The Effect of Phthalates on COPD Morbidity

项目摘要 慢性阻塞性肺疾病(COPD)是美国第四大死因 也是导致相当大的发病率和医疗保健利用率的原因。尽管烟草烟雾暴露是一项关键风险 慢性阻塞性肺病的因素，越来越多地关注环境对发展的贡献者和 慢性阻塞性肺疾病的严重性。在常见的环境暴露中，被称为邻苯二甲酸酯的化合物正在增长 由于它们可能对内分泌和呼吸健康产生不利影响，因此令人担忧。邻苯二甲酸酯是合成的 塑料和许多消费品中使用的工业化学品，成年人中普遍存在接触 在美国。邻苯二甲酸酯中分布最广的是邻苯二甲酸二乙基己酯(DEHP)，它是一种 广泛使用的塑料。接触邻苯二甲酸盐，包括DEHP，与呼吸道疾病有关，通过 氧化应激和增强过敏反应的机制。增加对DEHP和其他 在健康的非老年人中，邻苯二甲酸盐与肺功能的轻微但显著的下降有关 吸烟者，与对氧化应激遗传易感性增加的个人的关联性最强。 这种氧化应激本身会加重呼吸道阻塞，并加强污染物暴露的影响。 然而，邻苯二甲酸盐暴露是否与COPD患者的不良预后相关仍然存在。 未知。我们假设接触DEHP与个体的呼吸道发病率有关。 患有慢性阻塞性肺病。我们有初步数据显示邻苯二甲酸盐暴露与横截面相关 正在进行的COPD研究的一个子集的呼吸系统发病率；然而，因果关系不能与 这一数据和邻苯二甲酸酯暴露的人内可变性需要进行纵向评估研究。 曝光率。此外，接触来源及其与慢性阻塞性肺病的相关性尚不清楚，但对于更好地 设计潜在的修改策略。这项提议有两个新颖的目标。首先，确定关联 1a)个人和1b)个人累积邻苯二甲酸盐暴露对个人呼吸结局的影响 对于慢性阻塞性肺疾病，我们将在后续的研究访问中重复测量尿邻苯二甲酸盐浓度。 同时对几种呼吸结果进行评估。第二，评估邻苯二甲酸盐的决定因素 低收入慢性阻塞性肺病患者的暴露，以确定可改变的因素并告知未来 减少暴露的干预措施，我们将进行家庭检查和管理饮食调查，个人 在我们的研究中，护理产品的使用和医疗设备的使用来确定邻苯二甲酸盐的暴露来源 人口。这项研究的结果将为化学暴露(DEHP)的作用提供挑衅性的证据 以前与慢性阻塞性肺病没有联系，关于接触来源的信息可以被用来制定缓解措施 改善慢性阻塞性肺病预后的战略。

Project Summary Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in the United States and a cause of substantial morbidity and healthcare utilization. Although tobacco smoke exposure is a key risk factor for COPD, increasing attention has been paid to environmental contributors to the development and severity of COPD. Among common environmental exposures, compounds known as phthalates are of growing concern due to their possible adverse effects on endocrine and respiratory health. Phthalates are synthetic industrial chemicals used in plastics and numerous consumer products, with ubiquitous exposure among adults in the United States. Among the most widespread phthalates is Di-2-ethylhexyl phthalate (DEHP), a component of widely used plastics. Exposure to phthalates, including DEHP, has been linked with airway disease through mechanisms of oxidative stress and enhanced allergy responses. Increased exposure to DEHP and other phthalates has been associated with small but significant decreases in lung function among healthy non- smokers, with the strongest association in individuals with increased genetic susceptibility to oxidative stress. This oxidative stress can itself worsen airway obstruction as well as potentiate the effect of pollutant exposure. However, whether phthalate exposure is associated with poor outcomes in patients with COPD remains unknown. We hypothesize that exposure to DEHP is associated with respiratory morbidity among individuals with COPD. We have preliminary data showing a cross-sectional association with phthalate exposure and respiratory morbidity from a subset of an ongoing COPD study; however, causality cannot be established with this data, and intra-person variability in exposure to phthalates necessitates studies with longitudinal assessment of exposure. Further, sources of exposure and their relevance to COPD are unknown but are important to better design potential modification strategies. This proposal has two novel aims. First, to determine the association between 1a) individual and 1b) cumulative phthalate exposure on respiratory outcomes in individuals with COPD, we will conduct repeat measurement of urinary phthalate concentrations at a follow-up study visit paired with assessment of several respiratory outcomes. Second, to assess determinants of phthalate exposure among low-income individuals with COPD in order to identify modifiable factors and inform future exposure mitigation interventions, we will conduct home inspections and administer surveys of diet, personal care product use, and medical equipment use to determine the sources of exposure to phthalates in our study population. Results from this study will provide provocative evidence of the role of a chemical exposure (DEHP) not previously linked to COPD, and information on sources of exposure can be leveraged to develop mitigation strategies to improve COPD outcomes.