• google scholor
  • Views: 8924

  • PDF Downloads: 270

Urban Air Pollution and Human Health: A Review

Jaspreet Kaur * and Charu Jhamaria

1 Department of Environmental Science, IIS (Deemed to be University), Jaipur, Rajasthan India

Corresponding author Email: jaspreetchouhan95@gmail.com

DOI: http://dx.doi.org/10.12944/CWE.16.2.04

Rapid and unplanned industrialization and urbanization have led to an increase in air pollutants in the urban areas are not new phenomena. Findings of several pieces of research have shown that at every stage of life beginning from the effect on developing embryo till an older age. A strong relationship has been reported between urban air pollutants with a wide variety of diseases like respiratory diseases, cardiovascular diseases, adverse effects on the nervous system, endocrine system, prevalence of diseases like diabetes, premature births, etc. Highly susceptible groups are the children and elderly, making this problem a serious concern worldwide. Inhalation of an increasing amount of particulate matter with a variety of toxic chemicals adhered to its surface and gaseous pollutants emitted from various sources initiate complex chemical reactions in the body giving rise to several diseases. The particles move through the upper respiratory tract showing its effect in the form of pulmonary inflammation, chronic obstructive pulmonary disease (COPD), moving further affects the heart rate variability (HRV), Ischemic heart disease, crosses the Blood-brain barrier (BBB) leading to mental and behavior disorder as well as insulin resistance leading to diabetes. The health impacts of poor air quality are serious which require urgent attention. This comprehensive review article aims to provide comprehensive information that can be useful for environmentalists, researchers, engineers, and policymakers for incorporating the data for implementing robust action to combat the problem of increasing urban air pollution.

Blood-Brain Barrier; Cardiovascular Disease; Diabetes; Particulate Matter; Respiratory Diseases; Urban Air Pollution

Copy the following to cite this article:

Kaur J, Jhamaria C. Urban Air Pollution and Human Health: A Review. Curr World Environ 2021;16(1). DOI:http://dx.doi.org/10.12944/CWE.16.2.04

Copy the following to cite this URL:

Kaur J, Jhamaria C. Urban Air Pollution and Human Health: A Review. Curr World Environ 2021;16(1). Available From : https://bit.ly/3rVrGqT


Download article (pdf)
Citation Manager
Publish History


Article Publishing History

Received: 2020-09-06
Accepted: 2021-04-06
Reviewed by: Orcid Orcid Arpit bhatt
Second Review by: Orcid Orcid Alzira Dinis
Final Approval by: Dr. Umesh Chandra Kulshrestha


Introduction

Urban air pollutants comprise vehicular emissions, industrial emissions, and emissions due to developmental activities. They are known to cause several ill effects on human health and the environment. Atmospheric ultrafine particles with  pollutants bound on its surface  can enter our body, which can penetrating deep into the respiratory and circulatory system, causing damage to   lungs, heart, brain, and other vital organs. Global data for AOD (aerosol optical depth) collected for 189 megacities to evaluate the air quality status revealed that Indian subcontinent cities, Middle East, and North China are the most polluted cities due to their largest population growth which leads to more anthropogenic emissions as compared to Europe, the north-east of US, and South- East Asia countries.1 World health organization (WHO) reported 6.5 million deaths (approximately 12% of total deaths) annually, worldwide via exposure to indoor and ambient air pollution. Therefore approximately 92% of the world's population is living in an area, where the annual mean concentration level of fine particulate matter (PM2.5)  diameter ranges from (0.1-2.5 ?m) exceeds the WHO standards i.e. 10 ?g/m3.2

The concentration of various pollutants like Sulphur Dioxide (SO2 ), Nitrogen Dioxide (NO2), Suspended Particulate Matter (SPM), Respirable Suspended Particulate Matter (RSPM), ozone (O3), Benzene, Carbon Monoxide (CO), Lead (Pb) and Hydrocarbons (HCs) increases with an increasing rate of urbanization, industrialization, and vehicular emissions, burning of fossil fuels, agricultural activities, domestic practices as well as natural sources such as forest fire and wind erosion.3,4Particulate matter is one of the prominent air pollutants from the six major criteria air pollutants, which is positively linked with degradation of the environmental condition such as climate change, fog formation, cloud dynamics, acid rain, reduced visibility, affecting radiation budget in addition to causing adverse impact on human health causing mortality and morbidity.5,6,7The effect of Particulate matter (PM) depends on the aerodynamic size of aerosol which is classified as coarse particulate matter (PM10)  with aerodynamic size 10µm and fine particulate matter (PM2.5) with aerodynamic diameter 2.5 µm based on transportation potential in the atmosphere or inhaling capacity via respiratory system.8 Inhalation of fine particulate matter through the olfactory region or oral cavity leads to several health problems. Deposition in various region of lungs i.e. head tracheobronchial (TB) and pulmonary region9,10 and cause several disorders like asthma, chronic obstructive pulmonary disease, and even cancer7 Further it also causes Cardiopulmonary mortality and metabolic disorder like diabetes.11,12 The deposition of particulate matter inside the human body depends on the duration of exposure to particulate matter in ambient air in addition to various other factors such as nostril shape, weight, age, gender, ventilation, and exercise level.13 Inhalation of ultrafine particles deposited in the lungs can cause alveolar inflammation and several hematological disorders like coagulation of blood, plasma viscosity, fibrinogen, plasminogen activator inhibitor, can not only cause cardiovascular diseases but can also cause inflammatory reactions.14Ambient fine particulate matter PM2.5 ranked fifth to cause mortality in 2015 at the global level.15 Fine particulate matter size ? 2.5 µm when inhaled get deposited in the airway path and alveolar surface and trigger adverse effect on human health according to U.S. Environmental Protection Agency.16 Exposure to polycyclic aromatic hydrocarbons (PAHs) in humans via the respiratory tract, digestive tract, and skin, cause cancer in several organs like lungs, skin, esophagus, colon, pancreas, bladder, and breast in women.17

PM2.5 is also known to induce apoptosis due to the production of reactive oxygen species (ROS) as a result of the induction of endoplasmic reticulum (ER) stress and activation of unfolded protein response (UPR) in the lung and liver cells. Double-strand RNA-activated protein kinase-like ER kinase (PERK) leads to phosphorylation of translation initiation factor eIF2? and induction of C/EBP homologous transcription factor CHOP/GADD153 in turn production of ROS.18 A wide range of ill health effects due to short-term and long-term exposure to a mixture of air pollutants have been observed in urban populations throughout the world for a very long time. The present paper is an attempt to compile comprehensive data related to the adverse effects of air pollutants on various systems of the human body, which would help to form bases for further research.

Methodology

Database Sources

A comprehensive review of literature has been conducted by searching database in Web of Science and Google Scholar by using keywords such as sources and composition of particulate matter, respirable particulate matter (RPM), fine particulate pollution, the effect of particulate on the cardiovascular system, respiratory system, nervous system, reproductive health and prevalence of diabetes. Physiological mechanism related to the effect of air pollutants on different organs of the human body was also searched using specific keywords like effect on lung capacity, the effect of PM on myocardial muscles, nervous system, air pollutants and reproductive health and physiology of air pollutants causing diabetes. Research articles explaining the mechanism of the effect of pollutants at the cellular level were thoroughly studies to explain the effects on various organs.

Selection of Articles

A total of 483 articles were found while searching with the above-mentioned keywords which were thoroughly studied. Out of the total 483 articles,126 articles were found to be suitable for inclusion in the review paper which critically explain the mechanism of the adverse effect of air pollutants on the various organ of the human body. The Rest of the 357 articles were excluded as they were not found eligible based on their scientific outcome required for the present review article.

