Association between ambient air pollution and hospital admission for epilepsy in Eastern China

doi:10.1016/j.eplepsyres.2019.02.012

Epilepsy Research

Volume 152, May 2019, Pages 52-58

https://doi.org/10.1016/j.eplepsyres.2019.02.012 Get rights and content

Highlights

•
To our knowledge, this is the first multiple-center study regarding health impact on epilepsy of ambient air pollutants conducted in China.
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The conditional Poisson regression model served as a flexible and fast tool to adjust for over dispersion and auto-correlation.
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An interquartile (IQR) increase of NO2 and CO on concurrent days is correlated with slight increase in epilepsy admission.

Abstract

Background

We aimed to study the short-term association between air pollutants and hospitalization for epilepsy in 47 hospitals from 10 cities in eastern China.

Method

We identified hospital epilepsy admissions in 2014 and 2015. A conditional Poisson regression model was used to examine the association between air pollutants and hospital admission, with temperature and relative humidity adjusted using the natural spline (ns) function. Pollutants included sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and particulate matter (PM). The association was stratified by sex, age, and geographic region in single-pollutant and two-pollutant models.

Results

An interquartile (IQR) increase of NO₂ and CO on the concurrent day is correlated with an increased admission of 2.0% (0.5%, 3.6%) and 1.1% (0.1%, 2.1%), respectively. The association is stronger in children (≤18 years) and in northern China, but did not vary with sex. A positive association was also observed on the previous day for CO [1.5%, 95% confidence interval (CI): 0.3%, 2.6%], NO₂ (2.5%, 95% CI: 0.6%, 4.3%), and PM_2.5 (1.32%, 95% CI: 0.16%, 2.48%). Moving average concentration of 7 days for all pollutants was associated with decreased admission (CO: -1.29%, NO₂: -0.4.69%, SO₂:-2.12%, PM_2.5:-0.98%, PM₁₀:-1.70%).

Conclusion

Exposures to NO₂ and CO on concurrent days, and PM_2.5 on the previous day, are associated with increased epilepsy hospitalization, whereas cumulative exposure appeared protective.

Introduction

Epilepsy is a common neurologic disease characterized by abnormal neuronal excitability (Song et al., 2017), manifested as unpredicted and recurrent seizures (Fisher et al., 2005). It is a wide-reaching and complex disease, affecting over 70 million people ranging from neonates to the elderly (Singh and Trevick, 2016). According to a systematic review and meta-analysis, the prevalence of epilepsy in China has increased by 259% from 1990 to 2015 (Song et al., 2017). The impact of epilepsy is not only limited to physical damage, but also could cause psychological problems and psychiatric impact (Berg et al., 2017; Coppola et al., 2016; Kwon and Park, 2014; Lang et al., 2018; Radovic et al., 2017). Moreover, compromise in quality of life (QoL) and extra burden on the caregivers were also observed in epilepsy patients (Fong et al., 2018; Gutierrez-Angel et al., 2018; Puka et al., 2018).

Ambient air pollution is one of the crucial factors regarding health impact and economic burden in China (Lin et al., 2017; Niu et al., 2017). As the largest developing country in the world, China has faced the worst air pollution in decades, mainly due to its rapid economic development (Li et al., 2015). In January 2013, a hazardous dense haze affected more than 800 million people in Beijing, bringing attention to the health impact of air pollution (Zhang et al., 2017). Although the Chinese government has taken a series of actions to control emission load (Ge et al., 2017), over 80% of the Chinese population are exposed to pollution above the Interim Target-1 limit (35 μg/m³) proposed by the World Health Organization (WHO) in 2016 (Niu et al., 2017). Air pollutants is comprised of gaseous pollutants and particulate matter (Bourdrel et al., 2017; Ning et al., 2018; Zhou et al., 2018). The health impact of both types of pollutants was broadly studied, especially the impact on cardiovascular disease (Bourdrel et al., 2017; Fuller et al., 2017; Khaniabadi et al., 2017; Vidale et al., 2017) and respiratory diseases (Mo et al., 2018; Nunes-Silva et al., 2017; Saygin et al., 2017; Vardoulakis and Osborne, 2018) in relation to mortality, outpatient visits, and hospitalization. However, the association with neurological diseases was insufficiently investigated. Xu et al. found that carbon monoxide (CO), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂) were associated with increased outpatient visits for epilepsy based on a single-center study in China (Xu et al., 2016a). Before that, significant coefficients were also observed on epilepsy hospital admission in Chile (Cakmak et al., 2010). Moreover, all pollutants were observed to be associated with increased admissions, but the effect of each pollutant is inconsistent. In addition, neurotoxicity of the pollutants were also observed in controlled animal studies (Costa et al., 2014; Yun et al., 2013).

