Science of the Total Environment 543 (2016) 6166

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Science of the Total Environment

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The association of annual air pollution exposure with blood pressure

among patients with sleep-disordered breathing
Wen-Te Liu a,b,c,d,e, Kang-Yun Lee a,f, Hsin-Chien Lee d,g, Hsiao-Chi Chuang a,b, Dean Wu g,h,i,
Jer-Nan Juang c, Kai-Jen Chuang j,k,
a
Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
b
School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan
c
Department of Engineering Science, National Cheng Kung University, Tainan, Taiwan
d
Sleep Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
e
Sleep Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
f
Department of Internal Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
g
Department of Psychiatry, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
h
Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
i
Department of Neurology, School of Medicine, Taipei Medical University, Taipei, Taiwan
j
Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
k
School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan

H I G H L I G H T S G R A P H I C A L A B S T R A C T

Annual exposure to air pollution was

associated with blood pressure changes.
Annual air pollution-induced effect was
associated with autonomic imbalance.
Patients with severe sleep apnea were
sensitive to ne particle-induced ef-
fects.

a r t i c l e i n f o a b s t r a c t

Article history: While sleep-disordered breathing (SDB), high blood pressure (BP) and air pollution exposure have separately
Received 21 July 2015 been associated with increased risk of cardiopulmonary mortality, the association linking air pollution exposure
Received in revised form 27 October 2015 to BP among patients with sleep-disordered breathing is still unclear. We collected 3762 participants' data from
Accepted 27 October 2015
the Taipei Medical University Hospital's Sleep Center and air pollution data from the Taiwan Environmental Pro-
Available online 12 November 2015
tection Administration. Associations of 1-year mean criteria air pollutants [particulate matter with aerodynamic

Abbreviations: BP, Blood pressure; DBP, Diastolic blood pressure; NO2, Nitrogen dioxide; O3, Ozone; PM10, Particulate matter with aerodynamic diameters 10 m; PM2.5, Particulate
matter with aerodynamic diameters 2.5 m; SBP, Systolic blood pressure; SDB, Sleep-disordered breathing.
Corresponding author at: Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 110, Taiwan.
E-mail address: kjc@tmu.edu.tw (K.-J. Chuang).

http://dx.doi.org/10.1016/j.scitotenv.2015.10.135
0048-9697/ 2015 Elsevier B.V. All rights reserved.
62 W.-T. Liu et al. / Science of the Total Environment 543 (2016) 6166

Editor: D. Barcelo diameters 10 m (PM10), particulate matter with aerodynamic diameters 2.5 m (PM2.5), nitrogen dioxide
(NO2) and ozone (O3)] with systolic BP (SBP) and diastolic BP (DBP) were investigated by generalized additive
Keywords: models. After controlling for age, sex, body mass index (BMI), temperature and relative humidity, we observed
Air pollution that increases in air pollution levels were associated with decreased SBP and increased DBP. We also found
Blood pressure
that patients with apneahypopnea index (AHI) 30 showed a stronger BP response to increased levels of air
Apneahypopnea index
Sleep-disordered breathing
pollution exposure than those with AHI b 30. Stronger effects of air pollution exposure on BP were found in
Epidemiology overweight participants than in participants with normal BMI. We concluded that annual exposure to air pollu-
tion was associated with change of BP among patients with sleep-disordered breathing. The association between
annual air pollution exposure and BP could be modied by AHI and BMI.
2015 Elsevier B.V. All rights reserved.

