PM Exposure for Air Pollution Effects

Overseen By Patrice Ratliffe

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: U.S. EPA Human Studies Facility

Must not be taking: NSAIDs, Systemic steroids, Beta-blockers

Disqualifiers: COVID-19, Cardiovascular disease, Asthma, Smoking, others

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

Compensation: Varies

Number of Visits: 7

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You will need to stop taking over-the-counter pain medications like aspirin, ibuprofen, and naproxen for 48 hours before and after the exposures. If you take vitamins or supplements, you may need to stop them for at least two weeks before the study. Other medications may be reviewed by the investigators.

What data supports the effectiveness of the treatment for PM Exposure for Air Pollution Effects?

Research shows that exposure to fine particulate matter (tiny particles in the air) is linked to health problems like increased mortality and lung issues. While the studies don't directly show the effectiveness of filtered air exposure, they highlight the potential health benefits of reducing exposure to these harmful particles. ^{1 2 3 4 5}

Is PM2.5 exposure safe for humans?

Research indicates that exposure to fine particulate matter (PM2.5) can lead to various health issues, including diseases and premature death, suggesting it may not be safe for humans. ^{3 6 7 8 9}

How is PM exposure treatment different from other treatments for air pollution effects?

PM exposure treatment is unique because it involves studying the effects of fine particulate matter (tiny particles in the air) on health, rather than using a drug or therapy to treat a condition. This approach focuses on understanding how exposure to these particles affects the body, which is different from traditional treatments that aim to alleviate symptoms or cure diseases. ^{1 3 5 8 10}

What is the purpose of this trial?

Purpose: To determine whether 3-day consecutive exposures to levels of fine particulate matter (PM2.5) that are close to the current 24-hr national standard will cause changes in inflammatory and cardiopulmonary endpoints in healthy young individuals. Participants: 20 healthy males and females aged 18-35 years. Procedures (methods): Subjects will be randomly exposed to three consecutive days of filtered air (4 hr/day) and three consecutive days of PM2.5 (approximately 35 µg/m3; 4 hr/day) in an exposure chamber. Blood collection for inflammatory factors such as C-reactive protein (CRP), clotting factors; heart rate variability (HRV); spirometry; and a symptom questionnaire will be conducted before and after each exposure.

Eligibility Criteria

Healthy individuals aged 18-35 with normal lung function and heart health, not vaccinated for or recovered from COVID-19, non-smokers without chronic diseases. They must be able to exercise moderately and have a BMI between 19 and 30.

Inclusion Criteria

You are physically fit enough to do moderate exercise for 2 hours and can complete a specific exercise routine without going over 80% of your maximum heart rate.

I can do moderate exercise for 2 hours and handle specific breathing exercises without my heart rate going too high.

My lung function tests are within the normal range.

Exclusion Criteria

Individuals with a history of skin allergies to adhesives used in securing EKG electrodes

Individuals with a body mass index (BMI) >30 or <19. Body mass index is calculated by dividing the weight in kilograms by the square of the height in meters

Individuals who are allergic to chemical vapors or gases

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Filtered Air Exposure

Participants are exposed to filtered air for three consecutive days, 4 hours per day, in an exposure chamber.

3 days

3 visits (in-person)

PM2.5 Exposure

Participants are exposed to PM2.5 for three consecutive days, 4 hours per day, in an exposure chamber.

3 days

3 visits (in-person)

Follow-up

Participants are monitored for changes in inflammatory and cardiopulmonary endpoints after exposure.

4 days

1 visit (in-person)

Treatment Details

Interventions

• Filtered air exposure
• PM exposure

Trial Overview The trial tests the effects of breathing low levels of fine particulate matter (PM2.5) compared to filtered air on inflammation and heart/lung health in healthy young adults over three consecutive days.

Participant Groups

Group I: PM exposure Experimental Treatment 1 Intervention

Subjects will be randomly exposed to three consecutive days of PM2.5 exposure arm in a double-blind cross-over fashion in an exposure chamber, and exposures will be separated by a minimum of 13 days from the filtered air arm.

Group II: Filtered air exposure Experimental Treatment 1 Intervention

Subjects will be randomly exposed to three consecutive days of filtered air exposure arm in a double-blind cross-over fashion in an exposure chamber, and exposures will be separated by a minimum of 13 days from the PM2.5 arm.

Who Is Running the Clinical Trial?

U.S. EPA Human Studies Facility

Lead Sponsor

Trials

2

Recruited

80+

Findings from Research

Exposure to fine particulate matter (PM2.5) can lead to immediate decreases in endothelial function in individuals with type 2 diabetes, as shown in a study of 22 participants over four days.

The effects of PM2.5 on endothelial dysfunction were more pronounced in participants with higher body mass index, elevated blood sugar levels, and certain genetic factors, indicating that those with insulin resistance may be particularly vulnerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. Schneider, A., Neas, L., Herbst, MC., et al.[2022]

Exposure to fine particulate matter (PM10) is linked to increased mortality, with a 10 µg/m³ rise in PM10 correlating to a 0.5% increase in daily deaths, highlighting the serious health risks even at low concentrations.

