Health Care Burden of Cardiorespiratory Diseases ...

World Heart Journal Volume 9, Number 4

ISSN: 1556-4002 © Nova Science Publishers, Inc.

Health Care Burden of Cardiorespiratory Diseases Caused by Particulate Matter and Chemical Air Pollutants Mihir Invally1, Ginpreet Kaur1, Gavneet Kaur2, Sukhwinder Kaur Bhullar3,4, and Harpal S Buttar5, 1

Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s NMIMS, Vile Parle (west) Mumbai, Maharashtra, India 2 Department of Pharmaceuticals, Bridge Medical Consulting Ltd, New Delhi, India 3 Department of Mechanical Engineering, Bursa Technical University, Bursa, Turkey 4 Department of Mechanical Engineering, University of Victoria, BC, Canada 5 Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada

Abstract The public health care burden of cardiorespiratory diseases (CRDs) caused by chemical air pollutants (CO, O3, SO2, CS2, NO2 ) and particulate matter (PM) has escalated during the past few decades in developing countries throughout the world, including India. Air pollution-related CRDs are most often observed in urban areas which have increasing vehicular traffic and population congestion combined with urban sprawl and heavy industry. The high occurrence of both acute and chronic obstructive respiratory disorders (COPD), lung cancer, cardiovascular morbidity and mortality are linked with the adverse effects of air pollution and cigarette smoking. Several experimental, clinical and epidemiological studies have demonstrated increased risk of CRD events after both short- and long-term exposure to inhaled particulate matter (PM > 2.5 μm) found in the air. The fine and ultrafine aerodynamic PM is especially responsible for causing most severe CRDs due to its capacity to transport toxic substances deep into the lower airways. Children and elderly individuals are more prone to adverse health effects of airborne toxicants and often require emergency visits and hospitalization. Chemical air pollution and particulate matter generated by biomass burning, forest fires, automobile exhaust, coal and gas-powered industries is considered a serious health hazard problem worldwide. This universal issue has recently received considerable attention from the medical community, environmental activists, environment protection regulators and law makers. The objectives of this review article are to ponder and reflect on the occurrence and underlying mechanisms of CRDs and COPD caused by chemical air pollutants, airborne micro- and nanoparticles, as well as health care costs of CRDs/COPD in India and globally. Keywords: Chemical air pollution, particulate matter, wood smoke, cardio-respiratory diseases

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Introduction Corresponding Author: Harpal S. Buttar, D.V.M., M.Sc., Ph.D., FICN, FIACS. Department of Pathology & Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada. Telephone: 613-824-1532. E-mail: [email protected]

Chemical air pollution is the single biggest risk factor for cardio-respiratory diseases (CRDs), and has become a matter of great health care concern in India

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Mihir Invally, Ginpreet Kaur, Gavneet Kaur et al.

and all over the world. Increasing industrial and economic growth, rampant urbanization, energy consumption, mass transportation, ever increasing number of vehicles, and escalating global population have been key factors in driving the problem of chemical air pollution in large cities [1]. Overwhelmingly published studies have corroborated this issue further, retaining the correlation that shortand long-term exposure to chemical and particulate matter pollutants enhance the risk of respiratory illnesses, such as asthma, allergies, chronic obstructive pulmonary disorders (COPD), and lung cancer [2-4]. A growing body of evidence underscores an association between chemical air pollution and CRDs. In its 2016 report, WHO acknowledged that 3.7 million deaths occur annually due to outdoor air pollution, including 80% of those with heart disease and stroke [5] (Figure 1).

Abbreviations: COPD: Chronic obstructive pulmonary disorder; IHD: Ischemic heart disease; ALRI: Acute lower respiratory infection. Figure 1. Deaths attributed to air pollution in 2016 by WHO [5].

