Environmental Pollution 230 (2017) 234e241

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Environmental Pollution
journal homepage: www.elsevier.com/locate/envpol

Association between ambient air pollution and hospitalization for

ischemic and hemorrhagic stroke in China: A multicity case-crossover
study*
Hui Liu a, b, 1, Yaohua Tian a, 1, Yan Xu c, Zhe Huang a, Chao Huang a, Yonghua Hu a, **,
Jun Zhang c, *
a
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No.38 Xueyuan Road, 100191 Beijing, China
b
Medical Informatics Center, Peking University, No.38 Xueyuan Road, 100191 Beijing, China
c
Department of Neurology, Peking University People's Hospital, No.11 South Xizhimen Street, 100044 Beijing, China

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

Article history: There is growing interest in the association between ambient air pollution and stroke, but few studies
Received 14 April 2017 have investigated the association in developing countries. The primary objective of this study was to
Received in revised form examine the association between levels of ambient air pollutants and hospital admission for stroke in
15 June 2017
China. A time-stratified case-crossover analysis was conducted between 2014 and 2015 in 14 large
Accepted 17 June 2017
Chinese cities among 200,958 ischemic stroke and 41,746 hemorrhagic stroke hospitalizations. We used
conditional logistic regression to estimate the percentage changes in stroke admissions in relation to
interquartile range increases in air pollutants. Air pollution was positively associated with ischemic
Keywords:
Stroke
stroke. A difference of an interquartile range of the 6-day average for particulate matter less than 10 mm
Air pollution in aerodynamic diameter, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone corresponded to
Hospitalization 0.7% (95% CI: 0%, 1.4%), 1.6% (95% CI: 1.0%, 2.3%), 2.6% (95% CI: 1.8%, 3.5%), 0.5% (95% CI:
0.2%, 1.1%), and
China 1.3% (95% CI: 0.3%, 2.3%) increases in ischemic stroke admissions, respectively. For hemorrhagic stroke,
we observed the only significant association in relation to nitrogen dioxide on the current day (per-
centage change: 1.6%; 95% CI: 0.3%, 2.9%). Our findings contribute to the limited scientific literature
concerning the effect of ambient air pollution on stroke in developing countries. Our findings may have
significant public health implications for primary prevention of stroke in China.
© 2017 Elsevier Ltd. All rights reserved.

1. Introduction recent years (Liu et al., 2011). A nationally-representative popula-

Stroke is the second-leading cause of death and the third major
cause of adult disability worldwide (2015; Murray et al., 2015).
Approximately 10.3 million new cases of stroke were diagnosed in
2013, and 6.5 million people are estimated to have died of stroke
that year; two-thirds of all strokes occurred in low- and middle-
income countries (Feigin et al., 2015). In China, stroke has
emerged as the most common cause of death and adult disability in
*
This paper has been recommended for acceptance by Dr. Chen Da.
* Corresponding author.
** Corresponding author.
E-mail addresses: yhhu@bjmu.edu.cn (Y. Hu), jun_zhang@bjmu.edu.cn
(J. Zhang).
1 et al., 2010; Hong et al., 2002; Mateen and Brook, 2011;
Hui Liu and Yaohua Tian contributed equally to this study and should be
considered as coefirst authors.
tion-based survey involving 480,687 Chinese adults aged 20 years
estimated that the age-standardized incidence and mortality rates
of stroke were 246.8 and 114.8 per 100,000 person-years in 2013,
respectively (Wang et al., 2017). Despite the implementation of
several primary and secondary prevention strategies in various
countries that have been shown as effective in randomized trials
(Kernan et al., 2014; Wang et al., 2007), the incidence of stroke
continues to rise, particularly in economically transitioning coun-
tries (Feigin et al., 2014). Stroke exerts considerable patient
suffering and immense economic burdens (Liu et al., 2011; Tong
et al., 2016). Therefore, identification of modifiable risk factors for
stroke has significant public health implications.
Research has provided compelling evidence linking outdoor air
pollution to hospital admissions or death from stroke (Andersen
Wellenius et al., 2012). Unlike the established risk factors for

