Identifying individuals susceptible to wood smoke-induced inflammation

To Identify Persons Who Are Susceptible to WSP-induced Inflammation and Examine the Role of GSTM1 and Other Factors in This Susceptibility

This study is trying to see how some people react to wood smoke and if their genes make them more likely to have breathing problems or asthma from it.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years to 45 Years
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (Academic / other)
• Locations: 1 site (Chapel Hill, North Carolina)
• Trial ID: NCT02767973 on ClinicalTrials.gov

What this trial studies

This study aims to assess how individuals respond to wood smoke particles (WSP) and the influence of the GSTM1 genotype on this response. It will screen participants to identify those who show increased neutrophil responsiveness to WSP exposure, which is linked to airway inflammation and allergic asthma. The research focuses on understanding the health impacts of particulate matter from wood smoke, particularly in relation to respiratory and cardiovascular diseases. By identifying risk factors, the study seeks to better understand susceptibility to WSP-related health effects.

Who should consider this trial

Good fit: Ideal candidates include healthy volunteers aged 18-45 with no history of asthma and allergic asthmatic individuals with a physician diagnosis of asthma.

Not a fit: Patients with severe asthma or those with a high cardiovascular risk may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of airway inflammation in individuals exposed to wood smoke, particularly for those with asthma.

How similar studies have performed: While studies on particulate matter and respiratory health exist, this specific approach focusing on wood smoke particles and genetic susceptibility is relatively novel.

Eligibility criteria

Inclusion Criteria

1. Age 18-45 of both genders
2. Negative pregnancy test for females who are not s/p hysterectomy with oopherectomy
3. Calculated 10 year risk of CVD by the Framingham risk score of \<5%
4. Proof of Covid vaccination

Specific for Healthy Volunteers

4. No history of episodic wheezing, chest tightness or shortness of breath consistent with asthma, or physician diagnoses asthma.

5. FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .70

Specific for Allergic Asthmatic Volunteers

6. History of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician diagnosed asthma.

7. A POST-bronchodilator increase in FEV1 of at least 12%, OR a clinical history of asthma after the age of 6.

8. FEV1 of at least 75% of predicted without use of short acting bronchodilating medications for 12 hours, consistent with lung function of persons with no more than mild episodic or mild persistent asthma.

9. Mild persistent asthmatics must be well controlled (in accordance with NHLBI guidelines) and willing to discontinue Singulair, inhaled corticosteroids or cromolyn for a period of 2 weeks prior to study visits (except for use of cromolyn exclusively prior to exercise)

10. Allergic sensitization to at least one of the following allergen preparations: (House Dust Mite f, House dust mite p, Cockroach, Tree mix, Grass Mix, Weed Mix, Mold Mix 1, Mold Mix 2, Rat, Mouse, Guinea Pig, Rabbit, Cat or Dog) confirmed by positive immediate skin test response; or a clinical history consistent with seasonal or perennial allergy symptoms.

11. Subjects must be willing to avoid caffeine for 12 hours prior to all visits.

Allergy skin testing are performed as part of IRB98-0799, which a subject must complete in order to be considered for this protocol.

Exclusion Criteria

Patients who meet any of these criteria are not eligible for enrollment as study participants:

1. Clinical contraindications:

   1. Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections/immunodeficiency, history of tuberculosis.
   2. Viral upper respiratory tract infection within 4 weeks of challenge.
   3. Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge.
   4. Abnormal physical findings at the baseline visit, including but not limited to abnormalities on auscultation, temperature of 37.8° C, Systolic BP \> 150mm Hg or \< 85 mm Hg; or Diastolic BP \> 90 mm Hg or \< 50 mm Hg, or pulse oximetry saturation reading less than 94%.
   5. Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).
   6. Use of immunosuppressive or anticoagulant medications including routine use of NSAIDS. Oral contraceptives are acceptable, as are Antidepressants and other medications may be permitted if, in the opinion of the investigator, the medication will not interfere with the study procedures or compromise safety and if the dosage has been stable for 1 month
   7. Orthopedic in juries or impediments that would preclude bicycle or treadmill exercise.
   8. Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
   9. Medications which may impact the results of the WSP exposure, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents).
   10. Inability to avoid NSAIDS, Multivitamins, Vitamin C or E or herbal medications in the 4 days prior to the screening visit the exposure session.
   11. Symptomatic allergic rhinitis or current active allergies.
   12. Cigarette smoking \> 1 pack per month
   13. Current symptoms of Covid infection
   14. Positive Covid test in the past 90 days

       Specific for Healthy Volunteers
   15. Physician diagnosis of asthma.

       Specific for Asthmatic Volunteers
   16. Physician directed emergency treatment for an asthma exacerbation within the preceding 3 months
   17. Moderate or Severe asthma
   18. Exacerbation of asthma more than 2x/week which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
   19. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
   20. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
   21. History of intubation for asthma
   22. Use of systemic steroid therapy within the preceding 3 months for an asthma exacerbation. All use of systemic steroids in the last year will be reviewed by a study physician.
   23. Use of inhaled steroids, cromolyn or leukotriene inhibitors (Montelukast or Zafirlukast) except for use of cromolyn exclusively prior to exercise.
   24. Use of daily theophylline within the past month

Where this trial is running

Chapel Hill, North Carolina

• UNC Center For Environmental Medicine, Asthma and Lung Biology — Chapel Hill, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: David B Peden, M.D., M.S. — Professor
• Study coordinator: Chris Brooks, BS

Conditions Airway Inflammation; Allergic Asthma