Genetic Screening for Inflammation Response to Wood Smoke Particles

(SmokeScreen Trial)

Overseen By Chris Brooks, BS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Immunosuppressants, Anticoagulants, NSAIDs, others

Disqualifiers: Cardiovascular disease, Diabetes, Asthma, others

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

Compensation: Varies

Number of Visits: 3

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Purpose: This screening protocol is designed to assess PMN (neutrophil) responsiveness to wood smoke particles (WSP) and the effect of the GSTM1 null genotype on this response. The researches will identify persons responsive and resistant to the inflammatory effect of WSP. It is anticipated that the GSTM1 genotype will be a risk factor for increased response to WSP.

Do I need to stop taking my current medications for the trial?

If you have mild persistent asthma, you must stop taking Singulair, inhaled corticosteroids, or cromolyn for 2 weeks before the study visits, except for using cromolyn before exercise. Other medications may be allowed if they don't interfere with the study and have been stable for a month.

Is wood smoke particle exposure safe for humans?

Research indicates that exposure to wood smoke particles can cause inflammation and oxidative stress in humans, which are signs of potential harm. These particles can affect lung cells and may contribute to respiratory and systemic health issues. ^{1 2 3 4 5}

How does the treatment for inflammation response to wood smoke particles differ from other treatments?

This treatment is unique because it involves genetic screening to identify individuals who are more responsive to inflammation caused by wood smoke particles, allowing for personalized mitigation strategies. Unlike standard treatments, this approach focuses on understanding genetic factors like the GSTM1 genotype that may influence inflammation response. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Wood Smoke Particles (WSP)?

Research in mice suggests that sub-acute exposure to wood smoke particles (WSP) can improve the body's response to influenza infection, leading to better respiratory outcomes like reduced weight loss and increased blood oxygen levels. ^{1 2 7 8 9}

Who Is on the Research Team?

David B Peden, M.D., M.S.

Principal Investigator

Professor

Are You a Good Fit for This Trial?

This trial is for people aged 18-45 with mild asthma or allergies, who have good lung function and a low risk of cardiovascular disease. They must not smoke much, be willing to stop certain asthma medications temporarily, avoid caffeine before visits, and use reliable contraception if sexually active.

Inclusion Criteria

My lung function improved by at least 12% after treatment, or I was diagnosed with asthma after age 6.

I am allergic to specific allergens and have symptoms or a positive skin test.

I am not pregnant or have had a hysterectomy with oopherectomy.

Exclusion Criteria

I need albuterol daily for my asthma symptoms.

I experience coughing or wheezing at night more than once a week.

I am not on immunosuppressants or anticoagulants, but I may be taking antidepressants or oral contraceptives.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Woodsmoke Exposure

Participants are exposed to wood smoke particles to assess neutrophil responsiveness and the effect of the GSTM1 null genotype

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in % neutrophils in induced sputum at 4 hours and 24 hours post-exposure

1 day

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Wood Smoke Particles (WSP)

Trial Overview Researchers are testing how wood smoke particles (WSP) affect inflammation in the lungs, particularly looking at whether a genetic factor (GSTM1 null genotype) influences this response. The study aims to identify individuals who are more or less responsive to WSP-induced inflammation.

How Is the Trial Designed?

Group I: Woodsmoke Exposure Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute of Environmental Health Sciences (NIEHS)

Collaborator

Trials

294

Recruited

1,233,000+

Published Research Related to This Trial

In a study involving 10 healthy volunteers, exposure to wood smoke particles (WSP) resulted in increased systemic inflammation, as indicated by a higher percentage of neutrophils in blood tests taken 20 hours after exposure.

Despite the inflammation observed, there were no significant changes in symptoms or pulmonary function during the exposure, suggesting that even short-term exposure to WSP can trigger inflammatory responses without immediate respiratory distress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to wood smoke particles produces inflammation in healthy volunteers. Ghio, AJ., Soukup, JM., Case, M., et al.[2022]

Wood smoke particles (WSP) significantly increase the expression of interleukin-8 (IL-8) in primary human airway epithelial cells in a dose-dependent manner, indicating a potential inflammatory response.

The mechanism of IL-8 expression induced by WSP involves the activation of epidermal growth factor receptor (EGFR) and p38 kinase signaling pathways, suggesting targets for therapeutic intervention in airway inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect and mechanism of interleukin-8 expression induced by wood smoke particles in primary human airway epithelial cells]. Yan, YJ., Wu, WD., Liu, WJ., et al.[2019]

The study found that the 24-hour response to wood smoke particles (WSP) is more informative for assessing airway inflammation than the 6-hour response, with significant increases in inflammatory markers like IL-1beta, IL-6, and IL-8 at this later time point.

