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