Effect of Air Pollutants on Various Systems of the Human Body

Effect on Respiratory System

Every single human being is exposed to a variety of ambient air pollutants daily to a greater or lesser extent, whereas human health is affected at every stage of life from birth to death.19 Keeping in view the increasing levels of pollutants in the air several long-term and short-term studies have been done worldwide to correlate the effect of various air pollutants with human health. Short term exposure to particulate matter has been found to increase hospital admissions due to respiratory illness where PM10 and PM2.5 are found to be positively associated with chronic obstructive pulmonary disease (COPD) and asthma. Women and older age individuals (more than 65) are more vulnerable to PM2.5.20 It is well documented that traffic-related air pollution (TRAP) aggravates the condition of an asthmatic person. Studies have also shown an increase in new-onset asthma in both children and adults as a result of oxidative stress and immune dysregulation caused due to exposure to TRAP which includes a mixture of pollutants like Particulate matter, sulfur dioxide, nitrogen dioxides, and ozone.21,22,23,24,25,26,27,28,29,30,31 Exposure to traffic-related air pollutants for long duration have shown a significant association with risk the of Systemic lupus erythematosus (SLE), a multi-systemic chronic autoimmune disease.32 Inhalation of fine particulate matter is found to increase airway inflammation in childhood-onset systemic lupus erythematosus (CSLE) patients33 Chemical species of fine particulate matter (PM2.5) and gaseous pollutants comprising Elemental carbon (EC), Organic carbon (OC), SO2, NO2, and CO exerts prolonged inflammatory and thrombotic responses, whereas fine particulate matter (PM2.5) leads to an immediate autonomic imbalance in vulnerable individuals.34Traffic-related air pollution is also known to have the potential to disrupt the functioning of the endocrine system in adolescents35,36 and acute pulmonary edema and mortality with the exposure to elevated levels of nitrogen dioxide.37 Particle deposition in the lungs is dependent on the aerodynamic size of the particle and the region of deposition depends on the lung anatomy and pattern of airflow in the respiratory system.38 Fine particles with a size between 0.2-5µm can be transported easily to the airways and accumulate in the alveoli whereas coarse particles with a size above 5µm are restricted to the upper respiratory tract. Inhalation of ultrafine carbon particles adversely affects the pulmonary diffusing capacity due to the physiologic effects of particulates in the interstitium39 whereas inhalation of Ultrafine particles for 1 h can cross the epithelial barrier and reach the main lung tissue compartment in the cytoplasm and the nucleus of the cell to adversely affect the pulmonary diffusing capacity.40Due to the capacity to damage cells and disrupt their function, ambient air pollutants are found to be group 1 human carcinogen.41 While moving towards the alveoli, it produces several diseases in the respiratory system in addition to lung cancer.42,43 The high potential of the fine particulate matter to cause a wide range of diseases can be attributed to their larger surface area related to their mass which helps in more adsorption of pollutants and reactive metals on their surface making them more toxic.44,45Thus higher concentration of fine particles in ambient air leads to more toxic effects in the body. As fine particles (Ë‚ 2.5µm) have a probability of penetrating deeper into the lungs, they cause severe adverse health effects as these particles have a higher burden of toxins46Chronic obstructive pulmonary diseases (COPD) is presently the fourth most leading cause of death worldwide in adults older than 50 years.47 Several research studies have shown a strong association between long term exposure to air pollutants and increased lung cancer and mortality rate among the population. There is a strong association between vehicular exhaust and increased risk of lung cancer among people who never smoke a cigarette then ex-smoker or current smokers.48 Heavy metals emitted from industries and mining processes also lead to lung dysfunction and later it can cause lung cancer.49 In addition to particulates, secondary aerosols mainly nitrate (emitted from the combustion of fossil fuel, road transportation, space heating, aircraft, and ammonia oxidation from agriculture) and sulphate (sources include emission from the power plant, industrial emissions, oceans, plant, soil, and volcanic activities) cause an increased risk of respiratory illness in children50.Sulfur dioxide a water-soluble irritant gas that induces bronchoconstriction and mucus secretion which leads to airway cellular injury and subsequent proliferation of mucus-secreting goblet cells.51 Due to its damaging effect on the bronchioles, long term exposure even at a concentration lower than 1 ppm is known to cause a higher incidence of bronchitis.52 sulfuric acid as fine aerosols formed in the atmosphere shows adverse effects on various cells of the respiratory tract (e.g. phagocytes and epithelial cells) due to its high specific acidity and deposition deeper along the respiratory tract leading to bronchitis.53 Similarly nitrogen dioxide induces several adverse health effects on the respiratory system and general functioning of the body. Acute exposure to ambient Nitrogen dioxide leads to impaired diffusion capacity of lungs, restrictive and obstructive ventilatory defects, and hypoxemia54 Cortisol, a steroid hormone responsible for the regulation of immune and inflammatory responses in the airwaysis55 released at abnormal levels from the adrenal gland in the adolescents due to Chronic exposure to nitrogen dioxide and other traffic-related air pollutants.56 Leading to respiratory system dysfunction. Penetration of gasses into the lungs depends upon the water solubility factor. Gases that are highly water-soluble like SO2 do not penetrate unless the concentrations are very high whereas insoluble gasses such as NO2 and ozone penetrate deep inside the lungs and reach the smallest alveoli57,58 leading to severe damage. Inhalation of carbon monoxide gas reduces the oxygen level in blood and form carboxyhemoglobin by reacting with hemoglobin, therefore less hemoglobin is left to transport oxygen from the lungs to other parts of the body which results in dizziness, unconscious, and tiredness.59 Table 1 summarizes the significant effects of air pollution on the respiratory system.

Table 1: Effects of Air Pollutants on the Respiratory System.

Effects                               

Cause

Reference

Oxidative stress and immune dysregulation causing Asthma

Long term exposure to traffic-related air pollutants (TRAP)

21,22,23,24,25,26,27,28,29,30,31

Risk of Systemic lupus erythematosus (SLE), a multi-systemic chronic autoimmune disease.

32

Disruption in the functioning of the endocrine system in adolescents

35, 36

Asthma due to Chronic obstructive pulmonary diseases (COPD)

47

Lung cancer in nonsmokers

48

Bronchoconstriction and mucus secretion leading to airway cellular injury and subsequent proliferation of mucus-secreting goblet cells

Exposure to SO2

51

 


Effect on the Cardiovascular System

Air pollution leads to more than two-third of mortality particularly due to ischemic heart disease and cerebrovascular disease.60 The major cause of all cardiovascular diseases is oxidative stress (raised levels of blood malondialdehyde) leading to dysfunction of the cardiac system. Chronic exposure to enhanced levels of fine particle matter impairs vascular function, which can lead to myocardial infarction, arterial hypertension, stroke, and heart failure.2,61  Several epidemiological studies have reported atherothrombosis, thrombotic stroke, and thromboembolism due to exposure to air pollution, especially PM.62 Due to exposure to air pollutants excessive clotting is caused leading to thrombotic occlusion of arteries resulting in cardiovascular dysfunction. This process of thrombotic occlusion of arteries was studied by blood markers of pro-thrombotic pathways which have been linked to PM exposure, including fibrinogen, tissue factor, von Willebrand factor (vWF), P-selectin and decreases in activity of fibrinolytic pathways responsible for clot breakdown.62,63Studies have shown that even short term exposure to ultrafine particulate matter is associated with heart rate variability64 leading to adverse effects on the cardiovascular system. An increase in the concentration of particulate matter increases the risk of ischemic and Myocardial infarction and stroke.65,66,67,68

Three biological pathways associated with ambient particulate matter and its adverse effect on the cardiovascular system have been identified.19,61

1) Pro-inflammatory mediators or vasculoactive molecules are released from lung cells due to the inhalation of particles leading to the systemic chain reaction. This chain reaction cause changes in vascular function and induction of a pro-coagulation state with thrombus formation, ischemic response, and an increase of atherosclerotic lesions.

2) Changes in the autonomic nervous system or heart rhythm are caused due to particle deposition in the pulmonary system. This imbalance in the autonomic nervous system or heart rhythm is caused by stimulating pulmonary neural reflexes or by inducing oxidative stress leading to inflammation in the lungs cardiac arrhythmias and instability of a vascular plaque is further caused by alterations in autonomic tone.

