Human Biological Responses to Low Level Ozone
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid Immediately Post-Exposure From Baseline
研究概览
简要总结
To investigate if low level ozone exposure will cause measurable inflammation in nasal cells.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid Immediately Post-Exposure From Baseline
时间窗: Baseline, immediately post-exposure
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.
Change in % Polymorphonuclear Leukocytes (PMN) in Nasal Lavage Fluid 24 Hours Post-Exposure From Baseline
时间窗: Baseline, 24 hours post-exposure
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.
次要结局
- Interleukin-6 (IL-6) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change Immediately Post-Exposure From Baseline(Baseline, immediately post-exposure)
- % Polymorphonuclear Leukocytes (PMN) in Induced Sputum: Change 24 Hours Post-Exposure From Screening Visit(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(Baseline, immediately post-exposure)
- Interleukin-6 (IL-6) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change 24 Hours Post-Exposure From Baseline(Baseline, 24 hours post-exposure)
- Interleukin-8 (IL-8) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change Immediately Post-Exposure From Baseline(Baseline, immediately post-exposure)
- Interleukin-8 (IL-8) Concentrations in Nasal Epithelial Lining Fluid (ELF): Change 24 Hours Post-Exposure From Baseline(Baseline, 24 hours post-exposure)
- Left Ventricular Strain (LVS): Change Immediately Post-Exposure From Baseline(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(Screening visit and immediately post-exposure)
- Flow Mediated Dilation (FMD): Change Immediately Post-Exposure From Baseline(Baseline and immediately post-exposure)
- Change in Heart Rate Variability(baseline, immediately post exposure)
- Nasal Epithelial Cell IL-6R Gene Expression: Relative mRNA Counts Immediately Post-Exposure (Baseline-corrected), Ozone vs Filtered Air(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(Screening visit and immediately post-exposure)
- The Percentage of Predicted Forced Vital Capacity (% Predicted FVC): Change Immediately Post-Exposure From Baseline(Baseline, immediately post-exposure)