Analysis of lung tissues from victims of the 1952 London smog revealed a high presence of soot and various metal-bearing particles, suggesting that ultrafine carbonaceous and metal PM are particularly toxic and contribute significantly to health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicologic and epidemiologic clues from the characterization of the 1952 London smog fine particulate matter in archival autopsy lung tissues. Hunt, A., Abraham, JL., Judson, B., et al.[2018]

Exposure to particulate matter (PM10) significantly accelerates the release of monocytes from the bone marrow in Watanabe heritable hyperlipidemic (WHHL) rabbits, reducing their transit time to 23.2 hours compared to 30.4 hours in control rabbits.

The study suggests that PM10 exposure not only increases circulating monocyte counts but also correlates with the amount of particles engulfed by alveolar macrophages, indicating a link between air pollution and the progression of atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to ambient particles accelerates monocyte release from bone marrow in atherosclerotic rabbits. Goto, Y., Hogg, JC., Shih, CH., et al.[2020]

A study of 975 schoolchildren over three years found that higher levels of PM10 air pollution were linked to slower growth in lung function, specifically a decrease in forced expiratory volume (FEV1) by 84 mL per year and midexpiratory flow (MEF25-75) by 329 mL per year.

In addition to PM10, exposure to nitrogen dioxide and ozone also negatively impacted lung function growth, highlighting the significant effects of long-term air pollution on children's respiratory health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren. Horak, F., Studnicka, M., Gartner, C., et al.[2019]

Exposure to PM2.5 leads to increased oxidative stress and cell death in lung cells, but treatment with rosiglitazone, a PPARγ agonist, significantly reduces these harmful effects.

Rosiglitazone not only decreases ROS production and cell apoptosis in PM2.5-treated lung cells but also inhibits the activation of key signaling pathways (ERK1/2 and STAT3), suggesting its potential as a therapeutic agent for lung diseases caused by air pollution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosiglitazone inhibits PM2.5-induced cytotoxicity in human lung epithelial A549 cells. Pu, XJ., Li, J., Zhou, QL., et al.[2022]

Exposure to water-soluble components of PM2.5 significantly shortens lifespan and healthspan in nematodes, indicating serious adverse health effects from fine particulate matter.

The study suggests that the insulin/IGF-1 signaling (IIS) pathway and lipid metabolism are disrupted by WS-PM2.5 exposure, which may play a crucial role in the observed toxic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PM2.5 induce lifespan reduction, insulin/IGF-1 signaling pathway disruption and lipid metabolism disorder in Caenorhabditis elegans. Zhang, W., Li, Z., Li, G., et al.[2023]

PM2.5 samples from communities near railyards showed seasonal variations in chemical reactivities, with higher prooxidant levels in winter for Commerce and Long Beach, indicating that air pollution effects can vary by location and season.

The vapor phase of air pollution contained a higher concentration of electrophiles, which are reactive chemicals that can cause adverse health effects, highlighting the need to consider both PM2.5 and vapor phases when assessing air quality and health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemical reactivities of ambient air samples in three Southern California communities. Eiguren-Fernandez, A., Di Stefano, E., Schmitz, DA., et al.[2018]

In a year-long study involving 149 children with asthma, exposure to traffic-related fine particles (like those from motor vehicles) was linked to a significant increase in asthma symptoms and medication use, with a 10% higher likelihood of wheezing for every 5-microgram/m³ increase in these particles.

The study found that over half of the PM(2.5) exposure was from traffic sources, highlighting the importance of targeting specific pollution sources to improve respiratory health in children with asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptoms and medication use in children with asthma and traffic-related sources of fine particle pollution. Gent, JF., Koutrakis, P., Belanger, K., et al.[2021]

Exposure to fine particulate matter (PM2.5) significantly decreases circulating levels of endothelial progenitor cells (EPCs) in mice, which are crucial for vascular repair, without affecting stem cell levels.

The study found that PM2.5 exposure inhibits the mobilization of EPCs from the bone marrow to the bloodstream by disrupting signaling pathways triggered by vascular endothelial growth factor (VEGF), potentially leading to impaired vascular repair and increased cardiovascular disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow. Haberzettl, P., Lee, J., Duggineni, D., et al.[2021]

Exposure to PM2.5 from Jinchang, which contains significantly higher levels of nickel and other metals, leads to increased pulmonary inflammation and vascular dysfunction in mice, indicating that nickel is a key toxic component.

The study suggests that NADPH oxidase plays a major role in the vascular dysfunction caused by PM2.5 exposure, as its inhibition was effective in restoring normal blood vessel relaxation responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metal rich particulate matter impairs acetylcholine-mediated vasorelaxation of microvessels in mice. Cuevas, AK., Niu, J., Zhong, M., et al.[2019]

References

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

Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. [2022]

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

Toxicologic and epidemiologic clues from the characterization of the 1952 London smog fine particulate matter in archival autopsy lung tissues. [2018]

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

Exposure to ambient particles accelerates monocyte release from bone marrow in atherosclerotic rabbits. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren. [2019]

5. China pubmed.ncbi.nlm.nih.gov

Rosiglitazone inhibits PM2.5-induced cytotoxicity in human lung epithelial A549 cells. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

PM2.5 induce lifespan reduction, insulin/IGF-1 signaling pathway disruption and lipid metabolism disorder in Caenorhabditis elegans. [2023]

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

Chemical reactivities of ambient air samples in three Southern California communities. [2018]

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

Symptoms and medication use in children with asthma and traffic-related sources of fine particle pollution. [2021]

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

Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Metal rich particulate matter impairs acetylcholine-mediated vasorelaxation of microvessels in mice. [2019]