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Beskæftigelsesudvalget 2017-18
BEU Alm.del Bilag 13
Offentligt

Andersen

et al. Environmental Health

(2017) 16:96

DOI 10.1186/s12940-017-0303-8

RESEARCH

Open Access

Cardiovascular health effects following

exposure of human volunteers during fire

extinction exercises

Maria Helena Guerra Andersen

1,2

, Anne Thoustrup Saber

, Peter Bøgh Pedersen

, Steffen Loft

Åse Marie Hansen

2,4

, Ismo Kalevi Koponen

, Julie Elbæk Pedersen

, Niels Ebbehøj

, Eva-Carina Nørskov

Per Axel Clausen

, Anne Helene Garde

2,4

, Ulla Vogel

2,6

and Peter Møller

Abstract

Background:

Firefighters have increased risk of cardiovascular disease and of sudden death from coronary heart

disease on duty while suppressing fires. This study investigated the effect of firefighting activities, using appropriate

personal protective equipment (PPE), on biomarkers of cardiovascular effects in young conscripts training to

become firefighters.

Methods:

Healthy conscripts (n = 43) who participated in a rescue educational course for firefighting were enrolled

in the study. The exposure period consisted of a three-day training course where the conscripts participated in

various firefighting exercises in a constructed firehouse and flashover container. The subjects were instructed to

extinguish fires of either wood or wood with electrical cords and mattresses. The exposure to particulate matter

(PM) was assessed at various locations and personal exposure was assessed by portable PM samplers and urinary

excretion of 1-hydroxypyrene. Cardiovascular measurements included microvascular function and heart rate

variability (HRV).

Results:

The subjects were primarily exposed to PM in bystander positions, whereas self-contained breathing

apparatus effectively abolished pulmonary exposure. Firefighting training was associated with elevated urinary

excretion of 1-hydroxypyrene (105%, 95% CI: 52; 157%), increased body temperature, decreased microvascular

function (−18%, 95% CI: -26;

−9%)

and altered HRV. There was no difference in cardiovascular measurements

for the two types of fires.

Conclusion:

Observations from this fire extinction training show that PM exposure mainly occurs in situations

where firefighters removed the self-contained breathing apparatus. Altered cardiovascular disease endpoints after

the firefighting exercise period were most likely due to complex effects from PM exposure, physical exhaustion and

increased core body temperature.

Keywords:

Cardiovascular disease, Firefighter, Ultrafine particles

* Correspondence:

[email protected]

Department of Public Health, Section of Environmental Health, University of

Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark

Full list of author information is available at the end of the article

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0

International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and

reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to

the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver

(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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et al. Environmental Health

(2017) 16:96

Page 2 of 9

Background

Firefighters have high risk of on-duty death due to

cardiovascular diseases, whereas the life time risk is simi-

lar to the general population [1]. It has been shown that

deaths from coronary heart disease were most frequent

among firefighters who were actively engaged in suppress-

ing fires, whereas those with non-emergency duties had

the lowest mortality among on-duty firefighters [2]. The

excess mortality has been attributed to various factors

such as smoke, physical exhaustion, hyperthermia, dehy-

dration and mental stress. Controlled studies of 3 h during

fire extinction showed that firefighters had decreased left

ventricular contractility and stroke volume, tachycardia

and increased microvascular vasodilation within the first

30 min after cessation of the activities [3, 4]. Several stud-

ies have demonstrated that exposure to heat, associated

with increased body temperature, increases the peripheral

arterial compliance, shear stress and blood flow [5, 6].

Exercise also increases the body temperature and evokes a

number of hemodynamic changes, including vasodilation

[7]. Above all, these results demonstrate an immediate

and possibly transient effect of exercise and increased

body temperature on the cardiovascular physiology.

Exposure to particulate matter (PM) from combus-

tion of carbon-based materials such as fossil fuels is as-

sociated with increased risk of morbidity and mortality

of cardiovascular diseases [8]. Firefighters may be ex-

posed to PM when they remove their self-contained

breathing apparatus while not actively engaged in fire

suppression activities. Bystander exposure to smoke can

therefore occur and diesel exhaust from fire trucks or

pumps operated by firefighters may constitute add-

itional sources of PM exposure. A meta-analysis of epi-

demiological studies has shown an inverse relationship

between exposure to particulate air pollution and heart

rate variability (HRV) [9]. Likewise a number of studies

have documented associations between exposure to PM

and cardiovascular disease endpoints such as vaso-

motor dysfunction and progression of atherosclerosis in

animal models and humans [10, 11].

