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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how exposure to ozone, a common air pollutant, affects the lungs. Participants will breathe clean air (also called filtered or unpolluted air) and ozone on separate visits, focusing on lung reactions by analyzing cough samples. The trial seeks individuals vaccinated against COVID-19, without heart or lung diseases, and who haven't smoked in the past five years. As an unphased trial, it offers participants the chance to contribute to important research on air quality and lung health.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that breathing in ozone can affect the lungs. Studies have found that it might cause coughing, shortness of breath, and airway irritation. Some people may also experience worsened asthma or bronchitis symptoms. Ozone can lead to swelling and irritation in the air passages, making breathing difficult for some individuals. The effects often depend on the amount and duration of ozone exposure. While these effects are known, the study under consideration aims to understand them better. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how controlled ozone exposure might provide insights into lung injury caused by air pollution. Unlike typical treatments that focus on medications or therapies to alleviate symptoms, this trial uses ozone and clean air to directly study their effects on the lungs. By examining the response to these exposures, researchers hope to better understand the impact of air pollutants and potentially develop new strategies to protect lung health in polluted environments. This approach is unique as it uses real-world exposure scenarios to gather data, offering a different angle from the traditional treatment methods.

What evidence suggests that this trial's treatments could be effective for air pollution-related lung injury?

Research shows that breathing in ozone can cause serious lung problems. It links to coughing, shortness of breath, and worsening symptoms for people with asthma or bronchitis. Studies have found that ozone exposure can lead to swelling and damage in the airways. Long-term exposure might even slow lung growth in children and decrease lung function in young adults. In this trial, participants will breathe either clean air followed by ozone, or ozone followed by clean air, to study how ozone affects lung cells, with a focus on macrophages, which help fight infections. ^{1 2 3 6 7}

Who Is on the Research Team?

Howard M Kipen, MD

Principal Investigator

Rutgers School of Public Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7837374/

Health Effects of Ozone on Respiratory Diseases - PMC

Short-term exposure to high concentrations of ozone has been associated with increased mortality and cardiovascular and respiratory morbidity in many regions ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0160412025001424

Review article Ozone-induced lung injury and inflammation ...

Substantial evidence links O3 exposure to respiratory outcomes, including asthma and chronic obstructive pulmonary disease (COPD) exacerbation, and other ...

3.

epa.gov

epa.gov/ground-level-ozone-pollution/health-effects-ozone-pollution

Health Effects of Ozone Pollution

Inhaling ozone can cause coughing, shortness of breath, worse asthma or bronchitis symptoms, and irritation and damage to airways.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4872663/

Long-Term Ozone Exposure Increases the Risk ...

Chronic ozone exposure has been associated with decreased lung growth in children (26, 27) and decreased small airway function in young adults (28).

5.

thelancet.com

thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00148-5/fulltext

Impact of long-term exposure to ambient ozone on lung ...

The results consistently demonstrated that higher ambient ozone concentrations were associated with faster declines in spirometric lung function ...

6.

lung.org

lung.org/media/press-releases/state-of-the-air-2025

New Report: Nearly Half of People in U.S. Exposed to ...

Both ozone and particle pollution can cause premature death and other serious health effects such as asthma attacks, heart attacks and strokes, ...

7.

lung.org

lung.org/research/sota/health-risks

Health Impact of Pollution | State of the Air

When ozone levels are high, many people experience breathing problems such as chest tightness, coughing, and shortness of breath, often within hours of exposure ...