2. AE as an environmental disease
The picture of the reasons for the rapid increase in allergies and
atopic diseases remains incomplete to this day. For sure it cannot be
explained by genetics alone [15]. In fact, AE can potentially be
seen as an environmental disease occurring in susceptible individuals
[16-18]. A variety of intrinsic and extrinsic risk factors were
identified to influence AE development and exacerbation (Figure 1)
[19]. Intrinsic risk factors for AE include parental atopic history,
filaggrin (FLG) mutations, polysensitization, decreased short chain
fatty acids in the gut of children, and underlying medical conditions
[20-25]. However, extrinsic factors as low microbial exposure and
diversity, antibiotic exposure, urban environment, tobacco smoke
exposure, stress, food, and pollutants are as important for AE
development [16]. The lower and later exposure to microbes is
described by the “hygiene” or “old friends” hypothesis and is
associated with increased allergy prevalence [26, 27] [28]. The
relationship between host and microbes is symbiotic and bacteria shape
essential biological functions such as the development of a tolerogenic
immune response towards commensals [29]. In line, the prevalence of
AE was reported to be higher in urban than in rural areas [30]. The
hygiene theory could be supported recently in a birth cohort –
siblings, infections, and pet - especially dog keeping - were protective
for AE [28, 31]. However, contradicting results exist on the
influence of dog and cat ownership on disease development [32]
[33]. Also, cesarean section birth with lower microbial exposure
could recently not be confirmed to have a higher risk for AE than
vaginal delivery [34], whereas very preterm birth even seems to be
associated with decreased risk for AE development [20, 21]. A deeper
understanding of the complex interplay between microbes and host is
still needed [35]. Another environmental factor is the surrounding
climate in a given location, a combination of temperature, and
precipitation and therefore UV exposure and humidity [16]. Although
contradicting reports exist on the influence of the single factors on AE
development and exacerbation, they seem to be worth further
investigation, especially in times of climate change [16, 36]. The
patient’s residence also determines the exposure to air-pollutants which
are associated with AE development. One major component of environmental
air pollutants are Diesel exhaust particles, which triggers an
itch-scratch response by binding to the aryl hydrocarbon receptor AhR
[37, 38] [39]. Children seem to be more vulnerable than adults
to pollution as an AE exacerbation trigger [40]. The stress level
coming from the psychosocial environment is another extrinsic factor,
which is correlated with disease symptom severity and exacerbation
[6], leading to a vicious circle as AE is a strong psychological
burden for patients [41, 42]. In line, psychological interventions
had a positive effect on AE severity in a meta-analysis and were also
associated with other allergic diseases [43, 44].