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Research
of Edinburgh, University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom; 2Department of Public Health
and Clinical Medicine, Division of Medicine/Respiratory Medicine, Ume University, Ume, Sweden; 3National Institute for Public Health
and the Environment (RIVM), Bilthoven, the Netherlands
Background: Epidemiological studies have reported associations between air pollution exposure
and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence
cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac
arrhythmias, particularly in susceptible patient groups.
Objectives: We investigated the incidence of cardiac arrhythmias during and after controlled
exposure to air pollutants in healthy volunteers and patients with coronary heart disease.
M ethods : We analyzed data from 13 double-blind randomized crossover studies including
282participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from
whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was
recorded for each exposure and study population.
Results: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel
exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles,
or high ambient levels of air pollution in either healthy volunteers or patients with coronary
heart disease.
Conclusions: Acute controlled exposure to air pollutants did not increase the short-term risk of
arrhythmia in participants. Research employing these techniques remains crucial in identifying the
important pathophysiological pathways involved in the adverse effects of air pollution, and is vital
to inform environmental and public health policy decisions.
Citation: Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, LundbckM,
Cassee FR, Donaldson K, Sandstrm T, Blomberg A, Newby DE, Mills NL. 2014. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect 122:747753; http://
dx.doi.org/10.1289/ehp.1307337
Introduction
Methods
Data were extracted from 13 consecutive
randomized double-blind crossover studies
including healthy volunteers and patients
747
Langrish et al.
Diesel
exhaust
Wood smoke
O3
80
74 (93)
25 (1824)
243
6512
13817
729
14711
7612
29
21 (72)
26 (2035)
254
6213
12214
728
1469
7820
37
33 (89)
63 (5180)
273
578
13920
778
14011
7812
Ambient exposure
CAPs
Engineered
carbon NPs
Personal
monitoring
15
15 (100)
25 (2230)
NA
6813
15015
748
1489
NA
17
17 (100)
48 (2169)
253
6310
13920
778
14410
NA
14
14 (100)
21 (2044)
232
748
13212
688
14811
NA
14
2 (14)
27 (2045)
212
793
1138
736
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
12
12 (100)
59 (4568)
283
535
13810
8010
1487
10112
NA
NA
NA
NA
NA
NA
NA
NA
NA
93
80 (86)
63 (4577)
263
6710
13117
7910
14211
7616
23 (62)
0 (0)
25 (68)
8 (22)
14 (38)
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
7 (58)
0 (0)
12 (100)
4 (33)
5 (42)
NA
NA
NA
NA
NA
68 (73)
43 (46)
40 (43)
75 (81)
65 (70)
36 (97)
3 (8)
26 (70)
32 (87)
13 (35)
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
12 (100)
0 (0)
11 (92)
12 (100)
1 (8)
NA
NA
NA
NA
NA
87 (94)
16 (17)
67 (72)
73 (79)
28 (30)
Abbreviations: ACE, angiotensin-converting enzyme; BMI, body mass index; CAPs, concentrated ambient particles;
DBP, diastolic blood pressure; MI, myocardial infarction; NA, not applicable; NPs, nanoparticles; SBP, systolic blood
pressure. Values are expressed as n(%), meanSD, or median (IQR), as appropriate.
748
volume
Results
We identified 282 participants (140 healthy
volunteers and 142 patients with coronary
heart disease; Table1) who had been exposed
to dilute diesel exhaust (n =117) (Barath
etal. 2010; Cruts etal. 2008; Mills etal.
2005, 2007, 2011b), wood smoke (n=29),
Discussion
We have compiled the single largest series of
studies documenting continuous ECG monitoring in healthy volunteers and patients with
stable coronary heart disease on appropriate
medical therapy, who have been exposed to
a diverse range of environmental air pollutants in acute controlled-exposure studies. In
>12,500hr of ECG data, we identified no
evidence to suggest an increased tendency to
arrhythmia after brief controlled exposures.
