Particulate matter (PM) comprises a complex mixture of solid or liquid particles that vary in number, size, shape, surface area, chemical composition, solubility, toxicity and origin.12 PM is classified according to the size of its aerodynamic diameter in microns (μm): PM10 (aerodynamic diameter less than 10μm), PM2.5 (aerodynamic diameter less than 2.5μm) and PM0.1 (ultrafine, aerodynamic diameter less than 0.1μm).13 PM10 penetrates the respiratory system and is deposited in the bronchial airways, while PM2.5 and PM0.1 can penetrate deeper into the respiratory system, reach the bloodstream and generate oxidation reactions and systemic inflammation.14 The harmful potential of these pollutants depends on their composition and size. In terms of composition, particles from diesel vehicles are highly hazardous because they contain heavy metals. PM originates mainly from road traffic, in particular diesel engine vehicles, although other sources of PM are power plants and factories, the phenomena of resuspension of material deposited on the ground and natural sources of PM (such as desert dust or biomass combustion).9

Inhaled gases are absorbed in different locations in the respiratory system and at different depths depending on their solubility in water. For this reason, SO2 is absorbed in the airways, while O3 and NO2 reach the lower respiratory tract (LRT) and penetrate the alveoli. NO2 comes mainly from the burning of fossil fuels (mostly due to road traffic), although it can also come from power plants and factories, while tropospheric O3 is a secondary pollutant that originates from volatile organic compounds (VOCs) or nitrogen oxides (NOx) present in the atmosphere in stable conditions upon activation by ultraviolet radiation. It is therefore mainly produced at the warmest time of the day and in summer. The highest concentrations of O3 are usually found on the outskirts of large cities and parks.15

Daily life today involves spending time indoors, so it is important to consider the quality of these spaces. Ventilation may be inadequate due to insufficient air volume, high levels of recirculation, incorrect placement of ventilation points, poor allocation of space (with non-ventilated areas), and poor maintenance or incorrect design of filtration systems.16 The main indoor air pollutants include tobacco smoke, suspended particles generated indoors, carbon monoxide (CO) and carbon dioxide (CO2), nitric oxide (NO), radon, VOCs, formaldehyde, dust mites, animal allergens and mould, among others (Table 2). It is important to note that, according to WHO data, around 3 billion people are exposed to pollutant levels that are well above acceptable levels due to the use in their homes of open fires and stoves in which biomass (wood, animal excreta or agricultural residues) and coal are burned, a common practice in developing countries.

Several studies postulate that the inhalation of pollutants, especially diesel exhaust particles (DEP), can generate oxidative stress on the bronchial cell surface. If ROS levels on the cell surface are low, the activation of antioxidant defence mechanisms can counteract their effects. Exposure to moderate doses may cause activation of the Th2 inflammatory pathway (basically eosinophilic) triggered by the stimulation of dendritic cells induced by thymic stromal lymphopoietin (TSLP) released by the epithelium.18–20 High levels of pollutants could lead to disruption of the bronchial epithelium with cell shedding and release of adhesion proteins that would trigger IL-8 production and neutrophilic inflammation (Fig. 1).21 In addition, the hydrocarbon fraction present in some DEP can stimulate aryl hydrocarbon receptors (AhR), generate intracellular ROS (which can act as second messengers) and, after activation of nuclear factor kappa B (NF-κB), induce a Th2 or Th17 response according to the modulatory activity of tumour necrosis factor-α-induced protein 3 (TNFAIP3).22,23

Fig. 1.

Main components of inflammatory signalling in asthma triggered by exposure to environmental pollutants. The pollutants come into contact with the airway epithelium and trigger the generation of reactive oxygen species (ROS). Moderate or high levels of ROS may activate Th2 or Th17 inflammatory response mechanisms triggered by the release of different cytokines and proinflammatory factors and the involvement of different immune cell lineages (neutrophils, eosinophils). DEP: diesel exhaust particles; IL: interleukin; ILC-2: type 2 innate lymphoid cells; NLR: NOD-like receptor; ROS: reactive oxygen species; TLR: toll-like receptor; TSLP: thymic stromal lymphopoietin.