1. Introduction
The association of short-term and long-term air pollution exposure
with cardiovascular morbidity and mortality has been demonstrated
in previous studies (Brook et al., 2010; Mustac et al., 2012; Shah
et al., 2013). Such epidemiological association has been linked to the ef-
fects of air pollution on elevated blood pressure (BP), a possible mecha-
nism linking air pollution exposure to cardiovascular effects (Brook
et al., 2010) in several panel studies (Chuang et al., 2005; Ibald-Mulli
et al., 2001; Lin et al., 2009; Zanobetti et al., 2004). Sleep-disordered
breathing (SDB) is a bunch of physiopathologic conditions that are char-
acterized by an abnormal respiratory pattern during sleep, such as snor-
ing, sleep apneas, etc. It affects as much as 17% of U.S. adults (Young
et al., 1993), 59% of Taiwanese adults (Chuang et al., 2008) and may
be more prevalent in Asian adults (Mirrakhimov et al., 2013). The sever-
ity of sleep apnea can be indicated by using the apneahypopnea index
(AHI). The value of AHI is represented by the number of apnea and
hypopnea events per hour of sleep and categorized as normal (04) or
severe (30) (Ruehland et al., 2009).
SDB has been reported to be associated with increased risk of
autonomic dysfunction (Wang et al., 2008), increased BP (Peppard
et al., 2000) and cardiovascular mortality (Yumino et al., 2009). It is
biologically possible that patients with SDB might be susceptible to air
pollution exposure. However, the association of air pollution exposure
with BP in patients with SDB is still unclear. Therefore, we designed
this study to investigate whether annual exposure to ambient air
pollution was associated with BP change among patients with SDB.
Moreover, we also examined our hypothesis that patients with severe
sleep apnea had greater air pollution-induced effects on BP change
compared to those with AHI in normal range.
2. Materials and methods
2.1. Study design and participants
This prospective, observational study was designed to monitor chang-
es in BP and annual air pollution exposure in patients with SDB. Outpa-
tients were enrolled from the sleep center of Taipei Medical University
Hospital from November 2005 to November 2012. The exclusion criteria
were an age younger than 20 years or older than 80, coronary artery dis-
ease, heart failure, diabetes mellitus, bronchiectasis, acute exacerbation
within 1 month of the study or chronic respiratory failure. All patients
underwent polysomnography at night to identify SDB and conducted BP
measurement in the next day morning. Air pollution data from the
Taiwan Environmental Protection Administration were used to measure
patients' annual air pollution exposure. All patients received regular reha-
bilitation programs, and medical care did not change during the study pe-
riod. The joint institutional review board at the Taipei Medical University
in Taipei, Taiwan approved this study (TMU-JIRB No.: 201412036).
2.2. Polysomnography and blood pressure
Polysomnography was performed on all participants by using a
polysomnography digital system (Embla N7000, Medcare, Iceland)
and its related software (Somnologica, Medcare, Iceland) with standard
techniques. Sleep stages and arousals were scored according to the
AASM criteria (Ruehland et al., 2009). Respiratory efforts were measured
by respiratory plethysmography, and arterial oxygen saturation was
measured by pulse oximetry. Based on the polysomnography results,
SDB was categorized as AHI 04 was normal, 514 was mild sleep
apnea, 1529 was moderate sleep apnea, and 30 was severe sleep
apnea. Systolic BP (SBP) and diastolic BP (DBP) were calculated as the
average of two seated blood pressure readings (taken about 1 min
apart using a mercury sphygmomanometer) after polysomnography
examination in the following morning.
2.3. Air pollution and weather data
Eighteen xed-site monitoring stations operated by the Taiwan
Environmental Protection Administration (TEPA) throughout Taipei
metropolitan (Taipei City and New Taipei City) measured hourly air
pollution and weather data. Yearly concentrations of particulate matter
with aerodynamic diameters 10 m (PM10), particulate matter with
aerodynamic diameters 2.5 m (PM2.5), nitrogen dioxide (NO2)
and ozone (O3) were used to represent 3762 participants' annual air
pollution exposure. Each participant can be assigned to one monitoring
station which is the nearest one to his or her residence. All air pollution
and weather data were matched with the measuring date of blood
pressure. The data averaged over 365 days before the blood pressure
measuring date were used to estimate yearly pollution effects on
blood pressure. A map of the study area and distribution of the location
of monitoring stations is presented in Fig. 1 (TEPA (Taiwan Environ-
mental Protection Administration), 2015).
2.4. Statistical analyses
We applied generalized additive models to investigate the relation-
ship between air pollution and blood pressure (Hastie and Tibshirani,
1989) among 3762 participants. Previous studies have reported that
yearly air pollution exposure is associated with cardiovascular effects
(Chen and Schwartz, 2008; Chuang et al., 2011). Therefore, the exposure
variables were 1-year mean PM10, PM2.5, NO2 and O3, and the outcome
variables were SBP and DBP. Each regression model included age, sex
and BMI. The models also adjusted for smooth function terms as t by
penalized cubic regression spline to reect non-linear effects of contin-
uous covariates, including yearly mean temperature with 6 of freedom
and yearly mean relative humidity with 5 of freedom (Schwartz, 1994).
We further conducted subgroup analysis by using AHI to split the data in
to three groups which AHI were 04, 529 and 30. The model applied
in subgroup analysis was the same model used in all participants. The
sensitivity analyses were performed by excluding patients with unrea-
sonable high AHI, BMI and air pollution exposure.
Effect modication by AHI {30 (severe) vs. 04 (normal)} and BMI
{N25 (overweight) vs. 25 (normal)} (WHO (World Health
Organization), 2009) was assessed in a separate generalized additive
mixed model by including interaction terms between PM2.5 effect and
each potential effect modier among all participants. Model selections
were based on minimizing Akaike's Information Criterion (AIC).All
 W.-T. Liu et al. / Science of the Total Environment 543 (2016) 6166 63