3) Chemical constituents adhered to ultrafine particles and particulate matter are translocated in the blood leading to endothelial dysfunction and vasoconstriction, increased blood pressure, and platelet aggregation. Studies conducted near an area with high vehicular density with increased air pollutants like PM2.5, NO2, and O3 have also shown an increase in the risk of pregnancy-induced hypertensive disorders.69 Cardiorespiratory morbidity and mortality have also been found to be linked with the particulate matter with an aerodynamic diameter in the range of  10µm to less than 2.5 µm. An increase in 10µg/m3 of PM2.5 for the same day is found to increase 0.47% cardiovascular mortality and 0.5% respiratory mortality whereas 0.27% and 0.56% increase in cardiovascular and respiratory mortality respectively were reported for an increase in 10µg/m of PM10 for same-day.70 The acute and chronic exposure to ambient particulate matter (PM2.5) lead to a direct effect on the cardiovascular system whereas (UPFS) ultrafine particulate matter gets circulated from lungs to the heart or cause indirect injury by inducing systemic inflammation and oxidative stress, abnormal blood clotting function, vascular dysfunction, and nervous system dysfunction which lead to cardiovascular and nervous system dysfunction.71 Children and old age people are more susceptible to the adverse effects of air pollution. Studies have shown that Heart rate variability (HRV) is reduced when the individual between the age of 53 to 87 yrs is exposed to elevated levels of fine particulate matter PM2.5 and ozone.72 Increased pulse pressure (PP) and systolic blood pressure (SBP) is strongly associated with exposure to PM2.5 and the association is stronger in people highly exposed to road traffic.73 People living near major roads have an increased risk of cardiopulmonary mortality.74 Fine particulates, due to their higher penetration capacity are more harmful as compare to coarse particles. Short term exposure to fine particulate matter PM2.5 as low as for few hours to week can lead to cardiovascular disorders leading to mortality as well as certain nonfatal events whereas long term exposure for several months to a few years increases the risk of mortality to a greater extent and reduces the life span.61Long term exposure to PM2.5 is strongly associated with ischemic heart diseases, mortality, and increased risk of Systolic blood pressure, diastolic blood pressure, pulse pressure, and hypertension.75,76 Vehicular exhaust leads to an increase in the concentration of organic carbon in PM2.5 which directly affects human health by decreasing the artery diameter up to 0.09 mm.77 Long term exposure to road traffic noise and Particulate matter in residential areas has the potential to cause hypertension and Diastolic blood pressure. An increased concentration of PM2.5 by 1µg/m3 leads to a 15% high frequency of hypertension.78 Table 2 summarizes the diseases caused due to exposure to air pollutants.

Table 2: Effects of Air Pollutants on the Cardiovascular System.

Effects

Causes

References

Impairment of  vascular function, leading to myocardial infarction, arterial hypertension, stroke, and heart failure

Chronic exposure to enhanced levels of fine particle matter

67, 65, 66, 68, 61

Atherothrombosis, thrombotic stroke, and thromboembolism

62

Excessive clotting of blood leading to thrombotic occlusion of arteries resulting in cardiovascular dysfunction

 

Heart rate variability

64

Risk of pregnancy-induced hypertensive disorders

69

Increased pulse pressure (PP) and systolic blood pressure (SBP)

73



Effect on Nervous System

UFPM (Ultra Fine Particulate Matter) of size less than 0.1 µm is most effective in causing severe health effects (Table 3) due to its nanometer-size due to which can easily penetrate and accumulate in the lungs and cause a detrimental effect beyond the respiratory tract.79,80,81The most prominent effects caused by air pollution are oxidative stress and neuro-inflammation cause developmental neurotoxicity and may contribute to the etiology of neurodevelopmental disorders, including autism spectrum disorder.82 From the upper respiratory tract particulate matter is transferred to the brain leading to brain inflammation, disrupt normal brain activities and pathological function, decline neurocognitive abilities, and finally, it cause mental and behavioral disorders, and risk of Alzheimer’s and Parkinson’s diseases.83,84.85,86,87 The increased concentration of air pollution leads to olfactory bulb dysfunction by accumulating the ultrafine particulate matter in the Olfactory Bulbs basement membrane and endothelial cytoplasm.88 From the total air passing the nasal chamber, 5-20% air cross the olfactory region89 thus is affected by respiratory frequency affecting the PM olfactory deposition. As substantial time is spend outdoors by children as compare to adults and have high respiratory frequency to their body size, the olfactory deposition could be higher in them.90,91As their brains are in the developing stage92 and have less developed defensive barriers to avoid particles entering in lungs91,UFPM crosses the olfactory epithelium and get accumulated in the brain.93 Short term exposure to the high concentration of PM10 and PM2.5 increases hospital admissions for mental and behavioral disorders more in the winter season due to increased concentration of pollutants as a result of less dispersion as compared to the summer season.94 Furthermore, coarse and fine particulate matter, as well as nitrogen dioxide, is associated with depressive symptoms and depression in elderly women95 in addition to sleep disorder symptoms in elderly people exposed to traffic-related pollutants like PM10, PM2.5, NO2, SO2, and O3.96 Particulate matter with aerodynamic size less than 10µm (PM10) is also known to be associated with the increased risk of multiple sclerosis.97 an inflammatory demyelinating disorder of the central nervous system. Nano-size particles are found to injure endothelial cells and damage the BBB (Blood Brain Barrier) due to the reduction in microvascular endothelial cell viability, alteration of mitochondrial potential, Increased oxidative stress, and decreased tight junction protein expression.98

Table 3: Effects of Air Pollutants on Nervous System.

Effects         

Causes

References

Oxidative stress and neuro-inflammation causing developmental neurotoxicity, and etiology of neurodevelopmental disorders, including autism spectrum disorder

Exposure to particulate pollutants

82

A decline in  the neourocognitive abilities leading to mental and behavior disorders, and risk of Alzheimer’s and Parkinson’s diseases

82, 83,84,85,86

Multiple sclerosis, an inflammatory demyelinating disorder of the central nervous system.

 

 97

Injury of  endothelial cells and damage the BBB (Blood Brain Barrier)

98

Depressive symptoms and depression in elderly women

Exposure to nitrogen dioxide

95

 


