To investigate if low level ozone exposure will cause measurable inflammation in nasal cells.
Air pollutants including ozone have been implicated in affecting health outcomes. In particular, high level ozone exposure has been shown to affect pulmonary function and cause pulmonary inflammation. Troubling community-based work has implicated high ozone levels as being correlated with increased pediatric asthma emergency room visits. Because of adverse health effects, EPA standards for safe ozone levels have been set, currently at 0.07 ppm. Still, it is estimated that 100 million Americans live in areas where ozone levels periodically remain above the EPA standard. And while this EPA standard had been set based on available data, it remained unclear at the time whether naturalistic low-level ozone exposure, such as fluctuations between 0.06-0.08 ppm throughout the day, might affect health as well. This group previously examined lung function and inflammatory response in adults exposed to low-level ozone, 0.06 ppm exposure for 6.6 hours, while undergoing intermittent moderate exercise. The investigators found that in response to low-level ozone exposure (0.06 ppm) with exercise, lung function declines and neutrophilic airway inflammation is observed. What remains unclear, is whether low-level ozone alone - without exercise - will cause similar health effects. To mimic exposure to ozone on a typical summer day in a polluted city, the investigators will expose subjects to a varying level of ozone, form 0.06 ppm to 0.08 ppm, rather than a constant 0.07ppm. The variation from 0.06ppm to 0.08ppm, then back to 0.06ppm will occur each hour.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
15
Participants will be exposed to a concentration of ozone for 6.5 hours at a concentration that varies 0.06 to 0.08
Participants will be exposed to filtered clean air
Ozone and heart rate tracker
Center for Environmental Medicine, Asthma and Lung Biology
Chapel Hill, North Carolina, United States
Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid Immediately Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Nasal lavage fluid (NLF) will be collected from participants at a baseline visit within two weeks prior to each exposure, and at the following time points for each exposure: immediately after exiting the exposure chamber, and at 24 hours after the exposure. The % PMN as a percentage of total inflammatory cells (total of monocytes and macrophages, PMN, eosinophils, basophils, lymphocytes, and bronchial epithelial cells) will be determined in each NLF collection by differential counts of cells on cytospin slides. The change in the values from baseline to immediately Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3.
Time frame: Baseline, immediately post-exposure
Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid 24 Hours Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Nasal lavage fluid (NLF) will be collected from participants at a baseline visit within two weeks prior to each exposure, and at the following time points for each exposure: immediately after exiting the exposure chamber, and at 24 hours after the exposure. The % PMN as a percentage of total inflammatory cells (total of monocytes and macrophages, PMN, eosinophils, basophils, lymphocytes, and bronchial epithelial cells) will be determined in each NLF collection by differential counts of cells on cytospin slides. The change in the values from baseline to 24 hours Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3.
Time frame: Baseline, 24 hours post-exposure
Interleukin-6 (IL-6) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change Immediately Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Nasal epithelial lining (ELF) will be collected from participants at a baseline visit within two weeks prior to each exposure, and at the following time points for each exposure: immediately after exiting the exposure chamber, and at 24 hours after the exposure. The IL-6 concentration will be determined in each ELF sample by immunoassay. The change in IL-6 concentrations from baseline to immediately Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3 to determine the effect of ozone on the production of nasal IL-6.
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Time frame: Baseline, immediately post-exposure
% Polymorphonuclear Leukocytes (PMN) in Induced Sputum: Change 24 Hours Post-Exposure From Screening Visit
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Induced sputum will be collected from participants after inhaled hypertonic saline. Induced sputum will be collected at the screening visit within six weeks prior to the first exposure, and at 24 hours after each exposure. The % PMN as a percentage of total inflammatory cells (total of monocytes and macrophages, PMN, eosinophils, basophils, lymphocytes, and bronchial epithelial cells) will be determined in each induced sputum collection by differential counts of cells on cytospin slides. The change in the values from baseline to 24 hours Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3.
Time frame: Screening visit and 24 hours post-exposure
The Percentage of Predicted Forced Expiratory Volume in One Second (% Predicted FEV1): Change Immediately Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Standard spirometry to obtain FEV1 and forced vital capacity (FVC) measurements will be done at baseline within two weeks prior to first exposure, and immediately after exiting the exposure chamber for each exposure. The % Predicted FEV1 will be calculated from measured versus expected values. The change in % Predicted FEV1 from baseline to immediately Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3 to determine the effect of ozone on the % Predicted FEV1.
Time frame: Baseline, immediately post-exposure
Interleukin-6 (IL-6) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change 24 Hours Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Nasal epithelial lining (ELF) will be collected from participants at baseline within two weeks prior to first exposure, and at the following time points for each exposure: immediately after exiting the exposure chamber, and at 24 hours after the exposure. The IL-6 concentration will be determined in each ELF sample by immunoassay. The change in IL-6 concentrations from baseline to 24 hours Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3 to determine the effect of ozone on the production of nasal IL-6.