Fig. 1. Map of the study area, distribution of the location of the monitoring stations in Taipei City and New Taipei City. For a more detailed description, please visit the website of the Taiwan
Air Quality Monitoring Network (TAQMN) operated by the Taiwan Environmental Protection Administration (http://taqm.epa.gov.tw/taqm/en/default.aspx).

statistical analyses were performed using R Statistical Software, V.3.1.1 As shown in Table 4, we found effect modications of NO2 and PM2.5
(R Development Core Team, 2008). on elevated DBP by AHI and BMI. Participants with AHI 30 showed
signicant increases in DBP associated with air pollution exposure. In
3. Results contrast, participants with AHI b 30 showed no signicant change in
DBP. We also found stronger effects of NO2 and PM2.5 on elevated DBP
The participants recruited in this study were mostly female, over- in overweight participants (BMI N 25) than in participants with a
weight adults. The mean age of them was 46.7 years (standard devia- normal BMI. No effect modication of air pollution exposure on BP
tion, SD = 13.3). Their mean BMI was 26.7 kg/m2 (SD = 5.2), and the changes by sex was found in this study (data not shown).
male:female ratio was approximately 1:3. 39.2% of them had severe
sleep apnea and 23.9% of them were normal. The mean (SD) values of
SBP and DBP were 120.1 mmHg (17.2) and 81.5 (11.4), which were Table 1
within the normal range (20) (Table 1). The summary of air pollution Basic characteristics of 3762 study participants.
and weather data are shown in Table 2. The annual concentration of
Variables No (%)/mean standard deviation
PM2.5 was not only higher than National Ambient Air Quality Standard
in Taiwan (15 g/m3) (21) but also in US (12 g/m3) (22). The rest of Sex (no)
Female 2734 (72.7)
air pollutants' annual levels were under air quality standard. The weather
Male 1028 (27.3)
conditions were warm and humid. Age (years)
Table 3 lists the associations of SBP and DBP with yearly PM10, PM2.5, Mean 46.7 13.3
NO2 and O3 among all participants or the participants in the three differ- Range 2080
ent AHI groups estimated by generalized additive models. In general, Body mass index (kg/m2)
Mean 26.7 5.2
the models showed that decrease in SBP was signicantly associated Range 14.849.8
with increased levels in all air pollutants while increase in DBP was Systolic blood pressure (mm/Hg)
mainly associated with increased levels in particles and NO2. Changes Mean 120.1 17.2
in BP were more strongly associated with NO2 and PM2.5 than with Range 77.0205.0
Diastolic blood pressure (mm/Hg)
PM10 and O3. Moreover, the greatest effect of NO2 on DBP was observed
Mean 81.5 11.4
among the participants in the group with AHI 30, whereas small in- Range 40.0132.0
crease in DBP with NO2 exposure was observed among the participants Apneahypopnea index (no)
in the group with AHI 0-4. A similar pattern was found in the association 04 900 (23.9)
between PM2.5 exposure and elevated DBP among the participants in 529 1387 (36.9)
30 1475 (39.2)
the group with AHI 30 or AHI 04.
64 W.-T. Liu et al. / Science of the Total Environment 543 (2016) 6166

