Ozone Exposure for Air Pollution-related Lung Injury

Overseen By Adriana De Resende

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Antioxidants

Disqualifiers: Cardiovascular, Respiratory, Diabetes, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

120 Participants Needed

Trial Summary

What is the purpose of this trial?

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. The exposure visits will be at least 2 weeks apart. Subjects will be asked to produce sputum through coughing after each exposure. The samples will be analyzed for macrophage activity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take daily antioxidant supplements like Vitamin C or E, selenium, and others. If you take these less frequently, the principal investigator will review your eligibility.

Is ozone exposure safe for humans?

Ozone exposure can cause lung function problems, airway inflammation, and respiratory symptoms, especially at higher levels. Studies show that even at levels previously thought safe, ozone can lead to lung injury and other health issues. ^{1 2 3 4 5}

How does the treatment of Clean Air and Ozone differ from other treatments for air pollution-related lung injury?

This treatment is unique because it involves exposure to clean, unpolluted air and controlled ozone levels, which contrasts with traditional treatments that focus on medication or avoiding pollutants. The approach aims to understand the effects of ozone exposure on lung health, rather than directly treating symptoms with drugs. ^{2 6 7 8 9}

Research Team

Howard M Kipen, MD

Principal Investigator

Rutgers School of Public Health

Eligibility Criteria

This trial is for individuals vaccinated against COVID-19, without recent respiratory symptoms or a history of smoking in the past 5 years. They must not have diabetes, pregnancy, HIV infection, certain orthopedic conditions, daily use of specific antioxidant supplements (except multivitamins), cardiovascular disease, or respiratory disease.

Inclusion Criteria

I am vaccinated against COVID-19.

Exclusion Criteria

I do not take antioxidant supplements daily, except in a multivitamin.

I have diabetes.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Exposure

Participants undergo two exposure sessions: one to clean air and one to 0.2 ppm ozone, each lasting 3 hours and separated by at least 2 weeks

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after each exposure, with sputum, blood, and exhaled breath samples collected

1 week

2 visits (in-person)

Treatment Details

Interventions

• Clean Air
• Ozone

Trial Overview The study aims to understand lung injury from ozone by comparing effects of filtered air and ozone exposure on participants. Each participant will undergo two sessions with at least a two-week gap and provide sputum samples for macrophage activity analysis.

Participant Groups

Group I: Ozone, Then Clean Air Experimental Treatment 2 Interventions

Subjects will be exposed to 0.2 ppm ozone for 3 hours at the first exposure visit and clean air for 3 hours at the second exposure visit. The visits will be at least 2 weeks apart.

Group II: Clean Air, Then Ozone Experimental Treatment 2 Interventions

Subjects will be exposed to clean air for 3 hours at the first exposure visit and 0.2ppm ozone for 3 hours at the second exposure visit. The visits will be at least 2 weeks apart.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

National Institute of Environmental Health Sciences (NIEHS)

Collaborator

Trials

294

Recruited

1,233,000+

Findings from Research

In a study involving 9 subjects with mild atopic asthma, exposure to ozone at 0.16 ppm for 7.6 hours resulted in a significant 9.1% decrease in lung function (measured by FEV1), indicating that ozone exposure can impair respiratory health.

Following ozone exposure, subjects showed increased sensitivity to inhaled house dust mite allergens, requiring less allergen to trigger a significant decrease in lung function, suggesting that ozone may worsen asthma symptoms by enhancing airway reactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased specific airway reactivity of persons with mild allergic asthma after 7.6 hours of exposure to 0.16 ppm ozone. Kehrl, HR., Peden, DB., Ball, B., et al.[2019]

Short-term exposure to ozone can lead to immediate negative effects on lung function, increased airway inflammation, and higher rates of respiratory symptoms and hospital admissions.

Long-term exposure to elevated ozone levels is linked to chronic lung function decline, worsening asthma symptoms, and changes in airway cells and tissues, highlighting the need for quantitative health risk assessments using exposure-dose-response models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-effect models for ozone exposure: tool for quantitative risk estimation. van Bree, L., Marra, M., van Scheindelen, HJ., et al.[2019]

Exposure to low levels of ozone (as low as 0.005 ppm) caused significant lung inflammation and damage in mice, indicating that even concentrations below current safety guidelines can be harmful.