Global Incidences of Diseases and Deaths: Region-Wise Deaths Due to Air Pollution Air pollution has been an important risk factor for cardiorespiratory diseases and deaths. Total deaths have risen sharply since 2000, largely occurring in China

In 1990, 2.2 million air pollution particle (APM)related deaths were reported globally, increasing by 8% in 2000 to 2.4 million, and subsequently increasing by 21% in 2013 to 2.9 million. Three factors seem to have played a major role in the growing trend in the number of APM-related deaths: (i) increases in PM2.5 μm exposure in densely populated countries (China, India, Bangladesh, and Pakistan); (ii) population explosion of the aging population; and (iii) changes in the prevalence of diseases caused by air pollution. Although most deaths have been reported in East & South Asia and the Pacific regions, apart from Europe and Central Asia and North America, there has been an upsurge in the death rates associated with APM (Figure 2) [6]. Children and elderly individuals are more prone to the adverse health effects of ozone (O3), particulate matter (PM), and other airborne toxicants. Epidemiology studies have also linked chronic exposure to ubiquitous air pollutants, fine and ultrafine aerodynamic particulate matter causing cardiorespiratory morbidity and mortality in children and the elderly population [7]. PM consists of tiny airborne particles (PM > 2.5 μm), which when inhaled can penetrate deep into the lungs and cause malfunction of the respiratory system. Important geographical differences have been identified for exposure to air pollution. Short-term epidemiological studies provide substantial evidence of an association of daily variations in black carbon concentrations with short-term changes in health (all-cause and cardiovascular mortality, and cardiopulmonary hospital admissions). Cohort studies provide significant evidence of associations of all cause and cardiopulmonary mortality with long-term average black carbon exposure. Studies of short-term health effects suggest that black carbon is a better indicator of harmful particulate substances from combustion sources (especially traffic) than undifferentiated PM mass, but the evidence for the relative strength of association from long-term studies is inconclusive. A reduction in exposure to PM2.5 containing black carbon and other combustion-related PM material for which black carbon is an indirect indicator should lead to a reduction in the health effects associated with PM [8].

Air-pollutants-related cardiorespiratory diseases

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Source: World Bank and IHME, using data from IHME, GBD 2013. Note: Data are for a balanced sample of countries from which data are available for both 1990 and 2013.

Figure 2. Region-wise global deaths due to air pollution.

Types of Air Pollutants and Cardio-Respiratory Diseases Effects of Nitrogen Dioxide (NO2) Inhalation on Cardio-Respiratory Dysfunction Nitrogen dioxide (NO2) is considered a lethal air pollutant, and its implications on human health continue to be a matter of utmost concern. NO2 is derived from the oxidation of nitric oxide (NO), the major outdoor source of which is combustion emissions, especially from motor vehicles and stationary combustion sources such as electric utility and industrial boilers. Indoor NO2 exposure occurs from unvented combustion appliances [9-12]. Higher air levels of NO2 are associated with daily hospital emergency transports for ischemic heart diseases such as angina pectoris and myocardial infarction, as well as for subsequent cardiac insufficiency and arrhythmia. Several studies and meta-analysis have established a relation between CVDs and exposure to NO2. Results of a study conducted by Santurtún et al. [13] showed an association between NO2 exposure and cardiac arrhythmias. These investigators found statistically significant increased incidences of arrhythmias with concentration of NO2 throughout the year, and was especially pronounced in the winter season. The authors linked the adverse events to NO2-

induced disruption of autonomic nervous system in the heart. A meta-analysis conducted by Faustini et al. [14 showed an independent effect of NO2 on the cardiovascular and respiratory mortality and found NO2 equivalency to particulate matter (PM2.5). The incidence of cardiovascular mortality was 1.13 (95% CI: 1.09-1.18) for NO2 and 1.20 (95% CI: 1.09-1.31) for PM2.5. The NO2 effect on respiratory mortality was 1.03 (95% CI: 1.02-1.03) and 1.05 (95% CI: 1.01-1.09) for PM2.5. There is some evidence that the long-term effect of NO2 on cardio-respiratory mortality is as high as that of PM2.5. The Chinese perspective of NO2-induced and population-based cardio-respiratory disorders were assessed by Luo et al. [15]. In Beijing, China, densely populated districts with higher consumption of coal and larger number of civilian vehicles were most likely to have increased NO2-related cardiovascular and cerebrovascular mortality. Overall cardiovascular and ischemic heart disease mortality were higher in districts with larger percentages of illiterate population. The districts inhabiting more residents aged ≥ 65 years were more likely to have higher risks of NO2-related cerebrovascular mortality. This study depicts the latest trends in Asia regarding the association of NO2 and its detrimental effects on cardio-respiratory health.