To the best of our knowledge, limited studies have been performed regarding the health impact of air pollutants on epilepsy. Thus, we conducted this study in 10 provincial capital cities in eastern China to provide clues for air pollutants as potential risk factors and inspire further exploration of the mechanism.

Section snippets

Study population

The data in the present study were extracted from the database of top grade 3 A hospitals’ (tertiary hospitals) electronic hospitalization summary reports (HSRs) evaluated by the National Hospital Performance Evaluation Project conducted by the National Healthcare Data Center of China. The hospital infrastructure, medical service, management, technical level and efficiency, and quality and safety of clinical care were considered in the ranking system. The clinical information provided by HSR

Demographic characteristics of epilepsy admissions

The mean age [standard deviation (SD)] of the patients was 16.91 (18.66) years. Of the total of 51,523 admissions, 30,908 (60.0%) patients were male, 35,446 (68.8%) were less than 18 years of age, and 20,820 (40.4%) were from southern China (Table 1).

Air pollution and meteorological variables

Table 2 shows the concentration of air pollutants and meteorological statistics in the 10 studied cities. The concentration of air pollutants were 48.2 ± 21.5 μg/m³ for NO₂, 23.6 ± 29.9 μg/m³ for SO₂, 1.1 ± 0.7 μg/m³ for CO, 69.5 ± 57.5 μg/m³ for PM

Discussion

To the best of our knowledge, this study is the third study of association between air pollutants and epilepsy worldwide, and the first multi-center study performed in large hospitals (grade IIIA in China, i.e., > 500 beds) in China. We obtained 51,523 admissions from 47 hospitals in 10 cities in eastern China. The target hospitals in the present study are all grade IIIA hospitals; therefore, the HSR data are of high accuracy. In the present study, NO₂ and CO were significantly related to the

Conclusion

Short-term exposure to NO₂ and CO is associated with increased hospitalization for epilepsy. And, cumulative exposure of all pollutants in the present study appears to be a “protective factor.” Future research regarding different levels of exposure to air pollution and epilepsy based on population and animal models are warranted.

Conflict of interests

Authors of the article report no conflict of interests

Acknowledgment

No fund is involved in present study.

