Air pollution is one of the most significant health problems in the world; data from the World Health Organization (WHO) show that 9 out of 10 people breathe polluted air, and has been estimated that 7 million people die annually because of the combination of ambient and household air pollution [1]. However, this exposure to pollutants uniquely affects children because of a combination of behavioural, environmental, and physiological factors, thus making children more vulnerable to air pollution. Children have longer life expectancies, and therefore, longer exposure, and they breathe faster than adults, taking in more pollutants through the air. Children also live closer to the ground and may spend more time outside, exposing them to higher levels of air pollution. Physiologically, their bodies are rapidly changing and maturing, and therefore, are more vulnerable to damage from pollutants. Moreover, their powerlessness to change their environments is the reason that adults must be responsible to protect them from the threat of unsafe air [2].

2. Allergy and Immunology

Children exposed to oxidants, such as ozone (O₃) and nitrogen dioxide (NO₂), have been found to be more prone to develop asthma, allergic rhinitis, and eczema. The oxidants target the airway’s epithelium, and combined with an impaired ability for an antioxidant response, easily damage the airway’s epithelium. However, the evidence on early exposure to PM_2.5 and PM₁₀ resulting in risks of childhood respiratory and allergic conditions was conflicting ^[3][4][7,8]. Tobacco smoke, however, has a clearer relationship; environmental tobacco smoke (ETS) is strongly associated with asthma symptoms by increasing the airway’s hyperresponsiveness. ETS has a direct, toxic effect on the mucosa, impairing ciliary function and local immune defences, resulting in prolonged inflammation. Nicotine affects lung branching in utero, resulting in dysanaptic lung growth, decreasing airflow, increasing resistance and mucous viscosity, and therefore affects pulmonary function ^[5][6][9,10]. Because of the lowered immune responses, including airway clearance, the risk for respiratory infection is also increased. The relationship between air pollution and respiratory infection is fascinating and important, as the respiratory tract is the first line of defence against air pollution. Therefore, further resviearchw is needed in regard to the way that air pollution affects respiratory function, including infection and hypersensitivity. Air pollution increases the risk of respiratory infection by impairing immune responses in the respiratory tract. PM_2.5 causes direct lung cell injury, affecting the bacterial clearance from the airway ^[7][11]. PM_2.5 also reduces alveolar macrophage phagocytosis of bacteria ^[8][12]. Chronic exposure to diesel exhaust particles also directly kills cells, and therefore decreases responses towards the pathogen ^[9][13]. Air pollution also causes oxidative stress within respiratory cells, increasing susceptibility to infection by increasing viral attachment and entering cells ^[10][14]. Exposure to carbon black also changes the immune response from a Th1 to a Th2, which promotes allergic immune response. This shift promotes the exacerbation of a virus which, in this study, was respiratory syncytial virus in mice [15]. Microbiota play a huge role in this relationship, as previously discussed. Air pollutants that are ingested can alter gut microbiota compositions, creating dysbiosis by changing the gut environment. The air pollutant particles affect gut epithelial cells, both directly and after being metabolized by the gut microbiota. Both encourage reactive oxygen species (ROS) production and affect epithelial tight junctions, allowing microbial products and air pollutant particles to penetrate deeper to the gut wall. This penetration increases immunological cell interaction, causing pro-inflammatory reactions that change the gut microbiota’s composition to suit this environment. The inflammation itself and the microbiota composition change—the dysbiosis—will further increase gut permeability, creating a cycle of effects ^[11][16]. Gut microbiota dysbiosis caused by air pollution also plays a role in the increased risk of atopy and asthma. The microbiota plays a role in the regulation of immune functions by directly stimulating or producing several mediators that stimulate the production of regulatory T-cells (T-regs). T-regs are a type of T-cells that modulate the activity of the immune system. While asthma may have been more affected by the inhaled antigen and lung microbiota, gut microbiota dysbiosis has also been observed in asthmatic children, indicating the possible role of gut microbiota in systemic immune response and asthma ^[12][13][17,18]. The data also showed that, when the gut microbiota is altered, the susceptibility for infection, both in the gut compartment and in distant organs, such as the lungs, is increased. This is caused by the membrane component of the gut microbiota and also because metabolites produced by the microbiota can induce the interferon-mediated protection from viral infection, even in the distal respiratory system ^[14][19]. While the allergic and immunological pathway is one of the most significant pathways for air pollution to affect children’s health, in which the microbiota also plays a role, several pathways have also been identified in regard to the impact of air pollution on the alteration of the gut microbiota.