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Petit et al. [16] have examined the pathophysiological effects of inhaled NO2 and the oxidative damage caused to the cardiovascular system. The data corroborates the evidence that NO2-induced oxidation of low-density lipoproteins in the vascular endothelium is a precursor to atherosclerosis and subsequent plague formation. Chronic exposure to NO2 culminates in myocardial infarction and serious cardiovascular events.

Effects of Sulphur Dioxide (SO2) Inhalation on Cardio-Respiratory Dysfunction SO2 is an another important air pollutant, the sources of which include kerosene oil space heaters, burning of fossil fuels (coal and oil), combustion of sulfur-containing fuels, especially in power plants and diesel engines, and smelting of sulfur containing mineral ores [17, 18]. Oxidation of sulfur results in the formation of SO2, and because of its strong affinity for water, SO2 can be rapidly hydrated to form sulfuric acid [15]. According to the International Agency for Research on Cancer, which conducted a cohort study of workers in the pulp and paper industry, chronic exposure to SO2 causes lung cancer [16]. Increased levels of ambient suspended particles of sulphur and SO2 [15] increase blood viscosity and CVDs [17-19]. Quin et al. and several other researchers have reported that chronic exposure to SO2 induces mitochondrial dysfunction in the rat heart. After 30 days continuous exposure to SO2, the cardiac mitochondrial system was seriously damaged in rats, consequently leading to several cardiovascular ailments [20].

Effects of Carbon Monoxide (CO) Inhalation on Cardio-Respiratory Dysfunction The sources of carbon monoxide (CO) production and air pollution in most of the urban areas are automobiles, industrial processes, and burning of fossil fuels [19]. CO is a highly toxic gas produced by incomplete burning of coal and hydrocarbon fuels [20]. CO has a high affinity for hemoglobin, and impedes utilization of tissue oxygenation due to the production of carboxy-hemoglobin (COHb). The harmful effects of CO are profoundly manifested in the myocardium as compared to the peripheral tissues because of very high oxygen extraction by the myocardium [21]. The predominant mechanism of CO in causing heart disease is tissue hypoxia. Reboul

et al. noted that exposure to daily peaks of CO pollution intensified cardiac dysfunction and produced ischemic heart failure in rats due to precise targeting of mitochondria and generating oxidative stress and reactive oxygen species. The rats also showed decreased cardiac contractility due to the derangement of excitation-contractioncoupling in the heart [22].

Effects of Carbon Disulphide (CS2) Inhalation on Cardio-Respiratory Dysfunction Carbon disulphide (CS2) usually harms industrial workers because it is used as an industrial chemical for the manufacture of rayon, cellophane, and carbon tetrachloride as well as production of rubber chemicals and pesticides. A study by Drexler et al. [23] suggested that workers exposed chronically to CS2 for about 5 years showed excessive deaths due to coronary heart disease (CHD). Studies in experimental animals and few epidemiological studies have also confirmed harmful effects of CS2 on the cardiovascular system, including atherosclerosis, elevated serum cholesterol, phospholipids, and triglycerides [24]. Kotseva and De Bacquer [25] have reported increased concentrations of total cholesterol and risk of CHD following occupational exposure to CS2. The results also suggested a concentration-response relationship between the level and duration of CS2 exposure and the prevalence of CHD. Schramm et al. [26-27] reported that long-term CS2 exposure independently contributed to intima-media thickness of the carotid artery, which is considered as a biomarker of cardiovascular toxicity. The workers with long-term exposure to CS2 showed an increased thickness of intima-media, which lends additional support to the existing evidence unraveling the mechanism of CS2-induced cardiovascular dysfunction.