The chemical composition of the smoke varies substan-

tially from one fire to another. Fires in urban settings typ-

ically give rise to very complex mixtures because of the

combustion of household equipment, whereas combus-

tion of wood can be considered as a more

“clean”

type of

smoke. Studies on controlled exposure to wood smoke

have indicated little effect on microvascular vasomotor

function [12, 13], whereas HRV was decreased [14]. To

the best of our knowledge, no studies have assessed

biomarkers for cardiovascular disease after controlled ex-

posure to more complex fuels than wood, such as plastic

or household materials.

The aim of the present study was to assess whether fire-

fighting activities, using appropriate personal protective

equipment (PPE), were associated with cardiovascular

effects in young subjects training to become firefighters.

The subjects participated in smoke diving exercises to

supress wood fires with or without additional items that

occur in

“real”

fires (i.e. electrical cords and mattresses).

Markers of cardiovascular function and risk factors in-

cluded vasomotor function measurements by reactive

hyperemia index (RHI) and cardiac autonomic nervous

system regulation by HRV. Personal exposure to polycyc-

lic aromatic hydrocarbons (PAH) was assessed by urinary

excretion of 1-hydroxypyrene (1-OHP), which is a widely

used biomarker of exposure to combustion products in

environmental and occupational settings [15]. Biomarkers

of cardiovascular risk obtained after the firefighting exer-

cise were compared to control measurements performed

2 weeks before and 2 weeks after the firefighting course,

respectively.

Methods

Subjects

The subjects were healthy conscripts who participated

in a rescue specialist educational course, a nine-month

education under the Danish Emergency Management

Agency in 2015 and 2016. Self-reported pregnancy,

smoking, and drug or alcohol misuse were exclusion

criteria. Fifty-four subjects were enrolled in the study in

four different campaigns. One female subject dropped

out of the education and cardiovascular endpoints were

not measured from additional 10 subjects for logistic

reasons (5 subjects in each of the campaigns 3 and 4).

Consequently, the final study population consisted of

32 males and 11 females. The subjects were recruited

from four consecutive training classes (campaigns):

campaign 1) covered 8 conscripts in the summer; 2)

11 conscripts, autumn; 3) 17 conscripts, winter; and

4) 17 conscripts, spring. Table 1 shows the character-

istics of the subjects. The distribution of female sub-

jects between campaigns varied from 17 to 36%. The

age of the participants varied from 18 to 26 years.

Seventy-two percent of the subjects had a body mass

Table 1

Characteristics of the subjects

Characteristic

Age (years)

Height (cm)

Male (n = 32)

21.0 ± 1.3

181.4 ± 6.7

78.3 ± 11.4

23.7 ± 2.6

65.8 ± 6.6

Female (n = 11)

21.5 ± 2.1

172.1 ± 3.2

67.6 ± 10.0

22.8 ± 3.0

66.9 ± 7.4

Total (n = 43)

21.1 ± 1.6

179.0 ± 7.2

75.6 ± 11.9

23.5 ± 2.7

66.0 ± 6.7

Weight (kg)

BMI (kg/m

)

Subjects with

allergies (n)

cBL.HR (bpm)

BMI

body mass index,

cBL.HR

average baseline heart rate from the two control

measurements. Values are number or mean ± SD

Self-reported information

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et al. Environmental Health

(2017) 16:96

Page 3 of 9

index (BMI) between 18.5 and 24.9 kg/m

and 28% of

the subjects had BMIs between 25 and 30 kg/m

Study protocol

The design was a human exposure study, where the

participants were studied in three exposure scenarios,

serving as their own controls. In each campaign, the blood

sampling and physiological measurements after each ex-

posure scenario were conducted at the same time of the

day, separated by around 14 days with the exception of

campaign 3 where only 7 days separated the second and

third exposure scenario due to the Christmas holiday.

During the first exposure scenario, subjects were in a

classroom receiving theoretical information. During the

second exposure scenario, the subjects participated in a 3-

day smoke diving training program with various types of

activities in a constructed firehouse and in a flashover

container. The exercises increased in complexity as the

participants acquired skills and they were wearing full

PPE, including a self-contained breathing apparatus. In

the third exposure scenario, the subjects were having an-

other module component of their education unrelated to

firefighting. The first and third scenarios were control

measurements, whereas the second period was the expos-

ure situation. We designed two different types of fires.

