Health Effects of Occupational Exposure to Combustion Particles - a Study on Volunteers Performing as Train Conductors

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Diesel Combustion Generated Air Pollution on Cardiovascular Function and Oxidatively Damaged DNA in Healthy Volunteers

Conditions
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Cardiovascular Function, Genotoxicity

Intervention / Treatment
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* Other: Electric train
* Other: Diesel train


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers Legally competent subjects Exclusion Criteria: Current smokers Pregnancy Alcohol and drug abuse Prescriptionary use of anti-inflammatory or cardiovascular medication

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diesel train - exposure scenario<br>The same study person will be exposed to two different scenarios, at different times and for three consecutive days. It will be a lag time of 2 weeks between each exposure scenario. The exposure scenario is defined as a workday (6 hours) on the diesel ME-driven model regional train. The Diesel Train Scenario is performed twice. After the scenario completion (on the third day in defined train routes) the vascular function, lung function, blood and urine samplings are performed. | Other: Diesel train<br>* Exposure to air with high level of ultrafine particles (Diesel train)<br>|
| Sham Comparator: Electric train - low exposure scenario<br>The same study person will be exposed to two different scenarios, at different times and for three consecutive days. It will be a lag time of 2 weeks between each exposure scenario. The low exposure scenario is defined as a workday (6 hours) on the electric train. The Diesel Train Scenario is performed twice. After the scenario completion (on the third day in defined train routes) the vascular function, lung function, blood and urine samplings are performed. | Other: Electric train<br>* Exposure to air with low level of ultrafine particles (Electric train)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactive hyperemia index measured by peripheral arterial tonometry | 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]. | Peripheral arterial tonometry is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | 
| Heart rate variability | 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. | Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | 
| DNA damage in peripheral blood mononuclear cells | The levels of strand breaks and formamidopyrimidine-DNA-glycosylase (FPG) sites are measured with the single cell gel electrophoresis assay (comet assay) [7-13] | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function | 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. | The lung function is assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day) | 
| Systemic inflammatory markers | Acute phase reactants, pro-inflammatory cytokines and cell adhesion molecules | 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. | 
| Urinary excretion of 1-hydroxypyrene | 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 | 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. | 
| Serum/plasma bioactivity | To assess the potential effects on vascular and endothelial function [14, 15] | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Air pollution, Diesel exhaust, Ultrafine particles, Vascular function, Endothelium function, Heart rate variability, DNA damage