Carbon-Nanotubes-Induced Respiratory Toxicity Carbon nanotubes (CNTs) have been implicated to cause air pollution-related cardio-respiratory problems. Since CNTs possess many unique electronic and mechanical properties, they have novel industrial and biomedical applications. Increased production levels and uses of these nano-materials may pose potential risks to human health [28].

Air-pollutants-related cardiorespiratory diseases Exposure to CNTs mostly occurs at occupational settings where the workers could be directly exposed at the time of production as well as during their transport, storage, or incorporation into final products [28]. CNTs suspended in the inhaled air get deposited in the worker's lung tissue and can be easily observed by optical microscopy, since CNTs have a tendency to form agglomerates or aggregates [29]. Respiratory exposure to CNTs is often revealed by the formation of multifocal granulomas [28-30]. Granulomas containing macrophages are usually surrounded by carbon nanotube clusters and can be observed 6months after the initial exposure [31-32]. Fibrosis

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development can appear as soon as 15-days after the initial exposure to CNTs, and the fibrotic lesions can persist far up to 6-months [33-34]. Interestingly enough, in murine models of asthma, exposure to CNTs enhanced the susceptibility of mice to develop airway fibrosis [35-36]. Exacerbation of fibrotic response was observed when CNTs were administrated concomitantly with Grampositive (Listeria monocytogenes) and Gram-negative (E. Coli) bacteria lipopolysaccharide. In rats. CNTs exposure in combination with bacterial infection produced enhanced airway fibrosis as compared to bacterial infection alone [36-42].

Table 1. Summary of air pollutants and their effects on cardio-respiratory health in humans

Air pollutants and their sources

Adverse effect on health

Especially vulnerable populations

Particulate matter originates from biomass and fossil fuel combustion, from home heating, motor vehicle engines and industry, and cigarette smoke

Exacerbation and increased mortality from cardio-respiratory diseases, upper respiratory tract irritation and infection

Elderly people with preexisting cardio-respiratory diseases, children with asthma

Sulfur dioxide (SO2) and acid aerosols: Fossil fuel combustion, home heating, cooking with wood and coal, metal smelting, power generating and petrochemical industries

Exacerbation of cardio-respiratory diseases, including asthma, throat irritation

People with respiratory diseases, elderly persons with respiratory and cardiovascular diseases

Oxides of nitrogen (NO2): Fossil fuel combustion at high temperature

Upper respiratory tract infection, irritation of bronchi, exacerbation of asthma, eye irritation

People with respiratory diseases

Ozone (O3): Hydrocarbons and oxides of nitrogen, reaction product of sunlight and vehicle pollutants

Eye and throat irritation, reduced exercise capacity, exacerbation of respiratory diseases

People with respiratory diseases

Carbon monoxide (CO): Biomass and fossil fuel combustion, and cigarette smoke vehicle exhaust

Headache, nausea, dizziness, breathlessness, fatigue, visual disturbance, confusion, angina, coma, death, low birth weight

People with ischemic heart disease

Lead (Pb): Smelting plants, leaded petrol/gasoline

In adults: Hypertension, and classic lead poisoning. In children: Neuropsychological problems, cognitive deficit

Pregnant women and children

Other pollutants: hydrocarbons, aldehydes, organic compounds, asbestos

Lung cancer, asthma, eye irritation

Smokers, asbestos workers, adults and children with asthma

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Effects of Air Pollutants and Their Underlying Mechanisms The Perilous Camaraderie between Respiratory and Cardiovascular Disorders Cardiorespiratory illnesses such as chronic obstructive pulmonary disease and coronary artery disease have some overlapping risk factors and potentially similar

mechanistic pathways. Overwhelming evidence exists that suggests a common triggering mechanism for cardio-respiratory illnesses. As is illustrated in Figure 2, air pollution is one of the major risk factors behind the etiology of cardio-respiratory disease and the etiology of chronic obstructive pulmonary disease.

