Health Effects of Biodiesel Exhaust Exposure

Study Overview
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Brief Summary
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Urban air pollution is a major contributor to greenhouse gases and has been shown to increase cardiovascular mortality and morbidity. This century has seen a rebirth of biofuel marketing and research, with biodiesel emerging as one of the strongest contenders within international markets. The pursuit of alternative renewable fuels is incredibly complex and has powered research in agriculture, biotechnology, production, transportation, feedstocks, ecology and biomass manufacturing. In spite of this, health effects have been an almost completely overlooked aspect. The purpose of this study is to investigate whether 100% biodiesel exhaust exposure in healthy volunteers leads to cardiovascular and inflammatory responses. Further investigations into the chemical composition of biodiesel exhaust will also be performed.

Official Title
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Cardiovascular Effects of Exposure to 100% Biodiesel Exhaust in Man

Conditions
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Vascular Endothelium

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: Non-smoking, healthy male subjects. All subjects undergo a general health examination and are required to have normal clinical examination, ECG, blood tests and lung function. Exclusion Criteria: Diabetes Mellitus Cardiovascular disease Asthma Respiratory infection within 2 weeks of the study Antioxidant- and/or vitamin supplementation within 1 week prior to, as well as during the course of the study. (incl vitamin C, Acetylcysteine) Smokers or regular snus usage

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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 particle matter concentration 300 mcg/m3) during intermittent exercise | Other: Forearm venous occlusion plethysmography study<br>* Measurement of forearm blood flow during unilateral intrabrachial infusion of four vasodilator drugs in incremental doses separated with 20-min washout periods. Bradykinin (endothelial-dependent vasodilator that releases t-PA) was infused at 100, 300 and 1000 pmol/min; acetylcholine (endothelial independent vasodilator that does not release t-PA) was infused at 5, 10 and 20 mcg/min; sodium nitroprusside (endothelial independent vasodilator that does not release t-PA) was infused at 2, 4 and 8 mcg/min and verapamil (endothelial independent and NO independent vasodilator that does not release t-PA) was infused at 10, 30 and 100 mcg/min. Bradykinin, acetylcholine and sodium nitroprusside were given in random order and verapamil was administered last due to its long acting effects.<br>|
| Experimental: Biodiesel exhaust exposure<br>1 hour exposure to dilute biodiesel exhaust (generated at same running conditions as diesel exhaust) during intermittent exercise | Other: Forearm venous occlusion plethysmography study<br>* Measurement of forearm blood flow during unilateral intrabrachial infusion of four vasodilator drugs in incremental doses separated with 20-min washout periods. Bradykinin (endothelial-dependent vasodilator that releases t-PA) was infused at 100, 300 and 1000 pmol/min; acetylcholine (endothelial independent vasodilator that does not release t-PA) was infused at 5, 10 and 20 mcg/min; sodium nitroprusside (endothelial independent vasodilator that does not release t-PA) was infused at 2, 4 and 8 mcg/min and verapamil (endothelial independent and NO independent vasodilator that does not release t-PA) was infused at 10, 30 and 100 mcg/min. Bradykinin, acetylcholine and sodium nitroprusside were given in random order and verapamil was administered last due to its long acting effects.<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 and -independent vasodilators (bradykinin & acetylcholine and sodium nitroprusside & verapamil respectively). Tissue plasminogen activator and plasminogen activator inhibitor-1 were analysed in blood samples taken after bradykinin infusions in order to assess fibrinolytic function. These composite outcome measures will together indicate vascular vasomotor function. | 4-6 hours after exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory function tests | Basic spirometry and fraction of exhaled nitric oxide (FeNO) are performed at baseline, as well as 6 and 24 hours after exposure. | Baseline, 6 and 24 hours after exposure | 
| Effects of exposure on metabolomic markers in plasma | Blood samples taken at baseline as well as at 2, 4 and 24 hours post-exposure will be stored as plasma for metabolomic analysis. Since inflammatory mediators such as eicosanoids and other fatty acid metabolites have been seen as likely key players in air pollution response, particular interest will be directed towards the oxylipin metabolome, which will be analyzed according to established protocols. These samples are taken in EDTA tubes and placed on ice. They are centrifuged at a low temperature and then divided into 1ml allotments. These are then stored in a freezer until analysis. | Baseline and 2, 4 & 24 hours after exposure | 

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