Cardiovascular Function, Genotoxicity
Conditions
Keywords
Air pollution, Diesel exhaust, Ultrafine particles, Vascular function, Endothelium function, Heart rate variability, DNA damage
Brief summary
Ambient air pollution is a complex mixture of gaseous pollutants and particulate matter (PM). PM has a recognized important role in human health. There is a strong scientific consensus on the independent association of PM and adverse cardiovascular and respiratory effects, as well as cancer. It is reasonable to expect that the smaller particles (ultrafine particles, UFP) may have an enhanced toxicity relative to other PM size fractions, due to physical properties and potential to translocation beyond the lung. A recent Danish report concluded that train conductors on a working day, and in two specific diesel engine trains, are exposed to higher concentrations of diesel exhaust than by constant stay in a busy street. Indeed, the average exposure for train conductors on such engines was around 100,000-150,000 UFP per cm3 as compared with around 40,000 per cm3 on a busy street in Copenhagen \[1\]. The aim of this study is to investigate if this occupational exposure is associated with vascular and respiratory impairment and DNA damage.
Interventions
OTHERElectric train
Exposure to air with low level of ultrafine particles (Electric train)
OTHERDiesel train
Exposure to air with high level of ultrafine particles (Diesel train)
Sponsors
National Research Centre for the Working Environment, Denmark
University of Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers * Legally competent subjects
Exclusion criteria
* Current smokers * Pregnancy * Alcohol and drug abuse * Prescriptionary use of anti-inflammatory or cardiovascular medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart rate variability | Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | Heart rate variability is measured with the EndoPAT 2000 device during baseline recording. It includes time domain measures (SDNN, pNN50 and RMSSD), high (HF) and low frequency (LF) components as well as LF/HF ratio, based on measurements over 5 minutes. |
| Reactive hyperemia index measured by peripheral arterial tonometry | Peripheral arterial tonometry is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | The primary outcome will be measured in the form of post-ischemic variation followed by the measurement of the vasomotor function after the administration of nitroglycerin, to allow the investigation of the endothelium independent vasodilatation. The portable device EndoPAT 2000 will be used (Itamar Medical Ltd, Israel) \[2-6\]. |
| DNA damage in peripheral blood mononuclear cells | Blood is sampled, prepared and stored after each exposure scenario (on the third day after 6 hours on defined train routes per day). Analysis is performed after sample collection completion. | The levels of strand breaks and formamidopyrimidine-DNA-glycosylase (FPG) sites are measured with the single cell gel electrophoresis assay (comet assay) \[7-13\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum/plasma bioactivity | Blood is sampled, prepared and serum is stored after each exposure scenario (on the third day after 6 hours on defined train routes per day). Analysis is performed after sample collection completion. | To assess the potential effects on vascular and endothelial function \[14, 15\] |
| Urinary excretion of 1-hydroxypyrene | Morning urine is sampled, prepared and stored after each exposure scenario (on the morning of the third day after two days with 6 hours on defined train routes). Analysis is performed after sample collection completion. | The urinary biomarker of exposure to polycyclic aromatic hydrocarbons, 1-hydroxypyrene, is measured with reverse-phase HPLC and standardized for diuresis with the concentration of creatinine |
| Lung function | The lung function is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | The lung function is measured with EasyOne 2001 spirometer device (Switzerland). Lung function measurements includes forced vital capacity (FVC), forced expiratory volume after 1 second (FEV1), peak expiratory flow (PEF) and FEV1/FVC. |
| Systemic inflammatory markers | Blood is sampled, prepared and stored after each exposure scenario (on the third day after 6 hours on defined train routes per day). Analysis is performed after sample collection completion. | Acute phase reactants, pro-inflammatory cytokines and cell adhesion molecules |
Other
| Measure | Time frame | Description |
|---|---|---|
| Augmentation index | Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | Measured with the EndoPAT 2000 device during baseline recording. |
| Heart rate | Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | Measured with the EndoPAT 2000 device during baseline recording. |
| Blood pressure | Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | Measured with an aneroid sphygmomanometer. |
Countries
Denmark
Outcome results
None listed