Figure 3. Plausible mechanism of cardio-respiratory illnesses triggered by air pollution. Arrows in the diagram show how a respiratory trigger affects the cardiovascular system [43].

In spite of numerous advances in treating CRDs in the last few decades, COPD remains one leading cause of morbidity and mortality worldwide: high enough to attain a status of “the fourth leading cause of death globally”. Patients with COPD are at increased risk of cardiovascular events, including myocardial infarction (MI), ischemic heart disease and stroke, as compared with their non-COPD counterparts. In fact, up to 30% deaths in patients with COPD may be attributed to cardiovascular diseases [10]. Cardiovascular mortality has been reported to increase by 28% for every 10% reduction in forced expiratory volume per second [43].

The global increase in motor vehicles during the past few decades has posed a major threat for air pollution in many large metropolitan cities worldwide [44-46]. For example, it has been observed that in Kathmandu (Nepal), urbanization has helped the city to diversify the economy by facilitating the growth of the industrial base. But at the same time these industries have become a major source of pollutant emissions in the Kathmandu Valley. Currently, Kathmandu Valley accommodates 25% of the total units of the industries in the country [47]. The total amount of air pollutants emitted from 3,156 industries were found to be in the category of air polluting

Air-pollutants-related cardiorespiratory diseases industries, out of which the Kathmandu Valley accommodates 47.5% industries [48]. The brick and cement industries are the main culprits for air pollution. Himal Cement located in the Kathmandu Valley alone emits as much as 400 tons/year of dust [49]. Acute and chronic respiratory diseases have resulted from industrial pollutants, and lung ailment is one of the top five diseases reported in Nepal [50]. There also has been a strong correlation between the prevalence of chronic bronchitis and indoor smoke pollution in Nepal [51]. After the harvest season, farmers in India burn the paddy and wheat husks in their fields. This practice generates lots of smoke that seriously affects the air quality in both rural and urban areas. Many people have complained of headaches, eye irritation and respiratory problems, especially in the national capital region (Delhi), Punjab, Haryana and UP. Many air pollution studies have been published from China. The predominant air pollutants in China consists of coal smoke, suspended particulate matter (PM) and sulfur dioxide (SO2). Large cities in China have also experienced rapid increases in numbers of motor vehicles. Therefore, air pollution has gradually changed from the conventional coal combustion type to the motor vehicle emission type in China. In 2005, Peabody et al. [52, 53] found increased prevalence of COPD among women in homes that burned coal for cooking and heating. From a total number of 20,245 subjects in seven cities in China, the overall prevalence of COPD was found to be 8.4%. The prevalence of COPD was significantly higher among rural residents [53, 54]. Looking further at the high prevalence in rural areas, Liu et al. [55] found that COPD prevalence was significantly higher in women exposed to biomass fuels in a rural community compared to an urban community. Zhou et al. [55] reported that in Xuanwei County, Yunnan Province, China, rates of COPD were more than double the national average. It appears that China is still facing the worst air pollution problem in the world. In Mexico, it was found that an increase of 10 "g/m3 PM10 was related to a 2.9% and 4.1% increase in total respiratory and COPD deaths, respectively [56-58]. According to Nejjari et al. [59], a global excess risk of total mortality varied from 3% - 4%, with 1% to 6% for respiratory mortality, for an increase of 50"g/m in the pollution indicators. A study

