Clinical trial NCT02857283: Human Biological Responses to Low Level Ozone
Official title: Human Biological Responses to Low Level Ozone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Environmental Exposure
Nasal Inflammation
Keywords: Air pollution
Air pollutant exposure
Ozone
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Environmental Protection Agency (EPA)
First posted: 2016-08-05
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Males and females between 18 and 50 years of age.
* Vital signs within normal limits on admission to the study: Peripheral oxygen saturation (SpO2) \> 94%, systolic blood pressure between 150-90 mm Hg, diastolic blood pressure between 100-60 mm Hg, afebrile.
* Forced Expiratory Volume (FEV1) of at least 80% of predicted.

Exclusion Criteria:

* Any chronic medical condition considered by the PI as a contraindication to the exposure study, including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, chronic thyroid disease, or kidney disease.
* Use of systemic or inhaled steroids.
* Use of NSAID or aspirin within 7days of each study visit, and inability to withhold these medications prior to each session of the study.
* Pregnant or nursing women
* Use of cigarettes or other inhaled nicotine products within the past year, or more than a lifetime 5 pack year history of cigarette smoking.

Primary outcomes:
measure: Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid Immediately Post-Exposure From Baseline
timeFrame: Baseline, immediately post-exposure
measure: Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid 24 Hours Post-Exposure From Baseline
timeFrame: Baseline, 24 hours post-exposure
Secondary outcomes:
measure: Interleukin-6 (IL-6) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change Immediately Post-Exposure From Baseline
timeFrame: Baseline, immediately post-exposure
measure: % Polymorphonuclear Leukocytes (PMN) in Induced Sputum: Change 24 Hours Post-Exposure From Screening Visit
timeFrame: Screening visit and 24 hours post-exposure
measure: The Percentage of Predicted Forced Expiratory Volume in One Second (% Predicted FEV1): Change Immediately Post-Exposure From Baseline
timeFrame: Baseline, immediately post-exposure
measure: Interleukin-6 (IL-6) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change 24 Hours Post-Exposure From Baseline
timeFrame: Baseline, 24 hours post-exposure
measure: Interleukin-8 (IL-8) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change Immediately Post-Exposure From Baseline
timeFrame: Baseline, immediately post-exposure
measure: Interleukin-8 (IL-8) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change 24 Hours Post-Exposure From Baseline
timeFrame: Baseline, 24 hours post-exposure
measure: Left Ventricular Strain (LVS): Change Immediately Post-Exposure From Baseline
timeFrame: Baseline and immediately post-exposure
measure: Nasal Epithelial Cell IL-1 Beta Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air
timeFrame: Screening visit and immediately post-exposure
measure: Flow Mediated Dilation (FMD): Change Immediately Post-Exposure From Baseline
timeFrame: Baseline and immediately post-exposure
measure: Change in Heart Rate Variability
timeFrame: baseline, immediately post exposure
measure: Nasal Epithelial Cell IL-6R Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air
timeFrame: Screening visit and immediately post-exposure
measure: Nasal Epithelial Cell IL-8 Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air
timeFrame: Screening visit and immediately post-exposure
measure: The Percentage of Predicted Forced Vital Capacity (% Predicted FVC): Change Immediately Post-Exposure From Baseline
timeFrame: Baseline, immediately post-exposure
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Center for Environmental Medicine, Asthma and Lung Biology
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: David B Peden, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Little, R. J. and Rubin, D. B. (2014). Statistical analysis with missing data. John Wiley & Sons.