The Relationship Between Short-Term Exposure To Air Pollution With Hospitalization and Mortality of Cardiovascular (CVD) and Respiratory Diseases in Shahrekord, Iran


 Background and objectives: Air pollution has been widely considered as an important factor in causing heart disease, respiratory disease, and death. This study sought to determine the relationship between short-term exposure to air pollutants and hospital admissions, cardiovascular and respiratory deaths and total mortality rate in Shahrekord, Iran.Procedure: This is a time series and ecological research. We collected data on hospital admissions and cardiovascular mortality and total mortality from 2012 to 2018. The study used the quasi-Poisson regression combined with linear distributed lag models, adjusted for trend, seasonality, temperature, relative humidity, weekdays and holidays.Results: Our results show a direct and significant statistical relationship between: O3 exposure in lag4 for total mortality, PM10 exposure in lag1 for total mortality and in lag4 and lag1 for respiratory death, PM2.5 exposure for total cardiovascular admissions in lag5, respiratory mortality in lag4, total respiratory admissions in lag3, NO2 exposure to respiratory mortality in lag1, and cardiovascular mortality in lag0, increased risk of death and pathogenesis.The results show a statistically significant inverse relationship between: NO and total admissions in lag3 and for respiratory mortality in lag1 between PM2.5 and cardiovascular mortality in lag1, NO with respiratory mortality in lag1 and cardiovascular admissions in lag3, NO2 with cardiovascular admissions in lag1 and NOX with respiratory death in lag0, which reduces the risk of death and pathogenesis.Conclusion: Air pollution has a significant relationship with the number of hospital admissions and mortality in Shahrekord, Iran.


Introduction
Human health is widely affected by climatic and environmental conditions. Different natural and arti cial sources change the characteristics of open air (Dadbakhsh et al., 2016;Mansouri et al., 2013). Air pollution is now a public health problem. Air pollutant sources include: carbon monoxide, sulfur dioxide, sulfates, nitrogen monoxide, nitrogen dioxide, organic matter and particles (Tang et al. 2016). Overall, 3.7 million deaths, 3.1 million disabilities (DALY) are attributed to air pollution, which make it among the top 10 risk factors (Lim et al. 1990(Lim et al. -2010. Air pollution has been widely considered as an important factor in causing heart disease, and death (Brunekreef et al. 2009). Due to its negative effects on human health, it has become a major concern for mankind ( Dastoorpoor et al. 2016). Recently, two population groups (Canada and South Korea) have been subjected to cohort studies, showing air pollution as closely related to the increased prevalence of heart disease, especially atrial brillation (Kim et al. 2019; Shin et al. 2019). Epidemiological and clinical studies published in recent years provided compelling evidence that short-term exposure to particulate matter (PM 2.5 ) can lead to heart disease and cardiac accidents (Meo and Suraya 2015). The results of a meta-analysis study in China showed that with an increase of PM 2.5 per 10 micrograms per cubic meter, mortality rate increases by 68% (Zhao et al. 2017). Studies have con rmed that patients with congestive heart failure, a history of myocardial infarction, are at greater risk on days with higher pollution rates. The likelihood of cardiovascular and respiratory deaths due to exposure to air pollutants is higher than deaths from other causes. Several studies have been conducted to investigate the impact of air pollution on mortality rate of patients with cross-sectional, advancements and increased number of motor vehicles have contributed to more air pollution. Therefore, conducting research in different regions around the globe could help achieve a better understanding of challenges caused by global air pollution (Saldiva et al., 1994). Unlike conventional CVD risk factors, biomarkers (such as air pollution, noise, natural environment) can be considered as potential targets for the prevention and management of pollutants (Song et al., 2016). Health problems caused by air pollution have convinced government o cials and policy-makers to take action to protect and preserve the environment (Song et al., 2017). Due to dust emanating from countries neighboring Iran as well as human and environmental activities, particulate matter causes health, economic and environmental problems in the center, west and southwest, especially Chaharmahal and Bakhtiari Province (Gerivani et al., 2011). However, no study has been conducted to assess the severe effects of air pollution in Shahrekord (Western Iran). Data in this eld is obtained through studies conducted by the AirQ model to estimate the effects of air pollution on heart and respiratory diseases (Dobaradaran et al., 2013;Yari et al., 2013). Information and awareness about risks associated with air pollution might pave the way for adopting better public health strategies. This is a time-series study aiming at investigating the relationship between air pollution, mortality rates and CVD.

