Background:This study aimed to investigate the relation between air pollution and epilepsy admissions in Kerman, Iran.
Methods:In this ecological study, the concentrations of ambient air pollutants and meteorological data were obtained from Kerman Environmental Protection Agency and Kerman Meteorology Organization, respectively. Additionally, epilepsy admission data were obtained from Kerman’s Shafa hospital epilepsy registry. Generalized additive models with lags up to 7 days were used to estimate rate ratios (RRs).
Results:Within 2008 to 2020, 894 epilepsy admissions occurred in Kerman, 498 cases (55.7%) of whom were male. The strongest relations of epilepsy admission were observed in the over 59-year group for carbon monoxide (CO) in lag 0 (RR = 2.1455, 95% CI: 1.5823 - 2.9091), nitrogen dioxide (NO2) in lag 0 (RR = 1.0409, 95% CI: 1.0282 - 1.0537), and particulate matter under 2.5 microns (PM2.5) in lag 5 (RR = 1.0157, 95% CI: 1.0062 - 1.0252). There were also significant associations for particulate matter under 10 microns (PM10) in the under 18-year group in lag 2 (RR = 1.0064, 95% CI: 1.0029 - 1.0098), ozone in lag 0 (RR = 0.9671, 95% CI: 0.9581 - 0.9761), and sulfur dioxide in lag 5 (RR = 0.9937, 95% CI: 0.9891 - 0.9983).
Conclusions:Exposure to CO, NO2, PM2.5, or PM10 air pollutants might be a risk factor for epilepsy admissions in Kerman. Epilepsy patients should better stay away from exposure to polluted air. Staying at home on polluted days or residing in areas with less air pollution might be an option.
Epilepsy is one of the most common neurological diseases and affects individuals of all ages (1). Air pollution might cause central nervous system (CNS) damage and neurodegenerative disorders (2). The occurrence of seizures might be affected by the interaction of internal and pathologic factors and extrinsic factors, including medication and environmental factors (3, 4). Studies have shown that Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and stroke might be related to ambient air pollution (5, 6). Calderon et al. conducted a study in Mexico and reported that exposure to air pollutants could seriously affect children’s CNS (7). Another study in China also showed the possible relation between air pollution and neurodegenerative diseases (8). Fluegge and Fluegge reported hospitalization for epilepsy associated with changes in the concentrations of various pollutants, including nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), and particulate matter (PM). Additionally, Fluegge and Fluegge showed that air pollutants might be a risk factor for epilepsy hospital admissions (9).
However, the effect of air pollution on the CNS has not been thoroughly studied. Kerman has a population of about 740,000 individuals according to the 2016 census and is located in Kerman province in southeastern Iran (10). In addition to human-made air pollution, Kerman faces sandstorms and increased ambient dust in specific seasons. The prevalence of epilepsy in Kerman was 7.87 per 1000 individuals in 2011 (1). A recent review estimated that there are about 840,000 individuals with active epilepsy living in Iran, and epilepsy prevalence in Iran is 1% (11).
The present study aimed to evaluate hospital admissions in Kerman for epilepsy and its possible relation with air pollution.
In this ecological study, the concentrations of ambient air pollutants (i.e., CO, O3, NO2, SO2, and particulate matter under 10 and 2.5 microns [PM10 and PM2.5]) were obtained from Kerman Environmental Protection Agency within September 2008 to March 2020. The meteorological data, including temperature and relative humidity, were obtained from Kerman Meteorological Organization. The aforementioned variables were adjusted as confounders.
The epilepsy hospitalization data were obtained from Kerman’s Shafa hospital epilepsy registry and according to the International Classification of Diseases 10th Revision, which was code G40. The data were investigated regarding gender and age subgroups (under 18, within 18-59, and over 59 years). The data of all epilepsy patients that had stayed in the hospital for more than one day were included.
3.1. Statistical Analysis
Generalized additive models (GAMs) similar to the equation below were used to estimate the rate ratios (RRs) with lags up to 7 days. The time unit used was the day. The GAM has been used in numerous air pollution and health studies. This method can adjust for nonlinear confounding effects, such as seasonal changes and meteorological variables (12).
Several studies have shown that meteorological factors, such as temperature, are associated with hospital admissions for epilepsy attacks (3, 13-16). Therefore, the models were adjusted for average daily temperature and relative humidity. The time unit used in the analysis was the day. Microsoft Office Excel software (version 2010) and SPSS software (version 22) were used for the primary analysis. Then, the ‘mgcv’ package in R i386 4.0.3 software was used for GAM analysis.
In the less than 12-year period under study, 894 epilepsy admissions occurred in Kerman, 498 (55.7%) and 396 (44.3%) cases of whom were male and female, respectively. Table 1 shows the number of epilepsy admissions within 2008 to 2020 in different population subgroups. Table 2 shows descriptive statistics of daily air pollution and meteorological variables within 2008-2020. The findings showed that the mean daily concentrations of PM10, PM2.5, and SO2 were higher than the World Health Organization daily thresholds reported as 50, 25, and 20 μg/m3, respectively (17).