(0.42MB).

Immunological mechanisms have also been linked to the onset of asthma from air pollutants. Activation of Toll-like receptors (TLR) or NOD-like receptors (NLR) determines the activation of NF-κB, which induces the expression of different pro-inflammatory cytokines such as IL-1B, IL-6 and IL-8, responsible for an innate immune response that essentially produces neutrophil inflammation. Activation of these receptors can also generate the production of IL-33, IL-25, and TSLP (Fig. 1). These molecular patterns (or alarmins) induce a Th2 response, basically eosinophilic, either by activation of dendritic cells or ILC-2s.24 It has also been suggested that the contact of DEP with the bronchial epithelium may promote the release of IL-17A, IL-17F and CCL20, which may activate the Th17 lymphocytes and thus generate a typically neutrophilic response.25

Finally, air pollutants may activate transient receptor potential (TRP) channels such as the TRP vanilloid 1 (TRPV1) or TRP ankyrin (TPRA) channels and cause respiratory symptoms like cough and bronchospasm and the possible onset of asthma by non-inflammatory mechanisms.26

Although it has been suggested that exposure to air pollutants can cause asthma through indirect mechanisms such as epigenetic changes27–29 or modifications in the respiratory microbiome,30–32 the interaction between these pollutants and inhaled allergens is one of the best studied mechanisms for which there is greater evidence.

Allergens such as pollen form part of atmospheric pollutants. Pollen grains generally have a particle diameter >10μm. Fungal spores and pollen fragments with smaller sizes (<2.5μm; PM2.5) are also found in the air, and can penetrate the alveolar regions of the lung. The concentrations and allergenic capacity of these aeroallergens are undergoing changes on the planet due to climate change. Thus, longer periods with high temperatures favour the atmospheric abundance of bioaerosols and aeroallergens such as pollen and, therefore, increased exposure.33

Evidence shows that the immunogenicity of allergenic proteins may be altered due to coexposure with other air pollutants such as O3 and NO2. In this respect, there are several mechanisms that could explain the alteration in the allergenic capacity of these proteins.34 First, allergens can physically bind to pollutants such as the PM, which would act as an adjuvant, increasing the allergenic potential. In addition, this binding may alter the protein envelope and facilitate the release of allergenic substances such as pollen cytoplasmic granules. Furthermore, the binding of pollutants such as O3 with proteins such as pollen grains can induce the generation of intermediate ROS that facilitate the formation of protein aggregates (dimers) of greater allergenic potential.34

The effects of the interaction of allergens with pollutants have been studied in animal models of asthma. Muranaka et al. (1986) studied the effects of coexposure to DEP and an allergen such as ovalbumin in a murine model, and confirmed the adjuvant activity of DEP in the respiratory mucosa as well as amplification of the allergic response.35 In order to reproduce the nature of human asthma as closely as possible, antigens such as house dust mites, cockroaches or pollen, which are physiologically more relevant, have been used in research.36 These models have shown that joint exposure to DEP and allergens has a synergistic effect and induces the expression of some Th2 response-related cytokines, such as IL-4, IL-5 or IL-13 and in some cases, the expression of Th17 response cytokines (Fig. 2).37,38 In this regard, coexposure to soybean and DEP has been reported to trigger a stronger asthmatic response in which there is increased airway hyperresponsiveness and increased amounts of cytokines related to a combined Th2/Th17 response in the bronchoalveolar lavage.39

Fig. 2.

Inflammatory signalling triggered by the interaction of diesel exhaust particles and inhaled allergens. Exposure to low doses of allergens does not generate an immune response. However, this same exposure combined with exposure to diesel exhaust particles induces Th2-response-related IL-4, 5 or 13 expression and Th17-response-related IL-17A, 17F or cytokine CCL20 expression. Exposure to high doses of inhaled allergens generates a typical Th2 response. CCL20: chemokine ligand 20; DEP: diesel exhaust particles; IL: interleukin.

