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.