Biodiesel Exhaust, Acute Vascular and Endothelial Responses

Study Overview
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Brief Summary
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Exposure to particulate air pollution has been shown to increase cardiovascular mortality and morbidity, and in previous controlled exposure studies has been shown to have acute cardiovascular and respiratory effects. The last decade has seen an unprecedented drive towards finding a bioeconomical and renewable source of fuel in order to reduce our dependence on fossil fuels. Although both biodiesel and bioethanol have emerged as contenders for future fuels, biodiesel remains as the strongest contender within European markets. In 2007 researchers at the EPA released a commentary, which concluded that the assumed correlation between the chemical composition of biodiesel exhaust and a reduction in health effects was only hypothetical. They suggested that there was a clear need for the study of health effects in humans regarding biofuel exhaust. In this project the investigators aim to investigate the cardiovascular, respiratory and inflammatory responses to biofuel exhaust exposure in healthy volunteers.

Official Title
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Inhalation of Dilute Biodiesel Exhaust: Acute Vascular and Endothelial Responses

Conditions
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Healthy

Intervention / Treatment
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* Other: Forearm venous occlusion plethysmography study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 healthy, non-smoking subjects, age 20-55 year old, both genders. All subjects undergo a general health examination and are required to have: Normal clinical examination Normal EKG Normal routine blood tests Normal lung function Exclusion Criteria: Cardiovascular disease Diabetes Mellitus Asthma and/or allergy Respiratory infection within 3 weeks of the study Antioxidant- and/or vitamin supplementation within 2 weeks prior to, as well as during the course of the study. (incl vitamin C, Acetylcysteine) Female subjects will take a urinary pregnancy test before each exposure and will be excluded if this is positive.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diesel exhaust exposure<br>1 hour exposure to dilute diesel exhaust (approximate PM10 concentration 300 mcg/m3) during intermittent exercise | Other: Forearm venous occlusion plethysmography study<br>* Forearm venous occlusion plethysmography to measure forearm blood flow during unilateral intrabrachial infusion of endothelium-dependent (bradykinin [100, 300 & 1000 pmol/min]; acetylcholine [5, 10 & 20 µg/min]) and -independent [sodium nitroprusside [2, 4 & 8 µg/min]; verapamil [10, 30 & 100 µg/min]) vasodilators. Each drug to be infused for 6 mins at each dose in increasing concentrations. 0.9% sodium chloride will be infused for 20 min between each individual drug to allow washout.<br>|
| Experimental: Biodiesel exhaust exposure<br>1 hour exposure to dilute biodiesel exhaust (approximate PM10 concentration 300 mcg/m3) during intermittent exercise | Other: Forearm venous occlusion plethysmography study<br>* Forearm venous occlusion plethysmography to measure forearm blood flow during unilateral intrabrachial infusion of endothelium-dependent (bradykinin [100, 300 & 1000 pmol/min]; acetylcholine [5, 10 & 20 µg/min]) and -independent [sodium nitroprusside [2, 4 & 8 µg/min]; verapamil [10, 30 & 100 µg/min]) vasodilators. Each drug to be infused for 6 mins at each dose in increasing concentrations. 0.9% sodium chloride will be infused for 20 min between each individual drug to allow washout.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular vasomotor and fibrinolytic function | Forearm venous occlusion plethysmography to measure forearm blood flow during unilateral intrabrachial infusion of endothelial-dependent (bradykinin and acetylcholine) and -independent (sodium nitroprusside and verapamil) vasodilators. Fibrinolytic function assessed by blood sampling after infusion of bradykinin for tissue plasminogen activator and plasminogen activator inhibitor-1. | 4-6 hours after exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory function tests | Basic spirometry will be performed at baseline and 6 hours after each exposure | 6 hours after exposure | 
| Inflammatory markers | Blood samples will be taken and stored as plasma and serum for measurement of inflammatory mediators | Baseline and up to 24 hours after exposure | 
| Central arterial stiffness | Central arterial stiffness (PWV and PWA) will be measured at baseline and immediately after the exposure | Baseline and post exposure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Air Pollution, Diesel exhaust, Biodiesel exhaust, Vascular function, Fibrinolysis, Acute vascular and endothelial responses