http://dx.doi.org/10.1016/j.envpol.2017.06.057
0269-7491/© 2017 Elsevier Ltd. All rights reserved.
 H. Liu et al. / Environmental Pollution 230 (2017) 234e241
stroke, such as smoking, alcohol consumption, and physical inac-
tivity (O'Donnell et al., 2010), air pollution represents a potentially
modifiable risk factor that is independent of individual behavioral
change. Improving air quality may offer a unique advantage in
enhancing prevention efforts aimed at reducing the incidence of
stroke. However, most previous studies of this topic were con-
ducted in developed countries, and only limited research data have
been generated in developing countries. In view of the considerable
differences in pollutant characteristics (e.g., pollution levels and
components), meteorological patterns, population susceptibility,
and socio-demographic status (e.g., age structure and socioeco-
nomic characteristics) between developed and developing coun-
tries and the enormous stroke burden in the latter, an urgent need
remains to evaluate the effect of outdoor air pollution on the inci-
dence of stroke in developing countries.
China has been experiencing the worst air pollution problem in
the world (Kan et al., 2012). Ambient air pollution has been a major
cause of mortality and morbidity in China, accounting for an esti-
mated 1.2 million premature deaths and 25 million disability-
adjusted life years annually (Lim et al., 2012). The detrimental
health effects of air pollution are of increasing concern to the
public, particularly in relation to haze days. However, only a
handful of studies have examined the association between air
pollution and stroke in China, yielding inconsistent findings, and
these studies were restricted to a single city, such as Shanghai (Kan
et al., 2003), Wuhan (Xiang et al., 2013), and Beijing (Huang et al.,
2016). To the best of our knowledge, only one multicity study, the
China Air Pollution and Health Effects Study, has examined the
acute effects of air pollution on stroke mortality in eight Chinese
cities (Chen et al., 2013). However, this study did not differentiate
between ischemic and hemorrhagic stroke. In addition, the study
used death data rather hospitalization data. Stroke hospitalization
data would yield higher numbers of patients in a given population,
increasing the statistical power. Furthermore, hospitalization data
can better evaluate the temporal sequence between exposure to air
pollution and clinical presentation of stroke (Villeneuve et al.,
2006).
The objective of this study was to examine the association be-
tween short-term exposure to air pollution and hospital admission
for stroke in 14 large Chinese cities using a time-stratified case-
crossover design.
2. Methods
2.1. Study population
Data on daily admissions for ischemic and hemorrhagic stroke
were collected from electronic hospitalization summary reports
(HSRs) of the top-ranked hospitals for care safety and quality as
evaluated by the National Hospital Performance Evaluation Project
of the National Healthcare Data Center of China. The hospital
ranking system considers several aspects, including hospital
infrastructure, medical service and management, technical level
and efficiency, and quality and safety of clinical care. The infor-
mation recorded on the HSR includes basic demographics (e.g., sex
and age), date of admission and discharge, hospitalization and
discharge diagnoses and their corresponding International Classi-
fication of Diseases, 10th Revision (ICD-10) codes, treatments,
discharge status (survival status, drug allergy, and hospitalization
infection), and financial costs. The present study is considered
exempt from institutional review board approval since the data
used was collected for administrative purpose without any per-
sonal identifiers.
Daily hospital admissions with a primary discharge diagnosis of
ischemic stroke or hemorrhagic stroke between January 1, 2014,
235
and December 31, 2015, were identified from the HSR database
using ICD-10 codes I63, and I61 and I62, respectively. To decrease
the influence of coding inaccuracy, we used the corresponding di-
agnoses to check the identified hospitalizations. Individuals aged
<18 years were excluded from this study. 14 large cities across
China were analyzed in this study, including two municipalities
(Beijing and Tianjin), 11 provincial capital cities (Harbin, Shenyang,
Urumchi, Changchun, Yinchuan, Shijiazhuang, Jinan, Xining, Lanz-
hou, Xi'an, and Zhengzhou), and Dalian City (Fig. 1).
2.2. Air pollution and meteorological data
Data on air pollution, including levels of particulate matter less
than 10 mm in aerodynamic diameter (PM10), sulfur dioxide (SO2),
nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)
between January 1, 2014, and December 31, 2015, were obtained
from the China National Air Pollution Monitoring System, which is
run by the Ministry of Environmental Protection. There are 4e15
fixed-site air monitoring stations in each city. To fulfill the quality
assurance and quality control programs mandated by the Chinese
government, each monitoring station must provide hourly air
pollution data to the China National Air Pollution Monitoring Sys-
tem. For each city, the daily (24-h) mean concentrations for pol-
lutants were averaged from the available monitoring data across
various stations (Wong et al., 2008). All the hospitals included in
this study are located in the center of corresponding city. The
maximum distance between the hospitals and air monitoring sta-
tions were less than 40 km. It has been suggested that the moni-
toring data could be used as a proxy for personal exposure among
individuals residing <40 km from the monitoring station (Dockery
et al., 2005; Wellenius et al., 2012; Xie et al., 2015). To allow for the
potential confounding effects of meteorological conditions, daily
weather data on temperature ( C) and relative humidity (%) for
each city were obtained from the Chinese Meteorological Bureau.
2.3. Study design
A time-stratified case-crossover study design was applied to
assess the short-term effects of ambient air pollution on hospital
admissions for stroke. In this design, each case serves as its own
control (Carracedo-Martinez et al., 2010). For each case of stroke,
ambient air pollution exposure on the case day (the day of hospi-
talization) was compared with exposure on a series of referent days
occurring on the same days of the week within the same month and
Fig. 1. Locations of the 14 Chinese cities included in this study.
236 H. Liu et al. / Environmental Pollution 230 (2017) 234e241
year as the case day. This design allowed for controlling the influ-
ence of seasonality, time trends, sex, genetics, and other factors.
2.4. Statistical analysis
Spearman's correlation tests were used to estimate the associ-
ations between exposure variables. Conditional logistic regression
was used to examine the associations between air pollutants and
stroke. For adjustment of the delayed and non-linear effects of
temperature and humidity, the distributed lag non-linear models
with three degrees of freedom in the natural cubic splines and a
maximum lag of 3 days were used (Goldberg et al., 2011). Public
holiday was also incorporated in the model. To examine the tem-
poral association of air pollution with stroke, we fitted the models
with single-day lags (from lag0 to lag5) and multiple-day lags
(lag0e2 and lag0e5). Smoothing function with three degrees of
freedom in the natural cubic splines was applied to graphically
analyze the exposure-response associations between air pollutants
concentrations and ischemic stroke hospitalizations. To examine
the stability of air pollutants' effects, multi-pollutant analyses were
performed for air pollutants that were significant in the single
pollutant model, and the lag with the strongest univariate effect
was tested. To address the collinearity between air pollutants, only
those air pollutants with r < 0.7 were entered into the model (Ko
et al., 2007a, 2007b). To explore the potential modification, we
examined outcomes by age (65 years and <65 years) and by sex.
The differences between risk estimates from stratified analyses
were assessed using a Z-test (Altman and Bland, 2003). The results
are reported as the percentage change and 95% confidence intervals
(CIs) in the daily stroke admissions associated with a difference of
an interquartile range (IQR) in daily pollutant levels. Percentage
change equals odds ratio minus 1 and then multiplies by 100. All
analyses were conducted using the R programming language
(V.3.2.2, R Development Core Team). All statistical tests were two-
sided, and P < 0.05 was considered statistically significant.
3. Results
There were 200,958 hospital admissions for ischemic stroke and
41,746 admissions for hemorrhagic stroke that formed the basis for
this study (Table 1). Demographic characteristics of stroke admis-
sions are present in Table 1.
Table 2 shows the summary statistics of air pollutants and
meteorological variables in the 14 Chinese cities during the study
period. The air pollution levels in this study were much higher than
those reported in developed countries.
The daily concentrations of PM10, NO2, SO2, and CO were highly
and positively correlated with each other (correlation coefficient
r ¼ 0.56e0.65, p < 0.001). The daily concentrations of O3 were