Procedure
With an area of 70 square kilometers, Shahrekord is the center of Chaharmahal and Bakhtiari Province in Iran. The geographical coordinates of Shahrekord are 49º22 / E and 32º20 / N in the plains of Chaharmahal and Bakhtiari Province. According to the 2016 census, Shahrekord's population is 190,441 (statistics). This is a time series and ecological research. We collected data related to hospital admissions, total mortality, cardiovascular and respiratory mortality from 2012 to 2018 (7 years) on a daily basis from the two main hospitals: Shahrekord and Shahrekord University of Medical Sciences.
Daily concentrations of pollutants in seven years were collected from Chaharmahal and Bakhtiari Department of Environment. Data included: ozone, carbon monoxide, nitrogen dioxide (mono and nitrogen dioxide) particles ≤ 2.5 microns and 10 microns. Data were obtained from three monitoring stations in Jihad Square, Ostandari Square and Chaharmahal Square in Shahrekord. In these stations, air pollutants and particles ≤ 2.5 microns and particles ≤ 10 microns were measured separately in different ways. To measure suspended particles, we rst pumped the air into the measuring devices. The device measured and recorded particle concentration hourly based on absorption intensity. The researchers collected relative humidity and daily temperature from the Chaharmahal and Bakhtiari Meteorological Department.

Analysis
This ecological study used the generalized linear models (GLM) and distributed lag models (DLM) to determine the relationship between hospital admissions and cardiovascular and respiratory mortality with daily levels of air pollutants including O 3 , NO 2 , NO CO, NO X and PM 10  The effect of working days, as a confounding variable in the model, was mediated, because the days of the week seem to have an effect on hospital admissions and mortality. It seems that concentration of pollutants on weekends is different from other days. Therefore, we included the effect of holidays per week in the model as a confounding variable and took its effect into account. The results of the DLM model are reported for every 10 units of increase in pollutants from 7 − 0 days lag and RR rate with 95% con dence interval. All statistical analyses were performed using R software version 3.5.3 (package dlnm). Signi cance level was considered less than 0.05.  The results of the study indicate a statistically signi cant and direct relationship between exposure to PM 10 and total deaths in lag1 (RR = 1.105 (95% CI): 1.016-1.202), which was associated with a 10% increased risk of total mortality. A statistically signi cant and direct relationship between PM 10 exposure and respiratory mortality in lag4 (RR = 1.894 (95% CI): 1.281-2.799)), and lag1 (RR = 1.533 (95% CI):
This study found a statistically signi cant and inverse relationship between exposure to PM 2.5 and cardiovascular mortality in lag1, exposure to NO and respiratory mortality in lag1 and cardiovascular admissions in Lag3, NO 2 exposure and cardiovascular admissions in lag1 and NO X exposure and respiratory deaths in lag0 (Fig. 2 to 5)