Air Pollution and Diabetes

According to the American Diabetes Association99, Diabetes is a group of metabolic diseases that are identified as a high blood sugar level (hyperglycemia) occurring due to abnormal insulin secretions. Diabetes is a global concern and presently there are more than half a million children under the age of 14 who are suffering from type 1 diabetes and 415 million adults with the age group of  20-79 years are suffering from this non-communicable disease and 193  million adults are undiagnosed.100 In 2017 there were 451 million adults (18-99 years) worldwide reported by International Diabetes Federation101suffering from diabetes and estimated to rise by 693 million in 2045. The diabetes scenario of the Indian population is not so different from the whole world, due to its genetic profile like sedentary lifestyles, abhorrent eating habits, insomnia, and high-stress levels.102 In addition to the above-mentioned causes long-term exposure to PM2.5 and NO2 is found to be positively associated with increased risk of diabetes mortality.103 There are several clinical studies done to estimate the relationship between diabetes and ambient air pollutants like PM2.5, black carbon, O3, and NO2.104,105,106,107 Different physiological and biochemical changes are induced in the human body due to exposure to air pollutants leading to diabetes (Table 4). Long-term exposure to air pollution leads to reduced insulin secretion as a result of impaired ?-cell functioning and also decreases insulin-dependent glucose uptake which induces insulin resistance.108 Oxidative stress and systemic inflammation are shown to be caused as a result of insulin resistance and ?-cell dysfunction due to exposure to air pollutants indicating a significant correlation between type 2 diabetes and air pollution.109 Studies using several biomarkers have suggested a correlation between insulin resistance and the development of diabetes110,111Altered HOMA IR indicating reduced metabolic insulin sensitivity is found even at sub-acute periods of exposure to PM2.5 leading to the genesis of diabetes mellitus.112 Clinical studies were performed on rodents revealed that a high concentration of fine particulate matter (PM2.5) induces impaired glucose tolerance, HOMA- IR index indicating Insulin sensitivity was also found higher in exposed mice as compared to unexposed mice.113 Further, the effect of PM10 on lipids was found to be higher at low temperatures, whereas the effect of SOand NOwas found to be higher at high temperatures.114 Increased concentration of ambient air pollutants such as black carbon, NO2, and O3 leads to increased systemic inflammation in older adults suffering from diabetes, hypertension, and obesity.115 Studies have also shown that women are more susceptible to DM (Diabetes Mellitus) as compare to males when exposed to traffic-related pollution.114,116 Some studies have also identified a correlation between PM2.5 (Particulate matter), NOx (Nitrogen oxides), SO2 (Sulphur dioxide),  and O3 (ozone) with gestational diabetes. Oral glucose tolerance test (OGTT) indicating gestational diabetes in non-diabetic pregnant women exposed to PM2.5, where maternal exposure to SO2 and NOx in the first few weeks of pregnancy is correlated with gestational diabetes mellitus (GDM).117,118,119 Exposure to traffic-related air pollutants and PM2.5 leads to abnormal glycemia during pregnancy and positively correlated with impaired glucose tolerance (IGT).120 Long term exposure to air pollutants such as PM10 and NO2 are strongly correlated with an increased level of serum glucose and glycosylated hemoglobin (HbAlc), which indicates the increased risk of type 2 diabetes mellitus in the middle age urban population.121 Evidence also suggests that exposure to air pollutants especially traffic-related air pollutants such as NOmay lead to an increased risk of type 2 diabetes mellitus105 and have the strongest effect on diabetes etiology.122 It has been also found that exposure to a very high concentration of particulate matter (PM10) is interdependent with the occurrence of type2 diabetes mellitus and hypertension.123In patients with non-insulin-dependent diabetes mellitus, increased concentrations of low-density lipoprotein cholesterol decreased concentrations of high-density lipoprotein cholesterol, as well as increase triglyceride concentration, causes Coronary artery disease and high blood pressure.124 Air pollutants such as PM10, So2, and No2 are correlated with increased levels of lipids such as triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) among type 2 diabetes patients. This creates an imbalance in the cholesterol levels and increases Systolic and diastolic Blood Pressure114,125 aggravating the patient’s health conditions. A higher risk of Diabetic retinopathy has also been reported in patients with Diabetes mellitus.126 Thus it is evident that diabetes can affect a person of any age and can also cause additional health issues.

Table 4: Influence of Air Pollutants on the Cause of Diabetes.

Effects          

References

Impaired ?-cell functioning and decreased insulin-dependent glucose uptake inducing  insulin resistance

108

Increased level of serum glucose and glycosylated hemoglobin (HbAlc) indicating an increased risk of Type 2 diabetes mellitus

121

Impaired glucose tolerance

114

Diabetic retinopathy

126


Conclusions

The various outcomes of the clinical studies conducted to evaluate the effect of air pollutants on human health have been discussed in this review article. (Table 1,2,3 and 4) represents the key highlights of the effect of the findings of air pollutants on human health. Systemic lupus erythematosus (SLE), a multi-systemic chronic autoimmune disease, excessive clotting of blood leading to thrombotic occlusion of arteries resulting in cardiovascular dysfunction, multiple sclerosis, an inflammatory demyelinating disorder of the central nervous system and Impaired ?-cell functioning and decreased insulin-dependent glucose uptake inducing insulin resistance are few of the major reported systemic damage due to exposure to urban air pollutants. Keeping in view the array of diseases caused due to air pollution it is evident that strategies for pollution prevention is the most neglected aspects of the development plans of any region. Thus implementation of stringent pollution control strategies can prove to be beneficial in providing multiple benefits, both short-term and long-term, for the protection of human health, the economy, and the environmental components for societies at every level of income group. This review paper can form a base for further studies related to the health impacts of various air pollutants with changing atmospheric chemistry due to the inclusion of a variety of new air pollutants in the atmosphere including ultrafine particles. Keeping in view the present scenario, future research can be conducted correlating the health effects due to air pollution with changing climatic conditions globally.

Acknowledgment

The authors would like to thank IIS(Deemed to be University), Jaipur for granting the permission and facilities for conducting PhD research work in the Department of Environmental Science. The authors are also grateful to the University for providing internet facilities for retrieving and analyzing the online databases for writing the review paper.

Funding Sources

The author(s) have received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

The author(s) declares no conflict of interest.