negatively correlated with other air pollutants (correlation coeffi-
cient r ¼ (
0.38)e(
0.12), p < 0.001) (Table 3).
Table 4 summarizes the results of the single-pollutant model
(lag 0e5) for stroke hospitalizations after controlling for
Table 1
Demographic characteristics of stroke admissions in 14 Chinese cities in 2014e2015.
Variable Ischemic stroke Hemorrhagic stroke
Total 200,958 41,746
Gender
Male (%) 127,636 (63.5) 28,223 (67.6)
Female (%) 73,322 (36.5) 13,523 (32.4)
Age (year) (mean ± SD) 64.4 ± 12.6 59.0 ± 13.8
<65 (%) 102,275 (50.9) 27,626 (66.2)
65 (%) 98,693 (49.1) 24,120 (33.8)
temperature, relative humidity and public holiday. All analyzed air
pollutants, with the exception of CO, were positively associated
with ischemic stroke, while CO showed significant association at
lag 3 and lag 4 days. We also observed significant association of
hemorrhagic stroke with NO2 on the current day. The air pollutants
showed strong temporal associations with a 4e5 day lag (Fig. 2).
Fig. 3 shows the exposure-response associations between air
pollutants concentrations (lag 0e5 day) and hospital admissions for
ischemic stroke. Table 5 shows the associations between air pol-
lutants (a difference of an IQR in different best lag days) and stroke
in multi-pollutant models. The associations of ischemic stroke with
NO2, SO2, and O3 remained stable and significant after adjusting for
other air pollutants. However, the associations of PM10 and CO with
ischemic stroke were weakened even towards null. The association
between NO2 and hemorrhagic stroke even became stronger after
adjusting for other air pollutants. There was no evidence of effect
modification by sex or age in any lag structure (all p > 0.05) (Fig. S1).
4. Discussion
Our multicity analysis showed that all five major air pollutants
were positively associated with risk of hospital admission for
ischemic stroke in the study area. We also observed significant
association of NO2 with hospitalization for hemorrhagic stroke. To
the best of our knowledge, this is the first multicity study in
mainland China to examine the short-term effects of various air
pollutants on hospital admissions for stroke.
In the present study, a difference of an IQR of 6-day moving
average concentrations of PM10, NO2, SO2, CO, and O3 corresponded
to increases in hospital admissions for ischemic stroke, and an in-
crease in average concentration of NO2 was significantly associated
with admissions for hemorrhagic stroke. The magnitude of our risk
estimates was generally comparable with prior reports. For
example, Wellenius et al. (2005). examined the association of air
pollution with hospital admissions for ischemic and hemorrhagic
stroke in nine US cities, limiting the cohort to patients aged 65.
They found that a difference of an IQR of PM10, SO2, NO2, and CO
concentration was associated with 1.03%, 1.35%, 2.94%, and 2.83%
increases in hospital admissions for ischemic stroke, respectively.
However, for hemorrhagic stroke, no significant associations with
any pollutants were observed (Wellenius et al., 2005). Another
large-scale multicity analysis, the China Air Pollution and Health
Effects Study, estimated that a 10 mg/m3 increase of 2-day moving
average concentrations of PM10, SO2, and NO2 corresponded to a
0.54%, 0.88%, and 1.47% increase in stroke mortality, respectively
(Chen et al., 2013). In a meta-analysis of 103 studies on air pollution
and stroke morbidity and mortality, most of which were conducted
in Europe and North America, Shah et al. (2015). estimated that the
excess risks of stroke associated with a 10 ppb increase of SO2, NO2,
and O3 concentrations were 1.9%, 1.4%, and 0.1%, respectively. PM10
and CO were also significantly associated with increased risk of
stroke (Shah et al., 2015).
The broad consistency in the literature indicates that the asso-
ciation of air pollution with stroke is unlikely to be spurious due to
confounding, publication bias or flaws in study design. It should be
noted that, although the magnitude of risk estimates in this study
was similar to the magnitude indicated in previous reports, the
stroke burden resulting from exposure to air pollution is greater in
China than in developed countries because of higher air pollution
levels and consequent higher incidence.
While our study showed consistent positive associations be-
tween air pollution and ischemic stroke, the associations with
hemorrhagic stroke were more variable and imprecise; this finding
is consistent with those of earlier studies (Huang et al., 2016; Shah
et al., 2015; Villeneuve et al., 2006; Wellenius et al., 2005). The
 H. Liu et al. / Environmental Pollution 230 (2017) 234e241 237

