The Effect of Phthalates on COPD Morbidity

邻苯二甲酸盐对慢性阻塞性肺病发病率的影响

基本信息

批准号：
10066494
负责人：
Daniel Carpenter Belz
金额：
$ 7.82万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-07 至 2022-07-06
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10066494
关键词：
Accounting Address Adult Adverse effects Airway Disease Asthma Attention Baltimore Biology Biometry Cause of Death Chemical Exposure Chemicals Chronic Disease Chronic Obstructive Airway Disease Clinical Clinical Research Data Data Analyses Development Diet Diet Surveys Disease Outcome Dose Dyspnea Endocrine Enrollment Environment Environmental Exposure Environmental Health Epidemiology Equipment Etiology Evaluation Exposure to Follow-Up Studies Food Food Container Future Genetic Predisposition to Disease Health Home environment Individual Industrialization Inhalation Intervention Investigation Knowledge Link Low income Lung Measurement Medical Metabolism Modification Morbidity - disease rate Occupational Asthma Outcome Oxidative Stress Participant Patients Peat Persons Pharmaceutical Preparations Phenotype Plastics Pollution Polyvinyl Chloride Population Group Poverty Predisposition Process Product Container Production Pulmonology Quality of life Research Research Infrastructure Research Personnel Respiratory Signs and Symptoms Respiratory physiology Risk Risk Factors Role Rural Sampling Severities Source Tobacco smoke Training United States Urine Visit airway obstruction allergic response building materials cohort consumer product data management design ethnic minority population experience health care service utilization high risk population improved interest non-smoker novel patient oriented personal care products phthalates pollutant respiratory respiratory health respiratory morbidity skills study population urinary

项目摘要

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.

项目概要慢性阻塞性肺疾病（COPD）是美国第四大死因也是造成大量发病和医疗保健利用的一个原因。尽管接触烟草烟雾是一个主要风险慢性阻塞性肺病 (COPD) 的一个重要因素，人们越来越关注环境因素对其发展和慢性阻塞性肺病的严重程度。在常见的环境暴露中，邻苯二甲酸盐化合物的数量正在不断增加由于它们可能对内分泌和呼吸系统健康产生不利影响而引起关注。邻苯二甲酸盐是合成的用于塑料和众多消费品的工业化学品，成人普遍接触在美国。最广泛使用的邻苯二甲酸酯是邻苯二甲酸二-2-乙基己酯 (DEHP)，它是一种成分广泛使用的塑料。接触邻苯二甲酸盐（包括 DEHP）与气道疾病有关氧化应激和增强过敏反应的机制。增加接触 DEHP 和其他物质邻苯二甲酸盐与健康非健康人群的肺功能小幅但显着的下降有关。吸烟者，与氧化应激遗传易感性增加的个体的关联最强。这种氧化应激本身会加剧气道阻塞并增强污染物暴露的影响。然而，邻苯二甲酸盐暴露是否与慢性阻塞性肺病患者的不良预后相关仍然存在疑问。未知。我们假设接触 DEHP 与个体呼吸道疾病发病率相关患有慢性阻塞性肺病。我们有初步数据显示与邻苯二甲酸盐暴露的横截面关联正在进行的慢性阻塞性肺病研究的一部分的呼吸系统发病率；然而，因果关系不能建立该数据以及邻苯二甲酸盐暴露的人内差异需要进行纵向评估研究的曝光量。此外，暴露来源及其与慢性阻塞性肺病的相关性尚不清楚，但对于更好地改善慢性阻塞性肺病非常重要。设计潜在的修改策略。该提案有两个新颖的目标。一、确定关联 1a) 个人和 1b) 累积邻苯二甲酸盐暴露对个人呼吸系统结果的影响对于慢性阻塞性肺病，我们将在后续研究访视时重复测量尿邻苯二甲酸盐浓度结合对几种呼吸结果的评估。二、评估邻苯二甲酸酯的决定因素低收入慢性阻塞性肺病患者的暴露情况，以确定可改变的因素并为未来提供信息缓解暴露干预措施，我们将进行家庭检查并进行饮食、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物质暴露 (DEHP) 的作用提供令人兴奋的证据以前与慢性阻塞性肺病没有联系，并且可以利用有关暴露来源的信息来制定缓解措施改善慢性阻塞性肺病（COPD）结果的策略。