These data indicate that there is no significant
Group
PM2.5
(g/m3)
PM10
(g/m3)
Particle count
(104/cm3)
CO (ppm)
NOx (ppm)
NO (ppm)
NO2 (ppm)
O3 (ppm)
THC (ppm)
HV
Patients
HV
NA
NA
NA
307
294
363
79
103
120
6.57
3.82
3.50
4.08
3.29
0.60
4.45
2.46
0.40
1.10
0.83
0.20
NA
NA
NA
3.0
2.8
NA
HV
Patients
86
89
NA
NA
2.4
4.4
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
HV
HV
895 (PM1)
314 (PM1)
NA
NA
NA
NA
15.32
26.00
NA
0.41
0.53
NA
NA
NA
NA
NA
NA
NA
HV
NA
NA
NA
NA
NA
NA
NA
0.30
NA
HV & patients
NA
190
9.9
0.02
0.01
0.01
0.01
NA
NA
HV
NA
70
387
NA
NA
NA
NA
NA
NA
Abbreviations: HV, healthy volunteers; NA, not applicable; NO, nitric oxide; NO2, nitrogen dioxide; PM1, 1m in aerodynamic diameter; PM10, 10m in aerodynamic diameter; THC,
total hydrocarbons. Values are expressed as mean, except as noted.
749
Langrish et al.
Table3. Occurrence and number of arrhythmias in all participants (n=282) included in the study (OR of arrhythmia occurring after pollutant exposure as
compared with unexposed air controls).
No. of participants with
documentedarrhythmia
Exposure; arrhythmia
Diesel exhaust (n=117)
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
Ambient (n=107)
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
CAPs (n=29)
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
Wood smoke (n=29)
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
750
Unexposed
Exposed
OR (95% CI)
p-Value
Unexposed
Exposed
p-Value
2
36
1
1
1
9
60
2
0
7
4
58
61
1
37
0
4
3
11
57
2
0
3
4
54
65
0.50 (0.045.55)
1.04 (0.601.81)
0.33 (0.018.20)
4.11 (0.4537.32)
3.05 (0.3129.80)
1.25 (0.503.13)
0.90 (0.541.51)
1.00 (0.147.22)
NA
0.41 (0.101.64)
1.00 (0.244.10)
0.87 (0.521.46)
1.15 (0.691.92)
0.56
0.89
0.32
0.18
0.31
0.64
0.69
1.00
NA
0.20
1.00
0.60
0.60
0 (00)
0 (01)
0 (00)
0 (00)
0 (00)
0 (00)
1 (057)
0 (00)
NA
0 (00)
0 (00)
1 (04)
1 (06)
0 (00)
0 (01)
0 (00)
0 (00)
0 (00)
0 (00)
0 (035.5)
0 (00)
NA
0 (00)
0 (00)
0 (04.5)
0 (04.5)
>0.99
0.72
>0.99
0.56
>0.99
>0.99
0.30
>0.99
NA
0.96
0.50
0.75
0.90
0
1
1
1
1
9
25
2
0
16
4
87
86
0
2
2
2
0
4
21
5
1
18
5
86
88
NA
2.02 (0.1822.62)
2.02 (0.1822.62)
2.02 (0.1822.62)
0.33 (0.018.20)
0.42 (0.131.42)
0.8 (0.421.54)
2.57 (0.4913.57)
3.03 (0.1275.34)
1.15 (0.552.40)
1.26 (0.334.84)
0.94 (0.481.86)
1.13 (0.572.25)
NA
0.56
0.56
0.56
0.32
0.15
0.51
0.25
0.32
0.71
0.73
0.86
0.73
NA
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
7 (166)
5 (128)
NA
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
0 (00)
7 (183)
6 (128)
NA
>0.99
>0.99
>0.99
>0.99
0.24
0.82
0.45
>0.99
0.80
0.50
0.52
0.25
1
5
0
1
2
2
16
0
0
2
1
22
23
0
5
0
0
4
3
14
0
0
1
2
26
23
0.32 (0.018.24)
1.00 (0.263.91)
NA
0.32 (0.018.24)
2.16 (0.3612.85)
1.56 (0.2410.10
0.76 (0.272.13)
NA
NA
0.48 (0.045.64)
2.07 (0.1824.24)
2.76 (0.6411.96)
1.00 (0.283.56)
0.31
1.00
NA
0.31
0.39
0.64
0.60
NA
NA
0.55
0.55
0.16
1.00
0 (00)
0 (00)
NA
0 (00)
0 (00)
0 (00)
2 (033)
NA
NA
0 (00)
0 (00)
5 (0.534.5)
2 (18)
0 (00)
0 (00)
NA
0 (00)
0 (00)
0 (00)
0 (028.5)
NA
NA
0 (00)
0 (00)
4 (228.5)
4 (113)
>0.99
0.73
NA
>0.99
>0.99
>0.99
0.42
NA
NA
>0.99
>0.99
0.93
0.06
2
7
0
0
0
0
18
0
0
1
1
19
17
0
9
0
0
0
0
18
0
0
0
0
15
14
0.19 (0.014.06)
1.41 (0.444.51)
NA
NA
NA
NA
1.00 (0.352.90)
NA
NA
0.32 (0.018.24)
0.32 (0.018.24)
0.56 (0.201.62)
0.66 (0.231.86)
0.15
0.56
NA
NA
NA
NA
1.00
NA
NA
0.31
0.31
0.29
0.43
0 (00)
0 (00.5)
NA
NA
NA
NA
3 (0113)
NA
NA
0 (00)
0 (00)
0 (01)
3 (110.5)
0 (00)
0 (01)
NA
NA
NA
NA
5 (087.5)
NA
NA
0 (00)
0 (00)
0 (01)
2 (07.5)
volume
0.50
0.17
NA
NA
NA
NA
0.32
NA
NA
>0.99
>0.99
0.07
0.79
Table continued
Table3. Continued.