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by Schikowski in Rhine-Ruhr Basin, Germany, focused on the effects of air pollution on lung function in women living near major traffic roads. They followed 4,757 women longitudinally from 1985 to 1994 and found that chronic exposure to PM10 and NO2 and living near a major roadway increased the risk of developing COPD and other detrimental effects on lung function [60]. Human beings spend a large proportion of their time in indoor environments such as homes, workplaces, libraries, school class-rooms, shopping malls, etc. Important indoor pollutants include PM, SO2, NO2 and CO generated from cooking and heating activities, volatile organic compounds from paints, carpets and furniture, mold, and allergens from dampness as well as pets and environmental tobacco smoke [59]. According to the WHO, indoor air pollution is responsible for 1.6 million deaths annually [60-62]. It has been estimated that almost 3 billion people, or 50% of households worldwide, use biomass and coal as their main source of energy for cooking, heating and other household needs [61, 62]. Biofuels have higher emission factors for generating PM and other chemical pollutants, particularly during incomplete combustion at lower temperatures [63]. Biofuels generate indoor airborne particles at levels much higher than those of cleaner fuels [64], or outdoor air [65], and their overall levels are much higher in most polluted cities [66]. These micro- or nano-particles have small aerodynamic diameters [66], and have the ability to penetrate deep into the alveolar region to induce detrimental pulmonary and cardiac consequences.

Wood Smoke as Source of Potential Air Pollution and Health Hazard The hazards of wood smoke are always seen as resulting from the complex mixture of chemicals. Because wood smoke is made up of such a large mixture of different chemicals, it is not possible at present to accurately assess the health impacts by simply calculating the potential effects of individual wood smoke constituents. Nevertheless, the fine carbon particles represent the best metric to characterize exposures to smoke from residential wood combustion and resulting from wildfire smoke. There is no persuasive evidence that wood smoke

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particles are significantly less dangerous for causing respiratory diseases than other major categories of combustion-derived particles in the same size range. However, there is a paucity of information at present to make a judgment about the relative toxicity of wood smoke particles with respect to CRDs or cancer outcomes. Given the recent upward trend in the costs of oil and natural gas, it is more likely that the use of residential biomass combustion will become even more widespread in both the developed and developing countries. More concerted efforts are needed globally to reduce emissions from smallscale biomass smoke because it is likely to gain much attention in the near future in order to comply with air quality goals set to protect human health and wellbeing. There is insufficient evidence at present to conclude that wood smoke particles are significantly less or more damaging to health than general ambient fine particles. Nevertheless, given the importance of wood smoke as a contributor to particle concentrations in many locations, strategies to reduce wood smoke emissions may be an effective means for lowering air particle exposure [64].

Climate Change and Environmental Energy Pollutant Outcomes Recently, a new category of environmental energy pollutants such as heat, noise, light and radiation have been researched for adverse consequences on human health. These newly identified energy pollutants are considered to have profound impact on the overall health of humans worldwide. More importantly, heat is produced by a number of factors and air pollution is one of them. The surface temperatures of the earth are predicted to rise between 2°C and 6°C by the end of the 21st century due to the burning of fossil fuels and their subsequent emission. The deleterious effects can virtually stem from an elevation in the body temperature and related disorders, known as “thermal stress syndrome,” which if untreated, can damage the vital body systems, leading to a plethora of cardiorespiratory and neural events. Additionally, a pre-existing cardiac disease may predispose the individuals to the adverse outcomes of thermal stress, in the form of dehydration and heat stroke, with the latter posing a risk for a fatal emergency medical conditions [67].

Air-Pollution-Related Pregnancy Outcomes and Cardiovascular Disorders Intrauterine growth retardation and malformations of the cardiovascular system are the most frequently occurring congenital defects in children born from mothers exposed to polluted air [68]. The incidence of congenital heart disease is estimated at 8.1 per 1,000 births [68]. The actual rate may be underestimated, because some fetuses may die in utero and result in spontaneous abortion and stillbirths. Congenital heart malformations are generally associated with genetic defects, infections, radiation, medications, and toxic environmental inhalants [69-75]. Data from Eastern Europe suggest the possibility of increased heart defects from areas with high levels of industrial pollution [70]. A shortterm exposure refers to a few hours exposure to high levels of air pollution and could trigger the onset of ischemic events in the mother and fetus. For instance, Peters et al. and other experts [76-79] showed that exposure to high levels of particulate matter with diameter