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.