Effect on Markers of Cardiovascular, Reproductive and Cancer Risk From Firefighting Training

NCT05753254 | Completed

• 4 other identifiers: 72403FFIKA WP4.3AMFF 16-2022-03H-21068847
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

Epidemiological studies based on Danish registries have observed that Danish male firefighters have more cardiovascular disease, infertility diagnose and a trend to increased risk of cancer than other Danish employed males. Firefighting activities include a combination of stressors such as strenuous work under heat, smoke and soot known to be able to affect cardiovascular and reproductive health, with smoke and soot also being known to increase the risk of cancer. The training facilities of real-fire extinguishing exercises in Denmark operate using wood or natural gas fire, which will have differential gradients of smoke, soot and possibly heat. The investigators will use different training conditions to create gradients of the different stressors and investigate health effects thereof. With this approach, the investigators expect to be able to evaluate the individual contribution of the different stressors in markers of cardiovascular, cancer and reproductive health risk. The project will include approx. 35 young conscript participants on a firefighting course, followed in four sessions, three firefighting training sessions under different fire conditions (no fire, wood fire and gas fire) and one control scenario.

Conditions

Reactive Hyperemia; Micro RNA; Heart Rate Variability; DNA Strand Breaks; Oxidative Stress; Heat Stress

Keywords

Comet assay; 8-oxodG; PAH CALUX; hydroxyl-PAHs and nitro-PAH metabolites; microRNA; AhR activation; scrotal temperature; core body temperature; urine; serum; blood; follicle-stimulating hormone; inhibin B; EndoPAT

Outcome Measures

Primary Outcomes (16)

• Change in reactive hyperemia index - afternoon

  Reactive hyperemia index (RHI) measured with the device EndoPAT 2000. A reactive hyperemia is induced by a blood cuff on the upper arm and the peripheral vasodilation response is assessed in the small digital vessels of a fingertip with a portable device connected to a computer, with RHI determined by an algorithm from the device, with lower index values corresponding to a worsen situation.

  Baseline afternoon measurement, afternoon measurement immediately after firefighting without fire, afternoon measurement immediately after firefighting under wood fire and afternoon measurements immediately after firefighting under gas fire

• Change in reactive hyperemia index - morning

  Reactive hyperemia index (RHI) measured with the device EndoPAT 2000. A reactive hyperemia is induced by a blood cuff on the upper arm and the peripheral vasodilation response is assessed in the small digital vessels of a fingertip with a portable device connected to a computer, with RHI determined by an algorithm from the device, with lower index values corresponding to a worsen situation.

  Baseline morning measurement, morning measurement in subsequent day after firefighting without fire, morning measurement in subsequent day after firefighting under wood fire and morning measurement in subsequent day after firefighting under gas fire

• Change in Heart Rate Variability pNN50 at rest - afternoon

  Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. pNN50 is the proportion of successive NN intervals differing by more than 50 milliseconds divided by the total number of N intervals (given in percentage).

  Baseline afternoon measurement, afternoon measurement immediately after firefighting without fire, afternoon measurement immediately after firefighting under wood fire and afternoon measurements immediately after firefighting under gas fire

• Change in Heart Rate Variability pNN50 at rest - morning

  Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. pNN50 is the proportion of successive NN intervals differing by more than 50 milliseconds divided by the total number of N intervals (given in percentage).

  Baseline morning measurement, morning measurement in subsequent day after firefighting without fire, morning measurement in subsequent day after firefighting under wood fire and morning measurement in subsequent day after firefighting under gas fire

• Change in Heart Rate Variability RMSSD at rest - afternoon

  Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. RMSSD is the square root of the mean squared differences of successive NN intervals (given in milliseconds)

  Baseline afternoon measurement, afternoon measurement immediately after firefighting without fire, afternoon measurement immediately after firefighting under wood fire and afternoon measurements immediately after firefighting under gas fire

• Change in Heart Rate Variability RMSSD at rest - morning

  Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. RMSSD is the square root of the mean squared differences of successive NN intervals (given in milliseconds)

  Baseline morning measurement, morning measurement in subsequent day after firefighting without fire, morning measurement in subsequent day after firefighting under wood fire and morning measurement in subsequent day after firefighting under gas fire

• Change in Heart Rate Variability ratio LF/HF at rest - afternoon

  Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. Ratio of low frequency and high frequency bands

  Baseline afternoon measurement, afternoon measurement immediately after firefighting without fire, afternoon measurement immediately after firefighting under wood fire and afternoon measurements immediately after firefighting under gas fire

• Change in Heart Rate Variability ratio LF/HF at rest - morning

  Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. Ratio of low frequency and high frequency bands

  Baseline morning measurement, morning measurement in subsequent day after firefighting without fire, morning measurement in subsequent day after firefighting under wood fire and morning measurement in subsequent day after firefighting under gas fire

• Changes in levels of 8-oxodG excretion in first morning urine

  Oxidized nucleobase 8-oxodG will be measured in urine samples by High-performance liquid chromatography (HPLC) as marker of oxidative stress, together with creatinine, for adjusting for urine concentration. Data will be reported as nanomol 8-oxodG per millimol creatinine.

