Discussion
In this cohort of participants followed from 43 to 53 years of age,
based in Australia where pollution levels are generally low, we observed
that in males, higher exposure to ambient air pollution was associated
with increased risk of prevalent eczema (both atopic and non-atopic). In
contrast, for females, higher exposure to NO2 was
associated with a paradoxical protective effect of prevalent eczema
(both atopic and non-atopic). Additionally, there was evidence that
increased levels of PM2.5 exposure were associated with
increased risk of allergic sensitisation, in both males and females.
There are a limited number of previous studies that have considered the
association between ambient air pollution exposure and eczema prevalence
or incidence, and the results were inconsistent. Two paediatric
studies19,20 showed no association between ambient air
pollution and increased risk of eczema, while other studies suggested
increased eczema risk from ambient air pollution in
children7 and adults.21,22 A study
by Kim et al23 found similar results in that
NO2 was associated with the prevalence of AE in male but
not in female, however the study population were children. The reason
for these sex specific effects is not clear, but may be partly be due to
differences in skin morphology, occupational exposures in adults and
behaviour.24As has been reported previously in this
age group,25 women tend to spent more time indoors
compared to men, with men reported spending almost twice the amount of
time outside compared to women (supplementary file 9). Additionally,
women are more likely to care about skin issues and avoid exposure to
irritants compared to men.26 Therefore, residual
confounding may have introduced the sex-specific interaction in the
association estimates. On the other hand, Gilmour et
al.27 observed that not all oxidative stress responses
on the epithelial barrier are injurious and a lower level of oxidative
stress might be paradoxically protective. To further elucidate the
possible reasons for these sex specific effects, we recommend focused
exploration of the physiological, barrier function and immune responses
to ambient air pollution at low levels in men and women.
We were unable to replicate the results from the SALIA cohort of elderly
women study.6 However, we saw similar non-significant
trends of associations between ambient air pollution markers at
follow-up and NAE prevalence which may warrant further investigation.
There are several reasons why we may not have observed the same
associations. First, we used SPT results and hay fever rather than blood
IgE levels and hay fever, to determine atopic sensitisation. However
given the strong association between SPT and IgE28this would be unlikely to explain the differences in results between
these studies. Second, our cohort was younger (baseline at 43 years
followed-up to 53 years) than those in SALIA (baseline at 53 years
followed-up to 73 years of age), making this a different time in women’s
reproductive lives, and changes in sex hormone levels may help explain
the differences in results seen between these studies. Third, we
included both sexes in our main analyses, whereas the SALIA study
included only women. However, we did not observe increased risk in women
with higher ambient air pollution exposures. Finally, the sources of
ambient PM2.5 16 are different between
Australia (mainly from wood heaters, power stations and off-road
sources) and Germany (mainly on-road traffic) where the study was
conducted.6
Our findings suggest an association between PM2.5 and
aeroallergen sensitisation, agreeing with other
studies.29,30 In
a study with adult participants; living close to busy roads was
associated with a higher risk of sensitisation to
pollen.29 Furthermore, a previous cross-sectional
analysis using data from this cohort reported, in this low pollution
setting, that increased levels of ambient air pollution conferred an
increased risk of atopy.30 Of two studies that have
not observed an association between ambient air pollution and an
increased risk of allergic sensitisation, one study had a relatively
small sample size and low power.31 Another, in an
adult population, reported a cross sectional association with DMR and
NO2 and aeroallergen sensitisation, but did not assess
PM2.5.32
It has been proposed that air pollutants may lead to eczema and
sensitisation via inflammatory oxidative stress leading to skin barrier
dysfunction.3 Ambient air pollution may drive these
effects either through direct percutaneous absorption or indirectly
through inhalation and subsequent systemic
inflammation.3 These air pollutants produce reactive
oxygen species (ROS) and nitrogen species that lead to damage of
proteins, lipids, and DNA.33 Air pollutants can also
act as irritants and immunomodulators leading to elevated levels of
serum IgE.34 Specifically, PM2.5 may
activate the aryl hydrocarbon receptor to promote cell metabolism and
inflammation.34 Other proposed mechanisms are by
altering trans-epidermal water loss, increasing inflammatory signals and
modifying the skin pH and microbiome.35 Our results
support an effect of ambient air pollution on immune function, even in
this low ambient air pollution setting, with relatively higher exposure
levels being associated with eczematous skin symptoms in males and
overall increased aeroallergen sensitisation risk in the sample
population.
Our study has both strengths and limitations. Strengths include access
to a large population-based prospective cohort study with long follow-up
allowing for a 10 year assessment period, well-characterized definitions
of eczema with objective measures of SPT and land-use regression models.
While the questions and definitions used were well
validated,36 a limitation is the reliance on
self-reporting. Unfortunately, there were no data on the frequency or
severity of symptoms and the aero-allergen SPT data were only available
at follow-up, which may lead to some misclassification of atopy in the
eczema subgroups. It is possible that residual confounding could have
been an issue. As such, further replication of these findings is
required. Given the exploratory nature of these data with multiple
associations being assessed, we have attempted to interpret the pattern
of associations, rather than relying on any arbitrary p value threshold
to draw conclusions. Finally, as almost all the participants were
Caucasian and Anglo-Celtic, the findings may not be generalizable to
other ethnicities.