Number of Epilepsy Admissions within 2008 to 2020 in Different Population Subgroups
|Year||Male||Female||Male/Female Ratio||< 18 years||18 - 59 years||> 59 years|
|2020 (only 3 months)||1||0||-||0||0||1|
Descriptive Statistics of Daily Air Pollution and Meteorological Variables
|Mean ± SD||Median||Minimum||Maximum|
|O3 (ppb)||30.21 ± 11.91||29.72||1.92||79|
|CO (ppm)||1.07 ± 0.69||0.92||0.03||12.27|
|NO2 (ppb)||15.82 ± 7.96||15.41||0||78.45|
|SO2 (ppb)||26.12 ± 20.64||21||0||128.46|
|PM10 (μg/m3)||71.11 ± 47.45||63.48||0||382.76|
|PM2.5 (μg/m3)||27.47 ± 16.18||24.20||0||112|
|Temperature (°C)||16.75 ± 8.10||17.2||0||41|
|Humidity (%)||31.15 ± 17.30||27||3.5||100|
Table 3 shows the results of the adjusted GAM about the effect of air pollutants on overall epilepsy admissions in male, female, and age groups adjusted for average daily relative humidity and temperature. Increased epilepsy admissions in the total population were observed in various lags for CO, NO2, PM10, and PM2.5. Additionally, CO, NO2, PM10, and PM2.5 had a direct association with epilepsy admissions in male subjects. The strongest relations were observed in lag 4 for CO (RR = 1.2352, 95% CI: 1.0298 - 1.4815), lag 0 for NO2 (RR = 1.0409, 95% CI: 1.0282 - 1.0537), lag 2 for PM2.5 (RR = 1.0066, 95% CI: 1.0014 - 1.0118), and lag 0 for PM10 (RR = 1.0057, 95% CI: 1.0039 - 1.0075). PM10 and PM2.5 also had a direct association with epilepsy admissions in female subjects. The strongest relations were observed in lag 2 for PM2.5 (RR = 1.0071, 95% CI: 1.0015 - 1.0128) and lag 6 for PM10 (RR = 1.0031, 95% CI: 1.0011 - 1.0050).
In all age groups, CO, NO2, PM10, and PM2.5 showed direct relations with epilepsy admissions. The strongest relation between CO and epilepsy admissions was observed in the over 59-year group in lag 0 (RR = 2.1455, 95% CI: 1.5823 - 2.9091), NO2 in the over 59-year group in lag 0 (RR = 1.0407, 95% CI: 1.0139 - 1.0681), PM2.5 in the over 59-year group in lag 5 (RR = 1.0157, 95% CI: 1.0062 - 1.0252), and PM10 in the under 18-year group in lag 2 (RR = 1.0064, 95% CI: 1.0029 - 1.0098).
Results of Adjusted Generalized Additive Models about the Effect of Air Pollutants on Epilepsy Admissions in Total, Male, Female, and Age Groups Adjusted for Relative Humidity and Temperature
|O3||0.9816||0.9756 - 0.9877||0.0001|
|CO||0.9008||0.7906 - 1.0263||0.315|
|NO2||1.0266||1.0168 - 1.0364||0.001|
|SO2||0.9978||0.9945 - 1.0011||0.178|
|PM10||1.0037||1.0024 - 1.0050||0.0001|
|PM2.5||1.0017||0.9977 - 1.0057||0.402|
|O3||0.9942||0.9854 - 1.0029||0.718|
|CO||0.9543||0.8015 - 1.1360||0.598|
|NO2||1.0409||1.0282 - 1.0537||0.001|
|SO2||0.9967||0.9923 - 1.0012||0.234|
|PM10||1.0057||1.0039 - 1.0075||0.001|
|PM2.5||1.0001||0.9949 - 1.0054||0.581|
|O3||0.9671||0.9581 - 0.9761||0.001|
|CO||0.8665||0.7119 - 1.0547||0.240|
|NO2||1.0049||0.9894 - 1.0206||0.533|
|SO2||0.9988||0.9938 - 1.0038||0.560|
|PM10||1.0023||1.0002 - 1.0044||0.015|
|PM2.5||1.0042||0.9981 - 1.0104||0.215|
|< 18 years|
|O3||1.0062||0.9913 - 1.0212||0.089|
|CO||0.5803||0.4138 - 0.8139||0.001|
|NO2||1.0213||1.0000 - 1.0435||0.004|
|SO2||0.9985||0.9906 - 1.0064||0.510|
|PM10||1.0051||1.0021 - 1.0081||0.0001|
|PM2.5||1.0007||0.9915 - 1.0099||0.510|
|18 - 59 years|
|O3||0.9812||0.9736 - 0.9888||0.0001|
|CO||0.8188||0.6961 - 0.9632||0.015|
|NO2||1.0243||1.0123 - 1.0365||0.0001|
|SO2||0.9963||0.9922 - 1.0004||0.520|
|PM10||1.0039||1.0022 - 1.0056||0.0001|
|PM2.5||1.0005||0.9956 - 1.0053||0.540|
|> 59 years|
|O3||0.9545||0.9404 - 0.9689||0.0001|
|CO||2.1455||1.5823 - 2.9091||0.0001|
|NO2||1.0407||1.0139 - 1.0681||0.002|
|SO2||1.0031||0.9948 - 1.0115||0.151|