The subjects supressed fires of standard wooden EUR pal-

lets in absence (campaign 1 and 2) or presence (campaign

3 and 4) of foam mattresses and electrical cords. New ma-

terial (one-third of a mattress and 2 m electrical cord) was

added to the fires as each team of smoke divers entered

the building. In total, during each day of the 3-day smoke-

diving course, 6 mattresses and 20 m of electrical cords

were burned. The foam mattresses were purchased in

IKEA; they consisted of polyurethane (28 kg/m

) with a

cover fabric (64% polyester and 36% cotton) and the

weight of each mattress was 6 kg. A recycling station

delivered the electrical cords.

Exposure assessment

smoke. The subjects delivered morning urine samples on

the measurement day for the control measurements and

on the day after the exposure situation. The half-life of 1-

OHP is 6–35 h [16], thus the 1-OHP measurement cap-

tures the exposure period, although exposures closest to

the sampling contributes the most. Reverse-phase HPLC

was used for the quantitative measurement of 1-OHP in

urine using a previously published method [17]. We stan-

dardized for diuresis with the concentration of creatinine

as used in other studies [15].

We assessed the impact of fire-related activities on

the body temperature in an auxiliary experiment con-

ducted during a smoke diving module course in 2016.

The subjects performed smoke-diving exercises or ac-

quired skills in a flashover container. Body temperature

was recorded before, immediately after, and more than

20 min after fire-related activities using an ear therm-

ometer (ThermoScan® 7, Braun GmbH, Kronberg,

Germany). Two different activities were monitored:

fire-suppression in the firehouse (7 to 10 min inside the

firehouse with suppression or rescuing tasks to per-

form) and flashover container (30 min sitting inside a

container with fire). It was not possible to organize a

stringent exposure scenario due to logistic implications

of the exercise, as some participants had to do fire ex-

tinction exercises several times or they hurried on to

other exercises.

Cardiovascular measurements

The smoke exposure was assessed with various stationary

and person-borne equipment for PM measurements that

measured either the particle number or mass concentra-

tions. The supplement contains further description of the

exposure setting, including type and location of PM moni-

tors. Personal exposure to PM was assessed immediately

before, during and immediately after the fire extinction

exercise for 3 subjects in the first campaign. It was not

possible to obtain personal PM exposure for all subjects

due to a limited number of personal monitors. We there-

fore focussed on determining whether PM exposure oc-

curred when the subjects were wearing PPE, including

self-contained breathing apparatus. We used the urinary

excretion of 1-OHP as a biomarker of PAH exposure,

whereas PAH is used as an exposure marker of PM and

RHI and HRV measurements were primary outcomes,

which were measured non-invasively using the portable

EndoPAT2000 (Itamar Medical Ltd., Israel) as previously

described [18]. Briefly, finger-mountable pneumatic sen-

sors were placed on the index fingers measuring pulse

volume changes through three test stages: a baseline

recording (6–7 min), a brachial arterial occlusion of one

of the arms, induced by inflation of a blood pressure

cuff to a supra-systolic pressure (5 min), and a post-

occlusion recording of the induced reactive hyperemia

response (5 min). Blood pressure measurements were

done with a single measurement using one aneroid

sphygmomanometer, before the peripheral arterial to-

nometry (PAT) measurement. From the baseline re-

cording, the EndoPAT device determines the HRV

based on measurement over 5 min. The HRV results

include time domain measures (SDNN, pNN50 and

RMSSD), high (HF) and low frequency (LF) compo-

nents as well as the LF/HF ratio. Additionally the de-

vice determines the baseline heart rate (BL.HR) and the

augmentation index (AI). All the measures were done

in a quiet room with the subjects resting in a seated

position. The measurements in the second exposure

scenario were carried out between 20 min to 3 h after

cessation of the fire extinction exercise.

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et al. Environmental Health

(2017) 16:96

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Statistical analysis

We used R statistical language and the package

lme4

[19]

to perform a linear mixed effects analysis of the relation-

ship between the cardiovascular endpoints and exposure.

As fixed effects, we used factorial variables of exposure

(before/exposure/after) and sex (male/female) and con-

tinuous variable of BMI (without interaction terms) into

the model. The exposure term in the statistical analysis

was either exposure period (i.e. one exposure and two

non-exposure periods within each campaign) or type of

fire (i.e. wood or wood with mattresses and electrical

cords). Inclusion of campaign or the type of fire in the

statistical analysis using the exposure period as predictor

did not alter the size of the exposure-outcome relation-

ship; thus we have reported results that have not been ad-

justed for effects related to campaigns. As random effects,

we used by-subject intercepts.

