SHS: second-hand smoke

Mechanistic insights into air pollution exposure and the pathogenesis of asthma

Children seem to be particularly vulnerable to adverse effects of air pollution because of their relative respiratory and immune system immaturity. Although several mechanisms underlying the association between exposure to air pollutants and childhood asthma that involve environmental epigenetic regulations, such as DNA methylation, oxidative stress, and damage, disrupted barrier integrity, inflammatory pathways and immunological responses, and enhancement of respiratory sensitization to aeroallergens have been described, the mechanistic basis of air pollution effects on asthma remains elusive.
Exposure to air pollutants has been associated with the production of reactive oxygen species (ROS) and consequently inducing epithelial cell inflammation, airway hyperreactivity, tight junction barrier permeability and lung injury [61, 62]. Exposure to O3 and SO2 may affect the production of cytokines in airway epithelial cells, which promote Th2 phenotypic differentiation and the production of IgE [63]. Furthermore, DNA methylation of NOS genes may also be an important epigenetic mechanism that potentially modulates TRAP-induced inflammatory responses. Exposure to TRAP has been associated with higher levels of exhaled nitric oxide (NO) and lower levels of DNA methylation in the promoter regions of the NOS3 gene at various lag periods in children with asthma living in a seaport-adjacent community with a high density of diesel truck traffic [64]. The associations of BC exposure with demethylation of IL4 and NOS2A , loweringIL4 and inducing nitric oxide synthase encoded by NOS2Aand therefore exhaled NO levels appear to be stronger among the atopic compared with the non-atopic children [65].
DEP exposure produces reactive oxygen species in the lungs and the oxidative stress-induced can lead to sensory nerves stimulation responsible for reflex events and common respiratory symptoms, such as coughing and wheezing. PAHs, major constituents of DEP can directly activate airway C-fiber afferents and activation of the transient receptor potential ankyrin 1 (TRPA1) ion channel expressed on airway afferents through activation of AhR and subsequent mitochondrial ROS production, which is known to activate TRPA1 on nociceptive C-fibers [66].
Ozone exposure results in the accumulation of ROS most likely through lipid peroxidation processes of the pulmonary surfactant phospholipids and cell membranes. ROS in turn rapidly activates the release of alarmins leading to a cascade of pro-inflammatory changes in structural and immune cells in the respiratory mucosal tissue [67]. PM exposure has also been shown to disrupt epithelial tight junctions in a dose-dependent manner [68] therefore facilitating aeroallergen uptake and therefore promoting allergic sensitization. This hypothetical mechanism would also support a time lag between early childhood structural and functional changes in growing lungs with subsequent expression of asthma symptoms at an age when asthma can be distinctly identified.