|PM10||1.0022||0.9990 - 1.0054||0.216|
|PM2.5||1.0148||1.0038 - 1.0259||0.0001|
|O3||0.9908||0.9844 - 0.9972||0.0002|
|CO||1.0280||0.9148 - 1.1551||0.570|
|NO2||1.0083||1.0000 - 1.0178||0.001|
|SO2||0.9961||0.9928 - 0.9995||0.0201|
|PM10||1.0027||1.0010 - 1.0040||0.0001|
|PM2.5||1.0049||1.0010 - 1.0089||0.013|
|O3||0.9950||0.9864 - 1.0037||0.141|
|CO||1.0052||0.8471 - 1.1927||0.580|
|NO2||1.0080||0.9959 - 1.0203||0.713|
|SO2||0.9958||0.9913 - 1.0003||0.998|
|PM10||1.0033||1.0016 - 1.0050||0.026|
|PM2.5||1.0052||0.9999 - 1.0106||0.717|
|O3||0.9854||0.9759 - 0.9951||0.001|
|CO||1.0130||0.8486 - 1.2093||0.245|
|NO2||1.0068||0.9927 - 1.0211||0.107|
|SO2||0.9959||0.9909 - 1.0010||0.309|
|PM10||1.0022||1.0002 - 1.0042||0.020|
|PM2.5||1.0050||0.9990 - 1.0111||0.362|
|< 18 years|
|O3||0.9955||0.9807 - 1.0105||0.650|
|CO||0.9933||0.7675 - 1.2856||0.591|
|NO2||1.0138||0.9953 - 1.0326||0.256|
|SO2||0.9940||0.9960 - 1.0021||0.250|
|PM10||1.0047||1.0013 - 1.0080||0.0002|
|PM2.5||1.0012||0.9915 - 1.0110||0.550|
|18 - 59 years|
|O3||0.9936||0.9857 - 1.0015||0.315|
|CO||0.9894||0.8504 - 1.1512||0.510|
|NO2||1.0063||0.9944 - 1.0182||0.123|
|SO2||0.9954||0.9912 - 0.9996||0.013|
|PM10||1.0024||1.0008 - 1.0041||0.003|
|PM2.5||1.0046||0.9999 - 1.0095||0.050|
|> 59 years|
|O3||0.9707||0.9542 - 0.9875||0.0008|
|CO||1.2834||1.0073 - 1.6351||0.006|
|NO2||1.1013||0.9868 - 1.0405||0.112|
|SO2||1.0015||0.9931 - 1.0100||0.051|
|PM10||1.0022||0.9992 - 1.0053||0.255|
|PM2.5||1.0131||1.0003 - 1.0231||0.0006|
|O3||0.9882||0.9819 - 0.9947||0.0001|
|CO||1.1044||0.9748 - 1.2511||0.195|
|NO2||1.0099||1.0008 - 1.0192||0.012|
|SO2||0.9964||0.9931 - 0.9998||0.009|
|PM10||1.0028||1.0014 - 1.0042||0.0001|
|PM2.5||1.0066||1.0028 - 1.0104||0.0001|
|O3||0.9919||0.9833 - 1.0006||0.610|
|CO||1.1010||0.9261 - 1.3088||0.133|
|NO2||1.0119||1.0001 - 1.0239||0.006|
|SO2||0.9960||0.9915 - 1.0051||0.112|
|PM10||1.0029||1.0011 - 1.0048||0.018|
|PM2.5||1.0066||1.0014 - 1.0118||0.009|
|O3||0.9834||0.9739 - 0.9930||0.0001|
|CO||1.1324||0.9459 - 1.3557||0.209|
|NO2||1.0066||0.9926 - 1.0207||0.103|
|SO2||0.9963||0.9913 - 1.0014||0.224|
|PM10||1.0027||1.0008 - 1.0047||0.0003|
|PM2.5||1.0071||1.0015 - 1.0128||0.009|
|< 18 years|
|O3||0.9996||0.9848 - 1.0146||0.580|
|CO||0.9128||0.6928 - 1.2026||0.710|
|NO2||1.0144||0.9962 - 1.0329||0.308|
|SO2||0.9958||0.9880 - 1.0036||0.126|
|PM10||1.0064||1.0029 - 1.0098||0.003|
|PM2.5||1.0038||0.9945 - 1.0132||0.187|
|18 - 59 years|
|O3||0.9891||0.9813 - 0.9970||0.0001|
|CO||1.1089||0.9513 - 1.2925||0.197|
|NO2||1.0083||0.9971 - 1.0197||0.253|
|SO2||0.9955||0.9913 - 0.9997||0.009|
|PM10||1.0020||1.0003 - 1.0036||0.005|
|PM2.5||1.0049||1.0003 - 1.0096||0.010|
|> 59 years|
|O3||0.9653||0.9489 - 0.9818||0.0001|
|CO||1.0768||0.8739 - 1.3267||0.175|
|NO2||1.0100||0.9849 - 1.0358||0.284|
|SO2||1.0017||0.9932 - 1.0101||0.520|
|PM10||1.0030||0.9998 - 1.0062||0.30|
|PM2.5||1.0182||1.0088 - 1.0276||0.007|
|O3||0.9900||0.9836 - 0.9965||0.003|
|CO||1.1138||0.9875 - 1.2562||0.200|
|NO2||1.0083||1.0001 - 1.0176||0.002|
|SO2||0.9969||0.9935 - 1.0002||0.220|
|PM10||1.0030||1.0016 - 1.0045||0.0001|
|PM2.5||1.0042||1.0002 - 1.0082||0.0001|
|O3||0.9899||0.9813 - 0.9986||0.025|
|CO||1.1553||0.9787 - 1.3638||0.110|
|NO2||1.0095||0.9973 - 1.0220||0.291|
|SO2||0.9964||0.9919 - 1.0010||0.283|
|PM10||1.0038||1.0019 - 1.0057||0.0001|
|PM2.5||1.0048||0.9995 - 1.0102||0.220|
|O3||0.9895||0.9800 - 0.9992||0.011|
|CO||1.0374||0.8942 - 1.2036||0.580|
|NO2||1.0058||0.9924 - 1.0194||0.630|
|SO2||0.9970||0.9919 - 1.0020||0.149|
|PM10||1.0022||0.9999 - 1.0044||0.400|
|PM2.5||1.0036||0.9976 - 1.0097||0.155|
