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| Name | Class |
|---|---|
| Environmental Protection Agency (EPA) | FED |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Filtered Air, then Ozone | Experimental | Participants in this arm will first receive filtered clean air followed by ozone |
|
| Ozone, then Filtered Air | Experimental | Participants in this arm will first receive ozone followed by filtered clean air |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ozone | Other | Participants will be exposed to a concentration of ozone for 6.5 hours at a concentration that varies 0.06 to 0.08 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline, 24 hours post-exposure |
| Measure | Description | Time Frame |
|---|---|---|
| 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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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David B Peden, MD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Environmental Medicine, Asthma and Lung Biology | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 7735583 | Background | Peden DB, Setzer RW Jr, Devlin RB. Ozone exposure has both a priming effect on allergen-induced responses and an intrinsic inflammatory action in the nasal airways of perennially allergic asthmatics. Am J Respir Crit Care Med. 1995 May;151(5):1336-45. doi: 10.1164/ajrccm.151.5.7735583. | |
| Background | Little, R. J. and Rubin, D. B. (2014). Statistical analysis with missing data. John Wiley & Sons. |
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Two participants did not meet inclusion criteria, and 1 withdrew before undergoing the second exposure. All participants were free from acute illness
A total of 17 participants were screened between April 22, 2017 and May 1, 2019. Participants were recruited from a database of subjects at the Center for Environmental Medicine, Asthma and Lung Biology.
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| ID | Title | Description |
|---|---|---|
| FG000 | Filtered Air; Then Ozone | Participants were exposed to filtered clean air for 6.5 hours, and after a minimum of a 2-week washout, they returned and were exposed to 0.06-0.08 Parts Per Million (PPM) ozone for 6.5 hours. All participants wore a Health and Exposure Tracker (HET): Ozone and heart rate tracker during both exposures. |
| FG001 | Ozone; Then Filtered Air | Participants were exposed to 0.06-0.08 PPM ozone for 6.5 hours, and after a minimum of a 2-week washout, they returned and were exposed to filtered clean air for 6.5 hours. All participants wore a Health and Exposure Tracker (HET): Ozone and heart rate tracker during both exposures. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Exposure |
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| Washout (2 Weeks) |
| |||||||||||||||||||
| Second Exposure |
|
All participants who completed the study; one participant who dropped out after the first exposure (Filtered Air) is excluded
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| ID | Title | Description |
|---|---|---|
| BG000 | Filtered Air; Then Ozone | Participants were exposed to filtered clean air for 6.5 hours, and after a minimum of a 2-week washout, they returned and were exposed to 0.06-0.08 PPM ozone for 6.5 hours. All participants wore a Health and Exposure Tracker (HET): Ozone and heart rate tracker during both exposures |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Only 5 participants had paired pre and immediately post-filtered air exposure samples and only 3 had paired pre and immediately post-ozone exposure samples of adequate quality for analysis. Only 1 participant had paired samples from both exposure periods. The remainder of samples were of poor quality and contained insufficient cells for analysis. | Posted | Mean | Standard Error | percent PMNs in nasal lavage fluid | Baseline, immediately post-exposure |
Up 1 month after completion of the exposures.
Safety assessments included all participants who underwent any study procedures.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Filtered Air | Filtered Air: Participants will be exposed to filtered clean air for 6.5 hours |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michelle Hernandez, MD | UNC Center for Environmental Medicine, Asthma and Lung Biology | 919-843-5383 | michelle_hernandez@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 11, 2016 | Mar 23, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010126 | Ozone |
| ID | Term |
|---|---|
| D010100 | Oxygen |
| D005740 | Gases |
| D007287 | Inorganic Chemicals |
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| Filtered Air | Other | Participants will be exposed to filtered clean air |
|
| Health and Exposure Tracker (HET) | Device | Ozone and heart rate tracker |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 | 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. | 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. | 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. | Baseline, immediately post-exposure |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| Ozone; Then Filtered Air |
Participants were exposed to 0.06-0.08 PPM ozone for 6.5 hours, and after a minimum of a 2-week washout, they returned and were exposed to filtered clean air for 6.5 hours. All participants wore a Health and Exposure Tracker (HET): Ozone and heart rate tracker during both exposures |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | United States, Residents of North Carolina, all within 50 miles of Chapel Hill | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Filtered Air | Participants will be exposed to filtered clean air for 6.5 hours |
| OG001 | Ozone | Participants will be exposed to a concentration of ozone for 6.5 hours at a concentration that varies 0.06 to 0.08 Parts Per Million (PPM) |
|
|
| Primary | 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. | Only 5 participants had paired pre and 24h post-filtered air exposure samples and only 3 had paired pre and 24h post-ozone exposure samples of adequate quality for analysis. Only 1 participant had paired samples from both exposure periods. The remainder of samples were of poor quality and contained insufficient cells for analysis. | Posted | Mean | Standard Error | percent PMNs in nasal lavage fluid | Baseline, 24 hours post-exposure |
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Error | pg/mL | Baseline, immediately post-exposure |
|
|
|
|
| Secondary | % 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. | Participants who produced induced sputum containing at least 60000 inflammatory cells at both the screening visit and at 24 hours after at least one exposure | Posted | Mean | Standard Error | percent PMN | Screening visit and 24 hours post-exposure |
|
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Error | percent predicted FEV1 | Baseline, immediately post-exposure |
|
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Error | pg/ml | Baseline, 24 hours post-exposure |
|
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Error | pg/mL | Baseline, immediately post-exposure |
|
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Error | pg/mL | Baseline, 24 hours post-exposure |
|
|
|
|
| Secondary | 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. | One participant's LVS data was collected but was not able to undergo analysis due to the shutdown of university laboratories in response to the pandemic | Posted | Mean | Standard Error | percent change | Baseline and immediately post-exposure |
|
|
|
|
| Secondary | 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. | One participant did not have a pre-exposure nasal epithelial cell biopsy sample available for analysis. | Posted | Mean | Standard Deviation | relative mRNA counts | Screening visit and immediately post-exposure |
|
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Error | percent change | Baseline and immediately post-exposure |
|
|
|
|
| Secondary | 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 | No participants analyzed as equipment belonging to the EPA was not available | Posted | baseline, immediately post exposure |
|
|
| Secondary | 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. | One participant did not have a pre-exposure nasal epithelial cell biopsy sample available for analysis. | Posted | Mean | Standard Deviation | relative mRNA counts | Screening visit and immediately post-exposure |
|
|
|
|
| Secondary | 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. | One participant did not have a pre-exposure nasal epithelial cell biopsy sample available for analysis. | Posted | Mean | Standard Deviation | relative mRNA counts | Screening visit and immediately post-exposure |
|
|
|
|
| Secondary | 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. | All participants that completed the study | Posted | Mean | Standard Deviation | percent predicted FEV1 | Baseline, immediately post-exposure |
|
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Ozone | Ozone: Participants will be exposed to a concentration of ozone for 6.5 hours at a concentration that varies 0.06 to 0.08 PPM | 0 | 14 | 0 | 14 | 0 | 14 |
Not provided
Not provided
Not provided