Environmental risk factors for the development of asthma
Many environmental factors can affect the risk of developing asthma. The American Academy of Allergy Asthma and Immunology (AAAAI) and European Academy of Allergy and Clinical Immunology (EAACI) have discussed emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma. The complex network of exposome, genome, transcriptome, proteome, epigenome and metabolome in driving the disease phenotype and endotype is described.20
Air quality has an influence on asthma symptoms and on triggering asthma attacks. Kim et al. correlated measurements of air pollutants around patients’ houses, including particulate matter (PM), with asthma status and with the frequency of innate immune cells (ILC) in induced sputum. A significant positive correlation between the amount of PM with a diameter ≤10 µm and asthma control was reported accompanied by an increased frequency of ILC2s in induced sputum.6
Recently Yang et al. showed prenatal exposure to PM with an aerodynamic diameter of smaller than 10 μm (PM) has a higher association with airway hyperresponsiveness (AHR) and the risk of a new diagnosis of asthma at an early school age than current and lifetime exposure. Therefore, stricter monitoring and avoidance of exposure to PM might considerably reduce the onset of future asthma development in schoolchildren.21 Indoor air contaminants, containing endocrine‐disrupting chemicals (EDCs), can also increase the risk of asthma, as shown by Paciencia et al.22 The authors assessed the association between EDCs exposure and asthma in children from 20 schools and found that increased individual and combined EDCs levels were present in classrooms having more children with asthma and with an increased prevalence of nasal obstruction symptoms in the previous 3 months. EDCs are associated with changes in the autonomic nervous system, thus suggesting that EDCs may increase parasympathetic activity, resulting in a subsequent increase in the risk of asthma.22
Pollutants can induce type 2 over type 1 response in the airways of an allergic asthma mouse model upon co-stimulation with the house dust mite (HDM) allergen as shown by Brandt et al (Figure 1).23,24 Increased IL-33 signaling in the airway epithelium upon diesel exhaust particles (DEP) exposure can exhibit a synergistic effect with the type 2 cytokines IL-5 and IL-13 leading to severely increased AHR as well as a resistance to treatment with dexamethasone. IL-5/IL-13/IL-17A coproducing CD4+effector T-cells in the lungs of DEP and allergen co-stimulated mice were identified, potential promoters of asthma exacerbations.
The activation of Aryl hydrocarbon receptor (AhR) exacerbating an allergic response was previously demonstrated. Weng CM et al.25 showed that DEP activates AhR and with upregulation of IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) by means of T helper cell (Th) 2 activation. This finding further supports the link between pollution and allergic severe asthma. Another recent study has reported AhR signaling critical role in the benzo(a)prene and Der f 1 co-exposure, leading to epithelial cytokine release through regulation of reactive oxygen species (ROS) generation.26 Future studies on the AhR-ROS axis may provide new therapeutic approaches to asthma.
Artemisia  pollen allergy is a major cause of asthma in Northern China. Gao et al. observed that the frequency of sensitization and the IgE levels related to the four main allergens (nArt v 1, nArt ar 2, nArt v 3, nArt an 7) were significantly lower in subjects from the South of China compared to those from the North, who were more likely to have allergic asthma. The authors also reported that the co-sensitization to at least three of the most frequent allergens (Art v 1, Art v 3, and Art an 7) results in a higher risk of allergic asthma.27
The most common allergen in allergic asthma is group-1 grass pollen. A wave of exacerbations of allergic asthma can be observed in fall, when grass has undergone senescence and turned to straw, where mold lives.Alternaria alternata spores from the surface of straw have been shown to carry the same allergens as grass pollen and probably inducing allergen-mediated exacerbations in allergic asthma patients.28
Besides exposure to allergens, de novo sensitization toAspergillus fumigatus is also becoming recognized as a risk factor for asthma patients. From baseline to follow‐up over a 10-year observation period, asthmatic patients acquired noticeably increased frequencies for specific IgE levels to rAsp f 1.29 The presence of A. fumigatus was associated with reduced BAL macrophages, increased BAL levels of IL‐4, IL‐6, IL‐10, IL‐13 and TNF‐α, and increased plasma IL‐4, IL‐6, IL‐10, IL‐13, IL‐17, and TNF‐α. However, there was no relationship between the presence of A. fumigatus in the asthmatic airways and disease severity or control.30
Epidemic thunderstorm asthma is an emerging public health threat triggered by a combination of thunderstorms and massive loads of small pollen allergen particles, and people without a prior history of asthma can also be affected. D’amato et al. 5investigated why thunderstorms are associated with a rapid increase of asthmatic patients that in need of urgent medical care, due to asthma attacks. Thunderstorms can bring allergen particles down to ground level and rainfall during thunderstorms is able to rupture pollen grains and release bio-aerosols containing allergenic particles that penetrate deeply into the airways with acute severe allergic inflammation leading to asthma attacks with hospitalizations in people never experiencing before an asthma attack and suffering only of allergic rhinitis symptoms. A study from Melbourne investigated risk factors to predict severe asthma attacks requiring hospital admission during thunderstorm. Odds for hospital admission were higher in Asian patients born locally compared to those born overseas. Non-Asian patients had the lowest odds for hospital admission. This suggests gene-environment interactions playing a role in the susceptibility to severe thunderstorm asthma.31 Furthermore, Lol p 5, the major allergen of ryegrass pollen was reported to be responsible for triggering an epidemic of thunderstorm asthma.32 A systematic review and meta-analysis on the possible link between pollen exposure and asthma hospital admissions in children and adolescents aged <18 years with emergency department attendance demonstrated ambient grass pollen as an important trigger for childhood asthma exacerbations requiring emergency department attendance, especially in relation to thunderstorm asthma.33