Ozone Exposure for Lung Inflammation

(MOLI Trial)

Overseen By Claudia Salazar

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Robert Tighe, MD

Must not be taking: Antihistamines, NSAIDs, Antioxidants, Vitamins

Disqualifiers: Smoking, Pregnancy, Alcohol abuse, others

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

Compensation: Varies

Number of Visits: 5

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial involves participants breathing in clean air or ozone to see how their lungs react. It focuses on people who have had past respiratory infections to understand if these infections make their lungs more sensitive to pollution.

Will I have to stop taking my current medications?

Participants will need to stop taking antihistamines, nonsteroidal anti-inflammatory agents, antioxidants, and certain vitamins for 1 week before and during the testing period.

Is ozone exposure generally safe for humans?

Ozone exposure is not considered safe for humans as it can cause lung function problems, airway inflammation, and other respiratory issues. Long-term exposure may lead to more severe health effects like asthma exacerbation and lung tissue damage. ^{1 2 3 4 5}

How does the treatment Ozone differ from other treatments for lung inflammation?

Ozone exposure is unique as a treatment for lung inflammation because it involves inhaling a gas that can cause both acute and chronic respiratory effects, unlike traditional medications that are typically administered orally or intravenously. This treatment is novel in its approach, as it leverages the body's response to ozone exposure to study its effects on lung inflammation, rather than directly targeting inflammation with drugs. ^{1 5 6 7 8}

Who Is on the Research Team?

Robert Tighe, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with or without a history of mild to moderate COVID-19, who have recovered and are over 6 months post-infection with normal lung function. Excluded are those with substance abuse issues, pregnant or lactating women, individuals under the investigators' supervision, recent antibiotic use or respiratory infection, chronic cardio/pulmonary conditions, ongoing COVID-19 symptoms or abnormal lungs.

Inclusion Criteria

I had COVID-19, recovered over 6 months ago, and my lung function tests are normal.

I had COVID-19 more than 6 months ago.

I have never had COVID-19 or tested positive for it.

Exclusion Criteria

I had COVID-19 pneumonia, still have breathing issues, use oxygen, or my lung function isn't normal.

You had COVID-19 before, but you can't show a positive test result.

I can avoid taking antihistamines, NSAIDs, certain antioxidants, and vitamins for a week before and during the test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Initial Testing and Exposure

Participants undergo a two-day series of testing including blood draw, breathing test, and inhaled challenge with either filtered air or ozone

2 days

2 visits (in-person)

Follow-up

Participants receive follow-up phone calls 24 hours after each 2-day test series

1 day

Phone call

Second Testing and Exposure

Participants return 18-20 days later to repeat the two-day series of testing with the alternate exposure (filtered air or ozone)

2 days

2 visits (in-person)

Follow-up

Participants receive follow-up phone calls 24 hours after the second 2-day test series

1 day

Phone call

What Are the Treatments Tested in This Trial?

Interventions

• Ozone

Trial Overview The study aims to understand how previous respiratory infections like COVID-19 influence lung inflammation after being exposed to environmental factors like ozone. Participants will be divided into cohorts based on their SARS-CoV-2 infection history and assessed for lung inflammation response.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

SARS-CoV-2 pneumonia

Group II: Cohort 2 Experimental Treatment 1 Intervention

Documented mild SARS-CoV-2 infection

Group III: Cohort 1 Experimental Treatment 1 Intervention

No history of SARS-CoV-2

Who Is Running the Clinical Trial?

Robert Tighe, MD

Lead Sponsor

Trials

3

Recruited

140+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Environmental Health Sciences (NIEHS)

Collaborator

Trials

294

Recruited

1,233,000+

Published Research Related to This Trial

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]

Ozone exposure leads to increased activation of the epidermal growth factor receptor (EGFR) in human bronchial epithelial cells, which is linked to airway inflammation and pulmonary function issues.

The study found that inhibiting Src kinase activity can prevent the O3-induced activation of EGFR and the subsequent increase in interleukin 8 (IL-8) expression, suggesting a potential therapeutic target for mitigating ozone-related lung inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SRC-mediated EGF receptor activation regulates ozone-induced interleukin 8 expression in human bronchial epithelial cells. Wu, W., Wages, PA., Devlin, RB., et al.[2021]

Interleukin-10 (IL-10) plays a protective role against ozone (O₃)-induced pulmonary inflammation, as shown by significantly higher levels of inflammatory cells in IL-10 deficient mice compared to wild-type mice after O₃ exposure.

Gene expression analyses identified specific pathways and mediators, such as macrophage inflammatory protein 2 and cathepsin E, through which IL-10 modulates the immune response, suggesting potential therapeutic targets for protecting individuals from O₃-related lung damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective role of interleukin-10 in ozone-induced pulmonary inflammation. Backus, GS., Howden, R., Fostel, J., et al.[2021]

Exposure to ambient ozone leads to airway hyperreactivity and lung inflammation, primarily through oxidative stress that activates inflammasomes and releases inflammatory cytokines like IL-1.

Understanding the mechanisms of ozone-induced lung injury may help identify new biomarkers and therapeutic targets for treating related lung diseases, such as emphysema and respiratory failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammasome, IL-1 and inflammation in ozone-induced lung injury. Michaudel, C., Couturier-Maillard, A., Chenuet, P., et al.[2020]

Ground-level ozone is a respiratory irritant that can decrease lung function and is linked to various respiratory health issues, highlighting its potential dangers to public health.

While some studies suggest that short-term increases in ozone levels may lead to higher rates of cardiopulmonary mortality, other research has found no clear connection, indicating that the effects of ozone exposure can be complex and influenced by other pollutants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outdoor air pollution: ozone health effects. Chen, TM., Gokhale, J., Shofer, S., et al.[2013]

Short-term exposure to elevated ozone levels can lead to a range of respiratory effects, from mild and reversible symptoms to severe outcomes like hospital admissions.

There is a need for further research to understand the full spectrum of health effects from acute ozone exposure, including identifying sensitive groups and exploring the interaction between ozone and viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes. Ostro, BD.[2019]

A single high dose of ozone exposure in mice causes immediate damage to the respiratory epithelial barrier, leading to cell death and inflammation, but this damage is reversible if exposure is not chronic.

Chronic exposure to ozone results in irreversible lung damage, including emphysema and chronic inflammation, which is similar to the effects of other pollutants and is linked to the exacerbation of asthma and COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Respiratory Barrier Disruption by Ozone Exposure in Mice. Sokolowska, M., Quesniaux, VFJ., Akdis, CA., et al.[2020]

A study involving 14 healthy, athletic subjects exposed to 0.20 ppm ozone (O3) for 4 hours showed significant increases in airway inflammation, as indicated by higher total cell counts and lactate dehydrogenase (LDH) levels in the bronchial lavage compared to filtered air exposure.

The results demonstrated that O3 exposure leads to an acute influx of inflammatory cells, particularly neutrophils, into the airways, highlighting the airway as a significant site of O3-induced injury and inflammation in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy. Aris, RM., Christian, D., Hearne, PQ., et al.[2013]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

SRC-mediated EGF receptor activation regulates ozone-induced interleukin 8 expression in human bronchial epithelial cells. [2021]

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

Protective role of interleukin-10 in ozone-induced pulmonary inflammation. [2021]

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

Inflammasome, IL-1 and inflammation in ozone-induced lung injury. [2020]

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

Outdoor air pollution: ozone health effects. [2013]

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

Examining acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes. [2019]

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

Acute Respiratory Barrier Disruption by Ozone Exposure in Mice. [2020]

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

Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy. [2013]