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

NCT03104387 | Completed

• 3 other identifiers: H-16033227No grant number2015-57-0121 case SUND-2016-80
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Function; Genotoxicity

Keywords

Air pollution; Diesel exhaust; Ultrafine particles; Vascular function; Endothelium function; Heart rate variability; DNA damage

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Lung function

  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

  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

  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

  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.

Other Outcomes (3)

• Augmentation index

  Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)

• Blood pressure

  Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)

• Heart rate

  Assessed after each exposure scenario (on the third day after 6 hours on defined train routes per day)

Study Arms (2)

Diesel train - exposure scenario

EXPERIMENTAL

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

Electric train - low exposure scenario

SHAM COMPARATOR

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

Interventions

Electric train OTHER

Exposure to air with low level of ultrafine particles (Electric train)

Electric train - low exposure scenario

Diesel train OTHER

Exposure to air with high level of ultrafine particles (Diesel train)

Diesel train - exposure scenario

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers
• Legally competent subjects

You may not qualify if:

• Current smokers
• Pregnancy
• Alcohol and drug abuse
• Prescriptionary use of anti-inflammatory or cardiovascular medication

Sponsors & Collaborators

• University of Copenhagen: lead
• National Research Centre for the Working Environment, Denmark: collaborator

Study Sites (1)

University of Copenhagen

Copenhagen, Denmark

Location

Related Publications (16)

• Karottki G, Loft S. Rapport vedroerende maaling af udsaettelse for ultrafine partikler blandt ansatte i DSB, 1-48, 2015.

  BACKGROUND

• Brauner EV, Forchhammer L, Moller P, Barregard L, Gunnarsen L, Afshari A, Wahlin P, Glasius M, Dragsted LO, Basu S, Raaschou-Nielsen O, Loft S. Indoor particles affect vascular function in the aged: an air filtration-based intervention study. Am J Respir Crit Care Med. 2008 Feb 15;177(4):419-25. doi: 10.1164/rccm.200704-632OC. Epub 2007 Oct 11.

  PMID: 17932377 RESULT

• Olsen Y, Karottki DG, Jensen DM, Beko G, Kjeldsen BU, Clausen G, Hersoug LG, Holst GJ, Wierzbicka A, Sigsgaard T, Linneberg A, Moller P, Loft S. Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study. Environ Health. 2014 Dec 15;13:112. doi: 10.1186/1476-069X-13-112.

  PMID: 25512042 RESULT

• Karottki DG, Spilak M, Frederiksen M, Gunnarsen L, Brauner EV, Kolarik B, Andersen ZJ, Sigsgaard T, Barregard L, Strandberg B, Sallsten G, Moller P, Loft S. An indoor air filtration study in homes of elderly: cardiovascular and respiratory effects of exposure to particulate matter. Environ Health. 2013 Dec 28;12:116. doi: 10.1186/1476-069X-12-116.

  PMID: 24373585 RESULT

• Hemmingsen JG, Rissler J, Lykkesfeldt J, Sallsten G, Kristiansen J, Moller P P, Loft S. Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults. Part Fibre Toxicol. 2015 Mar 19;12:6. doi: 10.1186/s12989-015-0081-9.

  PMID: 25890359 RESULT

• Brauner EV, Moller P, Barregard L, Dragsted LO, Glasius M, Wahlin P, Vinzents P, Raaschou-Nielsen O, Loft S. Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy individuals. Part Fibre Toxicol. 2008 Oct 6;5:13. doi: 10.1186/1743-8977-5-13.

  PMID: 18837984 RESULT

• Forchhammer L, Moller P, Riddervold IS, Bonlokke J, Massling A, Sigsgaard T, Loft S. Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function. Part Fibre Toxicol. 2012 Mar 27;9:7. doi: 10.1186/1743-8977-9-7.

  PMID: 22452928 RESULT

• Brauner EV, Forchhammer L, Moller P, Simonsen J, Glasius M, Wahlin P, Raaschou-Nielsen O, Loft S. Exposure to ultrafine particles from ambient air and oxidative stress-induced DNA damage. Environ Health Perspect. 2007 Aug;115(8):1177-82. doi: 10.1289/ehp.9984.

  PMID: 17687444 RESULT

• Danielsen PH, Brauner EV, Barregard L, Sallsten G, Wallin M, Olinski R, Rozalski R, Moller P, Loft S. Oxidatively damaged DNA and its repair after experimental exposure to wood smoke in healthy humans. Mutat Res. 2008 Jul 3;642(1-2):37-42. doi: 10.1016/j.mrfmmm.2008.04.001. Epub 2008 Apr 14.

  PMID: 18495177 RESULT

• Hemmingsen JG, Jantzen K, Moller P, Loft S. No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly. Mutagenesis. 2015 Sep;30(5):635-42. doi: 10.1093/mutage/gev027. Epub 2015 Apr 22.

  PMID: 25904586 RESULT

• Moller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Klingberg H, Jensen DM, Christophersen DV, Hemmingsen JG, Cao Y, Loft S. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res Rev Mutat Res. 2014 Oct-Dec;762:133-66. doi: 10.1016/j.mrrev.2014.09.001. Epub 2014 Sep 16.

  PMID: 25475422 RESULT

• Moller P, Hemmingsen JG, Jensen DM, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Cao Y, Kermanizadeh A, Klingberg H, Christophersen DV, Hersoug LG, Loft S. Applications of the comet assay in particle toxicology: air pollution and engineered nanomaterials exposure. Mutagenesis. 2015 Jan;30(1):67-83. doi: 10.1093/mutage/geu035.

  PMID: 25527730 RESULT

• Moller P, Loft S. Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution. Environ Health Perspect. 2010 Aug;118(8):1126-36. doi: 10.1289/ehp.0901725. Epub 2010 Apr 27.

  PMID: 20423813 RESULT

• Aragon M, Erdely A, Bishop L, Salmen R, Weaver J, Liu J, Hall P, Eye T, Kodali V, Zeidler-Erdely P, Stafflinger JE, Ottens AK, Campen MJ. MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor. Toxicol Sci. 2016 Apr;150(2):488-98. doi: 10.1093/toxsci/kfw015. Epub 2016 Jan 21.

  PMID: 26801584 RESULT

• Aragon MJ, Chrobak I, Brower J, Roldan L, Fredenburgh LE, McDonald JD, Campen MJ. Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures. Cardiovasc Toxicol. 2016 Apr;16(2):163-71. doi: 10.1007/s12012-015-9325-z.

  PMID: 25900702 RESULT

• Andersen MHG, Frederiksen M, Saber AT, Wils RS, Fonseca AS, Koponen IK, Johannesson S, Roursgaard M, Loft S, Moller P, Vogel U. Health effects of exposure to diesel exhaust in diesel-powered trains. Part Fibre Toxicol. 2019 Jun 11;16(1):21. doi: 10.1186/s12989-019-0306-4.

  PMID: 31182122 DERIVED

Study Officials

• Peter Moller, PhD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 7, 2017
• Study Start: May 16, 2017
• Primary Completion: September 30, 2018
• Study Completion: May 1, 2020
• Last Updated: August 10, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)