Editorial to the special issue “Environmental influences on
childhood asthma”
Back in 1892, Sir William Osler gave an accurate description of asthma
as a disease that is associated with “spasm of the bronchial muscles,
inflammation of the smaller bronchioles, bizarre and extraordinary
variety of circumstances and cold infections, often running in families
(1,2). This is basically a true reflection of our modern understanding
of asthma which states that asthma is a complex genetic disorder that
involves interactions between genetic and environmental factors.
Since the human genetic makeup has not changed significantly in the last
couple of decades, there is reason to believe that the overall increase
in asthma prevalence (3) can be attributed to the changing environmental
conditions of modern life. The role of environment in asthma is not
limited to its role in the pathogenesis of the disease. Since it is
currently not possible to change the genetic make-up of an individual
underlying a complex genetic disorder such as asthma, modification of
environmental conditions emerges as a significant tool for its
treatment. Therefore, understanding the environmental factors that play
an important role in asthma is crucial in understanding the disease
pathogenesis as well as modification of factors that modulate the
inception and progress of the disease as well as its treatment.
Various studies published in the last years in the journal and included
in this virtual issue have addressed these questions. Garcia-Serna et
al. have found out that gestational exposure to traffic-related air
pollutants (TRAP) may increase the pro-inflammatory and Th2-related
cytokines in newborns which might influence immune system responses
later in life (4). Similarly, Pesce et al. (5) have investigated the
association between prenatal exposures to heavy metals and atopic
diseases. The serum concentrations of lead, cadmium and manganese were
assessed in maternal blood samples collected during pregnancy and in
cord blood of 651 mother-children pairs. The authors have concluded that
the levels of cadmium in cord blood were associated with greater risk of
asthma at the age of 8. Baek et al. have documented that exposure to
phthalates are associated with airway dysfunction in childhood and this
effect was partially attributable to increased serum periostin levels
(6). Regarding the association between the genes and environment,
Theodorou et al. (7) have investigated the role of mitogen-activated
protein kinase (MAPK) pathway in 232 children who were selected from two
cross-sectional cohorts and one birth cohort study. They have isolated
peripheral blood mononuclear cells (PBMC) from children with asthma
along with healthy controls and stimulated them with farm-dust extracts
or lipopolysaccharide. The results have shown that the children with
asthma have expressed significantly less dual-specificity phosphatase-1
(DUSP1) which is the negative regulator of MAPK pathway. They have
conclusively indicated the possible role of DUSP1 for future
therapeutical interventions regarding the anti-inflammatory features of
farming environments.
In an effort to further elucidate the environmental factors that are
central to our understanding of asthma, the journal has started a review
series to provide a comprehensive picture on the role of environment on
various aspect of asthma. Major subheadings included
- Biodiversity
- Urban exposures
- Gene-environment interactions
- Farm effect
- Air pollution
- Climate change
- Allergens
- Diet microbiome and obesity
In the virtual issue of the journal Tari Haahtela (8) has focused on the
effect of biodiversity. Evidence supports that the immunomodulating
roles of different micro-organisms may be protective for asthma and
allergic diseases. The studies from the neighboring Finnish and Russian
Karelia regions, which the author named as “the living laboratory”,
have shown strong evidence for the central role of environment and
lifestyle which modify the human microbiome, immune balance, and thus
allergy and asthma risk. Diversity of the human microbiome as well as
the diversity of the natural environment that we live in and more
contact with the nature are important determinants of physical health.
Grant et al. (9) have focused on the influence of urban exposures on
childhood asthma. The authors have meticulously summarized and analyzed
the results of previous studies which aimed to investigate the
interaction between indoor allergens, microbes, indoor and outdoor
pollutants, social determinants and childhood asthma along with the
opportunities for intervention. Multiple environmental exposures and
influences contribute to the increased incidence of asthma and excess
asthma morbidity among children with asthma living in urban communities.
Indoor pest allergen and mold exposures have been repeatedly linked to
increased asthma diagnosis, symptoms, and exacerbations in urban
children. However, studies in high-risk urban populations also found
that early life pest allergen exposure, along with microbial and
endotoxin exposure may be associated with a decreased risk of wheezing
and asthma suggesting that the association is more complex than
previously thought.
Since asthma prevalence varies widely depending on the socio-economical
level, changes to help reduce inequities and inequalities in social
determinants of health such as poverty, housing disrepair, higher rates
of obesity, and chronic stress may produce positive effects at the
population-level.
Hernandez-Pacheco et al (10) have reviewed the latest gene-environment
interaction (GxE) studies in childhood asthma. They have summarized the
role of various environmental exposures and the current state of
knowledge on asthma genetics. The field of GxE in asthma has drastically
evolved together with technological advances over the last years.
However, despite reports on the effect of numerous environmental factors
on childhood asthma, the availability of detailed and diverse exposure
data is limited. Tobacco smoke remains to be the most accessible and
extensively explored factor followed by traffic-related air pollution in
GxE studies.
Airway epithelium seems to be central in gene-environment interactions.
The effect of the exposure to certain environmental factors early in
life on the modification of the risk and severity of asthma later in
childhood is partially dependent on the functionality and integrity of
the airway epithelium. It is known that the environmental exposures can
trigger an inflammatory response and the disruption of the barrier and
mucociliary function.
Although there are several methodological and conceptual challenges with
GxE interaction studies, recent data have led to new insights into
childhood asthma pathophysiology which is best exemplified by the
17q12-21 asthma locus. Some of the SNPs at this locus seem to be
associated with the onset of childhood asthma, thereby highlighting the
importance of age related factors in gene environment interactions.
The need for longitudinal and functional studies which provide insights
into the biological mechanisms underlying the observed associations
between environmental exposures and epigenetic changes that modify the
asthma risk is highlighted.
Another extensively studied environmental factor that is associated with
childhood as is the so called “farm effect”. Frei et al. (11) have
summarized the current knowledge on how “farm effect” influences the
immune homeostasis during the intrauterine period and in childhood with
a focus on immune mechanisms induced by environmental microbial
diversity and microbial components. Farming lifestyle factors including
nutrition influence the immune homeostasis either by regulating the
innate immune system or by induction of regulatory T cells or TH1. We
see diversity as a significant factor also in the farm effect. Diversity
of environmental microbes, the diversity of the gut microbiome, or the
diversity of the nutrition emerge as significant factors.
Paciencia et al. (12) investigated the association and mechanisms
between air pollution and asthma in children along with the precautions
that should be taken to reduce the burden of air pollution on asthma.
Environmental conditions are not shared equally across the populations,
regions, and settings where people live, work, and spend their time.
Urban conditions and air quality are not only important features for
national and local authorities to shape healthy cities and protect their
citizens from environmental and health risks, but they also provide
opportunities to mitigate inequalities in the most deprived areas where
the environmental burden is highest. Actions to avoid exposure to indoor
and outdoor air pollutants should be complementary at different levels
–individual, local, and national levels – to take strong measures to
protect children.
Taken together, these reviews provide a very comprehensive coverage on
the role of environmental factors on childhood asthma and suggest that
efforts to modify these factors may have beneficial effects not only on
the individual level but also at the population level.
S. Tolga Yavuz1Ömer Kalayci2Philippe A. Eigenmann3