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To investigate the association between O₃ and the number of outpatient visits for epilepsy in Chongqing, the most populous municipality in China, we conducted a time-series study including 99,740 epilepsy outpatient visits from January 2014 to December 2019 (2191 days). During the study period, the mean maximum 8-h average O₃ was 70.63 μg/m³, which was below the WHO guideline (100 μg/m³). Negative and statistically significant associations of O₃ were observed at lag 0, lag 1, and lag 01 to lag 03. Meanwhile, O₃ exposure of lag 03 yielded the strongest estimates for outcomes: per 10-μg/m³ increase in O₃ at lag 03 corresponded to −0.770% (95% CI: −1.419%, −0.122%) decrease in outpatient visits for epilepsy. In addition, the effect estimates were stronger in females than in males, in people aged ≥65 years than in younger populations, and in cool seasons than in warm seasons. Taken together, there was a significant negative association between short-term exposure to low concentrations of O₃ and outpatient visits for epilepsy. These findings may contribute to the understanding of the relationship between air pollutants and epilepsy and other neurological diseases.
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However, there are several inconsistencies in previous studies of air pollution and childhood epilepsy attacks. For instance, we found increased childhood epilepsy risk from five pollutants (PM2.5, PM10-2.5, PM10, SO2, and NO2), while adverse effects of air pollution were previously reported only for two pollutants (SO2 and NO2) (Xu et al., 2016; Bao et al., 2019). One possible reason is due to geographical variations in pollutant characteristics (e.g., pollutant constituents), population sensitivity, and adaptation capacity.
Growing studies suggest that air pollution exposure is an emerging driver for neurological diseases, but existing evidence on the association between air pollution and epilepsy is scarce. Here, we aimed to quantitatively estimated the short-term effects of various air pollutants on childhood epilepsy hospitalizations in China.
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This study included 8,181 childhood epilepsy patients from 10 cities in Anhui province of China. The first stage case-crossover analysis in Anhui province found significant associations between higher concentrations of all air pollutants (except O₃) and increased risk of childhood epilepsy hospitalizations. Each 10 μg/m³ increase in PM_2.5, PM_10-2.5, PM₁₀, SO₂, and NO₂ concentrations was associated with an increase of 1.1 % [95 % confidence interval (CI): 0.1 %-2.1 %], 1.7 % (95 %CI: 0.5 %-2.9 %), 0.8 % (95 %CI: 0.1 %-1.4 %), 8.5 % (95 %CI: 1.5 %-16.0 %), and 4.3 % (95 %CI: 2.3 %-6.3 %) in epilepsy hospitalizations, respectively. We also observed greater effects of particulate matter in cold season. The second stage meta-analysis that additionally included two prior studies with 43,002 patients from other 11 cities found a marginally significant increase in childhood epilepsy attacks associated with PM_2.5, PM₁₀, and NO₂ in eastern China.
Short-term exposure to both particulate matter and gaseous air pollution was associated with an increased risk of childhood epilepsy exacerbation in eastern China. Our findings suggest that air pollution exposure especially in cold season needs to be considered by children’s parents or guardians to prevent epilepsy attacks.
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In addition, Hartz et al. (2008) showed that diesel exhaust particles as a component of air pollution alter blood-brain barrier function through oxidative stress and proinflammatory cytokine production. Since inflammation may also be a risk factor for epilepsy, it can be predicted that hospital admissions for epileptic attacks may increase on days with high air pollution (Fernandes et al., 2019; Bao et al., 2019). In addition, the increase in air pollution may cause anti-epileptic drug resistance by changing the ion channels in the cell membrane (Fernandes et al., 2019).
The aim of this study is to investigate the relationship between exposure to acute air pollution and meteorological factors on the frequency of epileptic attacks in children.
This retrospective study was carried using patient files from a children’s hospital in Diyarbakır, one of the largest cities in Turkey. In the present study, the possible relationship between epileptic attacks seen in children over a 10-year period, two air polluting factors (PM₁₀ and SO₂), and the meteorological factors (air pressure, humidity, precipitation, wind speed) affecting them were investigated. The effects of different variables on the number of epilepsy patients admitted to the pediatric emergency department were also evaluated through four different models utilizing Poisson Regression Analysis.
According to Model 2 and 3, the strongest relationship of the four Poisson Regression models, there was a significantly increased risk of pediatric emergency department admissions for seizures associated with a 10 µm/m³ increase in PM₁₀ (IRR=1.020; 95% CI: 1.018–1.022); IRR= 1.071; 95% CI: 1.050–1.081; respectively) and 10 µm/m³ increase in SO₂ (IRR=1.162; 95%CI: 1.151–1.173; IRR=1.092; 95% CI: 1.042–1.120; respectively). In Model 2, a 1 m/s increase in wind speed decrease the risk of daily of epileptic attack admitted to the emergency department and a 1 °C increase in temperature increased the risk of daily of epileptic attack admitted to the emergency department (IRR=0.840; 95% CI; 0.714–0.987; IRR=1.033; 95%CI: 1.007–1.059; respectively). In Model 3, 1% increase in humidity and 1 m/s increase in wind speed increased the number of daily epileptic attack admitted to the emergency department (IRR=1.008; 95%CI: 1.004–1.011; IRR=1.169; 95%CI: 1.056–1.294; respectively). The daily number of epilepsy patients was statistically significantly affected by the autumn (95%CI: 10.017–19.845) and winter (95%CI: −0.279 to 13.292) seasons.
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In 2010, a daily time series analysis was conducted using data from several cities in Chile; positive correlations between an increase in hospitalization for epilepsy and increases in the levels of NO2, CO, SO2, O3, PM10, and PM2.5 were reported [41]. Two studies from China have found that the number of emergency or hospital stays increased significantly after one day of exposure to high air pollution [42,43]. Of these two studies, the study by Bao et al. [43] is currently the only multicenter study to be based on data from 47 hospitals in 10 cities in eastern China.
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¹: These authors have contributed equally to the work.

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Association between ambient air pollution and hospital admission for epilepsy in Eastern China

Highlights

Abstract

Background

Method

Results

Conclusion

Introduction

Section snippets

Study population

Demographic characteristics of epilepsy admissions

Air pollution and meteorological variables

Discussion

Conclusion

Conflict of interests

Acknowledgment

Arch. Cardiovasc. Dis.

Environ. Int.

J. Card. Fail.

Epilepsy Behav.

Neurotoxicology

Epilepsy Behav.

Epilepsy Behav.

Toxicol. Lett.

Epilepsy Behav.

Chemosphere

Epilepsy Behav.

Environ. Int.

Neurotoxicology

Sci. Total Environ.

Epilepsy Behav.

J. Pediatr.

Neurol. Clin.

Int. J. Cardiol.

Front. Public Health

Environ. Res.

Int. J. Behav. Nutr. Phys. Act.

Chemosphere

Conditional Poisson models: a flexible alternative to conditional logistic case cross-over analysis

BMC Med. Res. Methodol.

Psychiatric and behavioral comorbidities in epilepsy: a critical reappraisal

Epilepsia

Front. Neurosci.

The effects of air pollution on asthma hospital admissions in Adelaide, South Australia, 2003-2013: time-series and case-crossover analyses

Clin. Exp. Allergy

Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: a controlled, blinded crossover study

Inhal. Toxicol.

Neurotoxicants are in the air: convergence of human, animal, and in vitro studies on the effects of air pollution on the brain

Biomed. Res. Int.