Advertisement

Topics

Epigenetic Effect Modifications With Ozone Exposure on Healthy Volunteers

2015-06-12 02:38:22 | BioPortfolio

Summary

The purpose of this protocol is to assess whether epigenetic factors in healthy individuals make a person more or less responsive to lung inflammation following ozone exposures.

Description

Controlled human exposure studies to ozone have reported decreases in lung function (Devlin et al. 2012; Kim et al. 2011) and increased inflammation (Kim et al. 2011; Koren et al. 1991; Liu et al. 2009; Romieu et al. 2008). However, the range of response to ozone in healthy young volunteers is an order of magnitude, and if individuals are exposed to ozone some months later they retain their hierarchy on the response curve, suggesting that long-lived factors are responsible. Several studies have demonstrated that polymorphisms in oxidative stress genes such as GSTM1 or NQO1 may be associated with responsiveness to air pollutants (Bergamaschi et al. 2001; Corradi et al. 2002). However, within the past decade, many researchers have started exploring the epigenome as a possible link between exposures to environmental toxicants and disease. Epigenetics refers to non-genetic mechanisms influencing gene expression and phenotype (Cortessis et al. 2012). Commonly studied epigenetic changes include DNA methylation, histone modification, and non-coding RNA expression (i.e. micro-RNA). Recently, work conducted at the Harvard School of Public Health looked at DNA methylation as an effect modifier to air pollution-induced adverse health effects (Bind et al. 2012). This group, using a cohort representing previous war veterans from the VA Normative Aging Study, observed stronger effects in cardiovascular disease-related blood biomarkers with DNA methylation status, both globally and within candidate genes. Additionally, Salam et al. found that fractional exhaled nitric oxide, a marker of lung inflammation, was interrelated with short-term PM 2.5 concentration as well as NOS2 epigenetic and genetic variations in children (2012). Thus, these studies suggest epigenetic changes could impact susceptibility to pollutants. Additionally, acute epigenetic changes, which are potential pathways of air pollution-induced health effects, have been associated with the inhalation of particulate matter and ambient gaseous pollutants (Baccarelli et al. 2009; Bellavia et al. 2013; Bollati et al. 2010; De Prins et al. 2013; Madrigano et al. 2011; Tarantini et al. 2009). Therefore, it is possible that an individual's epigenetic profile could make them more or less responsive to ozone, and that ozone exposure itself could cause acute changes in the epigenome which could in turn affect ozone-responsiveness.

Previous studies that have looked at epigenetic changes associated with air pollutants have difficultly disentangling the role of genetic and epigenetic factors. One way to do this is to study identical (MZ) twins. MZ twins arise when two or more daughter cells split from a single zygote during embryonic development, forming two individuals with identical genetic sequences (Fraga et al. 2005) but dissimilar epigenomes (Li et al. 2013; Szyf 2007). A number of diseases in which MZ twins are discordant, such as bipolar and schizophrenia disorders (Bonsch et al. 2012; Dempster et al. 2011), asthma (Runyon et al. 2012), autism spectrum disorder (Wong et al. 2013), and breast cancer (Heyn et al. 2013), implicate epigenetic variability as the cause. Therefore, as discordance for disease status has already been linked with epigenetic changes, this adds further plausibility to the notion that epigenetics could be responsible for the susceptibility of some subjects to ozone exposures while others seem non-responsive. By using MZ twins as one target population for this study, variability due only to epigenetics, without the influence of genetics, can be fully explored.

For this study, the investigators will measure changes in pulmonary inflammation after a controlled exposure in healthy subjects and healthy twin pairs to clean air and ozone. This endpoint was chosen because previous work has shown that the epithelial cells lining the airways are the first target of ozone and respond by making pro-inflammatory cytokines such as IL-6 and IL-8. Epigenetic changes are dependent on tissue type, and airway epithelial cells can be obtained by brush biopsies during bronchoscopy and assayed for epigenetic changes. The investigators will determine whether differences in baseline epigenetic profiles between subjects are associated with responsiveness to ozone and whether ozone exposure itself causes acute changes in a subject's epigenome.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Conditions

