Air pollutants can be classified as primary or secondary. Primary pollutants are emitted directly by sources such as CO, SO2, and particulate matter (PM), while secondary pollutants form in the atmosphere due to chemical and physical reactions (O3, NO2, sulfates, and ultra-fine particulates).6 They can be classified as gaseous or PM, depending on their composition. O3, nitrogen oxides (NOx), CO, CO2, volatile organic compounds (VOC), polycyclic aromatic hydrocarbons (PAH), and heavy metals are among the gaseous compounds.6

The PM (solid and liquid particles) can be subdivided by taking its aerodynamic diameter into account in: PM10 (< 10 µm), PM2.5 (< 2.5 µm), and PM0.1 (ultra-fine particulates; < 0.1 µm).5 PM's gaseous compounds negatively affect the airways, and it has a significant impact on the respiratory system (Table 1).6

In the last decades, many countries have developed projects to reduce the emission of pollutants into the atmosphere, where many of these have not been fulfilled or are in the early stages of implementation. As the case of developing countries that still need industrialization to grow are seeing air pollution levels increase. Thus, 80% of individuals living in urban areas are exposed to air pollution levels that exceed WHO guidelines.7Table 2 shows the air quality standards in Brazil, according to the countrys National Council for the Environment (CONAMA) – 2018.8

The leading pollutants inside the home are released by burning solid fuels (SF) and tobacco smoke. It is thought that between 2.5 to 3 billion people in the world (about 50% of the world's population) and up to 90% of families living in rural areas use SF to cook, heat, and light their homes.9

Burning SF (biomass and coal) for heating and cooking is considered the dominant source of indoor air pollution in rural areas, a common practice given the lack of modern energy sources. The inefficient and incomplete burning of SF by using traditional methods (stoves and open fireplaces in environments without adequate ventilation) leads to higher levels of several pollutants: PAH, heavy metals, VOC, black carbon, PM, SO2, CO, and NO.10 Incomplete SF combustion is one of the primary sources of intra-household PM and mainly releases fine and ultra-fine (<1 mm in diameter) particulates.10

Most cigarettes' basic components are tobacco, chemical additives, a filter, and paper packaging. Smokers are exposed to a toxic mixture of more than 7,000 chemicals and up of more than 60 known carcinogens compound when they inhale cigarette smoke (Table 3), and the United States Food and Drug Administration has listed 93 of them.11

Besides the compounds found in tobacco leaves, artificial industrial additives are also incorporated to add flavor, reduce the irritation smoke causes in the respiratory tract, and enhance the effects of nicotine. Nicotine is considered a stimulant as it excites many brain cells. It is not as harmful as tar and CO, but it is addictive. The amount of nicotine varies depending on the cigarette, but the amount the smoker inhales is what matters. Smoking one cigarette results in the uptake of 1 to 2 mg of nicotine, which is reflected in mean arterial plasma concentrations of about 0.03 mg/L (30 ng/mL).11

Air pollutants exert their most harmful action on the respiratory system after inhalation. Both gaseous components (O3, VOC, CO, and NOx) and PM are well-established inflammatory stimuli to the mucosa of the respiratory tract. Depending on the aerodynamic diameter of PM, its action can occur at different points in the respiratory tract: PM10 is deposited in the nasal cavity and central airways.

Exposure to air pollutants can increase the adaptive immune response of T helper type 2 (Th2) and Th17 lymphocytes as in asthma and disrupt the antiviral immune response.12

The role of PM in understanding the damage of respiratory epithelial cells occurs via a toll-like receptor (TLR) 4 pattern recognition and/or TLR2 activation via NFk-B signaling and NLRP3 inflammasome resulting in induced production of the pro-inflammatory mediators – interleukin (IL)-1a, IL-1b, IL-6, CXCL8, and colony-stimulating factor (GM-CSF).6,12 The PM10s and PM2.5s lead to the activation of the NLRP3 inflammasome via the production of reactive oxygen substances (ROS) and, consequently, alveolar macrophages, neutrophils, and dendritic cells.6,12 Once processed by dendritic cells, the antigens will be introduced to T lymphocytes and, depending on co-stimulatory molecules released by dendritic cells, a Th1- or Th2-type immune response will be established. Thus, in short, PM will lead to airway inflammation (Figure 1).12

Figure 1.

Interaction between particulate matter and immune system cells involved in respiratory tract homeostasis – Adapted from Glencross et al., 2020.12

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Additionally, exposure to fine particulate matter (PM2.5) was linked to altered methylation of most CpG sites for the important immunoregulatory genes FOXP3, IL-4, IL-10, and IFNγ. Their dysregulation has a high potential to cause loss of epithelial barrier integrity, DNA damage, oxidative stress, mitochondrial damage, changes associated with pulmonary fibrosis.13,14 Exposure to PM, even subchronic, in mice leads to alterations in both the lung and intestinal microbiome (dysbiosis), leading to lung and intestine damage and systemic inflammation impact the development of allergic disease over the lifespan.13-16

O3 exposure's direct action on the respiratory epithelium induces the release of cytokines and arachidonic acid metabolites, the leukotrienes formed from the cycloxygenase and lipoxygenase activity, which impairs mucociliary depuration and increases the production of free radicals.17

