NCT02767973

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

• Status: Suspended
• Phase: N/A
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Detailed description

Particulate matter (PM) is a leading cause of respiratory tract and cardiovascular disease in the United States and world-wide. Wood smoke particles (WSP) derived from wild land and other fires account for a significant fraction of ambient air PM. Health effects associated with WSP include acute bronchitis, asthma exacerbation, pneumonia, cough and systemic inflammation. While these effects are seen in both healthy and asthmatic individuals, many studies indicate that asthmatics have increased susceptibility to the effects of WSP. Though WSP-related effects on cardiovascular (CV) disease are less well documented, WSP do contribute to PM levels, and PM exposure is linked to CV health effects (changes in heart rate variability, vascular reactivity, and lipid profiles). WSP from wild land fires can cause abrupt increases in ambient air PM 2.5 levels (mean levels \~250µg/m3, peak levels \>1000 µg/m3). Avoidance of rapidly increasing PM air pollution due to wild land fires is not feasible, as many people cannot leave the burn region. This is a screening protocol to ensure that there ultimately will be adequate subjects available for testing gamma tocopherol in an appropriate population. It will identify volunteers who have a ≥10% increase in %PMNs following WSP challenge over baseline values (SA1). This screening procedure will identify various risk factors that may increase risk of experiencing airway inflammation and related adverse health outcomes following WSP exposure. The GSTM1- genotype is a risk factor that has been extensively explored. Researchers at the CEMALB have reported that GSTM1- healthy volunteers (HVs) have increased inflammatory and systemic responses to O3 and various components of PM (LPS70 and Diesel exhaust particles). Using the 10% increase in %PMNs to define PMN responsiveness, results showed that GSTM1- volunteers had a 13 fold higher risk of being PMN responders to 0.06 ppm O3. When examining %PMNs as a continuous measure, it was observed that GSTM1- volunteers have increased airway PMN response O3 as well as increased airway and systemic PMN response to LPS70. The researchers at the CEMALB have also examined various response features of 27 individuals (13 healthy, 4 allergic non asthmatics, 10 allergic asthmatics) defined as being responsive (R, n=18) or non-responsive (NR, n=9) to O3 based on airway PMN influx (%PMNs). Among the factors explored were inflammatory responses, baseline characteristics and gene expression profiles in recovered sputum cells. The researchers have also observed that within individuals, PMN response to O3 and LPS correlate, and anticipate that WSP will induce inflammatory responses via mechanisms similar to those for these pollutants.

Conditions

• Airway Inflammation
• Allergic Asthma

Interventions

Type	Name	Description
OTHER	Wood Smoke Particles (WSP)	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.

Timeline

• Start date: 2016-05-01
• Primary completion: 2027-05-01
• Completion: 2027-05-01
• First posted: 2016-05-11
• Last updated: 2025-08-11

Locations

1 site across 1 country: United States