To Identify Persons Who Are Susceptible to WSP-induced Inflammation and Examine the Role of GSTM1 and Other Factors in This Susceptibility (SmokeScreen)
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|ClinicalTrials.gov Identifier: NCT02767973|
Recruitment Status : Recruiting
First Posted : May 11, 2016
Last Update Posted : January 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Airway Inflammation Allergic Asthma||Other: Wood Smoke Particles (WSP)||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||To Identify Persons Who Are Susceptible to WSP-induced Inflammation and Examine the Role of GSTM1 and Other Factors in This Susceptibility|
|Study Start Date :||May 2016|
|Estimated Primary Completion Date :||May 2020|
|Estimated Study Completion Date :||May 2021|
|Experimental: Woodsmoke Exposure||
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.
- Change in % neutrophils in induced sputum, comparing the 4 hr post wood smoke exposure to the baseline [ Time Frame: baseline, and 4 hours post exposure ]Induced sputum will be collected and % neutrophils will be measured after each exposure and will be compared to baseline and each other.
- Change from baseline in post wood smoke airway neutrophil influx between GSTM1 null genotype compared to GSTM1 sufficient subjects [ Time Frame: baseline, and 4 hours post exposure ]Quantitative RT PCR will be used to measure the presence or absence of the GSTM1 transcript from blood obtained by venipuncture
- 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 [ Time Frame: baseline, 4 hours and 24 hours post exposure ]Induced sputum will be collected and % neutrophils will be measured after each exposure and will be compared to baseline and each other.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02767973
|Contact: Katherine H Mills, B.A.||email@example.com|
|United States, North Carolina|
|UNC Center For Environmental Medicine, Asthma and Lung Biology||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Katie Mills 919-843-6598 firstname.lastname@example.org|
|Principal Investigator:||David B Peden, M.D., M.S.||Professor|