The Effect of Phthalates on COPD Morbidity

项目总结

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.