References

  1. Alpert P., Shvainshtein O., Kishcha P. AOD trends over megacities Based on space monitoring using MODIS and MISR. Am. J. Clim. 2012;1(3):117–131.
    CrossRef
  2. World Health Organization. Ambient air pollution: A global assessment of exposure and burden of disease. Geneva: WHO;2016.121p. https://apps.who.int/iris/handle/10665/250141. Accessed 22 September 2016.
  3. Samet J., & Krewski D. Health effects associated with exposure to ambient air pollution. J. Toxicol. Environ. Health Part A, 2007;70(3-4):227-242.
    CrossRef
  4. Goyal S. K., Ghatge S. V., Nema P. S. M. T., & Tamhane S. M. Understanding urban vehicular pollution problem vis-a-vis ambient air quality–case study of a megacity (Delhi, India). Environ. Monit. Assess.2006;119(1-3):557-569.
    CrossRef
  5. Pillai P. S., Babu S. S., & Moorthy K. K. A study of PM, PM10 and PM2. 5 concentration at a tropical coastal station. Atmos. Res.2002;61(2):149-167.
    CrossRef
  6. Singh N., Mittal S., Awasthi A., Agarwal R., & Gupta P. K. Chemical Characterization of Atmospheric Particulate Matter for K, Cu, Ni and Zn Metals Collected from Agricultural, Semi-Urban and Commercial Locations in NW India. J Environ Anal Chem.2017;4(197): 2.
    CrossRef
  7. Manojkumar N., Srimuruganandam B., & Nagendra S. S. Application of multiple-path particle dosimetry model for quantifying age specified deposition of particulate matter in human airway. Ecotoxicol. Environ. Saf.2019;168:241-248.
    CrossRef
  8. Esworthy, R. Air quality: EPA's 2013 changes to the particulate matter (PM) standard. Library of Congress, Congressional Research Service: 2013.49p. http://www.nationalaglawcenter.org/wp-content/uploads/assets/crs/R42934.pdf. Accessed 23 January 2013.
  9. Cheng Y. S. Mechanisms of pharmaceutical aerosol deposition in the respiratory tract. AAPS PharmSciTech.2014;15(3):630-640.
    CrossRef
  10. Füri P., Hofmann W., Jókay Á., Balásházy I., Moustafa M., Czitrovszky B.,& Farkas Á. Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site. Inhal. Toxicol.2017;29(4):147-159.
    CrossRef
  11. Pope III C. A., Burnett R. T., Thun M. J., Calle E. E., Krewski D., Ito K., & Thurston G. D. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. Jama.2002;287(9):1132-1141.
    CrossRef
  12. Heck T. G., Fiorin P. B. G., Frizzo M. N., & Ludwig M. S. Fine Particulate Matter (PM2.5) Air Pollution and Type 2 Diabetes Mellitus (T2DM): When Experimental Data Explains Epidemiological Facts. J. Diabetes Complicat.2018;71.
    CrossRef
  13. Bennett W. D., & Zeman K. L. Effect of race on fine particle deposition for oral and nasal breathing. Inhal. Toxicol. 2005;17(12):641-648.
    CrossRef
  14. Seaton A., Godden D., MacNee W., & Donaldson K. Particulate air pollution and acute health effects. The lancet.1995;345(8943):176-178.
    CrossRef
  15. Cohen A. J., Brauer M., Burnett R., Anderson H. R., Frostad J., Estep K., Balakrishnan K., Brunkreef B., Dandona L., Dandona R., Feigin V., Freedman G., Hubbell B., Jobling A., Kan H., Knibbs L., Liu Y., Martin R., Morawska L., Pope C.A., Shin H., Staif k., Shaddick G., Thomas M., Dingenen R.V., Donkelaar A.V., Vos T., Murray C.J.L & Forouzanfart M.H. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet. 2017;389(10082):1907-1918.
    CrossRef
  16. EPA, U. The particle pollution report: current understanding of air quality and emissions through 2003. Research Triangle Park, NC, US Environmental Protection Agency.2004 https://www.epa.gov/sites/production/files/201711/documents/pp_report_2003.pdf. Accessed December 2004.
  17. Boström C. E., Gerde P., Hanberg A., Jernström B., Johansson C., Kyrklund T., Rannug A., Tornqvist M., victorin K., and Westerholm R. Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air. Environ. Health Perspect.2002;110:(Suppl 3):S451-S488.
    CrossRef
  18. Laing S., Wang G., Briazova T., Zhang C., Wang A., Zheng Z., Gow A., Chen A.L., Rajagopalan S., Chen L.C., Sun Q., & Zhang K. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am. J. Physiol. Cell Physiol.2010;299(4); C736-C749.
    CrossRef
  19. Rückerl R., Schneider A., Breitner S., Cyrys J., & Peters A. Health effects of particulate air pollution: a review of epidemiological evidence. Inhal. Toxicol.2011;23(10): 555-592.
    CrossRef
  20. Xie J., Teng J., Fan Y., Xie R., & Shen A. The short-term effects of air pollutants on hospitalizations for respiratory disease in Hefei, China. Int J Biometeorol. 2019;63(3):315-326.
    CrossRef
  21. Anderson H. R., Favarato G., & Atkinson R.W. Long-term exposure to air pollution and the incidence of asthma: meta-analysis of cohort studies. AIR QUAL ATMOS HLTH. 2013; 6(1):47-56.
    CrossRef
  22. Carlsten C., Dybuncio A., Becker A., Chan-Yeung M., & Brauer M. Traffic-related air pollution and incident asthma in a high-risk birth cohort. OCCUP ENVIRON MED.2011;68(4):291-295.
    CrossRef
  23. Clark N. A., Demers P. A., Karr C. J., Koehoorn M., Lencar C., Tamburic L., & Brauer M. Effect of early life exposure to air pollution on development of childhood asthma. Environ Health Perspect.2009;118(2):284-290.
    CrossRef
  24. Dong G. H., Chen T., Liu M. M., Wang D., Ma Y. N., Ren W. H.,  Lee Y.L., Zhao Y.D., & He Q. C. Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study. PloS one.2011;6(7): e22470.
    CrossRef
  25. Jacquemin B., Sunyer J., Forsberg B., Aguilera I., Briggs D., García-Esteban R., Gotschi T., Heinrich J., Jarvholm B., Jarvis D., Vienneau D., & Kunzli  N. Home outdoor NO2 and new onset of self-reported asthma in adults. Int. J. Epidemiol.2009;20:119-126.
    CrossRef
  26. Jerrett M., Shankardass K., Berhane K., Gauderman W. J., Künzli N., Avol E., & Thomas D.C.Traffic-related air pollution and asthma onset in children: a prospective cohort study with individual exposure measurement. Environ. Health Perspect. 2008;116(10):1433-1438.
    CrossRef
  27. Künzli N., Bridevaux P. O., Liu L.S., Garcia-Esteban R., Schindler C., Gerbase M. W., Sunyer J., Keidel D., & Rochat T. Traffic-related air pollution correlates with adult-onset asthma among never-smokers. Thorax.2009;64(8): 664-670.
    CrossRef
  28. McConnell R., Islam T., Shankardass K., Jerrett M., Lurmann F., Gilliland F., Gauderman J., Avol,  E., Kunzli N., Yao L., Peters J., & Berhane K. Childhood incident asthma and traffic-related air pollution at home and school. Environ. Health Perspect. 2010;118(7):1021-1026.
    CrossRef
  29. Modig L., Torén K., Janson C., Jarvholm B., & Forsberg B. Vehicle exhaust outside the home and onset of asthma among adults.EUR RESPIR J.2009;33(6): 1261-1267.
    CrossRef
  30. Nishimura K. K., Galanter J. M., Roth L. A., Oh S. S., Thakur N., Nguyen E. A., Thyne S., Farber H.J., Serebrisky D., Kumar R., Brigino-Buenaventura E., Davis A., Lenoir M.A., Meade K., Rodriguez-Cintron W., Avila P.C., Borrell L.N., Bibbins-Domingo k., Rodriguez-Santana J.R., Sen S., Lurmann F., Balmes J.R., & Burchard E.G. Early-life air pollution and asthma risk in minority children. The GALA II and SAGE II studies. Am J Respir Crit Care Med.2013;188(3):309-318.
    CrossRef
  31. Zhou C., Baïz N., Zhang T., Banerjee S., & Annesi-Maesano I. Modifiable exposures to air pollutants related to asthma phenotypes in the first year of life in children of the EDEN mother-child cohort study. BMC Public Health.2013;13(1):506.
    CrossRef
  32. Jung C. R., Chung W. T., Chen W. T., Lee R. Y., & Hwang B. F. Long-term exposure to traffic-related air pollution and systemic lupus erythematosus in Taiwan: A cohort study.SCI TOTAL ENVIRON.2019;668: 342-349.