Table 2
Summary statistics for air pollutants concentrations and meteorological variables in 14 Chinese cities in 2014e2015.

Variable Mean ± SD Minimum Percentile Maximum IQR

25th 50th 75th

PM10 (mg/m3) 127.1 ± 82.2 8.9 73.1 108.4 158.8 977.3 85.7
NO2 (mg/m3) 46.6 ± 20.6 5.6 31.8 42.8 57.2 170.9 25.4
SO2 (mg/m3) 39.6 ± 41.2 1.9 12.5 25.4 50.8 316.9 38.3
CO (mg/m3) 1.28 ± 0.78 0.14 0.76 1.07 1.57 8.41 0.81
O3 (mg/m3) 91.5 ± 51.1 2 54 80 121 290 67
Temperature ( C) 11.2 ± 12.0
25.7 1.9 12.8 21.5 35.5 19.6
Relative humidity (%) 62.0 ± 45.4 8 42 57 71 95 53

IQR: interquartile range.

Table 3 previous reports (Chen et al., 2013; Villeneuve et al., 2006). NO2
Spearman correlation coefficients among the exposure variables in 14 Chinese cities generally serves as a surrogate measure for vehicular pollution
in 2014e2015.
because of its close association with vehicle exhaust emissions
Variables PM10 NO2 SO2 CO O3 Temp RH (Seaton and Dennekamp, 2003). It is possible that other traffic-
PM10 1.00 0.61a 0.56a 0.63a
0.12a
0.18a
0.12a related components, such as ultrafine particles, are responsible
NO2 e 1.00 0.56a 0.65a
0.27a
0.33a 0.10a for the observed effects. However, the robust and consistent risk
SO2 e e 1.00 0.56a
0.38a
0.59a 0.01a
CO e e e 1.00
0.35a
0.37a 0.12a
O3 e e e e 1.00 0.76a
0.16a
Temp e e e e e 1.00 0.18a
RH e e e e e e 1.00

Temp: temperature ( C); RH: relative humidity (%).

a
P < 0.001.

underlying mechanism of cardiovascular changes in relation to air

pollution and the differences in the etiology of stroke subtype may
partly explain the heterogeneity in the association between stroke
subtype and air pollution. Several plausible biological mechanistic
pathways for the adverse health effects associated with air pollu-
tion have been advanced. Epidemiological and toxicological evi-
dence indicates that air pollution exposure may provoke platelet
activation, leading to enhanced blood coagulation and thrombosis
formation (Franchini and Mannucci, 2011; Lucking et al., 2008).
Several studies have posited associations between exposure to air
pollution and artery calcification (Kaufman et al., 2016) or vascular
endothelial dysfunction (Tornqvist et al., 2007). This hypothesis is
also supported by findings in animal models (Sun et al., 2005).
Exposure to air pollution has been associated with increased levels
of plasma cytokines including tumor necrosis factor alpha, inter-
leukin 1 beta, and interleukin 6 (van Eeden et al., 2001), suggesting
that systemic inflammatory responses induced by air pollution may
also play a role in the development of stroke. These pathophysio-
logic changes associated with air pollution may be related to the
development and progression of ischemic stroke. The lower inci-
dence of hemorrhagic stroke may lead to larger imprecision in the Fig. 2. Percentage change (95% CI) in hospital admissions for ischemic stroke and
hemorrhagic stroke associated with a difference of an interquartile range (IQR) of PM10
estimates (Shah et al., 2015).
(85.7 mg/m3), NO2 (25.4 mg/m3), SO2 (38.3 mg/m3), CO (0.81 mg/m3), and O3 (67 mg/m3)
The risk estimates from multi-pollutant models found that NO2 for different lag structures in 14 Chinese cities, 2014e2015. PM10, particulate matter
contributed most to the increased risk of stroke, in line with less than 10 mm in aerodynamic diameter; NO2, nitrogen dioxide; SO2, sulfur dioxide;
CO, carbon monoxide; O3, ozone.

