Health Effects of Biodiesel Exhaust Exposure (BD100)

Cardiovascular Effects of Exposure to 100% Biodiesel Exhaust in Man

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.

Study Overview

• Status: Completed
• Conditions: Vascular Endothelium
• Intervention / Treatment: Other: Forearm venous occlusion plethysmography study

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Umeå, Sweden, 90185
    • Umeå University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diesel exhaust exposure; 1 hour exposure to dilute diesel exhaust (approximate particle matter concentration 300 mcg/m3) during intermittent exercise	Other: Forearm venous occlusion plethysmography study; 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.
EXPERIMENTAL: Biodiesel exhaust exposure; 1 hour exposure to dilute biodiesel exhaust (generated at same running conditions as diesel exhaust) during intermittent exercise	Other: Forearm venous occlusion plethysmography study; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: University of Edinburgh

Publications and helpful links

General Publications

• Unosson J, Kabele M, Boman C, Nystrom R, Sadiktsis I, Westerholm R, Mudway IS, Purdie E, Raftis J, Miller MR, Mills NL, Newby DE, Blomberg A, Sandstrom T, Bosson JA. Acute cardiovascular effects of controlled exposure to dilute Petrodiesel and biodiesel exhaust in healthy volunteers: a crossover study. Part Fibre Toxicol. 2021 Jun 14;18(1):22. doi: 10.1186/s12989-021-00412-3.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: April 30, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (ESTIMATE): June 21, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): June 21, 2013
• Last Update Submitted That Met QC Criteria: June 18, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Air Pollution; Biodiesel exhaust; Diesel exhaust; Vascular function; Fibrinolysis; Acute endothelial responses
• Other Study ID Numbers: UMU-12-14031