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in levels of DNA strand breaks in peripheral blood mononuclear cells

  DNA strand breaks will be measured by comet assay, and reported as number of lesions per 10\^6 base pairs, transformed from percentage of DNA in tail using the calibration curve from the well-establish relationship between ionizing radiation dose and yield of strand breaks in DNA.

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in core temperature

  Core body temperature will be assessed by an ingestible pill thermometer with data recorded and reported as time series during the period in transit.

  Baseline day, during the day of firefighting without fire, during the day of firefighting under wood fire and during the day of firefighting under gas fire.

• Changes in scrotal temperature

  Scrotal temperature will be assessed by skin sensor placed in the scrotum of male participants and reported as scrotal skin temperature time series.

  Baseline day, during the day of firefighting without fire, during the day of firefighting under wood fire and during the day of firefighting under gas fire.

• Changes in scrotal thermoregulation

  Core body temperature will be assessed by an ingestible pill thermometer and scrotal temperature will be assessed by skin sensor placed in the scrotum of male participants, to assess the thermoregulation of the scrotum during firefighting exercises. Time series of core body temperature and scrotal skin temperature will be analysed for eventual thermoregulation disruption.

  Baseline day, during the day of firefighting without fire, during the day of firefighting under wood fire and during the day of firefighting under gas fire.

• Changes in levels of circulating micro RNA

  Circulating micro RNA candidates will be measured by RNA extraction from serum samples, reverse transcribed into complementary DNA (cDNA) and analysed with quantitative polymerase chain reaction (qPCR).

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in urinary potency of AhR activation

  The aryl hydrocarbon receptor (AhR) activation will be assessed in vitro using urine samples on the PAH CALUX (Chemical Activated LUciferase gene eXpression bioassay) reporter assay. The smoke and soot exposures are complex mixtures of compounds with potential toxic effect. Routine measurements of PAHs are usually quantified for a target list of 16 common soot elements and even less chemical species for urinary metabolites, but many other compounds are present in both soot and metabolites mixtures. The toxicity of PAHs is primarily caused through the binding to AhR, and induction of AhR related genes and subsequent toxic pathways. The outcome will be measured in the form of benzo\[a\]pyrene equivalence.

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in potency of AhR activation from skin deposits

  The aryl hydrocarbon receptor (AhR) activation will be assessed in vitro using wipe samples on the PAH CALUX (Chemical Activated LUciferase gene eXpression bioassay) reporter assay. The smoke and soot exposures are complex mixtures of compounds with potential toxic effect. Routine measurements of PAHs are usually quantified for a target list of 16 common soot elements, but many other compounds are present in soot mixtures. The toxicity of PAHs is primarily caused through the binding to AhR, and induction of AhR related genes and subsequent toxic pathways. The outcome will be measured in the form of benzo\[a\]pyrene equivalence.

  Baseline, before firefighting without fire, immediately after firefighting without fire, before firefighting under wood fire, immediately after firefighting under wood fire, before firefighting under gas fire, immediately after firefighting under gas

Secondary Outcomes (10)

• Changes in levels of follicle-stimulating hormone in serum

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in levels of serum inhibin B

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in urinary levels of PAH metabolites excretion

  Baseline, before firefighting without fire, day after firefighting without fire, before firefighting under wood fire, day after firefighting under wood fire, before firefighting under gas fire, day after firefighting under gas fire

• Changes in levels of PAHs in skin wipes from the neck

  Baseline, before firefighting without fire, immediately after firefighting without fire, before firefighting under wood fire, immediately after firefighting under wood fire, before firefighting under gas fire, immediately after firefighting under gas

• Changes in FEV1 spirometric measurements

  Baseline, immediately after firefighting without fire, immediately after firefighting under wood fire and immediately after firefighting under gas fire

Study Arms (4)

Baseline session

NO INTERVENTION

Baseline measurements will be performed in the same schedule as measurements in the three other arms. In the baseline session, participants are in classroom before starting any firefighting exercise

Firefighting exercises without fire

EXPERIMENTAL

Firefighting equivalent work, with exercises performed in a clean environment, without fire (no ambient temperature, soot or smoke). This type of exercise usually precedes or complements the training under real fire conditions.

