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

NCT02767973 | Suspended

• 2 other identifiers: 15-17751R01ES025124-01A1
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Airway Inflammation; Allergic Asthma

Outcome Measures

Primary Outcomes (2)

• Change in % neutrophils in induced sputum, comparing the 4 hr post wood smoke exposure to the baseline

  Induced sputum will be collected and % neutrophils will be measured after each exposure and will be compared to baseline and each other.

  baseline, and 4 hours post exposure

• Change from baseline in post wood smoke airway neutrophil influx between GSTM1 null genotype compared to GSTM1 sufficient subjects

  Quantitative RT PCR will be used to measure the presence or absence of the GSTM1 transcript from blood obtained by venipuncture

  baseline, and 4 hours post exposure

Secondary Outcomes (1)

• Change in % neutrophils in induced sputum, comparing the 24 hr post wood smoke exposure to the baseline and the change in % neutrophils from 24 hr to 4 hr post wood smoke exposure

  baseline, 4 hours and 24 hours post exposure

Study Arms (1)

Woodsmoke Exposure

EXPERIMENTAL

Other: Wood Smoke Particles (WSP)

Interventions

Wood Smoke Particles (WSP) OTHER

After baseline (pre-exposure) assessment (which includes recovery of induced sputum), these volunteers will then undergo an exposure to 500μg/m3 wood smoke particles for 2 hours, with alternating 15 min of exercise (cycle ergometer) with 15 min rest to achieve 25 l/m2 body surface/min minute ventilation, followed by sputum induction after 6 and 24 hours after initiation of the challenge.

Woodsmoke Exposure

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 of both genders
• Negative pregnancy test for females who are not s/p hysterectomy with oopherectomy
• Calculated 10 year risk of CVD by the Framingham risk score of \<5%
• Proof of Covid vaccination
• Specific for Healthy Volunteers
• \. No history of episodic wheezing, chest tightness or shortness of breath consistent with asthma, or physician diagnoses asthma.
• \. FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .70
• Specific for Allergic Asthmatic Volunteers
• \. History of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician diagnosed asthma.
• \. A POST-bronchodilator increase in FEV1 of at least 12%, OR a clinical history of asthma after the age of 6.
• \. 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.
• \. 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)
• \. 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.
• \. 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.

You may not qualify if:

• Patients who meet any of these criteria are not eligible for enrollment as study participants:
• Clinical contraindications:
• 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.
• Viral upper respiratory tract infection within 4 weeks of challenge.
• Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge.
• 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%.
• Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).
• 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
• Orthopedic in juries or impediments that would preclude bicycle or treadmill exercise.
• 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.
• 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).
• Inability to avoid NSAIDS, Multivitamins, Vitamin C or E or herbal medications in the 4 days prior to the screening visit the exposure session.
• Symptomatic allergic rhinitis or current active allergies.
• Cigarette smoking \> 1 pack per month
• Current symptoms of Covid infection

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Environmental Health Sciences (NIEHS): collaborator

Study Sites (1)

UNC Center For Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599, United States

Location

Study Officials

• David B Peden, M.D., M.S.

  Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 11, 2016
• Study Start: May 1, 2016
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)