Discussion
This study sought to determine the relationship between short-term exposure to air pollutants and hospital admissions and cardiovascular and respiratory mortality in Shahrekord, Iran.
We found a direct and signi cant statistical relationship between O 3 in lag4 with total mortality (RR = 1.616 (95% CI: 1.092-2.390)) which is associated with a 61% increase in total mortality risk. A study by Jerrett M. in the United States found no signi cant association between ozone and cardiac mortality and total deaths. However, after modi cation of PM 2.5 , a slightly positive correlation was observed between ozone and mortality due to heart disease . The results of this study showed a statistically signi cant and direct relationship between exposure to PM 10 and total deaths in lag1 (RR = 1.105 (95% CI: 1.016-1.202)), which was associated with a 10% increased risk of total death. There was also a statistically signi cant and direct relationship between PM 10 exposure and respiratory mortality in lag4 (RR = 1.894 (95% CI: 1.281-2.799)), and lag1 (RR = 1.533 (95% CI: 1.019-2.308)), which was associated with 89% and 53% increases in risk, respectively.
A study in Ahvaz showed that the toxicity and risk of PM 10 for the lung is more severe on dusty days than on other days due to more inhalation of pollutants (Naimabadi et al. 2016).
The EPA has shown that PM 10 is exposed to oxidative stress and increased in ammatory markers in A multicenter meta-analysis study in Shanghai, China, East Asia suggested that for every 10 micrograms per cubic meter of PM 2.5 increased by 0.96%, 0.96% (95% CI: 0.46%, 1.46%), there was an increase in mortality from heart disease, which is relatively similar to this study (Lee et al., 2015).
A signi cant relationship was found between daily mortality with an increase in PM 2.5 and PM 10 in one day and a cumulative delay of 6 days in Taiyuan, which is consistent with previous studies (Liang et al., 2018). A statistically signi cant relationship was found between NO 2 exposure and death from loss of respiration in lag1 (RR = 1.236 (95% CI: 1.017-1.502)), with a 23% increased risk as well as cardiovascular mortality in lag0 (RR = 1.057 (95% CI: 1.008-1.109)), with a 5% increase in risk.
Multivariate regulated analysis used in a study on relationship between air pollution and mortality in French showed that relative risk of deaths from heart disease is 1.27 NO 2 micrograms per cubic meter (95% CI: 1.04-1.56), which is statistically signi cant (Filleul et al., 2005).
Dadbakhsh et al. in Shiraz found that NO and NO X had a signi cant and direct relationship with total deaths from heart disease and female deaths in the same month and the following month (Dadbakhsh et al., 2016).
The strengths of this study were: Firstly, all data related to diseases and mortality were collected from government and trusted organizations in Chaharmahal and Bakhtiari Province (Shahrekord), making it a relatively large sample size. Secondly, a 7-year period and the large amount of data allowed us to examine interactions with a high level of validity and reliability. Thirdly, inclusion of three air pollution monitoring sites provided us the basis for better demonstration of the effects of air pollution compared to other studies.
Another strength of our study is taking advantage of approaches and methodology used in studies conducted in Europe, examining the potential role of dust as a mediator of the relationship between exposure to particles and mortality.
Our research has some limitations. Similar to other studies, the effects and interplay between air pollutants and health (mortality and hospital admission) requires further research. The effect might vary for each region.

Conclusion
Air pollution is signi cantly associated with hospital admissions and mortality in Shahrekord, Iran. Effective interventions and environmental policies need to be implemented and adopted to mitigate air pollution and minimize exposure to pollutants.

Declarations
Declarations: The authors declare that they have no known competing nancial interests or personal relationships that could have appeared to in uence the work reported in this paper. This statement is to certify that all Authors have seen and approved the manuscript being submitted. We warrant that the article is the Authors' original work. We warrant that the article has not received prior publication and is not under consideration for publication elsewhere. On behalf of all Co-Authors, the corresponding Author shall bear full responsibility for the submission. This research has not been submitted for publication nor has it been published in whole or in part elsewhere. We attest to the fact that all Authors listed on the title page have contributed signi cantly to the work, have read the manuscript, attest to the validity and legitimacy of the data and its interpretation, and agree to its submission to the Journal of Environmental Research.
All authors agree that author list is correct in its content and order and that no modi cation to the author list can be made without the formal approval of the Editor-in-Chief, and all authors accept that the Editorin-Chief's decisions over acceptance or rejection or in the event of any breach of the Principles of Ethical Publishing in the Journal of Environmental Science and Pollution Research being discovered of retraction are nal.
No additional authors will be added post submission, unless editors receive agreement from all authors and detailed information is supplied as to why the author list should be amended.  Figure 1 RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in PM10 according to single lag, adjusted unconstrained and constrained DLM models RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in PM2.5 according to single lag, adjusted unconstrained and constrained DLM models Figure 3 RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in NO according to single lag, adjusted unconstrained and constrained DLM models RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in NO2 according to single lag, adjusted unconstrained and constrained DLM models RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in NOX according to single lag, adjusted unconstrained and constrained DLM models RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in O3 according to single lag, adjusted unconstrained and constrained DLM models RRs (95% CIs) of hospitalization and mortality of cardiovascular (CVD) and respiratory diseases and total mortality with an increase of 10 μg/m3 in CO according to single lag, adjusted unconstrained and constrained DLM models