Other: Firefighting training exercises with no fire

Firefighting under wood fire

EXPERIMENTAL

Firefighting under wood fire, with exposure to ambient heat, smoke and soot. This is the most common training scenario used in the training centres. The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models

Other: Firefighting training exercises under wood fire

Firefighting under gas fire

EXPERIMENTAL

Firefighting under gas fire, with exposure to ambient heat, and expectably less smoke and soot than with wood fire. These conditions are used in some Danish training centres, with logistical advantages (ease of turning or putting out the fire and managing the fire fuel) and unknown effect relating to exposure prevention (smoke and soot). The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models

Other: Firefighting training exercises under gas fire

Interventions

Firefighting training exercises with no fire OTHER

The participants will be performing firefighting equivalent work in a clean environment, without fire (no ambient temperature, soot or smoke).

Firefighting exercises without fire

Firefighting training exercises under wood fire OTHER

The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models), under wood fire conditions.

Firefighting under wood fire

Firefighting training exercises under gas fire OTHER

The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models), under gas fire conditions.

Firefighting under gas fire

Eligibility Criteria

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

You may qualify if:

• legally competent,
• conscript subjects following a Rescue Specialist Educational course

You may not qualify if:

• current smoking status,
• pregnancy,
• on prescribed medication,
• body mass index (BMI) bellow 19 or over 30,
• alcohol or drug abuse.

Sponsors & Collaborators

• National Research Centre for the Working Environment, Denmark: lead
• University of Copenhagen: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (2)

The National Research Centre for the Working Environment

Copenhagen, 2100, Denmark

Location

Maria Helena Guerra Andersen

København Ø, 4700, Denmark

Location

Related Publications (18)

• Andersen MHG, Saber AT, Pedersen PB, Loft S, Hansen AM, Koponen IK, Pedersen JE, Ebbehoj N, Norskov EC, Clausen PA, Garde AH, Vogel U, Moller P. Cardiovascular health effects following exposure of human volunteers during fire extinction exercises. Environ Health. 2017 Sep 6;16(1):96. doi: 10.1186/s12940-017-0303-8.

  PMID: 28877717 BACKGROUND

• Andersen MHG, Saber AT, Clausen PA, Pedersen JE, Lohr M, Kermanizadeh A, Loft S, Ebbehoj N, Hansen AM, Pedersen PB, Koponen IK, Norskov EC, Moller P, Vogel U. Association between polycyclic aromatic hydrocarbon exposure and peripheral blood mononuclear cell DNA damage in human volunteers during fire extinction exercises. Mutagenesis. 2018 Feb 24;33(1):105-115. doi: 10.1093/mutage/gex021.

  PMID: 29045708 BACKGROUND

• Andersen MHG, Saber AT, Pedersen JE, Pedersen PB, Clausen PA, Lohr M, Kermanizadeh A, Loft S, Ebbehoj NE, Hansen AM, Kalevi Koponen I, Norskov EC, Vogel U, Moller P. Assessment of polycyclic aromatic hydrocarbon exposure, lung function, systemic inflammation, and genotoxicity in peripheral blood mononuclear cells from firefighters before and after a work shift. Environ Mol Mutagen. 2018 Jul;59(6):539-548. doi: 10.1002/em.22193. Epub 2018 May 15.

  PMID: 29761929 BACKGROUND

• Andersen MHG, Saber AT, Frederiksen M, Clausen PA, Sejbaek CS, Hemmingsen CH, Ebbehoj NE, Catalan J, Aimonen K, Koivisto J, Loft S, Moller P, Vogel U. Occupational exposure and markers of genetic damage, systemic inflammation and lung function: a Danish cross-sectional study among air force personnel. Sci Rep. 2021 Sep 9;11(1):17998. doi: 10.1038/s41598-021-97382-5.

  PMID: 34504215 BACKGROUND

• Beitel SC, Flahr LM, Hoppe-Jones C, Burgess JL, Littau SR, Gulotta J, Moore P, Wallentine D, Snyder SA. Assessment of the toxicity of firefighter exposures using the PAH CALUX bioassay. Environ Int. 2020 Feb;135:105207. doi: 10.1016/j.envint.2019.105207. Epub 2019 Dec 4.

  PMID: 31812113 BACKGROUND

• Henriksen T, Weimann A, Larsen EL, Poulsen HE. Quantification of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-guanosine concentrations in urine and plasma for estimating 24-h urinary output. Free Radic Biol Med. 2021 Aug 20;172:350-357. doi: 10.1016/j.freeradbiomed.2021.06.014. Epub 2021 Jun 22.

  PMID: 34166769 BACKGROUND

• Hjollund NH, Storgaard L, Ernst E, Bonde JP, Olsen J. Impact of diurnal scrotal temperature on semen quality. Reprod Toxicol. 2002 May-Jun;16(3):215-21. doi: 10.1016/s0890-6238(02)00025-4.