Table 2 Table 4
Long-term air pollution exposure and weather conditions of 3762 study Beta coefcients (95% condence interval) for effect modication of the association
participants. between diastolic blood pressure and 1-year mean air pollution exposure.

Variables Mean standard deviation PM2.5 NO2

1-year mean PM10 (g/m3) Apneahypopnea index 30

Mean 48.3 2.0 Yes 0.49 (0.01, 0.97) 0.58 (0.03, 1.14)
Range 37.652.2 No 0.35 (0.94, 0.24) 0.27 (0.88, 0.34)
1-year mean PM2.5 (g/m3) P-value for interaction 0.03 0.02
Mean 27.1 1.2 Body mass index N25
Range 22.330.5 Yes 0.57 (0.12, 1.02) 0.73 (0.24, 1.22)
1-year mean NO2 (ppb) No 0.04 (0.36, 0.40) 0.10 (0.46, 0.26)
Mean 21.2 1.1 P-value for interaction 0.04 0.03
Range 18.023.7
NO2, nitrogen dioxide; PM2.5, particles with aerodynamic diameters less than 2.5 m.
1-year mean O3 (ppb)
All models were adjusted for sex, age, body mass index, temperature, relative humidity.
Mean 27.0 1.0
Range 24.328.7
1-year mean temperature (C) pollution and blood pressure in 24,845 Chinese adults and found DBP
Mean 23.3 0.2 increased by 0.32 mmHg (95% CI, 0.080.56) per 19 g/m3 interquartile
Range 22.723.7
increase in PM10 and 0.37 mmHg (95% CI, 0.140.61) per 22 g/m3
1-year mean humidity (%)
Mean 74.2 0.8 interquartile increase in O3. Foraster et al. (2014) analyzed cohort data
Range 72.476.1 from 1926 participants in Girona, Spain and found the marginal signi-
NO2, nitrogen dioxide; O3, ozone; PM10, particles with aerodynamic diameters
cant association between annual average outdoor NO2 and increased
less than 2.5 m; PM2.5, particles with aerodynamic diameters less than 2.5 m. DBP (beta coefcient = 0.56; 95% condence interval: 0.03, 1.14).
Chen et al. (2015) analyzed cross-sectional data from 27,752 Taipei
City residents over 65 years of age and found one-year exposures to
4. Discussion PM10, PM2.5 absorbance, and NO2 were associated with higher DBP,
with estimates 0.73 [95% condence interval (CI): 0.44, 1.03], 0.62
The present study is the rst one to demonstrate the association (95% CI: 0.24, 0.99), and 0.65 (95% CI: 0.44, 0.85) mmHg for PM10
between annual air pollution exposure and BP changes among patients (10 g/m3), PM2.5 absorbance (105m1), and NO2 (10 g/m3), respec-
with SDB. Although increased level of air pollution was associated with tively. Our previous study also reported the association of increased DBP
elevated DBP, opposed effect of air pollution exposure on SBP was with annual average air pollutants among 1023 elderly in Taipei, Taiwan.
observed in this study. Moreover, estimated effects of air pollution on The estimated increases in DBP were 14.87 mmHg (95% CI, 12.7317.02)
BP were stronger in overweight subjects and subjects with severe per 48 g/m3 interquartile increase in PM10, 31.29 mmHg (95% CI, 25.43
sleep apnea. 37.14) per 20.42 g/m3 interquartile increase in PM2.5, and 12.43 mmHg
The association between short-term air pollution exposure and BP (95% CI, 10.6314.23) per 12.83 g/m3 interquartile increase in NO2
changes has been demonstrated in several epidemiological studies (Chuang et al., 2011). Taken together, the effect magnitudes of air
(Chen et al., 2012; Chuang et al., 2005; Hoffmann et al., 2012; pollutants on DBP among these studies are similar and comparable to
Ibald-Mulli et al., 2001; Lin et al., 2009; Zanobetti et al., 2004) and our study ndings. Our study results further conrm previous epidemio-