|< 18 years|
|O3||1.0039||0.9893 - 1.0188||0.610|
|CO||0.9110||0.6910 - 1.2008||0.172|
|NO2||1.0068||0.9881 - 1.0259||0.177|
|SO2||0.9964||0.9887 - 1.0042||0.199|
|PM10||1.0060||1.0027 - 1.0093||0.0002|
|PM2.5||1.0010||0.9912 - 1.0108||0.343|
|18 - 59 years|
|O3||0.9878||0.9800 - 0.9957||0.002|
|CO||1.1581||0.9906 - 1.3539||0.302|
|NO2||1.0077||0.9964 - 1.0193||0.203|
|SO2||0.9963||0.9921 - 1.0004||0.100|
|PM10||1.0034||1.0015 - 1.0052||0.0001|
|PM2.5||1.0042||0.9994 - 1.0090||0.110|
|> 59 years|
|O3||0.9817||0.9653 - 0.9983||0.014|
|CO||1.3500||0.9461 - 1.3615||0.213|
|NO2||1.0092||0.9862 - 1.0328||0.185|
|SO2||1.0026||0.9942 - 1.0110||0.168|
|PM10||1.0022||0.9989 - 1.0055||0.202|
|PM2.5||1.0111||1.0004 - 1.0218||0.008|
|O3||0.9923||0.9859 - 0.9988||0.032|
|CO||1.1114||0.9834 - 1.2561||0.110|
|NO2||1.0098||1.0008 - 1.0190||0.012|
|SO2||0.9965||0.9932 - 0.9999||0.006|
|PM10||1.0024||1.0010 - 1.0038||0.0001|
|PM2.5||1.0019||0.9978 - 1.0059||0.102|
|O3||0.9929||0.9844 - 1.0016||0.325|
|CO||1.2352||1.0298 - 1.4815||0.022|
|NO2||1.0111||0.9993 - 1.0231||0.300|
|SO2||0.9954||0.9909 - 1.0000||0.500|
|PM10||1.0027||1.0010 - 1.0045||0.001|
|PM2.5||1.0015||0.9959 - 1.0071||0.610|
|O3||0.9909||0.9814 - 1.0005||0.151|
|CO||1.0568||0.9836 - 1.2497||0.170|
|NO2||1.0068||0.9936 - 1.0202||0.118|
|SO2||0.9971||0.9921 - 1.0022||0.134|
|PM10||1.0030||1.0008 - 1.0052||0.0001|
|PM2.5||1.0026||0.9965 - 1.0087||0.193|
|< 18 years|
|O3||1.0008||0.9862 - 1.0156||0.155|
|CO||1.0455||0.7878 - 1.3874||0.151|
|NO2||1.0121||0.9938 - 1.0309||0.188|
|SO2||0.9969||0.9895 - 1.0043||0.188|
|PM10||1.0047||1.0015 - 1.0080||0.0008|
|PM2.5||1.0007||0.9910 - 1.0104||0.141|
|18 - 59 years|
|O3||0.9917||0.9839 - 0.9996||0.007|
|CO||1.0844||0.9349 - 1.2579||0.129|
|NO2||1.0103||1.0001 - 1.0219||0.002|
|SO2||0.9956||0.9914 - 0.9998||0.007|
|PM10||1.0021||1.0004 - 1.0038||0.009|
|PM2.5||1.0009||0.9959 - 1.0058||0.151|
|> 59 years|
|O3||0.9826||0.9664 - 0.9991||0.008|
|CO||1.1031||0.8878 - 1.3705||0.197|
|NO2||1.0045||0.9829 - 1.0265||0.153|
|SO2||1.0015||0.9931 - 1.0099||0.151|
|PM10||1.0004||0.9999 - 1.0038||0.155|
|PM2.5||1.0090||0.9988 - 1.0193||0.200|
|O3||0.9925||0.9861 - 0.9989||0.025|
|CO||1.0090||0.8982 - 1.1336||0.878|
|NO2||1.0123||1.0023 - 1.0225||0.015|
|SO2||0.9953||0.9918 - 0.9987||0.007|
|PM10||1.0026||1.0011 - 1.0042||0.0001|
|PM2.5||1.0024||0.9983 - 1.0065||0.235|
|O3||0.9956||0.9868 - 1.0044||0.349|
|CO||1.0078||0.8475 - 1.1984||0.932|
|NO2||1.0155||1.0022 - 1.0290||0.027|
|SO2||0.9937||0.9891 - 0.9983||0.012|
|PM10||1.0029||1.0011 - 1.0047||0.001|
|PM2.5||1.0007||0.9949 - 1.0065||0.849|
|O3||0.9885||0.9793 - 0.9978||0.015|
|CO||1.1199||0.9404 - 1.3337||0.180|
|NO2||1.0037||0.9891 - 1.0184||0.616|
|SO2||0.9972||0.9480 - 1.0489||0.285|
|PM10||1.0021||1.0000 - 1.0042||0.045|
|PM2.5||1.0046||0.9986 - 1.0107||0.291|
|< 18 years|
|O3||1.0119||0.9972 - 1.0267||0.331|
|CO||0.7856||0.5749 - 1.0737||0.282|
|NO2||1.0058||0.9860 - 1.0260||0.563|
|SO2||0.9927||0.9849 - 1.0000||0.072|
|PM10||1.0060||1.0028 - 1.0093||0.0002|
|PM2.5||0.9990||0.9890 - 1.0092||0.855|
|18 - 59 years|
|O3||0.9920||0.9841 - 0.9998||0.053|
|CO||1.0189||0.8838 - 1.1747||0.795|
|NO2||1.0110||0.9988 - 1.0234||0.072|
|SO2||0.9955||0.9913 - 0.9997||0.036|
|PM10||1.0019||1.0002 - 1.0036||0.018|
|PM2.5||0.9993||0.9942 - 1.0045||0.808|
|> 59 years|
|O3||0.9726||0.9577 - 0.9877||0.001|
|CO||1.2800||0.9305 - 1.3672||0.167|
|NO2||1.0073||0.9821 - 1.0332||0.569|
|SO2||0.9994||0.9908 - 1.0081||0.908|
|PM10||1.0007||0.9971 - 1.0044||0.671|
|PM2.5||1.0157||1.0062 - 1.0252||0.001|
|O3||0.9936||0.9871 - 1.0000||0.054|