Table 4
Percentage change with 95% CI in ischemic and hemorrhagic stroke admissions associated with an interquartile range increases in air pollutants in 14 Chinese cities in
2014e2015.

Variables Ischemic stroke Hemorrhagic stroke

Percentage changea 95% CI P Percentage change 95% CI P

PM10 0.7 0e1.4 0.0479 0.3
1.1e1.8 0.641

NO2 1.6 1.0e2.3 3.54e-07 0.6
0.7e2 0.342
SO2 2.6 1.8e3.5 8.45e-10 1.4
0.4e3.2 0.125
CO 0.5
0.2e1.1 0.176
0.8
2.2e0.7 0.287
O3 1.3 0.3e2.3 0.0103 2
0.2e4.3 0.0771
a
The association was adjusted for temperature, relative humidity and public holiday.
238 H. Liu et al. / Environmental Pollution 230 (2017) 234e241

Fig. 3. The exposure-response curves for 6-day (lag0e5) moving average concentrations of particulate matter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone (degree
of freedom ¼ 3) associated with hospital admissions for ischemic stroke in 14 Chinese cities, 2014e2015. Note: The X-axis is the 6-day (lag0e5) moving average concentrations of air
pollutants. The Y-axis is the log relative risk (RR). The solid line represents the predicted log relative risk (RR), and the dotted lines represent the 95% CI.