P-values

were obtained

with the function

glht

from

multcomp

[20]. The percent

changes were obtained by dividing the estimate change

with the intercept value from the mixed model graph

line and multiplying with 100. As the RHI was

expressed on a logarithmic scale, the percent change

was obtained directly from the effect estimate using the

expression: (exp

estimate

−

1)*100. The biomarker of ex-

posure was also analysed with the same mixed model

function, using the creatinine-adjusted urinary 1-OHP

concentration, sex and BMI as fixed effects. The analysis

of the association between the fire extinction exercise and

urinary excretion of 1-OHP demonstrated a skewed distri-

bution of residuals. A cubic root transformation of the

data and removal of one outlier did not change the statis-

tical significance of the association; thus, we have reported

the statistics of the non-transformed data. Welch t-test

was used to compare the difference in means of effect

change between exposed and unexposed scenarios be-

tween the different types of fire. Paired t-test was used to

compare the mean body temperature difference between

different exposure conditions.

P-values

<0.05 were consid-

ered statistically significant. Since many of the assessed

biomarkers are inter-dependent, correction for multiple

testing was not performed.

The subjects were exposed to higher particle number

concentrations in situations when they were not wear-

ing the self-contained breathing apparatus. This oc-

curred when they received instructions or feedback at

locations that were considered as

“safe

zones”. The

mean aerosol particle number concentrations in the in-

halation zone varied substantially among the subjects

when they were not wearing the self-contained breath-

ing apparatus (50,000–250,000 particles/cm

). Further

information on the exposure assessment is available in

the supplemental material.

Urinary excretion of 1-hydroxypyrene

Figure 1 shows the creatinine-adjusted urinary 1-OHP

concentrations in the three exposure scenarios (control

measurement before, exposure and control measurement

after). Results from 6 males were excluded due to missing

data for the exposure measurement (n = 5) or for both

control measurements (n = 1). The exposure during the

fire extinction exercise increased the urinary excretion of

1-OHP by 105% (95% CI: 52,157%) based on the mixed ef-

fects model. The association was especially driven by cam-

paign 2 (Additional file 1, Figure S10).

Effect of fire-suppression activity on the body

temperature

The fire extinction exercise in the firehouse increased

the body temperature (average increase = 1.1°C, 95% CI:

0.7, 1.4,

= 16,

< 0.001, paired t-test) immediately

after the exercise. This was followed by an average

Results

Exposure to particulate matter

The PM exposure assessment showed that the PPE with

the self-contained breathing apparatus very efficiently pro-

tected the conscripts from PM exposure by inhalation

during fire-suppression activities. The mean particle num-

ber concentrations in the inhalation zone inside the self-

contained breathing apparatus during fire suppression ac-

tivities were less than 1000 particles/cm

(Additional file

1: Table S2). We were unable to assess PM levels in the

fire room, but at the floor landing above the fire extinction

exercises, the total PM mass concentration was 32 mg/m

Fig. 1

Creatinine-adjusted urinary concentration of 1-hydroxypyrene

in three exposure scenarios (before and after as control measurements,

and exposure measurement). Grey symbols and dashed lines are

individual results in each subject. Black line is a graphical output of the

mixed effect model

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(2017) 16:96

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decrease of 1.6°C (95% CI: -2.0,

−1.1,

= 13,

< 0.001,

paired t-test), compared to the temperature immediately

after the exercise, measured at 60 min or more after the

exercise. Following the flashover container exercise, we

observed an average increase of 0.8

°C

(95% CI: 0.6, 1.0,

= 8,

< 0.001, paired t-test) followed by an average de-

crease of 1.3

°C

(95% CI: -1.8,

−0.8,

= 7,

< 0.001,

paired t-test), measured after 20 min and compared to

the temperature immediately after the exercise. It should

be noted that carryover effects cannot be ruled out as

the subjects did both exercises on the same day in rela-

tively close succession.

Cardiovascular measurements

Figure 2 presents the effect of exposure to firefighting on

the cardiovascular endpoints. One female subject was

eliminated from RHI analysis and one male subject was

eliminated from HRV analysis, due to missing data for

both control measurements. Exposure to firefighting was

associated with decreased levels of RHI and time domain

HRV. Table 2 presents the estimated changes for each of

the cardiovascular measurements between different ex-

posure scenarios showing a significant effect of exposure

to firefighting as categorical variable on RHI, HRV both in

time and frequency domains and in baseline heart rate.

The mean baseline PAT signal amplitude was only mod-

estly altered after the fire extinction exercise (change of

−0.03%,

< 0.001). However adjustment for the baseline

PAT signal in the statistical model did not substantially

change the exposure-effect relationship of cardiovascular

measurements (e.g. the percent change in RHI was de-

creased from

−21.9%

(95% CI: -32.0,-10.3) to

−16.5%

(95%

CI: -26.1,

−5.6).