The study revealed that ozone exposure led to systemic and pulmonary toxicity, characterized by cellular damage, inflammatory responses, and disrupted respiratory mechanics, highlighting the need for reevaluation of ozone safety standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of low-dose ozone-induced murine acute lung injury. Aulakh, GK., Brocos Duda, JA., Guerrero Soler, CM., et al.[2021]

Exposure to ozone leads to a dose-dependent increase in inflammatory and repair pathways in airway cells, with asthmatic individuals showing significantly higher expression of pro-inflammatory genes, indicating a heightened response to oxidative stress.

The gene osteopontin was identified as a key player in promoting epithelial wound healing, suggesting that targeting this pathway could be beneficial for repairing airway damage caused by ozone exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammatory and repair pathways induced in human bronchoalveolar lavage cells with ozone inhalation. Leroy, P., Tham, A., Wong, H., et al.[2020]

Ozone exposures below 72 ppb do not show a causal association with adverse lung function effects, as any observed effects are not statistically significant compared to filtered air exposure.

The current National Ambient Air Quality Standard of 75 ppb is supported by evidence indicating that lung function effects at this level are transient, reversible, and do not lead to permanent respiratory injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of adverse human lung function effects in controlled ozone exposure studies. Goodman, JE., Prueitt, RL., Chandalia, J., et al.[2014]

Ozone exposure in the air can lead to serious health issues, including reduced lung function, increased airway reactivity, and higher mortality, with adverse effects observed at concentrations as low as 100 micrograms/m3.

To safeguard public health, Norway has set air quality guidelines recommending maximum ozone levels of 100 micrograms/m3 for 1-hour averages and 80 micrograms/m3 for 8-hour averages, and must alert the public when levels exceed 180 micrograms/m3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Health effects of ozone in the environment]. Låg, M., Schwarze, PE.[2013]

Inhaled ozone can cause significant respiratory issues, including inflammation and obstructive ventilatory impairment, which may trigger asthma in healthy individuals and worsen symptoms in those with existing asthma.

Even low concentrations of ozone (up to 120 micrograms/m3) can lead to slight lung function defects, and long-term exposure to ozone and other air pollutants is linked to increased respiratory symptoms and reduced lung function in polluted areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Asthma and ozone]. Keller, R.[2013]

Ozone is a challenging air pollutant to control, and even healthy individuals can experience respiratory symptoms and reversible lung function effects during high summer concentrations, especially with heavy outdoor exercise.

While prolonged exposure to ozone can lead to increased airway responsiveness and inflammation, no specific 'high-risk' group has been identified, unlike with other pollutants such as sulfur dioxide, and ongoing studies are investigating potential chronic effects of ozone exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ozone, air pollution, and respiratory health. Beckett, WS.[2018]

Exposure to elevated levels of ozone (O3) can lead to reversible reductions in lung function and symptoms like airway hyperreactivity and lung inflammation, particularly during summer months in urban areas.

The US Environmental Protection Agency has set a revised standard for ozone levels (0.08 ppm over 8 hours) to protect vulnerable populations, reflecting the recognized health risks associated with ozone exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ozone on lung function and lung diseases. Uysal, N., Schapira, RM.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Increased specific airway reactivity of persons with mild allergic asthma after 7.6 hours of exposure to 0.16 ppm ozone. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Dose-effect models for ozone exposure: tool for quantitative risk estimation. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Characterization of low-dose ozone-induced murine acute lung injury. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Inflammatory and repair pathways induced in human bronchoalveolar lavage cells with ozone inhalation. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of adverse human lung function effects in controlled ozone exposure studies. [2014]

6. Norway pubmed.ncbi.nlm.nih.gov

[Health effects of ozone in the environment]. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Asthma and ozone]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Ozone, air pollution, and respiratory health. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of ozone on lung function and lung diseases. [2019]