3. Neurodevelopment

Behavioural development is significantly affected by air pollution; one example is that exposure to NO2 and PM2.5 increases the risk for attention deficit hyperactivity disorder (ADHD). The mechanism is thought to be chronic brain inflammation, leading to the damage and diffuse loss of neural tissue. Affected areas include the prefrontal cortex, olfactory bulb, and midbrain, which is central to the development of behaviour and cognitive function ^[15][20]. The same mechanism is thought to underlie other behavioural development problems, such as Alzheimer disease pathology ^[16][21]. Another mechanism by which air pollution affects neurodevelopment is by affecting the gut microbiota balance ^[17][4]. Brain development is modulated by microbiota through several mechanisms: metabolic, immune, endocrine, and neural pathways. Gut microbiota, such as Bifidobacterium infantis, regulates central neurotransmitters, such as serotonin, by modifying its precursor, tryptophan. Tryptophan is stored in limited quantities in brain and therefore requires continuous supplementation from the digestive system. Other metabolites produced by gut microbiota that may affect brain development are short-chain fatty acids. Other than metabolic products, gut microbiota can also synthesize neurotransmitters, such as gamma-aminobutyric acid (GABA), norepinephrine, dopamine, and acetylcholine; how they affect the brain directly is debatable because of their limited capability to cross the blood–brain barrier. Immune signalling through cytokines produced by the microbiota can also affect brain areas, such as the hypothalamus and circumventricular organs, activating the core stress system, and releasing cortisol. Cortisol will later affect tryptophan metabolism.

4. Cardiometabolic Risk

Elevated blood pressure in children is associated with long exposure to PM, especially PM2.5 and NO2. Elevated blood pressure in children is a risk for hypertension and metabolic syndrome later in life. Evidence demonstrates that the effect of air pollution on cardiovascular risk is related to systemic inflammation and immunological responses. The direct contact of pollutants with upper and lower epithelial cells will generate airway oxidative stress and induce local airway inflammation, opening the epithelial’s tight junction barrier, and letting the pollutants enter the bloodstream. There is also a spillover of local lung immune response to the system. This systemic inflammation causes endothelial injury and increases platelet activation, which encourages atherosclerosis and thrombosis. This isystemic inflammation also alters the autonomic nervous system and the autorhythmic cells in sinoatrial node and causes cardiac arrhythmias. The combination of all of this increases the risk of cardiovascular diseases, including stroke and myocardial infarction ^[5][18][9,25]. Oxidative stress and systemic inflammation also impair lipoprotein functionality, alter adipocyte behaviour, and disrupt the endocrine process (such as by increasing insulin resistance), and therefore encourage obesity, diabetes mellitus, and dyslipidaemia. All three metabolic risks are strongly associated with cardiovascular risk in the future ^[5][19][9,26]. PM2.5 is the most well-known culprit although PM10 and NO2 also have roles. Coming from ambient or household air pollution and also tobacco smoke, PM exposure has been associated with hypertension, obesity, insulin resistance, dyslipidaemia, cardiac arrhythmia, stroke, and atherosclerosis. Polycyclic aromatic hydrocarbons, however, are the pollutants most strongly associated with obesity ^[5][19][9,26]. Gut microbiota dysbiosis, which can be affected by air pollution, may also increase the risk of cardiometabolic disease in the future. Gut microbiota has been linked with obesity, for example, being one of the risk factors for cardiometabolic diseases. Some of the gut microbiota can hydrolyse and ferment a wide variety of complex polysaccharides that are otherwise indigestible by humans because they lack the specific enzymes. The digestion process will increase the body fat percentage from this energy consumption ^[20][27]. The increased plasma concentration of bacterial lipopolysaccharides (LPS), linked with the increased gut permeability caused by the disturbed tight junction, can increase the systemic inflammation linked with obesity and insulin resistance. LPS activates toll-like receptors (TLR), which in turn increase the production of diabetogenic, pro-inflammatory cytokines. This process is called “metabolic endotoxemia” ^[19][26]. On the other hand, some species have shown their protection against obesity and insulin resistance by inhibiting pro-inflammatory cytokines, upregulating the expression of tight junction genes, reducing gut permeability and, therefore, decreasing the level of LPS in the plasma. Some species can directly influence glucose homeostasis in metabolic organs, such as the liver, muscles, and fat by increasing the expression of various antidiabetic enzymes. Some of the microbiota, through its metabolism of indigestible complex polysaccharides into short-chain fatty acids (SCFA), such as butyrates, modulate gut hormones and enzymes, improving insulin resistance ^[21][28]. While obesity and insulin resistance have been linked to the shifting of the microbial community structure from obligate to facultative anaerobes, no clear pattern has emerged regarding the species ^[22][29].