There was no significant difference be-

tween campaigns in the exposure-effect relationship for

any of the cardiovascular measurements. There were no

statistically significant relationship between LnRHI and

HRV measurements and urinary 1-OHP excretion (Add-

itional file 1: Table S6). Addition of information on self-

reported allergies in the statistical model did not affect the

exposure-effect relationship. Outcome average results for

each exposure scenario are presented in Additional file 1:

Table S5.

Table 3 presents the average effect change for each of

the cardiovascular endpoints between exposure and unex-

posed situations for the two different types of fire: wood

and wood with mattresses and electrical cords. The results

Fig. 2

Cardiovascular endpoints in the three exposure scenarios (before and after as control measurements, and exposure measurement). Natural

base log of reactive hyperemia index (one subject was eliminated due to missing data in both control measurements) (a), time domain heart rate

variability in pNN50 (b) and RMSSD (c), frequency domain heart rate variability (d), augmentation index corrected for 75 bpm (e) and baseline

heart rate (f). Grey symbols and dashed lines are individual results in each subject. Black line is a graphical output of the mixed effect model.

pNN50, proportion of successive NN intervals differing by more than 50 milliseconds divided by total number of NN intervals; RMSSD, square

root of the mean squared differences of successive NN intervals; bpm, beat per minute; ms, millisecond

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Table 2

Percent change (95% confidence interval) in outcome levels estimated by mixed effects model adjusted for sex and body

mass index

Outcome

RHI

SDNN

pNN50

RMSSD

LF/HF

AI.75

BL.HR

Exposure vs Before

−21.9

(−32.0,-10.3)***

−17.3

(−28.3,

−6.4)**

−36.1

(−52.3,

−19.9)***

−26.9

(−41.0,

−12.7)***

27.0 (11.3, 42.8)***

−15.4

(−26.2,

−4.7)**

41.4 (15.0, 67.9)**

−4.4

(−8.0,

−0.7)*

−3.2

(−8.6, 2.3)

−8.8

(−24.8, 7.3)

12.7 (9.0, 16.3)***

Exposure vs After

−14.3

(−25.3,

−1.6)**

−10.3

(−21.7, 1.2)

−25.1

(−43.4,

−6.8)**

−18.6

(−33.9,

−3.4)*

17.8 (3.7, 31.9)*

−4.4

(−16.1, 7.4)

17.1 (−3.9, 38.2)

−0.3

(−4.2, 3.5)

5.8 (−0.2, 11.8)

−15.3

(−30.2,

−0.4)*

9.4 (5.8, 12.9)***

After vs Before

−8.9

(−20.7, 4.6)

−7.9

(−18.9, 3.1)

−14.7

(−31.0, 1.6)

−10.2

(−24.4, 4.1)

7.8 (−8.1, 23.7)

−11.6

(−22.4,

−0.7)*

20.7 (−6.0, 47.4)

−4.0

(−7.7,

−0.3)*

−8.5

(−14.0,

−3.0)**

7.7 (−8.3, 23.8)

3.0 (−0.7, 6.7)

Exposure vs Unexposed

−18.0

(−26.0,

−9.2)***

−13.2

(−22.9,

−3.6)**

−28.6

(−45.3,

−11.8)***

−21.5

(−33.4,

−9.7)***

21.1 (7.9, 34.2)**

−9.1

(−19.2, 1.0)

26.4 (6.7, 46.2)**

−2.4

(−5.7, 1.0)

1.1 (−3.5, 5.7)

−12.2

(−26.4, 2.1)

11.0 (7.7, 14.3)***

RHI

reactive hyperemia index,

SDNN

standard deviation of all NN intervals,

pNN50

proportion of successive NN intervals differing by more than 50 milliseconds

divided by total number of NN intervals,

RMSSD

square root of the mean squared differences of successive NN intervals,

power in low frequency range (0.04–

0.15 Hz) in ms

power in high frequency range (0.15–0.4 Hz) in ms

LF/HF

ratio LF(ms

)/HF(ms

systolic blood pressure (mmHg),

diastolic blood

pressure (mmHg),

AI.75

augmentation index corrected for 75 bpm,

BL.HR

baseline heart rate (bpm)

Results are percent change from the mixed effect model in Fig.

except for RHI where percent change was obtained directly from the effect estimate due to the

logarithmic transformation. The data are based on 43 individuals with measurements in both fire extinction exercise and control exposure condition

(measurements of control exposure condition were missing for one subject in RHI and heart rate variability outcomes)

*,**,*** Significantly different (p < 0.05,

< 0.01 and

< 0.001 respectively)

Unexposed corresponds to the mean between

“Before”

and

“After”

for each subject

One subject was eliminated due to missing data in both control measurements

show no difference between the two different types of fire

for our primary outcomes, except for blood pressure,

where a statistically significant difference was observed.