controlled studies (Brook et al., 2002; Gong et al., 2003; Trnqvist logical evidence for chronic, air pollution-induced effects on BP changes
et al., 2007). Only a few studies explored the association of annual air and support the views of the American Heart Association's expert panel
pollution exposure with BP changes. The observed increase in DBP on biological mechanisms of air pollution-induced effects on BP through
with annual air pollution exposure in the present study is consistent autonomic imbalance and endothelial dysfunction (Brook et al., 2010).
with previous ndings among human subjects. Dong et al. (2013) inves- We found opposing BP responses with annual air pollution expo-
tigated the association between residential long-term exposure to air sure, with decreases in SBP and increases in DBP. Although the potential
biological mechanisms that mediate these responses remain unclear,
Table 3 such ndings may imply the complicated physiologic balance of hemo-
Beta coefcients (95% condence interval) for increases in long-term air pollution expo- dynamic systems in charge of BP regulation in response to air pollution
sure with changes in blood pressure among patients with sleep-disordered breathing. exposure. A decrease in SBP may reect a decrease in cardiac contractil-
Systolic blood pressure Diastolic blood pressure ity. Previous studies have reported the association between air pollution
All study participants
exposure and increase in the square root of the mean of squared differ-
1-year mean PM10 (g/m3) 1.47 (1.76, 1.19) 0.21 (0.01, 0.41) ences between adjacent NN intervals (r-MSSD) or high-frequency
1-year mean PM2.5 (g/m3) 2.39 (2.81, 1.97) 0.37 (0.08, 0.67) power, the parameters inuenced by parasympathetic nervous system
1-year mean NO2 (ppb) 2.43 (2.90, 1.96) 0.45 (0.12, 0.78) (Peretz et al., 2008; Fakhri et al., 2009; Davoodi et al., 2010). A shift of
1-year mean O3 (ppb) 1.54 (2.11, 0.98) 0.27 (0.12, 0.66)
autonomic nervous system (ANS) to increased parasympathetic
Apneahypopnea index 04
1-year mean PM10 (g/m3) 2.10 (2.64, 1.57) 0.41 (0.80, 0.02) nervous system may reduce cardiac contractility, heart rate and then
1-year mean PM2.5 (g/m3) 3.33 (4.11, 2.56) 0.32 (0.89, 0.26) blood pressure.
1-year mean NO2 (ppb) 3.28 (4.11, 2.46) 0.33 (0.94, 0.28) Our ndings suggest that patients with severe sleep apnea may be
1-year mean O3 (ppb) 1.92 (2.96, 0.87) 0.10 (0.85, 0.65) susceptible to air pollution-associated BP changes. Previous studies
Apneahypopnea index 529
have demonstrated that patients with cardiopulmonary diseases are at
1-year mean PM10 (g/m3) 1.56 (2.04, 1.09) 0.23 (0.09, 0.54)
1-year mean PM2.5 (g/m3) 2.86 (3.55, 2.17) 0.27 (0.19, 0.72) an increased risk of morbidity (Zanobetti et al., 2000) and mortality
1-year mean NO2 (ppb) 2.91 (3.68, 2.13) 0.31 (0.21, 0.82) (Bateson and Schwartz, 2004; Sunyer et al., 2000) associated with air
1-year mean O3 (ppb) 1.20 (2.12, 0.27) 0.70 (0.10, 1.30) pollution exposure. To our best knowledge, no study explore whether
Apneahypopnea index 30
patients with severe sleep apnea are a risk group for air pollution-
1-year mean PM10 (g/m3) 1.17 (1.63, 0.71) 0.38 (0.06, 0.69)
1-year mean PM2.5 (g/m3) 1.75 (2.44, 1.05) 0.52 (0.04, 1.00) induced BP changes. Previous studies have reported that SDB is a risk
1-year mean NO2 (ppb) 1.85 (2.65, 1.05) 0.66 (0.11, 1.22) factor for autonomic dysfunction (Wang et al., 2008), increased BP