Exposure to Environmental Pollution, Non-occupational

Intervention

Clean air, Ozone

Location

EPA Human Studies Facility
Chapel Hill
North Carolina
United States
27514

Status

Recruiting

Source

Environmental Protection Agency (EPA)

Results (where available)

View Results

Links

Published on BioPortfolio: 2015-06-12T02:38:22-0400

Clinical Trials [960 Associated Clinical Trials listed on BioPortfolio]

Air Pollution Study: The Effect of Ozone on the Lung

The purpose of the study is to better understand the mechanisms of lung injury from ozone exposure. Subjects will participate in two exposure sessions: filtered air and 0.2 ppm ozone. Subj...

The Effect of Low Level Ozone Exposure on Healthy Volunteers

The purpose of this research study is to learn more about the effects of 0.12 ppm ozone exposure on humans. We know from other studies that exposure to levels of ozone that are seen on ba...

Human Biological Responses to Low Level Ozone

To investigate if low level ozone exposure will cause measurable inflammation in nasal cells.

Efficacy of Fish Oil or Olive Oil Supplementation on the Health Effects of Ozone Exposure in Healthy Young Subjects

Purpose: A growing body of epidemiological data suggests an increased risk of cardiovascular events associated with air pollution. One of the common air pollutants, ozone, has been shown t...

Effects of Fish Oil in Alleviating Health Hazards Associated With Ozone Exposure

This study aims to evaluate whether dietary supplementation with fish oil can protect against the cardiopulmonary effects induced by ozone exposure.

PubMed Articles [12325 Associated PubMed Articles listed on BioPortfolio]

A review of the cohorts with environmental and occupational mineral fiber exposure.

The aim of the study was to examine factors associated with Malignant Mesothelioma (MM) incidence rate of the groups with occupational asbestos and environmental asbestos or erionite exposure in rural...

Inhalation of House Dust and Ozone Alters Systemic Levels of Endothelial Progenitor Cells, Oxidative Stress, and Inflammation in Elderly Subjects.

Ambient air pollution including ozone and especially particulate matter represents important causes of cardiovascular disease. However, there is limited knowledge on indoor air dust with respect to th...

The burden of ozone pollution on years of life lost from chronic obstructive pulmonary disease in a city of Yangtze River Delta, China.

Ambient ozone is one of the most important air pollutants with respect to its impacts on human health and its increasing concentrations globally. However, studies which explored the burden of ozone po...

Dioxin Pollution and Occupational Inhalation Exposure of PCDD/Fs in Municipal Solid Waste Incinerator.

To assess the pollution levels, characteristics, and the pollution sources and occupational inhalation exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs)in the workshops,ambient ...

Physiological responses of date palm (Phoenix dactylifera) seedlings to acute ozone exposure at high temperature.

Vegetation in the Arabian Peninsula is facing high and steadily rising tropospheric ozone pollution. However, little is known about the impacts of elevated ozone on date palms, one of the most importa...

Medical and Biotech [MESH] Definitions

A shift in the balance between production and destruction of STRATOSPHERIC OZONE that results in a decline of the amount of OZONE in the lower stratosphere.

Ozone in the Earth's stratosphere. It is produced continuously by the action of solar ULTRAVIOLET RAYS on oxygen in the stratosphere. The stratospheric ozone (especially at the ozone layer) blocks much of the solar UV radiation of wavelengths of 320 nanometers or less from being transmitted to lower ATMOSPHERE of the Earth.

The study of ENVIRONMENTAL POLLUTION and the toxic effects of ENVIRONMENTAL POLLUTANTS on the ECOSYSTEM. The term was coined by Truhaut in 1969.

The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals.

A factor associated with the well-being of living organisms that is used as a measure of environmental change and or influence. For example, aldehyde dehydrogenase expression in earthworm tissue is used as an indication of heavy metal pollution in soils. Distinguish from BIOMARKERS.

More From BioPortfolio on "Epigenetic Effect Modifications With Ozone Exposure on Healthy Volunteers"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Epigenetics
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...

Pulmonary
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Mental Health
Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...


Searches Linking to this Trial