Time frame: Baseline, 24 hours post-exposure
Interleukin-8 (IL-8) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change Immediately Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Nasal epithelial lining (ELF) will be collected from participants at baseline within two weeks prior to first exposure, and at the following time points for each exposure: immediately after exiting the exposure chamber, and at 24 hours after the exposure. The IL-8 concentration will be determined in each ELF sample by immunoassay. The change in IL-8 concentrations from baseline to immediately Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3 to determine the effect of ozone on the production of nasal IL-8.
Time frame: Baseline, immediately post-exposure
Interleukin-8 (IL-8) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change 24 Hours Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Nasal epithelial lining (ELF) will be collected from participants at baseline within two weeks prior to first exposure, and at the following time points for each exposure: immediately after exiting the exposure chamber, and at 24 hours after the exposure. The IL-8 concentration will be determined in each ELF sample by immunoassay. The change in IL-8 concentrations from baseline to 24 hours Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3 to determine the effect of ozone on the production of nasal IL-8.
Time frame: Baseline, 24 hours post-exposure
Left Ventricular Strain (LVS): Change Immediately Post-Exposure From Baseline
Left ventricular strain will be assessed at baseline prior to exposure (within two weeks), and immediately after the exposure by measuring global longitudinal strain (GLS), an echocardiographic measure of myocardial mechanics. GLS is measured using speckle tracking, a technique by which small myocardial footprints, or speckles, are tracked over the cardiac cycle to enable quantification of left ventricular systolic function. GLS is more sensitive than traditional measures of ventricular function, such as ejection fraction, in detecting clinically inapparent but prognostically important decrements in contractility. The change in global longitudinal strain will be calculated to determine the effect of ozone on left ventricular strain.
Time frame: Baseline and immediately post-exposure
Nasal Epithelial Cell IL-1 Beta Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air
RNA isolated from nasal epithelial cell biopsies collected at the screening visit (baseline) within six weeks prior to the first exposure and immediately after each exposure. RNA will be analyzed via real-time quantitative polymerase chain reaction (qPCR) to determine the impact of O3 on inflammatory gene expression.
Time frame: Screening visit and immediately post-exposure
Flow Mediated Dilation (FMD): Change Immediately Post-Exposure From Baseline
Participants will undergo assesment of flow-mediated brachial artery dilation by brachial ultrasound at baseline prior to exposure (within two weeks), and immediately after exposure to either FA or O3 to assess the impact of O3 exposure on endothelial function. Flow mediated dilation of the brachial artery (FMD) is a noninvasive index of vascular endothelial function. FMD is measured using high-frequency ultrasound, and is expressed as the percent change in arterial diameter in response to the reactive hyperemia induced by 5 minutes of forearm ischemia. Impaired endothelial function leads to atherosclerosis and is associated with an increased risk of cardiovascular events.
Time frame: Baseline and immediately post-exposure
Change in Heart Rate Variability
Measure was not performed as the equipment (ECG leads and monitor recording heart rate and rhythm) belonged to the EPA and was not made available for this study
Time frame: baseline, immediately post exposure
Nasal Epithelial Cell IL-6R Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air
RNA isolated from nasal epithelial cell biopsies collected at the screening visit (baseline) within six weeks prior to the first exposure and immediately after each exposure. RNA will be analyzed via real-time quantitative polymerase chain reaction (qPCR) to determine the impact of O3 on inflammatory gene expression.
Time frame: Screening visit and immediately post-exposure
Nasal Epithelial Cell IL-8 Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air
RNA isolated from nasal epithelial cell biopsies collected at the screening visit (baseline) within six weeks prior to the first exposure and immediately after each exposure. RNA will be analyzed via real-time quantitative polymerase chain reaction (qPCR) to determine the impact of O3 on inflammatory gene expression.
Time frame: Screening visit and immediately post-exposure
The Percentage of Predicted Forced Vital Capacity (% Predicted FVC): Change Immediately Post-Exposure From Baseline
Participants will be exposed to either filtered air (FA), then ozone (O3), or O3, then FA. Standard spirometry to obtain FEV1 and forced vital capacity (FVC) measurements will be done at baseline within two weeks prior to first exposure, and immediately after exiting the exposure chamber for each exposure. The % Predicted FVC will be calculated from measured versus expected values. The change in % Predicted FVC from baseline to immediately Post-Exposure will be calculated for each participant for each exposure. Values will be compared between FA and O3 to determine the effect of ozone on the % Predicted FVC.
Time frame: Baseline, immediately post-exposure