Climate change and environmental air pollution also determine changes in the environmental microbiota, which in turn is reflected in the infant's colonization and, consequently, in its microbiota: cutaneous, respiratory, intestinal, among others.18 This dysbiosis can be followed by significant changes in the infant's immune system, such as altered TLR expressions, altered T-cell function, altered antiviral responses, and altered allergic sensitization.18 Many of these changes are believed to be due to epigenetic changes, acquired in utero and transmitted to subsequent offspring, and by co-exposure to allergenic and non-allergenic stimuli. The airway microbiota has acute and long-term effects on respiratory health, while the intestinal microbiota influences airway health indirectly through the gut-lung axis.18

The gastrointestinal tract can also be involved with air pollution, just like the respiratory and cardiovascular tracts, although there is controversy among researchers. Experimental studies with animals that received high doses of urban PM by gavage showed increased intestinal permeability due to loss of tight junctions between enterocytes, increased IL-6 expression, and apoptosis of colon epithelial cells. Prolonged exposure to PM10, in addition to the previous alterations, determined alterations in the intestinal microbiota and in the homeostasis of fatty acids. Furthermore, PAHs, components of air pollutants, can significantly interfere in the balance between aryl hydrocarbon receptor (AhR) ligands derived from commensal bacteria in the gastrointestinal tract and from regulatory Th cells and epithelial Th17,12 a critical step for the onset of inflammatory bowel disease and food allergy.19

The action pollutants have on the cells of the immune system compromises the immune tolerance mechanisms and the antiviral and antibacterial defense mechanisms, making infections by respiratory agents more frequent (Table 4).12

The impacts of exposure to air pollution during the prenatal period can affect organogenesis and the development of organs (i.e., the lungs), which can lead to long-term complications, affecting respiratory health in different manners.22

Recent studies have shown the accumulation of black carbon on the fetal side of the placenta, suggesting that environmental particulates can be transported to the fetus and represents a potential mechanism that could explain the detrimental health effects of pollution from early in life.23

Exposure during pregnancy (24th to 36th weeks) at 2 μg/m3 or more than PM2.5 during the saccular phase of lung growth was associated with a 1.29-fold higher risk of asthma (95%CI: 1.06-1.58), current asthma (RR: 1.27; 95%CI: 1.04-1.54), but not current wheezing.24,25 Impaired lung development also contributes to infant mortality.22-26

Exposure to PM10 from heavy road traffic during pregnancy was associated with significant reductions in lung function.23 Maternal exposure to traffic-related NO2, especially in the first trimester of pregnancy, has been associated with an increased risk of developing asthma, rhinitis, and eczema in children.27

Components of cigarette smoke are potentially toxic to the developing fetus, including lead, nicotine, cotinine, cyanide, cadmium, mercury, CO, and PAH. CO reduces the fetus's supply of O2, leading to hypoxia since it binds to hemoglobin with an affinity 200 times greater than O2 and makes it difficult to release the O2 to the cells. Chronic mild hypoxia of fetal tissue may persist for five to six hours after the mother has stopped smoking.28

A recent meta-analysis evaluated the deleterious effects of exposure to tobacco smoke during pregnancy, associated with harmful effects on the fetus and the newborn in the first two years of life.29 Regarding the respiratory system, exposure during pregnancy and passive exposure after birth was associated with increased risk of wheezing in children under two years of age, higher frequency of respiratory tract infections in children under two years (including bronchiolitis, pneumonia, bronchitis, pulmonary tuberculosis, otitis media), and increased risk of developing asthma.29 It is thought that at the epigenetic level, exposure to tobacco smoke during pregnancy may alter DNA methylation and messenger RNA expression in placental tissue, which may determine alterations in the expression of genes that affect the development of health conditions in the offspring.30

Exposure to PM has been associated with impaired lung function in children, documented by the decrease in peak expiratory flow rates and forced expiratory volume in the first second, especially among asthmatic children, and clinically externalized by the increase in the number of exacerbations, visits to emergency rooms, hospitalizations, and child deaths.31,32

Exposure to PM10 and NO2 has been associated with reduced eosinophilic and neutrophilic inflammation of the respiratory mucosa in children with no wheezing. On the other hand, prolonged exposure to PM10 has been associated with eosinophilic inflammation in children with wheezing, suggesting that it may contribute to developing asthma, inflammation, and promoting airway remodeling.33

Passive exposure to tobacco smoke or nicotine-releasing devices has been associated with an increased risk of wheezing and asthma in children.29

The increase in global warming-related to climate change is associated in changes in pollen seasons, making them longer.34 Scientific evidence shows that components of air pollution may also interact with airborne allergens and enhance the risk of atopic sensitization and exacerbation of symptoms in sensitized individuals. PM, O3, CO2, Diesel Exhaust Particles, SO4, and NOX have been shown to enable the release of pro-inflammatory mediators that can accelerate IgE-mediated sensitization and allergy of susceptible subjects. Additionally, air pollution has been shown to increase pollen allergenicity.35,36

Although house dust mites (HDMs) and fungal spores are important sources of allergens inducing asthma and rhinitis, which are very sensitive to microenvironment modifications. Therefore, global or regional changes in temperature, humidity, air pollution, or other environmental conditions could modify natural HDMs and molds growth, survival, and allergen production.37 Consequently, sensitization to HDMs and molds has increased in some regions of the world, especially in the subtropical and tropical areas.38,39 The synergistic effects between extreme heat and aeroallergens intensify the toxic effect of air pollutants, which in turn increases the allergenicity of aeroallergens.39