Table 3

Within-subject effect change between exposure and

unexposed situations for two different types of fires: wood

pallets and wood pallets with mattresses and electrical cords

Outcome

LnRHI

SDNN

pNN50

RMSSD

LF/HF

AI.75

BL.HR

Difference

with pallet fuel

−0.1

± 0.3

−9.3

± 24.9

−0.05

± 0.1

−14.2

± 29.8

12.8 ± 71.0

−18.7

± 71.0

0.2 ± 0.7

−8.2

± 12.4

−3.3

± 7.2

2.9 ± 7.8

6.2 ± 6.7

Difference

with mixed fuel

−0.3

± 0.3

−9.8

± 22.2

−0.04

± 0.1

−14.1

± 22.9

56.6 ± 74.2

−15.1

± 54.7

0.5 ± 1.0

1.6 ± 11.8

3.9 ± 10.5

1.6 ± 9,1

8.1 ± 7.8

Welch t-test

p-value

0.166

0.942

0.879

0.991

0.075

0.857

0.174

0.013

0.012

0.614

0.400

LnRHI

natural logarithm of the reactive hyperemia index,

SDNN

standard

deviation of all NN intervals,

pNN50

proportion of successive NN intervals

differing by more than 50 milliseconds divided by total number of NN

intervals,

RMSSD

square root of the mean squared differences of successive

NN intervals,

power in low frequency range (0.04–0.15 Hz) in ms

power

in high frequency range (0.15–0.4 Hz) in ms

LF/HF

ratio LF(ms

)/HF(ms

systolic blood pressure (mmHg),

diastolic blood pressure (mmHg),

AI.75

augmentation index corrected for 75 bpm,

baseline heart rate (bpm).

Values are mean ± SD

Average difference between the exposed and unexposed situations within

each subject

Discussion

The present study showed that participation in fire ex-

tinction exercise did not cause PM exposure during fire-

fighting using the PPE with self-contained breathing

apparatus, whereas PM exposure occurred when the

self-contained breathing apparatus was taken off in areas

considered safe. Participation in firefight training re-

sulted in exposure to PAHs in terms of increased urinary

excretion of 1-OHP, increased body temperature and

with cardiovascular risk markers in terms of both

decreased microvascular function and changed HRV.

In the present study, there was no association between

urinary excretion of 1-OHP and cardiovascular risk

markers. Urinary excretion of 1-OHP has been established

as a reliable biomarker of internal dose of PAHs in popu-

lations exposed to urban air pollution [21]. Our results

demonstrate that the subjects were exposed to PAHs, al-

though we did not appoint sources of PAHs in the present

study. PAH exposure occurs both by inhalation of PM and

by dermal exposure to soot [22]. Our results indicate that

the exposure to PAH is a weak predictor of cardiovascular

risk markers as compared to other risk factors such as

physical exhaustion and heat. Both of these alter blood

flow. Nevertheless, it should be noted that the firefighting

exercises encompassed simultaneous exposure to smoke,

heat and physical activity. It is not possible to separate the

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et al. Environmental Health

(2017) 16:96

Page 7 of 9

effect of smoke exposure on cardiovascular endpoints

from that of heat and physical activity in the present

study. It is possible that the observed short-term vascular

effects predominantly reflects effects related to increased

blood flow in order to ameliorate peripheral built-up of

waste products from the physical exercise and reduce the

core body temperature related to the last of the smoke

diving exercises in the 3-day course. We did not observe

any difference in the microvascular function and HRV be-

tween fires with or without mattresses and electrical

cords. In parallel to the biomarkers of cardiovascular risk

described in the present study, PAH exposure on skin and

biomarkers of inflammation and genotoxicity in blood

were assessed for the 53 study subjects [23]. Firefighting

did not affect blood levels of C-reactive protein, serum

amyloid A, IL6 and IL8 concentrations, whereas there was

increased level of oxidatively damaged DNA (i.e. formami-

dopyrimidine DNA glycosylase sensitive sites measured by

the comet assay) in peripheral blood mononuclear cells

compared to the mean of two control measurements per-

formed 2 weeks before and 2 weeks after the fire fighting

course [23]. The results suggest systemic oxidative stress,

which is linked to cardiovascular disease.

