究。

 DESCRIPTION (provided by applicant): Arsenic (As) from drinking water is a major public health problem affecting over 200 million people around the world. Epidemiologic research, including our own, has demonstrated associations of As with non- malignant respiratory outcomes including impaired lung function and also with pulmonary infections. While the physiological mechanisms by which As induces non-malignant lung diseases remain largely unknown, emerging evidence from animal studies suggests disruption of the immune system as a plausible mode of action. The role of As on immune mechanisms underlying respiratory dysfunction has not been evaluated in humans. In this study, we propose to examine effects of long term As exposure from drinking water on respiratory outcomes and related immune function by measuring pulmonary function tests and activated T-cell function in 630 well-characterized adults in the HEALS cohort. Additionally, we will explore a possible protective role of vitamin D, an immune modulator, on lung function in the same population. By design, we carefully selected the following three groups of individuals (210 in each) from our population cohort based on their water and urinary As levels measured at baseline in 2000 and at three follow- up visits over 3-10 years. Group 1 includes subjects consistently exposed to low water As (<10µg/L) since baseline; Group 2 includes subjects exposed to high levels of water As (>50µg/L) at baseline who then switched to low water As; and Group 3 includes subjects consistently exposed to high water As. We will compare the study outcomes (lung function and T-cell function) across groups 1, 2 and 3 and evaluate trends across these groups. We will consider water As, urinary As and urinary As metabolites as markers of As exposure. We will also construct a Cumulative Arsenic Index (CAI) as a measure of As exposure. Findings from this highly feasible and cost-efficient study will be able to provide important data, for the first time, from a prospective population-based study on pulmonary and immune effects of low-to-moderate doses of As exposure.