(0.45MB).

Although experimental evidence of the relationship between air pollution and asthma is strong, the epidemiological evidence is less consistent, as some authors have been unable to demonstrate any significant relationship between this exposure and the incidence of asthma.40–43 Several studies seem to support an increased risk in the incidence and prevalence of asthma in children, associated with exposure to air pollutants, even in the population whose exposure does not exceed WHO-recommended limits.41,44–46 The prospective ACCESS study that included pregnant women from various hospitals in the Boston area (USA) analyzed data from 736 children, and found that prenatal exposure to high levels of PM2.5 was associated with a higher incidence of asthma at 6 years old, especially in males and if the exposure occurred in the second trimester of pregnancy.47 Data from the ISAAC study showed that increased exposure to road traffic was associated with an increase in asthma symptoms, although the results were not homogeneous and differences were observed between countries in terms of the most affected age group (in countries in northern and eastern Europe, this association was observed in the 13–14-year-old age group, while in populations in western Europe and North America, asthma symptoms increased in the 6–7-year-old group but not in the older group).45 Another study conducted using this same methodology in the Spanish population showed that the prevalence of asthma symptoms increased significantly in boys aged 6–7 years who had increased exposure to traffic. However, there was no significant increase in these symptoms in the 13–14-year-old group or in 6–7-year-old girls.41

A meta-analysis by Bowatte et al. (2015) concluded that exposure to elevated levels of PM2.5 was consistently associated with an increased incidence of childhood asthma. Similar results were obtained for exposure to NO2 and black carbon, although the results were less consistent and the association was only significant in some age groups but not in others.44

The results of the Southern California Children's Health study showed that increased exposure to elevated levels of NO2, O3, PM10 or PM2.5, both at school and at home, was associated with a higher incidence of asthma,42 similar to that observed in a later European multicentre study.40 In contrast, data analysis from five European cohorts failed to establish any significant relationship between exposure to pollutants and the incidence of asthma.43

In conclusion, increased exposure to air pollutants appears to be associated with an increased incidence of asthma. The effect may vary depending on some variables such as age, sex, or time of exposure.

Pollution can trigger asthma in individuals with no previous history of the disease due to a number of determinants such as genetic (polymorphisms in genes encoding antioxidant agents) and epigenetic changes (methylation of genes involved in innate immunity and asthma or changes in the microbiome), or immunological changes (Th2 and Th17 immune response triggered by exposure to DEP), among others.48 While the prenatal and early postnatal stages are considered key time windows of genetic susceptibility to any environmental exposure that may contribute to the subsequent development of asthma, further research is still needed in other stages, such as adolescence and older adulthood.49–52

Age is a risk factor for developing pollution-induced asthma, as reflected by a higher number of hospitalizations for asthma between age 6 and 18 years (incidence that decreases until age 50). At older ages, misdiagnosis between asthma and chronic obstructive pulmonary disease (COPD) is an added difficulty in clarifying the relationship of pollution with the development of airway disease.53

Several studies that have failed to show a clear relationship between pollution and incident asthma pose methodological problems that, if addressed, could change the evidence.43 More reliable data are needed on household pollution, the relevance of the distance to main roads and accurate measurement of particulate levels, among other issues.54 In adults but not children, there is an association between CO exposure and asthma exacerbations55; however, this pollutant is not always analyzed, so its weight in the development of the disease may be underestimated. Air pollution is normally measured using fixed air pollution stations, so it does not reflect individual exposure to these pollutants. Moreover, asthma is a globally underdiagnosed disease, which also contributes to the lack of sufficient evidence of the relationship between air pollution and asthma development.