|CO||1.0437||0.9369 - 1.1628||0.436|
|NO2||1.0096||0.9999 - 1.0195||0.051|
|SO2||0.9959||0.9925 - 0.9993||0.018|
|PM10||1.0027||1.0013 - 1.0040||0.0001|
|PM2.5||1.0022||0.9981 - 1.0064||0.278|
|O3||0.9973||0.9886 - 1.0062||0.560|
|CO||1.0608||0.8948 - 1.2575||0.496|
|NO2||1.0143||1.0011 - 1.0277||0.033|
|SO2||0.9955||0.9909 - 1.0001||0.053|
|PM10||1.0021||1.0003 - 1.0039||0.019|
|PM2.5||0.9995||0.9937 - 1.0053||0.807|
|O3||0.9879||0.9787 - 0.9972||0.011|
|CO||1.0555||0.9220 - 1.2083||0.433|
|NO2||1.0099||0.9956 - 1.0244||0.211|
|SO2||0.9966||0.9915 - 1.0017||0.186|
|PM10||1.0031||1.0011 - 1.0050||0.001|
|PM2.5||1.0055||0.9994 - 1.0116||0.072|
|< 18 years|
|O3||1.0100||0.9952 - 1.0250||0.201|
|CO||0.9225||0.9090 - 0.9361||0.586|
|NO2||1.0005||0.9803 - 1.0211||0.958|
|SO2||0.9923||0.9842 - 1.0005||0.068|
|PM10||1.0053||1.0023 - 1.0082||0.0001|
|PM2.5||1.0036||0.9940 - 1.0132||0.461|
|18 - 59 years|
|O3||0.9939||0.9860 - 1.0019||0.137|
|CO||1.0478||0.9168 - 1.1976||0.492|
|NO2||1.0123||1.0005 - 1.0242||0.039|
|SO2||0.9961||0.9920 - 1.0003||0.071|
|PM10||1.0018||1.0001 - 1.0036||0.037|
|PM2.5||0.9985||0.9932 - 1.0037||0.577|
|> 59 years|
|O3||0.9728||0.9560 - 0.9898||0.001|
|CO||1.1216||0.9217 - 1.3648||0.251|
|NO2||1.0021||0.9770 - 1.0278||0.866|
|SO2||1.0011||0.9926 - 1.0098||0.784|
|PM10||1.0020||0.9988 - 1.0052||0.182|
|PM2.5||1.0148||1.0051 - 1.0245||0.003|
|O3||0.9911||0.9848 - 0.9975||0.006|
|CO||1.0272||0.9233 - 1.1427||0.621|
|NO2||1.0102||1.0002 - 1.0203||0.043|
|SO2||0.9947||0.9913 - 0.9982||0.001|
|PM10||1.0031||1.0017 - 1.0045||0.0001|
|PM2.5||1.0026||0.9638 - 1.0429||0.190|
|O3||0.9967||0.9879 - 1.0056||0.494|
|CO||1.1097||0.9176 - 1.3420||0.272|
|NO2||1.0148||1.0015 - 1.0283||0.016|
|SO2||0.9950||0.9905 - 0.9996||0.045|
|PM10||1.0031||1.0012 - 1.0050||0.001|
|PM2.5||0.9998||0.9943 - 1.0054||0.951|
|O3||0.9874||0.9779 - 0.9971||0.011|
|CO||1.0615||0.9289 - 1.2129||0.377|
|NO2||1.0041||0.9890 - 1.0193||0.838|
|SO2||0.9952||0.9901 - 1.0003||0.062|
|PM10||1.0030||1.0010 - 1.0049||0.002|
|PM2.5||1.0049||0.9990 - 1.0109||0.096|
|< 18 years|
|O3||1.0074||0.9925 - 1.0225||0.112|
|CO||0.8833||0.6405 - 1.2179||0.449|
|NO2||0.9990||0.9786 - 1.0197||0.925|
|SO2||0.9925||0.9843 - 1.0007||0.075|
|PM10||1.0055||1.0023 - 1.0087||0.0001|
|PM2.5||1.0102||1.0017 - 1.0187||0.018|
|18 - 59 years|
|O3||0.9914||0.9836 - 0.9993||0.035|
|CO||1.0565||0.9242 - 1.2079||0.420|
|NO2||1.0109||0.9998 - 1.0229||0.067|
|SO2||0.9942||0.9900 - 0.9984||0.007|
|PM10||1.0025||1.0009 - 1.0041||0.001|
|PM2.5||0.9980||0.9928 - 1.0032||0.453|
|> 59 years|
|O3||0.9707||0.9540 - 0.9877||0.0001|
|CO||1.0964||0.8781 - 1.3690||0.416|
|NO2||1.0074||0.9792 - 1.0364||0.790|
|SO2||1.0025||0.9938 - 1.0114||0.560|
|PM10||1.0014||0.9981 - 1.0046||0.396|
|PM2.5||1.0110||1.0009 - 1.0212||0.030|
This study showed significant relations between short-term exposure to air pollutants CO, NO2, PM10, and PM2.5 with epilepsy admissions in Kerman, Iran. In this study, CO increased epilepsy admissions. Consistent with the results of this study, Bao et al.’s study in China showed an association between CO and increased epilepsy hospitalization (1.1%, 95% CI: 0.1 - 2.1%) (18). In addition, in Mexico, there was an association between ambient CO and epilepsy admissions (RR = 1.098, 95% CI: 1.045 - 1.155) (19).