    CrossRef
  33. Alves A. G. F., de Azevedo Giacomin M.F., Braga A. L. F., Sallum A.M.E., Pereira L.A. A., Farhat L. C., Stufaldi F. L., de Faria Coimbra Lichtenfels A. J., de Santana Carvalho T Nakagawa N. K., Silva C. A., & Farhat S.C.L. Influence of air pollution on airway inflammation and disease activity in childhood-systemic lupus erythematosus. Clin. Rheumatol. 2018;37(3):683-690.
    CrossRef
  34. Chen S. Y., Chan C. C., & Su T. C. Particulate and gaseous pollutants on inflammation, thrombosis, and autonomic imbalance in subjects at risk for cardiovascular disease. Environ. Pollut.2017;223:403-408.
    CrossRef
  35. Odermatt A., Gumy C., Atanasov A. G., & Dzyakanchuk A. A. Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance. J STEROID BIOCHEM.2006;102(1-5):222-231.
    CrossRef
  36. Rudel R. A., & Perovich L. J. Endocrine disrupting chemicals in indoor and outdoor air.Atmos. Environ.2009;43(1):170-181.
    CrossRef
  37. Lowry T., & Schuman L.M. Silo-filler's disease—a syndrome caused by nitrogen dioxide. JAMA-J AM MED ASSOC.1956;162(3):153-160.
    CrossRef
  38. Miller F. J. Dosimetry of particles in laboratory animals and humans. Toxicology of the Lung. 3rd edn. Taylor & Francis, Philadelphia PA.1999;513-556.
  39. Pietropaoli A. P., Frampton M. W., Hyde R. W., Morrow P. E., Oberdörster G., Cox C., Speers D.M., Frasier L.M., Chalupa D.C., Huang L.S., & Utell M. J. Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhal. Toxicol. 2004;16(sup1): 59-72.
    CrossRef
  40. Geiser M., Rothen-Rutishauser B., Kapp N., Schürch S., Kreyling W., Schulz H., Semmler M., Hof V.I., Heyder J., & Gehr P. Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ. Health Perspect.2005;113(11):1555-1560.
    CrossRef
  41. IARC 2016, International Agency for Research on Cancer (IARC) monographs on the evaluation of carcinogenic risks to humans: outdoor air pollution. IARC Monogr: 109p. https://monographs.iarc.fr/wp-content/uploads/2018/06/mono109.pdf. Accessed 17 December 2015
  42. Falcon-Rodriguez C. I., Osornio-Vargas A. R., Sada-Ovalle I., & Segura-Medina P. Aeroparticles, composition, and lung diseases. FRONT IMMUNOL.2016;7: 3.
    CrossRef
  43. Gauderman W. J., Urman R., Avol E., Berhane K., McConnell R., Rappaport E., Chang R., Lurmann F., & Gilliland F. Association of improved air quality with lung development in children. N. Engl. J. Med. 2015;372(10):905-913.
    CrossRef
  44. Oberdörster G., Oberdörster E., & Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles.Environ Health Perspect.2005a ;113(7): 823-839.
    CrossRef
  45. Oberdörster G., Maynard A., Donaldson K., Castranova V., Fitzpatrick J., Ausman K., Carter J., Karn B., Kryling W., Lai D., Olin S., Monteiro-Riviere N., Warheit D., Yang H., & A report from the ILSI Research Foundation/Risk Science Institute Nanomaterial Toxicity Screening Working Group Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. PART FIBRE TOXICOL.2005b;2(1):8.
    CrossRef
  46. Satsangi P. G., Kulshrestha A., Taneja A., & Rao P. S. P. Measurements of PM 10 and PM 2.5 aerosols in Agra, a semi-arid region of India. Indian J. Radio Space Phys. 2011;40: 203-210.
  47. Duijts L., Reiss I. K., Brusselle G., & de Jongste J. C. Early origins of chronic obstructive lung diseases across the life course. Eur. J. Epidemiol.2014; 29(12): 871-885.
    CrossRef
  48. Beelen R., Hoek G., van den Brandt P.A., Goldbohm R. A., Fischer  P., Schouten L. J., Armstrong B., & Brunekreef B. Long-term exposure to traffic-related air pollution and lung cancer risk. Int. J. Epidemiol. 2008;19(5):702-710.
    CrossRef
  49. Kampa M., & Castanas E. Human health effects of air pollution. Environ. Pollut. 2008;151(2):362-367.
    CrossRef
  50. Pirani M., Best N., Blangiardo M., Liverani S., Atkinson R. W., & Fuller G. W. Analysing the health effects of simultaneous exposure to physical and chemical properties of airborne particles. Environ. Int.2015;79:56-64.
    CrossRef
  51. Kodavanti U. P., Mebane R., Ledbetter A., Krantz T., McGee J., Jackson M. C., & Costa D. L. Variable pulmonary responses from exposure to concentrated ambient air particles in a rat model of bronchitis. Toxicol. Sci.2000; 54(2):441-451.
    CrossRef
  52. Von Mutius E., Martinez F. D., Fritzsch C. H. R. I. S. T. I. A. N., Nicolai T. H. O. M. A. S., Roell G. A. B. R. I. E. L. E., & Thiemann H. H. Prevalence of asthma and atopy in two areas of West and East Germany. Am. J. Respir. Crit. Care Med.1994;149(2):358-364.
    CrossRef
  53. Schlesinger R. B. Comparative irritant potency of inhaled sulfate aerosols—effects on bronchial mucociliary clearance. Environ. Res.1984;34(2): 268-279.
    CrossRef
  54. Horvath E. P., Barbee R.A., & Dickie H.A. Nitrogen dioxide-induced pulmonary disease: five new cases and a review of the leterature. J Occup Med.1978;20(2):103-110.
    CrossRef
  55. Chen E., & Miller G. E. Stress and inflammation in exacerbations of asthma. BRAIN BEHAV IMMUN.2007;21(8):993-999.
    CrossRef
  56. Wing  S. E., Bandoli  G., Telesca D., Su J. G., & Ritz B. Chronic exposure to inhaled, traffic-related nitrogen dioxide and a blunted cortisol response in adolescents. Environ. Res.2018;163:201-207.
    CrossRef
  57. Kimball J. S., & Miller F. J. Regional respiratory-tract absorption of inhaled reactive gases: A modeling approach. Toxicology of the Lung.1999;3:557-597.
  58. Medinsky M. A., Bond J. A., Schlosser P. M., & Morris J. B. Mechanisms and models for respiratory tract uptake of volatile organic chemicals. Toxicology of the Lung. 1999;483-512.
  59. Arulprakasajothi M., Chandrasekhar U., Yuvarajan D., & Teja M.B. An analysis of the implications of air pollutants in Chennai. International Journal of Ambient Energy. 2020;41(2):209-213.
    CrossRef
  60. Lelieveld J., Klingmüller K., Pozzer A., Pöschl U., Fnais M., Daiber A., & Münzel T. Cardiovascular disease burden from ambient air pollution in Europe reassessed using novel hazard ratio functions. EUR HEART J.2019;40(20):1590-1596.
    CrossRef
  61. Brook R. D., Rajagopalan S., Pope III C. A., Brook J. R., Bhatnagar A., Diez-Roux A. V., Holguin F., Hong Y., Luepker R.V., Mittleman M.A., Peters A., Siscovick D., Smith Jr S.C., Whitsel L., Kaufman J.D. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331-2378.
    CrossRef
  62. Franchini M., Mannucci P.M. Air pollution and cardiovascular disease. Thromb.Res.2012;129:230-234.
    CrossRef
  63. Delfino R. J., Staimer N., Tjoa T., Gillen D. L., Polidori A., Arhami M., Kleinman T., Vaziri N.D., Longhurst J.D Sioutas, C. Air pollution exposures and circulating biomarkers of effect in a susceptible population: clues to potential causal component mixtures and mechanisms. Environmental health perspectives.2009;117(8):1232-1238.
    CrossRef
  64. Rizza V., Stabile L., Vistocco D., Russi A., Pardi S., & Buonanno G. Effects of the exposure to ultrafine particles on heart rate in a healthy population. SCI TOTAL ENVIRON.2019;650:2403-2410.
    CrossRef
  65. Brook R. D., Franklin B., Cascio W., Hong Y., Howard G., Lipsett M., Luepker R., Mittleman M., Samet J., Smith Jr S.C., & Tager I. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation. 2004;109(21):2655-2671.
    CrossRef
  66. Ruidavets J. B., Cournot M., Cassadou S., Giroux M., Meybeck M., & Ferrières J. Ozone air pollution is associated with acute myocardial infarction. Circulation.2005;111(5):563-569.
    CrossRef
