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

• 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
• 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

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.

项目摘要 慢性阻塞性肺疾病（COPD）是美国第四大死亡原因 以及大量发病率和医疗保健利用的原因。虽然烟草烟雾暴露是关键风险 COPD的因素，越来越关注的环境贡献者为发展和 COPD的严重程度。在常见的环境暴露中，称为邻苯二甲酸盐的化合物正在增长 由于其可能对内分泌和呼吸健康的不利影响而关注。邻苯二甲酸酯是合成的 塑料和众多消费产品中使用的工业化学品，成人无处不在 在美国。最广泛的邻苯二甲酸盐是邻苯二甲酸苯甲酸酯（DEHP），一个成分 广泛使用的塑料。包括DEHP在内的邻苯二甲酸盐的暴露与气道疾病有关 氧化应激的机制和增强过敏反应的机制。增加了DEHP和其他DEHP的接触 邻苯二甲酸盐与健康的非 - 非 - 吸烟者，在遗传易感性增加氧化应激的个体中的关联最强。 这种氧化应激本身可能会使气道阻塞恶化，并增强污染物暴露的作用。 但是，邻苯二甲酸盐暴露是否与COPD患者的结局差有关 未知。我们假设暴露于DEHP与个体之间的呼吸道发病有关 与COPD。我们有初步数据，显示与邻苯二甲酸盐暴露和 正在进行的COPD研究子集的呼吸发病率；但是，因果关系无法建立 这些数据以及接触邻苯二甲酸盐的人体内变异性需要进行纵向评估的研究 暴露。此外，暴露源及其与COPD的相关性尚不清楚，但对更好的 设计潜在的修改策略。该提议有两个新颖的目标。首先，确定关联 在1a）之间和1B）促邻苯二甲酸盐对个体的呼吸结果暴露 使用COPD，我们将在随访研究中对尿邻苯二甲酸盐浓度进行重复测量 与评估几种呼吸结局的评估。第二，评估邻苯二甲酸酯的决定因素 低收入COPD的人之间的接触，以识别可修改的因素并为未来提供信息 曝光缓解干预措施，我们将进行房屋检查并管理饮食调查，个人检查 护理产品的使用以及医疗设备在我们的研究中用于确定暴露于邻苯二甲酸盐的来源 人口。这项研究的结果将提供化学暴露作用（DEHP）的挑衅性证据 以前没有链接到COPD，并且可以利用有关暴露源的信息来制定缓解措施 改善COPD成果的策略。