In this study, NO2 had a significant relation with epilepsy admissions in total and several different age groups, and the strongest relation was observed in male subjects. Automobile exhaust is one of the most important sources of NO2. Wang et al.’s study in China demonstrated a significant association between the NO2 of automobile exhaust and neurobehavioral function in school-age children. In the aforementioned study, two primary schools were chosen. One school was located in a clear area and the other in a traffic dense and polluted area. NO2 had been monitored for the effect of traffic-related air pollution on the school campuses and classrooms. Children participated in assisted neurobehavioral testing to assess neurobehavioral performance (20).
A systematic review in 2017 concluded that high concentrations of NO2 in polluted air significantly affect the CNS in children and adults and represent a significant risk factor for human health (21). A study in China showed a significant relation between the increasing concentration of NO2 with epilepsy attacks (2%, 95% CI: 0.5 - 3.6%) (18). Furthermore, in Mexico, an ecological study showed a significant relation between NO2 and epilepsy attacks (RR = 1.083, 95% CI: 1.038 - 1.13) (19). In a cohort study in Denmark, residential exposure to road traffic and air pollution was associated with a higher risk for febrile seizures (IRR = 1.05, 95% CI: 1.02 - 1.07) (22). A study in southern Spain showed that even low levels of NO2 exposure and traffic-related air pollution had adverse effects on children’s neurodevelopment (23). Xu et al.’s study in China showed that the RR for epilepsy attacks was 3.17 (95% CI: 1.41 - 4.93) per 10 μg/m3 increase of NO2 (13). However, a study in the USA showed a protective effect for N2O on epilepsy (IRR = 0.85, 95% CI: 0.74 - 0.97) (9). N2O is a different compound and is derived mainly from agricultural fertilizers and natural sources; nonetheless, NO2 is mainly produced by vehicles.
Another pollutant evaluated in this study was PM10, which had a significant relation with epilepsy admissions in total and several subgroups, with the strongest relation observed in the under 18-year subgroup. Several studies have shown relations between ambient PM10 and epilepsy attacks (19, 24, 25). Consistent with the results of this study, Cakmak et al. in Mexico showed an association between PM10 and hospital admissions for epilepsy (RR = 1.083, 95% CI: 1.038 - 1.13) (19). A study in six cities in Italy demonstrated positive associations between PM10 exposure and total emergency calls within 2002 to 2006 (26). Additionally, increased emergency calls for epilepsy attacks were observed with exposure to PM10 in China (RR = 1.5, 95% CI: 1.1 - 2.0) (24). Radmanesh et al.’s study in Iran showed that patients with different types of headaches and epilepsy increased on dusty days, compared to clean days, and there were significant associations between increased concentrations of ambient PM10 and hospital admissions for these problems (25). Another study from Iran showed that exposure to PM10 increased oxidative stress and the expression of inducible nitric oxide synthase messenger ribonucleic acid levels and reduced the concentrations of antioxidant enzymes (27).
In this study, PM2.5 had a significant relation with epilepsy admissions in total, and several subgroups, with the strongest relation, observed in the over 59-year subgroup. Consistent with the results of this study, a significant association was observed between PM2.5 and epilepsy attacks in Mexico (RR = 1.065, 95% CI: 1.002 - 1.132) (19). Other studies have shown that oxidative stress, neuroinflammation, glial activation, and cerebrovascular damage are the primary pathways for inducing brain pathology by air pollution (28). Oxidative stress, changes in autonomous function, and progression of atherosclerosis can be exacerbated by exposure to ambient PM (29).