The assessment of ambient air levels of PM indicated

high concentrations inside and outside the firehouse. PM

inside the firehouse came from the fire, whereas outdoor

exposure represents dispersion of smoke from the fire-

house and exhaust from a diesel-driven fire truck near the

entrance of the firehouse. Other studies have demon-

strated elevated levels of 1-OHP in subjects participating

in firefighting exercises using diesel as fuel [24] and real-

life fires [25]. Firefighting activities on wood fire have

yielded rather low urinary levels of 1-OHP, whereas other

types of urinary hydroxylated PAHs have been elevated

post-exposure [26–28]. We did not obtain information on

the total personal exposure to PM because of limited

number of samplers and because we chose to assess PM

exposure during firefighting while wearing PPE for more

subjects instead of assessing whole day exposure for one

or two subjects. During firefighting there was little PM

inhalation exposure because the self-contained breath-

ing apparatus was a highly efficient barrier toward par-

ticles. Pulmonary exposure was only observed when the

subjects were not wearing the full PPE. The exposure

assessment indicated substantial PM exposure in the

areas considered safe.

We found a decreased microvascular function, mea-

sured by RHI, after the fire extinction exercise compared

to the no-exposure scenario. A decreased microvascular

function, using EndoPAT, has previously been described

in exposure studies on air pollution particles in susceptible

groups such as elderly [18, 29], whereas mixed results

were reported for young and healthy subjects [30, 31].

Likewise, short-term controlled exposure studies on diesel

exhaust have shown associations with reduced vasodila-

tory response [32]. However, short-term controlled expos-

ure to high concentrations of wood smoke, i.e. several

hundred micrograms per cubic meter, have demonstrated

unaltered or even increased vasodilation response [12, 13].

Low level of flow-mediated vasodilation corrected for

shear stress is a risk factor to cardiovascular disease in

firefighters; other additive risk factors are Framingham

risk score and carotid intima-media thickness [33].

Altered HRV was manifested in both time and fre-

quency domains. The fire extinction exercise was associ-

ated with decreased time domain HRV measures (SDNN,

pNN50 and RMSSD), reduced high frequency compo-

nents (HF), increased low frequency components (LF) and

increased LF/HF ratio. Overall, it indicates an imbalance

in the autonomic activation of the heart with reduced

vagal activity and increased sympathetic activity. A meta-

analysis has recently shown reduced measures of HRV in

humans after exposure to particulate air pollution [9],

whereas a review of panel studies concluded that the stud-

ies did not convincingly show inverse associations be-

tween ambient air PM

2.5

concentrations and HRV [34].

Two controlled studies reported no association between

short-term diesel exhaust (100–300

μg/m

for 2 h) and

HRV [35, 36]. However, a short-term controlled exposure

to wood smoke study (314

μg/m

for 3 h) showed reduced

HRV and increased heart rate during a 1-h post-exposure

period [14]. Reduced HRV has been shown to be associ-

ated with increased risk of a first cardiovascular event in

people without cardiovascular diseases [37].

Despite the demand for physical fitness, firefighters as a

group seem to harbour several risk factors for cardiovas-

cular diseases. In a recent study on young career fire-

fighters (<45 years), increased risk of sudden cardiac death

was found to be largely attributed to obesity, hypertension

and smoking [38]. Therefore, to avoid effect modification

due to lifestyle factors, we used young and non-smoking

conscripts who were generally healthy in our study. It is

generally acknowledged that exposure to air pollution has

an immediate effect, e.g. precipitation of myocardial

infarction, and a chronic effect related to progression of

atherosclerosis. Consequences of this difference in effect

are apparent in the risk estimates from short-term and

long-term exposure in epidemiological studies, whereas a

time-integrated exposure metric suggests a monotonic

exposure-effect relationship [39]. Our study is by design

revealing short-term effects on both the vasculature and

myocardium. The observation suggests that a reduced

microvascular vasodilation response would be associated

with increased peripheral resistance and progression to-

ward hypertension and left ventricular cardiac overload

due to backward failure. Indeed, HRV is reduced in pa-

tients with hypertension [40]. Increased physical workload,

heat and dehydration also can be independent risk factors

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Andersen

et al. Environmental Health

(2017) 16:96

Page 8 of 9

for increased risk of mortality from coronary heart disease

among on-duty firefighters, whereas conditional risk fac-

tors for cardiovascular disease such as obesity, dyslipid-

emia, hypertension and diabetes may put certain subjects

in high-risk category for sudden cardiac death.