estimates for NO2 when controlling for other air pollutants point to
an independent effect. This should be interpreted with caution
because of the high correlation between pollutants. Future studies
are required to identify the specific toxic agent which is directly
responsible for increased risk of stroke.
Possibly because of the higher levels of air pollution in China, a
stronger temporal association was observed compared with prior
reports of a 1e2 day lag (Andersen et al., 2010; Villeneuve et al.,
2006; Wellenius et al., 2005, 2012). However, it should be noted
that these risk estimates were based on hospital admission data
rather than on the timing of symptom onset, possibly leading to
misclassification of time and underestimation of effects (Zeger
et al., 2000). However, because stroke events usually require ur-
gent care and hospitalizations, the confounding bias caused by
 H. Liu et al. / Environmental Pollution 230 (2017) 234e241
Table 5
Percentage change with 95% CI in ischemic and hemorrhagic stroke admissions associated with an interquartile range increases in air pollutants concentrations in different
best lag days in multi-pollutant models.
Variable PM10 NO2
Ischemic stroke
0.2 (
0.9e0.5) 1.9 (1.0e2.9)a
Hemorrhagic stroke 0.6 (
0.9e2.1) 3.7 (1.7e5.7)a
a
P < 0.05 (The association was adjusted for temperature, relative humidity and public holiday).
exposure misclassification is expected to be minor. A population-
based study of 1101 acute ischemic stroke patients in one city in
the U.S. found that hospital admission occurred a median of one
calendar day after the onset of symptoms, and this delay in pre-
sentation was likely to result in underestimation of the strength of
association between air pollution and stroke (Lokken et al., 2009).
Therefore, the lag effects of ambient air pollution exposure on
stroke should be interpreted with caution.
Unlike the majority of previous studies, which had been con-
ducted in Western developed nations where air pollution levels are
generally low, this study was carried out in multiple heavily
polluted cities. We were therefore able to examine the exposure-
response relationship in a much wider range of air pollution
levels, and have an opportunity to sketch a more complete picture
of the association. Our study also had some potential limitations.
First, the data used in this study were derived from 14 large cities.
Due to the topography of China, also in relation to the variability in
air pollution levels across varying city sizes, the generalizability of
our findings to smaller cities should be interpreted with caution.
The association between air pollution and stroke in smaller cities
should be examined in future studies. Second, the use of citywide
average air pollution levels calculated from various monitoring
stations as a proxy for personal exposure is expected to result in
exposure measurement error, which may underestimate the effects
of air pollution (Goldman et al., 2011). Third, PM2.5 has also been
shown to contribute to stroke risk. However, data on PM2.5 is not
available in this study. Future studies are needed to evaluate the
effect of PM2.5 on stroke risk in China. In addition, we were not able
to differentiate the ischemic stroke subtypes, because that infor-
mation was not available in our database. Future studies are needed
to examine whether the acute effects of air pollution differed across
strata defined by ischemic stroke etiology. Moreover, we could not
determine if individuals that are admitted for stroke are from
outside areas of the city, or what if those that are the ones exposed
to the pollution at those levels present at another hospital outside
of the city. However, according to China's medical system, patients
ought to go to their designated local hospitals to seek medical care
(Babiarz et al., 2010; Dong, 2009; Xu et al., 1995). In addition, stroke
events usually require urgent care and hospitalizations. A previous
study indicated that hospital admission occurred a median of one
calendar day after the onset of symptoms (Lokken et al., 2009).
Therefore, the confounding bias caused by this potential exposure
misclassification is expected to be minor. Another limitation was
our inability to account for factors associated with personal air
pollution exposure, e.g., activities of daily living for individual pa-
tients. The potential misclassifications for the diseases diagnosis
should also be considered when interpreting the findings. How-
ever, all the hospitals included in this study are top-ranked public
hospitals, and enjoy the prestigious esteems for quality in all as-
pects of healthcare, including treatment, diagnosis, coding, hospital
management, and electronic medical record systems. The Beijing
Municipal Health Bureau had conducted quality control study, and
demonstrated that over 95% of diagnostic codes on the HSR were
accurate according to manual examinations of electronic medical
records (Zhao et al., 2013). Only inclusion of top-ranked hospitals in
this study can help with eliminating the potential misclassifications
239
SO2 CO O3
0.9 (0.3e1.5)a
0.5 (
1.3e0.3) 1.6 (0.8e2.4)a
0.4 (
1.0e1.8)
0.9 (
2.5e0.8) 1.7 (
0.2e3.6)
for the diseases diagnosis. In addition, the corresponding Chinese
diagnoses were applied to check the identified admissions. Natural
language processing has been suggested to be an efficient method
for identifying cases in large clinical databases (Data, 2016;
Nadkarni et al., 2011). Both ICD codes and the corresponding pa-
tient diagnoses were used to identify eligible hospital admissions
for stroke, which would significantly reduce the potential bias
caused by misclassification of stroke. However, on the other hand,
only inclusion of top-ranked hospitals may cause selection bias.
Finally, although the associations between air pollutants and stroke
remained significant after Bonferroni correction, we acknowledged
that the results could be due to chance because of multiple testing
and the sparsely significant results. Future studies are warranted to
confirm our findings.
In conclusion, our study found that short-term exposure to air
pollution was significantly associated with increased hospital ad-
missions for stroke in China. Our findings contribute to the limited
scientific literature concerning the effect of air pollution on stroke
in developing countries, where air pollution is more severe. Our
findings may have significant public health implications for pre-
vention of stroke in China.
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgments
This research work was funded by the National Natural Science
Foundation of China (Grant No. 71402003).
Appendix A. Supplementary data
Supplementary data related to this chapter can be found at
http://dx.doi.org/10.1016/j.envpol.2017.06.057.
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