4 | Discussion
Skin damage attributed to PM primarily results from oxidative stress and
subsequent inflammation.21 Upon exposure to PM with
polycyclic aromatic hydrocarbons (PAHs), human keratinocytes increase
production of reactive oxygen species (ROS).22PM2.5 can also stimulated IL-6 production in human
keratinocytes via ROS production and oxidative
stress.23 In addition, keratinocytes exposed to PM can
upregulate cytokine expression, indirectly leading to diminished
expression of skin barrier proteins and skin barrier dysfunction.
PM2.5 exposure can induce the expression of tumor
necrosis factor (TNF)- α in human keratinocytes, which subsequently
suppresses the expression of filaggrin (FLG) and loricrin (LOR) through
an aryl hydrocarbon receptor (AhR)-dependent
pathway.24 PAHs as components of PM are known to
penetrate the stratum corneum effectively due to their lipophilic
properties, initiating skin inflammation through binding to the AhR, a
ligand-dependent transcription factor.25 PM can also
triggers the release of alarmins such as thymic stromal lymphopoietin
(TSLP) from keratinocytes, which can then promotes Th2-type immune
response and reduce FLG expression.26 These findings
indicate that PM can alter the molecular structure and function of the
epidermal barrier, thereby exacerbating AD.
The objective of this investigation was to elucidate the impact of
chronic exposure to PM on the progression of AD in infants. A
methodological challenge was how to accurately quantify individual
patient exposure to ambient PM. To address this, we utilized an advanced
exposure assessment approach, integrating data from AQMS with the CMAQ
modeling outputs and updating the relocation of patients’ residences for
3 years. This fusion technique of exposure assessment is more
advantageous than AQMS only in urban environments with spatial
variability and limited monitoring resources, making our results more
reliable.
In this study, a significant association between AD persistence and
prolonged exposure to PM in subjects with moderate or severe AD was
observed. Conversely, this association was not evident in the mild AD
group. This disparity might be attributed to increased susceptibility of
the skin with moderate or severe AD to PM penetration and subsequent
inflammatory response, as compared to the skin with mild AD.
Pollen sensitization is associated with PM exposure,27and is increased in patients with AD.28 Exposure to
pollen, in turn, leads to an exacerbation of AD
symptoms.29 Indeed, bioaerosols from pollen adhere to
PM and facilitate penetration into the human body, potentially
exacerbating allergic responses.30 Consequently, the
identification and mitigation of risk factors contributing to pollen
sensitization in infants with AD are important for favorable disease
prognosis. This study demonstrated the effect of long-term exposure to
PM on pollen sensitization among infants with moderate or severe AD. Our
finding supports the implementation of proactive strategies aimed at
reducing PM exposure in infants with AD to modify the disease course.
In contrast to pollen exposed outdoors, the present study demonstrated
that sensitization to HDM, an indoor allergen, did not have an
association with PM exposure. This result is not consistent with a
previous report showing that epicutaneous sensitization to various
allergens including HDM could occur.8 Our observation
might be attributed to the estimation of long-term PM exposure based on
ambient PM concentrations. However, upon examining the relationship
between PM exposure and HDM sensitization in patients with severe AD,
the P value was close to 0.05. This suggests that an increase in
the sample size of moderate or severe AD patients might yield
statistically significant results.
One of the limitations of this study was that chronic exposure to PM was
estimated from birth to age of 3 years rather than commencing from AD
onset to age 3. The reason was that the exact time of AD onset could not
be identified. Rather, pathophysiological changes of AD might have begun
immediately after birth. Another limitation was that we did not include
indoor environments in exposure assessments, including indoor PM,
temperature, relative humidity, volatile organic compounds, and so on.
However, it is impossible to monitor indoor environmental factors at
each patient’s residence for a long period covering over 3 years. Since
indoor PM originates partly from the outside, assessing indoor PM
exposure was not completely excluded. Selection bias was also possible
in the present study.
In conclusion, chronic exposure to ambient PM10 in
infants with AD might affect the disease course by decreasing remission
and increasing sensitization to pollen at age 3. In infants with AD,
efforts are needed to reduce short-term and long-term exposure to PM in
early life to prevent acute exacerbation and improve disease
prognosis.