Availability of data and materials

The datasets analysed during the current study are available from the

corresponding author on reasonable request.

Authors’ contributions

MHGA collected the data on vasculature effects and body temperature, assisted

in the exposure measurements, analysed the results, and wrote the first draft of

the manuscript. ATS designed and coordinated the study, supervised the data

analysis and the writing of the manuscript. PBP measured and reported the

exposure. SL designed the study and was a major contributor in the analysis

and interpretation of results. AMH supervised the analysis and report of 1-OHP

and was a contributor in writing the manuscript. IKK assisted in the exposure

assessment. JEP collected and reported the data from the questionnaires. NE

designed the study and contributed to the analysis and interpretation of results.

ECN assisted in the collection of data of body temperature. PAC assisted in

the exposure assessment and contributed to the writing manuscript. AHG

contributed to the analysis of 1-OHP and the writing the manuscript. UV

designed and supervised the study and was a major contributor in writing

the manuscript. PM designed and supervised the study and was a major

contributor to the analysis, interpretation and writing of the manuscript. All

authors read and approved the final manuscript.

Authors’ information

Correspondence regarding this study should be addressed to UV ([email protected])

or PM ([email protected]).

Ethics approval and consent to participate

The Danish Committee on Health Research Ethics of the Capital Region

(H-15003862) approved the study and study subjects participated in

information meeting and provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Conclusions

In the present study, exposure of human volunteers fol-

lowing a 3-day firefighting training program with various

types of exercises in a firehouse was associated with al-

tered cardiovascular effects in terms of decreased micro-

vascular function and altered HRV. The subjects were

very efficiently protected against pulmonary PM expos-

ure when using the full personal protective equipment

including the self-contained breathing apparatus. Signifi-

cant PM exposure was observed when the subjects took

off their self-contained breathing apparatus in areas con-

sidered safe. Fire extinction exercises were associated

with increased urinary 1-OHP levels indicating exposure

to PAH. However, the association between urinary excre-

tion of 1-OHP and cardiovascular effects was not statisti-

cally significant in models that included smoke exposure

as categorical variable. Physical activity and heat are also

conditions that occur during the fire extinction exercise,

which alter blood flow. Thus, the altered cardiovascular

responses after fire extinction exercises are most likely

due to complex effects from PM exposure, physical ex-

haustion and increased core body temperature.

Additional file

Additional file 1:

Supplementary material. (DOC 4338 kb)

Abbreviations

1-OHP:

1-hydroxypyrene; AI: Augmentation index; BL.HR: Base line heart rate;

BMI: Body mass index; CI: Confidence interval; DP: Diastolic blood pressure;

HF: High frequency; HPLC: High performance liquid chromatography;

HRV: Heart rate variability; LF: Low frequency; PAH: Polycyclic aromatic

hydrocarbons; PAT: Peripheral arterial tonometry; PM: Particulate matter;

pNN50: proportion of normal-to-normal intervals differing by more than 50

miliseconds; PPE: Personal protective equipment; RHI: Reactive hyperemia

index; RMSSD: Root mean square of the successive differences;

SDNN: Standard deviation of normal-to-normal intervals; SP: Systolic blood

pressure

Acknowledgments

The technical assistance from Anne Abildtrup, Ulla Tegner and Inge

Christiansen is gratefully acknowledged. A special thanks goes to the

Danish Emergency Management Agency where the measurements took

place. We are also grateful to the study participants for the considerable

time and willingness put into this study. We established a reference

group which includes stakeholders from e.g. fire brigades, trade unions

and The Danish Emergency Management Agency. We thank the

reference group for involvement in the overall study design.

Funding

The research leading to these results has received funding from The Danish

Working Environment Research Fund (BIOBRAND, grant 34–2014-09 /

20,140,072,567), Danish Centre for Nanosafety, grant 20,110,092,173/3 and

Danish Centre for Nanosafety II).

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in

published maps and institutional affiliations.

Author details

Department of Public Health, Section of Environmental Health, University of

Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.

The National Research Centre for the Working Environment, Lersø Parkalle

105, DK-2100 Copenhagen Ø, Denmark.

Danish Technological Institute,

Teknologiparken, Kongsvang Allé 29, DK-8000 Aarhus C, Denmark.

Department of Public Health, Section of Social Medicine, University of

Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.

Department of Occupational and Environmental Medicine, Bispebjerg

Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, NV, Denmark.

Department of Micro- and Nanotechnology, Technical University of

Denmark, DK-2800 Kgs. Lyngby, Denmark.

Received: 29 March 2017 Accepted: 25 August 2017

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