No. of participants with
documentedarrhythmia
Exposure; arrhythmia
Engineered carbon NPs (n=14)
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
O3 (n=15)
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
Unexposed
Exposed
OR (95% CI)
p-Value
0
14
0
0
0
0
7
0
0
0
0
7
9
0
12
0
0
0
0
6
0
0
0
0
9
10
NA
0.17 (0.013.94)
NA
NA
NA
NA
0.75 (0.173.32)
NA
NA
NA
NA
1.80 (0.408.19)
1.39 (0.286.84)
NA
0.14
NA
NA
NA
NA
0.70
NA
NA
NA
NA
0.45
0.69
1
5
0
0
0
0
12
0
0
0
0
12
9
1
8
0
0
0
0
11
0
0
0
0
8
12
1.00 (0.0617.63)
2.29 (0.5210.01)
NA
NA
NA
NA
0.69 (0.123.79)
NA
NA
NA
NA
0.29 (0.061.44)
2.67 (0.5213.66)
1.00
0.27
NA
NA
NA
NA
0.67
NA
NA
NA
NA
0.25
0.23
Unexposed
Exposed
p-Value
NA
6 (2.7514)
NA
NA
NA
NA
0.5 (064)
NA
NA
NA
NA
0.5 (07.25)
2.5 (05)
NA
6.5 (3.2513.75)
NA
NA
NA
NA
0 (026)
NA
NA
NA
NA
1 (05.5)
2 (05)
NA
0.88
NA
NA
NA
NA
0.74
NA
NA
NA
NA
0.64
0.42
0 (00)
0 (01)
NA
NA
NA
NA
18 (1271)
NA
NA
NA
NA
2 (13)
1 (03)
0 (00)
1 (04)
NA
NA
NA
NA
14 (033)
NA
NA
NA
NA
1 (02)
1 (13)
>0.99
0.23
NA
NA
NA
NA
0.12
NA
NA
NA
NA
0.21
0.86
Abbreviations: NA, not applicable; SVE, supraventricular ectopic beat; SVT, supraventricular tachycardia including AF; VE, ventricular ectopic beat; VT, ventricular tachycardia.
Bradycardia is defined as HR <50 bpm. Data expressed as n or median (IQR), as appropriate. p-Values and ORs from chi-square analysis and Wilcoxon matched-pairs signed rank test,
as appropriate.
Ambient
Diesel exhaust
CAPs
Wood smoke
Carbon NPs
Ozone
Pause
Dropped beat
VT
Salvo
Triplet
Couplet
Bradycardia
SVT
AF
Bigeminy
Trigeminy
VE
SVE
6
6 6 4
6 6 4
6 6 4
6 6 4
6 6 4
Figure1. Forest plots showing the risk of arrhythmias during and after exposure to air pollutants compared with a control air exposure (or in the presence of a
highly efficient facemask for the ambient exposures). Abbreviations: SVE, supraventricular ectopy; SVT, supraventricular tachycardia; VE, ventricular ectopy; VT,
ventricular tachycardia. p>0.05 for all (chi-square analysis).
751
Langrish et al.
752
Conclusions
Our data suggest that acute controlled
exposures to air pollutants are safe and do not
significantly increase the short-term risk of
arrhythmia among individuals at low risk of
arrhythmia. Research employing these techniques, when scientifically and ethically justified (National Research Council 2004; Rom
etal. 2013), should continue and remains
crucial in identifying pathophysiological
pathways involved in the adverse effects of air
pollution identified at the population level.
These studies can be performed with minimal risk and have the potential for substantial
societal benefit, informing environmental and
public health policy decisions.
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