  PMID: 12128094 BACKGROUND

• Jung A, Schuppe HC. Influence of genital heat stress on semen quality in humans. Andrologia. 2007 Dec;39(6):203-15. doi: 10.1111/j.1439-0272.2007.00794.x.

  PMID: 18076419 BACKGROUND

• Kales SN, Soteriades ES, Christophi CA, Christiani DC. Emergency duties and deaths from heart disease among firefighters in the United States. N Engl J Med. 2007 Mar 22;356(12):1207-15. doi: 10.1056/NEJMoa060357.

  PMID: 17377158 BACKGROUND

• Keir JLA, Akhtar US, Matschke DMJ, Kirkham TL, Chan HM, Ayotte P, White PA, Blais JM. Elevated Exposures to Polycyclic Aromatic Hydrocarbons and Other Organic Mutagens in Ottawa Firefighters Participating in Emergency, On-Shift Fire Suppression. Environ Sci Technol. 2017 Nov 7;51(21):12745-12755. doi: 10.1021/acs.est.7b02850. Epub 2017 Oct 18.

  PMID: 29043785 BACKGROUND

• Kumar K, Trzybulska D, Tsatsanis C, Giwercman A, Almstrup K. Identification of circulating small non-coding RNAs in relation to male subfertility and reproductive hormones. Mol Cell Endocrinol. 2019 Jul 15;492:110443. doi: 10.1016/j.mce.2019.05.002. Epub 2019 May 8.

  PMID: 31077744 BACKGROUND

• Morup N, Rajpert-De Meyts E, Juul A, Daugaard G, Almstrup K. Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up-A Copenhagen Experience. Cancers (Basel). 2020 Mar 23;12(3):759. doi: 10.3390/cancers12030759.

  PMID: 32210101 BACKGROUND

• Pedersen JE, Ugelvig Petersen K, Ebbehoj NE, Bonde JP, Hansen J. Incidence of cardiovascular disease in a historical cohort of Danish firefighters. Occup Environ Med. 2018 May;75(5):337-343. doi: 10.1136/oemed-2017-104734. Epub 2018 Jan 26.

  PMID: 29374097 BACKGROUND

• Petersen KU, Hansen J, Ebbehoej NE, Bonde JP. Infertility in a Cohort of Male Danish Firefighters: A Register-Based Study. Am J Epidemiol. 2019 Feb 1;188(2):339-346. doi: 10.1093/aje/kwy235.

  PMID: 30452532 BACKGROUND

• Kirstine Ugelvig Petersen K, Pedersen JE, Bonde JP, Ebbehoej NE, Hansen J. Long-term follow-up for cancer incidence in a cohort of Danish firefighters. Occup Environ Med. 2018 Apr;75(4):263-269. doi: 10.1136/oemed-2017-104660. Epub 2017 Oct 21.

  PMID: 29055884 BACKGROUND

• Pieterse B, Felzel E, Winter R, van der Burg B, Brouwer A. PAH-CALUX, an optimized bioassay for AhR-mediated hazard identification of polycyclic aromatic hydrocarbons (PAHs) as individual compounds and in complex mixtures. Environ Sci Technol. 2013 Oct 15;47(20):11651-9. doi: 10.1021/es403810w. Epub 2013 Sep 25.

  PMID: 23987121 BACKGROUND

• Schwartz C, Bolling AK, Carlsten C. Controlled human exposures to wood smoke: a synthesis of the evidence. Part Fibre Toxicol. 2020 Oct 2;17(1):49. doi: 10.1186/s12989-020-00375-x.

  PMID: 33008417 BACKGROUND

• Alhamdow A, Lindh C, Albin M, Gustavsson P, Tinnerberg H, Broberg K. Early markers of cardiovascular disease are associated with occupational exposure to polycyclic aromatic hydrocarbons. Sci Rep. 2017 Aug 25;7(1):9426. doi: 10.1038/s41598-017-09956-x.

  PMID: 28842704 BACKGROUND

MeSH Terms

Conditions

Hyperemia; Heat Stress Disorders

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries

Study Officials

• Maria Helena G Andersen, PhD

  The National Research Centre for the Working Environment (NRCWE)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: It is not possible to blind the participants to the different scenarios, neither the field staff, but all the samples will be blinded for the subsequent laboratory analysis, namely blood analysis, urine analysis, wipe samples analysis will all be blinded.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher

Model Details: Participants will perform firefighting full day exercises under 3 different conditions (without fire, under wood fire and under gas fire), sessions which will occur with weeks in between, and biological markers will be assessed and compared in relation to a baseline session, where the participants are having theoretical classes.

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: March 3, 2023
• Study Start: March 10, 2023
• Primary Completion: July 5, 2024
• Study Completion: July 5, 2024
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)