  67. Tsai S.S., Goggins W.B., Chiu H.F., & Yang C. Y. Evidence for an association between air pollution and daily stroke admissions in Kaohsiung, Taiwan. Stroke, 2003;34(11): 2612-2616.
    CrossRef
  68. Wellenius G. A., Schwartz J., & Mittleman M. A. Air pollution and hospital admissions for ischemic and hemorrhagic stroke among medicare beneficiaries. Stroke. 2005;36(12): 2549-2553.
    CrossRef
  69. Pedersen M., Stayner L., Slama R., Sørensen M., Figueras F., Nieuwenhuijsen M. J., Raaschou-Nielsen O., & Dadvand P. Ambient air pollution and pregnancy-induced hypertensive disorders: a systematic review and meta-analysis. Hypertension.2014;64(3): 494-500.
    CrossRef
  70. Newell K., Kartsonaki C., Lam K. B. H., & Kurmi O. P. Cardiorespiratory health effects of particulate ambient air pollution exposure in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Planet. Health.2017; 1(9): e368-e380.
    CrossRef
  71. An Z., Jin Y., Li J., Li W., & Wu W. Impact of Particulate Air Pollution on Cardiovascular Health. CURR ALLERGY ASTHM R.2018;18(3):15.
    CrossRef
  72. Gold D. R., Litonjua A., Schwartz J., Lovett E., Larson A., Nearing B., Allen G., Verrier M., Cherry R., & Verrier R. Ambient pollution and heart rate variability. Circulation.2000;101(11):1267-1273.
    CrossRef
  73. Auchincloss A. H., Diez Roux A. V., Dvonch J. T., Brown P. L., Barr  R. G., Daviglus M. L., Goff Jr D.C., Kaufman J.D., & O’Neill M. S. Associations between recent exposure to ambient fine particulate matter and blood pressure in the Multi-Ethnic Study of Atherosclerosis (MESA). Environ. Health Perspect.2008;116(4):486-491.
    CrossRef
  74. Hoek G., Brunekreef B., Goldbohm S., Fischer P., & van den Brandt P. A. Association between mortality and indicators of traffic-related air pollution in the Netherlands: a cohort study. Lancet.2002;360(9341):1203-1209.
    CrossRef
  75. Crouse D. L., Peters P. A., van Donkelaar A., Goldberg M. S., Villeneuve P. J., Brion O., Khan S., Atari D.O.,  Jerrett  M., Pope C.A., Brauer M., Brook J.R., Martin R.V., Stieb D., & Burnett R.T. Risk of non accidental and cardiovascular mortality in relation to long-term exposure to low concentrations of fine particulate matter: a Canadian national-level cohort study. Environ. Health Perspect.2012 ;120(5):708-714.
    CrossRef
  76. Zhang Z., Guo C., Lau A. K., Chan T. C., Chuang Y. C., Lin C.,Jiang W.K., Yeoh E.K., Tam T., Woo k.s., Yan B.P., Chang L.Y., Wong M.C.S., Lao X.Q. Long-term exposure to fine particulate matter, blood pressure, and incident hypertension in Taiwanese adults. Environ. Health Perspect.2018;126(1):017008.
    CrossRef
  77. Urch, B., Brook, J. R., Wasserstein, D., Brook, R. D., Rajagopalan, S., Corey, P., & Silverman, F. Relative contributions of PM2. 5 chemical constituents to acute arterial vasoconstriction in humans. Inhal. Toxicol. 2004;16(6-7):345-352.
    CrossRef
  78. Pitchika A., Hampel R., Wolf K., Kraus U., Cyrys J., Babisch W., Peters A, & Schneider A. Long-term associations of modeled and self-reported measures of exposure to air pollution and noise at residence on prevalent hypertension and blood pressure. SCI TOTAL ENVIRON.2017;593:337-346.
    CrossRef
  79. Muhlfeld C., Rothen-Rutishauser B., Blank F., Vanhecke D., Ochs M., & Gehr P. Interactions of nanoparticles with pulmonary structures and cellular responses. AM J PHYSIOL-LUNG C. 2008;294(5):L817-L829.
    CrossRef
  80. Valavanidis A., Fiotakis K., & Vlachogianni T. Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. J ENVIRON SCI HEAL C.2008;26(4):339-362.
    CrossRef
  81. Rothen-Rutishauser B., Müller L., Blank F., Brandenberger C., Mühlfeld C., & Gehr P. A newly developed in vitro model of the human epithelial airway barrier to study the toxic potential of nanoparticles. ALTEX-ALTERN ANIM EX, 2008 ;25(3):191-196.
    CrossRef
  82. Costa L. G., Cole T. B., Dao K., Chang Y. C., Coburn  J., & Garrick J. M. Effects of air pollution on the nervous system and its possible role in neurodevelopmental and neurodegenerative disorders. Pharmacol. Ther.2020;210:107523.
    CrossRef
  83. Calderon-Garciduenas L., Reed W., Maronpot R.R., Henriquez-Roldan C., Delgado- Chavez R., Calderon-Garciduenas A., Dragustinovis I., Franco-Lira M., Aragon-Flores M., Solt A.C., Altenburg M., Torres-Jardon R., & Swenberg J.A. Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution. Toxicol. Pathol.2004;32(6):650-658.
    CrossRef
  84. Calderón-Garcidueñas L., Franco-Lira M., Torres-Jardon R., Henriquez-Roldan C., Barragan-Mejia G., Valencia-Salazar G., Gonzalez-Maciel A., Reynoso-Robles R., Villarreal-Calderon R., Reed W. Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology. Toxicol. Pathol.2007;35(1):154-162.
    CrossRef
  85. Calderón-Garcidueñas L., Solt A. C., Henríquez-Roldán C., Torres-Jardón R., Nuse B., Herritt L., Villarreal-Calderon R., Osnaya N., Stone I., Garcia R., Brooks D.M., Gonzalez-Maciel A., Reynoso-Robles R., Delgado-Chavez R & Reed W. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid ?-42 and ?-synuclein in children and young adults. Toxicol. Pathol.2008;36(2):289-310.
    CrossRef
  86. Xu X., Ha S. U., & Basnet R. A review of epidemiological research on adverse neurological effects of exposure to ambient air pollution. Public Health Front. 2016;4:157.
    CrossRef
  87. Costa  L. G., Cole T. B., Dao K., Chang Y. C., Coburn J., & Garrick J. M. Effects of air pollution on the nervous system and its possible role in neurodevelopmental and neurodegenerative disorders. PHARMACOL THERAPEUT.2020;107523.
    CrossRef
  88. Calderón-Garcidueñas L., Franco-Lira M., Henríquez-Roldán C., Osnaya N., González-Maciel A., Reynoso-Robles R., Villarreal-Calderon R., Herritt L., Brooks D., Keefe S.,  Palacios-Moreno J., Villarrel-Calderon R., Torres-Jardon R., Medina-Cortina H., Delgado-Chavez R., Aiello-Mora M., Maronpot R.R., Doty R.L. Urban air pollution: influences on olfactory function and pathology in exposed children and young adults. EXP TOXICOL PATHOL.2010; 62(1):91-102.
    CrossRef
  89. Hahn I., Scherer P. W., & Mozell M. M. Velocity profiles measured for airflow through a large-scale model of the human nasal cavity. J. Appl. Physiol. 1993;75(5):2273-2287.
    CrossRef
  90. Schroeter J. D., Kimbell J. S., & Asgharian B. Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model. J AEROSOL MED PULM D.2006,19(3):301-313.
    CrossRef
  91. Brockmeyer S., & D’Angiulli A. How air pollution alters brain development: the role of neuroinflammation. Transl. Neurosci.2016;7(1):24-30.
    CrossRef
  92. Rice D., & Barone Jr S. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ. Health Perspect. 2000;108(suppl 3):511-533.
    CrossRef
  93. Oberdörster G. Kinetics of inhaled ultrafine particles in the organism. Effects of Air Contaminants on the Respiratory Tract–Interpretations from Molecules to Meta Analysis (Heinrich U, ed). Stuttgart, Germany: Fraunhofer IRB Verlag.2004;121-143.
  94. Song J., Zheng L., Lu M., Gui L., Xu D., Wu W., & Liu Y. Acute effects of ambient particulate matter pollution on hospital admissions for mental and behavioral disorders: a time-series study in Shijiazhuang, China.SCI TOTAL ENVIRON.2018;636: 205-211.
    CrossRef
  95. AltuÄŸ H., Fuks K. B., Hüls A, Mayer A. K., Tham R., Krutmann J., & Schikowski T. Air pollution is associated with depressive symptoms in elderly women with cognitive impairment. Environ. Int.2020;136,105448.
    CrossRef
  96. Tang M., Li D., Liew Z., Wei F., Wang J., Jin M., Chen L., Ritz B. The association of short-term effects of air pollution and sleep disorders among elderly residents in China. SCI TOTAL ENVIRON.2020;708:134846.
