Traffic Exposures and Metabolic Responses in Commuters 公开

Ladva, Chandresh Nanji (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/bz60cw64q?locale=zh
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Abstract

Atlanta commuters, more than 78% of the working age population, are spending an estimated 31 minutes on the road each way to work. The resulting traffic air pollution exposure has become the subject of extensive research. Air pollution exposures elicit mixtures of biological responses across many scales, from organ-scale wheezing, asthma, and lung cancer to molecular-scale systemic inflammation. Complexity also extends to the exposures themselves. Traffic pollution components, like black carbon, polycyclic aromatic hydrocarbons, fine particulate matter or PM2.5, and metals, contribute to toxicity through particle size or oxidative potential. To capture the complexity of both exposure and response, new scales of measurement and data integration with established methods are necessary. Traditional exposure assessment methods married to tools for analyzing the exposome--an accumulation of environmental factors and corresponding biological responses over a lifespan--may aid in the investigations of traffic pollution related human health responses.

The present body of work explores the high-dimensional natures of traffic pollution and human biology with the expectation of elucidating the connections between them. The first aim assessed the short-term covariance between two important aspects of traffic exposure: particle pollution and noise. High temporal resolution measures of exposure revealed varying patterns of covariance of PM2.5, BC, and pb-PAHs with noise that changed depending on the roadway environment being sampled while PNC and noise had stable covariance. The second aim turned to internal mixtures and was the first examination of metabolomic profiling of plasma, saliva, and exhaled breath condensate together. There was good correlation between features shared between matrices, and those correlations were stable over time. This aim opened potential for identifying markers of traffic pollution exposure in these three matrices using a newer chemical measurement tool called high-resolution metabolomics. Finally, the third aim used a panel study of commuters to examine whether in-vehicle traffic pollution exposures were associated with changes in inflammation and metabolomic profiles. Particulate metal exposures were found to induce changes in plasma metabolism consistent with inflammation.

The dissertation demonstrates that high-resolution measurements can capture the complexity of both traffic exposure and human response for new insights on associations between them.

Table of Contents

Table of Contents List of Tables.................................................................................................................................. 1 List of Figures................................................................................................................................. 2 Chapter 1: Introduction.................................................................................................................... 3 References.................................................................................................................................... 8 Overview of Dissertation................................................................................................................ 11

Chapter 2: Assessing Short-Term Covariance between In-Vehicle Particulate Pollution and Noise............. 1 3

Abstract....................................................................................................................................... 14 Introduction................................................................................................................................. 15 Methods....................................................................................................................................... 17 Results and Discussion................................................................................................................... 22 Conclusions.................................................................................................................................. 30 References.................................................................................................................................... 31 Tables and Figures......................................................................................................................... 35

Chapter 3: Metabolomic Profiles of Plasma, Exhaled Breath Condensate, and Saliva are Correlated with

Potential for Air Toxics Detection..................................................................................................... 40

Abstract....................................................................................................................................... 41 Introduction................................................................................................................................. 42 Methods....................................................................................................................................... 44 Results......................................................................................................................................... 48 Discussion.................................................................................................................................... 50 References.................................................................................................................................... 58 Tables and Figures......................................................................................................................... 62

Chapter 4: In-Vehicle, Particulate Metal Exposures Induce Detectable Changes in the Plasma Metabolome

in a Commuter Panel Study............................................................................................................. 69

Abstract........................................................................................................................................ 70 Introduction.................................................................................................................................. 71 Methods........................................................................................................................................ 73 Results......................................................................................................................................... 78 Discussion..................................................................................................................................... 80 References.................................................................................................................................... 88 Tables and Figures.......................................................................................................................... 91 Chapter 5: Conclusions.................................................................................................................. 100 References................................................................................................................................... 104 Appendices................................................................................................................................... 105 Chapter 2 Supplementary Figures.................................................................................................... 106 Chapter 3 Supplementary Figures.................................................................................................... 107 Chapter 4 Supplementary Figures.................................................................................................... 108

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