1-year mean O3 (ppb) 1.54 (2.48, 0.61) 0.19 (0.46, 0.84) (Peppard et al., 2000) and cardiovascular morbidity and mortality
All models were adjusted for sex, age, body mass index, temperature, relative humidity. (Jordan et al., 2014; Yumino et al., 2009). Air pollution, especially partic-
p-value b 0.05. ulate air pollutant has been demonstrated to translocate from the nose
 W.-T. Liu et al. / Science of the Total Environment 543 (2016) 6166
up the olfactory nerve into the brain (Elder et al., 2006), induce brain
inammation (Campbell et al., 2005) and neurotransmitter changes
(Kleinman et al., 2008), and then inuence sleep quality. Particulate
air pollution has also been reported to interact with lung receptors or
nerves, inuence systemic ANS balance and heart rhythm and then
result in BP changes (Brook et al., 2010). Therefore, patients with
sleep apnea are vulnerable to air pollution is biologically plausible.
Our study also found that the effect of air pollution was modied by
BMI. The results showed that having a BMI over 25 may put subjects at
higher risk of air pollution-induced BP changes than subjects with nor-
mal BMI. Such ndings are consistent with previous studies showing
that people with abnormal BMIs may be vulnerable to air pollution
exposure (Chahine et al., 2007; Schikowski et al., 2013).
We recognize that our study has a major limitation. Exposure mis-
classication and measurement error may bias our ndings toward
either positive or null results due to the lack of information regarding
household air pollution exposure, the number of air monitoring
stations, air conditioning status, environmental tobacco smoke and
subjects' daily activity patterns. Furthermore, we only adjusted sex,
age and BMI for individual-level confounders. Therefore, we could not
rule out the possibility of unmeasured confounding due to various
physical and psychosocial stressors associated with both cardiovascular
risks and air pollution levels such as socio-economic status, physical
activity, diet, alcohol consumption, complete smoking status, environ-
mental tobacco smoke exposure, noise exposure, diabetes, medication
and family history of cardiovascular diseases.
5. Conclusion
We found changes in BP after annual air pollution exposure that
resulted from both decreases in SBP and increases in DBP suggesting
that annual air pollution exposure might decrease stroke volume by
decreasing cardiac contractility or increasing vascular resistance. AHI
and BMI could modify the effect of air pollution exposure on increased
DBP implying that annual air pollution mediated hemodynamic changes
might be important for vulnerable subjects, especially those were
overweight and with SDB. Although the observed BP changes after
annual air pollution exposure are small, the subsequent autonomic
system imbalance, vasomotor dysfunction, reduced cardiac ow and in-
creased risk of cardiovascular diseases among general and vulnerable
population may be considerable. Future studies are needed to clarify
the possible mechanisms between the air pollutants exposure and the
regulation of BP changes.
Acknowledgments
This study was supported by grants (MOST 103-2621-M-038-001
and 104TMU-SHH-26) from the Ministry of Science and Technology of
Taiwan and Taipei Medical University. The funders had no role in
study design, data collection and analysis, decision to publish, or prepa-
ration of the manuscript.
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