    CrossRef
  97. Bergamaschi R., Cortese A., Pichiecchio A., Berzolari F. G., Borrelli P., Mallucci G., Bollati V., Romani A., Nosari G., Villa S., & Montomoli, C. Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. MULT SCLER J. 2018;24(12):1578-1584.
    CrossRef
  98. Chen L., Yokel R. A., Hennig B., & Toborek M.. Manufactured aluminum oxide nanoparticles decrease expression of tight junction proteins in brain vasculature. J NEUROIMMUNE PHARM. 2008;3(4):286-295.
    CrossRef
  99. American Diabetes Association. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37(Suppl.):S81-S90.
    CrossRef
  100. Sanz M., Ceriello A., Buysschaert M., Chapple I., Demmer R. T., Graziani F., Herrera D., Jepsen S., Lione L., Madianos P., Mathur M., Montanya E., Shapira L., Tonetti M., & Vegh D. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J. Clin. Periodontol.2018;45(2):138-149.
    CrossRef
  101. Cho N., Shaw J. E., Karuranga S., Huang Y., da Rocha Fernandes J. D., Ohlrogge A. W., & Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract.2018;138:271-281.
    CrossRef
  102. Jena S., Mishra B., Yadav A., & Desai P. Challenges in diabetology research in India. Diabetes Metab Synd.2018;12(3):349-355.
    CrossRef
  103. Lim C. C., Hayes R. B., Ahn J., Shao Y., Silverman D. T., Jones R. R., Garcia C., & Thurston G. D. Association between long-term exposure to ambient air pollution and diabetes mortality in the US. Environ. Res.2018;165: 330-336.
    CrossRef
  104. Chen H., Burnett R. T., Kwong J. C., Villeneuve P. J., Goldberg M. S., Brook R. D.,  Copes R. Risk of incident diabetes in relation to long-term exposure to fine particulate matter in Ontario, Canada. Environ. Health Perspect. 2013;121(7):804-810.
    CrossRef
  105. Coogan P. F., White L. F., Jerrett M., Brook R. D., Su J. G., Seto E., Burnett R., Palmer J.R & Rosenberg L. Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles.Circulation.2012;125(6):767-772.
    CrossRef
  106. Krämer U., Herder C., Sugiri D., Strassburger K., Schikowski T., Ranft U., & Rathmann W. Traffic-related air pollution and incident type 2 diabetes: results from the SALIA cohort study. Environ. Health Perspect.2010;118(9):1273-1279.
    CrossRef
  107. O'Donovan G., Chudasama Y., Grocock S., Leigh R., Dalton A.M., Gray L.J., Yates T., Edwardson C., Hill S., Henson J., Webb D., Khunti K., Davies M.J., Jones A.P, Bodicoat D.H., Wells A. The association between air pollution and type 2 diabetes in a large cross-sectional study in Leicester: The CHAMPIONS Study. Environ. Int.2017;104: 41-47.
    CrossRef
  108. Park, S. K. Ambient air pollution and type 2 diabetes: do the metabolic effects of air pollution start early in life?. Diabetes.2017;66(7):1755-1757.
    CrossRef
  109. Rajagopalan S., & Brook R. D. Air pollution and type 2 diabetes: mechanistic insights. Diabetes. 2012;61(12):3037-3045.
    CrossRef
  110. Yang B.Y., Qian Z. M., Li S., Chen G., Bloom M. S., Elliott M., Syberg K.W., Heinrich J., Markevych L., Wang S.Q., Chen D., Ma H., Chen D.H., Liu Y., Komppula M., Leskinen A., Liu  K.K., Zeng  X.W., Hu L.W., Guo Y., & Dong G.H. Ambient air pollution in relation to diabetes and glucose-homoeostasis markers in China: a cross-sectional study with findings from the 33 Communities Chinese Health Study. Lancet Planet. Health.2018;2(2): e64-e73.
    CrossRef
  111. Lucht S., Hennig F., Moebus S., Führer-Sakel D., Herder C., Jöckel K. H., Hoffmann B., & Heinz Nixdorf Recall Study Investigative Group.Air pollution and diabetes-related biomarkers in non-diabetic adults: A pathway to impaired glucose metabolism?. Environ. Int.2019;124:370-392.
    CrossRef
  112. Brook R.D., Xu X., Bard R.L., Dvonch J.T., Morishita M., Kaciroti N., & Rajagopalan S.. Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. SCI TOTAL ENVIRON.2013;448: 66-71.
    CrossRef
  113. Xu X., Liu C., Xu Z., Tzan K., Zhong M., Wang A., Lippmann M., Chen L.C., Rajagopalan S., & Sun Q. Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. Toxicol. Sci. 2011;124(1):88-98.
    CrossRef
  114. Wang M., Zheng S., Nie Y., Weng J., Cheng N., Hu X., Ren X., Pei H & Bai Y. Association between Short-Term Exposure to Air Pollution and Dyslipidemias among Type 2 Diabetic Patients in Northwest China: A Population-Based Study. INT J ENV RES PUB HE.2018;15(4):631.
    CrossRef
  115. Dubowsky S. D., Suh H., Schwartz J., Coull B. A., & Gold D. R. Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation. Environ. Health Perspect.2006;114(7):992-998.
    CrossRef
  116. Brook R. D., Jerrett M., Brook J. R., Bard R. L., & Finkelstein M. M. The relationship between diabetes mellitus and traffic-related air pollution. J. Occup. Environ. Med.2008;50(1):32-38.
    CrossRef
  117. Lu M. C., Wang P., Cheng T. J., Yang C. P., & Yan Y. H. Association of temporal distribution of fine particulate matter with glucose homeostasis during pregnancy in women of Chiayi City, Taiwan. Environ. Res. 2017;152: 81-87.
    CrossRef
  118. Robledo C. A., Mendola P., Yeung E., Männistö T., Sundaram R., Liu D., Ying Q., Sherman S., & Grantz K. L. Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus. Environ. Res.2015;137:316-322.
    CrossRef
  119. Lavigne E., Yasseen III A. S., Stieb D. M., Hystad P., Van Donkelaar A., Martin R. V., Brook J.R., Crouse D. L., Burnett R.T., Chen H., Weichenthal S., Johnson M., Villeneuve P.J., & Walker M. Ambient air pollution and adverse birth outcomes: differences by maternal comorbidities. Environ. Res. 2016;148: 457-466.
    CrossRef
  120. Fleisch A. F., Gold D. R., Rifas-Shiman S. L., Koutrakis P., Schwartz J. D., Kloog I., Melly S., Coull B.A., Zanobetti A., Gillman M.W., & Oken E. Air pollution exposure and abnormal glucose tolerance during pregnancy: the project Viva cohort. Environ. Health Perspect.2014;122(4):378-383.
    CrossRef
  121. Riant M., Meirhaeghe A., Giovannelli J., Occelli F., Havet A., Cuny D., Amouyel P.,  & Dauchet L. Associations between long-term exposure to air pollution, glycosylated hemoglobin, fasting blood glucose and diabetes mellitus in northern France. Environ. Int. 2018;120:121-129.
    CrossRef
  122. Paul L.A., Burnett R. T., Kwong J.C., Hystad P., Donkelaar V. A., Bai L., Goldberg S.M., Lavigne E., Copes R., Martin R.V.,  Kopp A., Chen H. The impact of air pollution on the incidence of diabetes and survival among prevalent diabetes cases. Environ. Int.2020;134:105333.
    CrossRef
  123. Hassanvand M. S., Naddafi K., Malek M., Valojerdi A. E., Mirzadeh M., Samavat T., Hezaveh A.M., Hodjatzadeh A., & Khamseh M. E. Effect of long-term exposure to ambient particulate matter on prevalence of type 2 diabetes and hypertension in Iranian adults: an ecologic study. Environ. Sci. Pollut. Res. 2018;25(2):1713-1718.
    CrossRef
  124. Turner R. C., Millns H., Neil H. A. W., Stratton I. M., Manley S. E., Matthews D. R., & Holman R. R. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS:  23). Bmj, 1998;316(7134):823-828.
    CrossRef
  125. Li D., Wang J. B., Yu Z. B., Lin H. B., & Chen K. Air pollution exposures and blood pressure variation in type-2 diabetes mellitus patients: A retrospective cohort study in China. ECOTOX ENVIRON SAFE.2019;171: 206-210.
    CrossRef
  126. Pan S. C., Huang C. C., Chin W. S., Chen B. Y., Chan C. C., & Guo Y. L. Association between air pollution exposure and diabetic retinopathy among diabetics. Environ. Res. 2020;181: 108960.
    CrossRef