The GSTM1 null genotype and asthma status were identified as significant factors that enhance the neutrophil response to WSP exposure, indicating that genetic and health background should be considered in future studies on airways inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers. Alexis, NE., Zhou, LY., Burbank, AJ., et al.[2023]

Sub-acute exposure to wood smoke particles (WSP) in rodents improved the host response to influenza infection, leading to reduced weight loss and increased blood oxygen saturation compared to controls.

Acute WSP exposure increased airspace macrophages, while sub-acute exposure resulted in a dose-dependent increase in neutrophils, indicating that WSP exposure can modulate immune cell responses during viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wood smoke particle exposure in mice reduces the severity of influenza infection. Vose, A., McCravy, M., Birukova, A., et al.[2022]

Inhalation of hardwood smoke (HWS) by ovalbumin-sensitized mice can lead to a significant increase in eosinophils in the lungs, indicating exacerbation of allergic airway inflammation, particularly at a particulate matter concentration of 300 microg/m3.

However, HWS exposure did not significantly affect levels of key cytokines (IL-2, IL-4, IL-13, and IFN-gamma) associated with allergic responses, suggesting that while HWS can worsen some aspects of inflammation, it does not alter the overall cytokine profile in this model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of hardwood smoke exposure on allergic airway inflammation in mice. Barrett, EG., Henson, RD., Seilkop, SK., et al.[2019]

Wood smoke particles (WSP) significantly increase reactive oxygen species in lung cells, indicating potential oxidative stress, but do not affect cell vitality or the inflammatory cytokine interleukin-8.

The toxicity of wood smoke is primarily driven by its constituents—soot, metals, and polycyclic aromatic hydrocarbons (PAHs)—with PAHs being particularly concerning due to their carcinogenic properties, suggesting that effective mitigation strategies should target all these components.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of wood smoke particles in human A549 lung epithelial cells: the role of PAHs, soot and zinc. Dilger, M., Orasche, J., Zimmermann, R., et al.[2019]

Wood smoke particles (WSPs) from different combustion phases have similar pro-inflammatory effects, but those from medium-temperature combustion are more cytotoxic than those from high-temperature combustion, indicating that combustion conditions significantly influence toxicity.

The toxicity of WSPs is largely determined by their organic fraction, which includes compounds beyond the commonly measured polycyclic aromatic hydrocarbons (PAHs), suggesting that other organic components also play a critical role in their harmful effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines. Bølling, AK., Totlandsdal, AI., Sallsten, G., et al.[2022]

In a study involving 20 non-smoking atopic subjects, controlled exposure to wood smoke particles did not lead to significant changes in systemic inflammation, oxidative stress, or microvascular function, indicating a lack of acute harmful effects in this population.

Despite exposure to varying concentrations of wood smoke, markers of DNA damage and inflammatory responses remained unchanged, suggesting that atopic individuals may have a different response to wood smoke compared to non-atopic individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function. Forchhammer, L., Møller, P., Riddervold, IS., et al.[2021]

The study identified a specific signaling pathway in lung epithelial cells that leads to the production of interleukin-8 in response to wood smoke exposure, involving NADPH oxidase, reactive oxygen species, and AMP-activated protein kinase.

In a mouse model, blocking this pathway with Compound C reduced lung inflammation and interleukin-8 levels, suggesting that targeting this signaling mechanism could be a potential therapeutic strategy for smoke inhalation injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammatory role of AMP-activated protein kinase signaling in an experimental model of toxic smoke inhalation injury. Perng, DW., Chang, TM., Wang, JY., et al.[2017]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Exposure to wood smoke particles produces inflammation in healthy volunteers. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Effect and mechanism of interleukin-8 expression induced by wood smoke particles in primary human airway epithelial cells]. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers. [2023]

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

Wood smoke particle exposure in mice reduces the severity of influenza infection. [2022]

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

Effects of hardwood smoke exposure on allergic airway inflammation in mice. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Toxicity of wood smoke particles in human A549 lung epithelial cells: the role of PAHs, soot and zinc. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function. [2021]

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

Inflammatory role of AMP-activated protein kinase signaling in an experimental model of toxic smoke inhalation injury. [2017]