In this study, O3 and SO2 were inversely related to epilepsy admissions. In an ecological study in China, Xu et al. also reported negative associations between ambient O3 and epilepsy attacks (-0.84%, 95% Cl: -1.58 - 0.09%) (13). An interventional study showed that O3 could be protective against pentylenetetrazole-induced epilepsy attacks (30). However, in another study conducted in Mexico, a significant direct association was observed between O3 and hospital admissions for epilepsy attacks (RR = 1.100, 95% CI: 1.025 - 1.181) (19). In Fluegge and Fluegge’s study in the USA, no significant relation was observed between O3 and epilepsy attacks (9). In the current study the average concentration of O3 was 30.21±11.19 ppb, which is less that Xu et al.’s study (mean = 100 ± 63 ppb) (13) which showed a negative association, and Cakmak et al.’s study (mean = 93.26 ppb) (19). Further research is needed to clarify the effect of O3 exposure on epilepsy.
Some of the strengths of this study included about 12-year data on air pollution and epilepsy admissions and the use of GAMs to adjust for nonlinear confounder variables. However, given the ecological nature of this study, the results cannot be easily inferred at the individual level.
Exposure to ambient CO, NO2, PM10, and PM2.5 might be related to epilepsy admissions in Kerman. This study further emphasizes the necessity to control and reduce ambient air pollutants. Additionally, epilepsy patients should better stay away from exposure to polluted air. Staying at home on polluted days or residing in areas with less air pollution might be an option.
Ebrahimi H, Shafa M, Hakimzadeh Asl S. Prevalence of active epilepsy in Kerman, Iran: a house based survey. Acta Neurol Taiwan. 2012;21(3):115-24. [PubMed ID: 23196731].
Genc S, Zadeoglulari Z, Fuss SH, Genc K. The adverse effects of air pollution on the nervous system. J Toxicol. 2012;2012:782462. [PubMed ID: 22523490]. [PubMed Central ID: PMC3317189]. https://doi.org/10.1155/2012/782462.
Chang KC, Wu TH, Fann JC, Chen SL, Yen AM, Chiu SY, et al. Low ambient temperature as the only meteorological risk factor of seizure occurrence: A multivariate study. Epilepsy Behav. 2019;100(Pt A):106283. [PubMed ID: 31525555]. https://doi.org/10.1016/j.yebeh.2019.04.036.
Kim SH, Kim JS, Jin MH, Lee JH. The effects of weather on pediatric seizure: A single-center retrospective study (2005-2015). Sci Total Environ. 2017;609:535-40. [PubMed ID: 28763650]. https://doi.org/10.1016/j.scitotenv.2017.06.256.
Farahmandfard MA, Naghibzadeh-Tahami A, Khanjani N. Ambient air pollution and multiple sclerosis: a systematic review. Rev Environ Health. 2021;36(4):535-44. [PubMed ID: 34821118]. https://doi.org/10.1515/reveh-2020-0079.
Wellenius GA, Burger MR, Coull BA, Schwartz J, Suh HH, Koutrakis P, et al. Ambient air pollution and the risk of acute ischemic stroke. Arch Intern Med. 2012;172(3):229-34. [PubMed ID: 22332153]. [PubMed Central ID: PMC3639313]. https://doi.org/10.1001/archinternmed.2011.732.
Calderon-Garciduenas L, Kulesza RJ, Doty RL, D'Angiulli A, Torres-Jardon R. Megacities air pollution problems: Mexico City Metropolitan Area critical issues on the central nervous system pediatric impact. Environ Res. 2015;137:157-69. [PubMed ID: 25543546]. https://doi.org/10.1016/j.envres.2014.12.012.
Migliore L, Coppede F. Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res. 2009;674(1-2):73-84. [PubMed ID: 18952194]. https://doi.org/10.1016/j.mrgentox.2008.09.013.
Fluegge K, Fluegge K. Air pollution and risk of hospitalization for epilepsy: the role of farm use of nitrogen fertilizers and emissions of the agricultural air pollutant, nitrous oxide. Arq Neuropsiquiatr. 2017;75(9):614-9. [PubMed ID: 28977140]. https://doi.org/10.1590/0004-282X20170107.
Aboubakri O, Khanjani N, Jahani Y, Bakhtiari B. The impact of heat waves on mortality and years of life lost in a dry region of Iran (Kerman) during 2005-2017. Int J Biometeorol. 2019;63(9):1139-49. [PubMed ID: 31127424]. https://doi.org/10.1007/s00484-019-01726-w.
Dehghan A, Khanjani N, Bahrampour A, Goudarzi G, Yunesian M. Short-term effects of ambient (outdoor) air pollution on cardiovascular death in Tehran, Iran–a time series study. Toxin Reviews. 2020;39(2):167-79. https://doi.org/10.1080/15569543.2018.1488263.
Xu C, Fan YN, Kan HD, Chen RJ, Liu JH, Li YF, et al. The Novel Relationship between Urban Air Pollution and Epilepsy: A Time Series Study. PLoS One. 2016;11(8). e0161992. [PubMed ID: 27571507]. [PubMed Central ID: PMC5003346]. https://doi.org/10.1371/journal.pone.0161992.