Recent studies show mixed results. In a cohort of women under long-term follow-up, the five pollutants analyzed were associated with incident COPD and none were related to the onset of asthma.56 A study that analyzed the impact of traffic-related air pollution (TRAP) in participants of a longitudinal health study at 45- and 50-year follow-ups concluded that living less than 200m from a major road was correlated with asthma, wheezing and reduced forced vital capacity, and this correlation was more evident in individuals with certain genetic variants of the enzyme glutathione S-transferase, probably due to deficient antioxidation.57 Another study that included follow-up of an adult cohort of 23,000 nurses showed a relationship between the NO2 and PM2.5 levels and the development of asthma, even though the exposure level was below the limit considered harmful by the EU.58

One poorly researched aspect is the development of COPD in adult asthmatic patients. In the context of incident asthma, patients exposed to higher levels of PM2.5 and O3 are three times more likely to develop asthma-COPD overlap syndrome (ACOS), possibly mediated by an underlying mechanism of intensified remodelling.59,60

Thus, even with still limited data, there is growing evidence of the potential impact of air pollution on the incidence of asthma in adults. A better understanding of the relationship between genetics and epigenetics and the development of technological advances that allow for more accurate determination of exposure to air pollution (such as the use of remote sensing by satellite or individual GPS-guided mobile sensors to obtain customized data) will greatly advance this knowledge.61

Asthma is responsible for approximately 250,000 preventable deaths annually worldwide.62 The leading cause of asthma mortality is exacerbations, which in turn are responsible for a high number of emergency department (ED) visits and hospital admissions each year.63 About 20% of asthmatics have exacerbations that require ED visits or even hospitalization, accounting for more than 80% of the total direct costs associated with the disease.64,65 It is therefore a priority to take into account both risk factors for exacerbations and those related to individual and environmental factors such as allergens, infections and air pollution.63,66–68

Multiple epidemiological studies suggest that air pollution is associated with asthma exacerbations. Elevated levels of PM, O3, CO, SO2 and NO2 can precipitate the onset of exacerbations, increasing ED visits and hospitalizations across all age ranges. In addition, exposure to PM2.5, NO2 and O3 has been associated with higher mortality in asthmatic individuals. Hospital admission due to asthma exacerbations in the paediatric population are more strongly associated with CO, NO2, SO2 and PM, while in adults, they are more strongly associated with CO, NO2 and SO2.69–73 Asthmatic individuals with allergies appear to be more susceptible to O3 and PM2.5 compared to non-allergic individuals.74

The pathophysiological mechanisms of asthma exacerbations related to air pollution exposure are not yet fully known, despite recent advances. Exposure to air pollution triggers oxidative stress in the lungs. The cells involved in the response increase the production of ROS with consequent lung injury and activation of signalling pathways leading to local inflammation and airway hyper-responsiveness.85,86 Children are more vulnerable because of their higher respiratory rate, immaturity of their respiratory system, and greater exposure to outside air.81

• •

  Use close-fitting particulate respirators, such as N95 masks, when air pollution levels are high or when travelling to areas with high ambient air pollution levels.

• •

  Switch from motorized to active transport (walking or cycling).

• •

  Choose travel routes that minimize near-road air pollution exposure, avoid major intersections and traffic jams, choose routes with open spaces, minimize travel during peak times, and avoid delays in areas of high air pollution.

• •

  Optimize driving style and apply measures such as driving with windows closed when in traffic. Maintain car air filtration systems and avoid keeping the engine idling.

• •

  Exercise outdoors regularly, but with moderate intensity, when air pollution levels are high.

• •

  Healthcare professionals should encourage patients to check their local air quality, and patients should be aware of air quality alerts and learn how to implement adequate protective behaviour on high air pollution days.

• •

  Use clean fuels and make sure the home has good ventilation as well as more efficient cookstoves.

• •

  Use portable air purifiers combined with measures to reduce sources of household air pollution and strategies to improve ventilation.

• •

  In the case of asthmatic patients, follow the planned treatment plan, since having well-controlled asthma is crucial to reduce or prevent the risks of air pollution.