Motta E, Golba A, Bal A, Kazibutowska Z, Strzala-Orzel M. Seizure frequency and bioelectric brain activity in epileptic patients in stable and unstable atmospheric pressure and temperature in different seasons of the year--a preliminary report. Neurol Neurochir Pol. 2011;45(6):561-6. [PubMed ID: 22212986]. https://doi.org/10.1016/S0028-3843(14)60123-7.
Rakers F, Walther M, Schiffner R, Rupprecht S, Rasche M, Kockler M, et al. Weather as a risk factor for epileptic seizures: A case-crossover study. Epilepsia. 2017;58(7):1287-95. [PubMed ID: 28480567]. https://doi.org/10.1111/epi.13776.
Bras PC, Barros A, Vaz S, Sequeira J, Melancia D, Fernandes A, et al. Influence of weather on seizure frequency - Clinical experience in the emergency room of a tertiary hospital. Epilepsy Behav. 2018;86:25-30. [PubMed ID: 30059889]. https://doi.org/10.1016/j.yebeh.2018.07.010.
Dehghan A, Khanjani N, Bahrampour A, Goudarzi G, Yunesian M. The relation between air pollution and respiratory deaths in Tehran, Iran- using generalized additive models. BMC Pulm Med. 2018;18(1):49. [PubMed ID: 29558916]. [PubMed Central ID: PMC5859399]. https://doi.org/10.1186/s12890-018-0613-9.
Bao X, Tian X, Yang C, Li Y, Hu Y. Association between ambient air pollution and hospital admission for epilepsy in Eastern China. Epilepsy Res. 2019;152:52-8. [PubMed ID: 30909052]. https://doi.org/10.1016/j.eplepsyres.2019.02.012.
Wang S, Zhang J, Zeng X, Zeng Y, Wang S, Chen S. Association of traffic-related air pollution with children's neurobehavioral functions in Quanzhou, China. Environ Health Perspect. 2009;117(10):1612-8. [PubMed ID: 20019914]. [PubMed Central ID: PMC2790518]. https://doi.org/10.1289/ehp.0800023.
Sram RJ, Veleminsky MJ, Veleminsky MS, Stejskalova J. The impact of air pollution to central nervous system in children and adults. Neuro Endocrinol Lett. 2017;38(6):389-96. [PubMed ID: 29298278].
Hjortebjerg D, Nybo Andersen AM, Ketzel M, Raaschou-Nielsen O, Sorensen M. Exposure to traffic noise and air pollution and risk for febrile seizure: a cohort study. Scand J Work Environ Health. 2018;44(5):539-46. [PubMed ID: 29574476]. https://doi.org/10.5271/sjweh.3724.
Freire C, Ramos R, Puertas R, Lopez-Espinosa MJ, Julvez J, Aguilera I, et al. Association of traffic-related air pollution with cognitive development in children. J Epidemiol Community Health. 2010;64(3):223-8. [PubMed ID: 19679705]. https://doi.org/10.1136/jech.2008.084574.
Cui L, Conway GA, Jin L, Zhou J, Zhang J, Li X, et al. Increase in Medical Emergency Calls and Calls for Central Nervous System Symptoms During a Severe Air Pollution Event, January 2013, Jinan City, China. Epidemiology. 2017;28 Suppl 1:S67-73. [PubMed ID: 29028678]. https://doi.org/10.1097/EDE.0000000000000739.
Radmanesh E, Maleki H, Goudarzi G, Zahedi A, Ghorbani Kalkhajeh S, Hopke PK, et al. Cerebral ischemic attack, epilepsy and hospital admitted patients with types of headaches attributed to PM10 mass concentration in Abadan, Iran. Aeolian Research. 2019;41:100541. https://doi.org/10.1016/j.aeolia.2019.100541.
Zauli Sajani S, Alessandrini E, Marchesi S, Lauriola P. Are day-to-day variations of airborne particles associated with emergency ambulance dispatches? Int J Occup Environ Health. 2014;20(1):71-6. [PubMed ID: 24075310]. [PubMed Central ID: PMC4137806]. https://doi.org/10.1179/2049396713Y.0000000045.
Dianat M, Radmanesh E, Badavi M, Mard SA, Goudarzi G. Disturbance effects of PM(1)(0) on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia-reperfusion injury in isolated rat heart: protective role of vanillic acid. Environ Sci Pollut Res Int. 2016;23(6):5154-65. [PubMed ID: 26552794]. https://doi.org/10.1007/s11356-015-5759-x.
Block ML, Calderon-Garciduenas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 2009;32(9):506-16. [PubMed ID: 19716187]. [PubMed Central ID: PMC2743793]. https://doi.org/10.1016/j.tins.2009.05.009.
Peters A, Veronesi B, Calderon-Garciduenas L, Gehr P, Chen LC, Geiser M, et al. Translocation and potential neurological effects of fine and ultrafine particles a critical update. Part Fibre Toxicol. 2006;3:1-13. [PubMed ID: 16961926]. [PubMed Central ID: PMC1570474]. https://doi.org/10.1186/1743-8977-3-13.
Mallok A, Vaillant JD, Soto MT, Viebahn-Hansler R, Viart Mde L, Perez AF, et al. Ozone protective effects against PTZ-induced generalized seizures are mediated by reestablishment of cellular redox balance and A1 adenosine receptors. Neurol Res. 2015;37(3):204-10. [PubMed ID: 25258110]. https://doi.org/10.1179/1743132814Y.0000000445.