Discussion
The prevalence of PFAS in Korean
children aged 6–10 years was 4.7%, and the mean age of onset was 6.74
years. Kiwi, tomato, and peach were the most common triggers of PFAS.
Food allergy, AD, and sensitization to foods in early childhood were
associated with the development of PFAS in schoolchildren. Sensitization
to inhalant allergens at 3 years did not increase the risk of school-age
PFAS. Therefore, sensitization to food antigens and food allergy in
early childhood was related to PFAS in schoolchildren, particularly in
those with AR. To the best of our knowledge, this is the first general
population-based cohort study that demonstrates the association between
allergic diseases in early childhood and PFAS.
Most studies on the prevalence of PFAS have focused on high-risk
patients who visited hospitals for treatment or suffered from allergic
diseases, recording a prevalence of 4.7% to more than 20% in children
and 13–58% in adults.12,21,22 In Korea, a
multicenter cross-sectional study reported a PFAS prevalence of 42.7%
in children with pollinosis.9 However, there is a
possibility that prevalence in high-risk populations is overestimated
compared with the general population. In addition, the diversity of risk
factors directly affected prevalence, so these results are difficult to
generalize or compare against other studies. Only two cross-sectional
studies were conducted to investigate PFAS in the general population
cohort. A Danish study has reported a PFAS prevalence of 16.7% in young
adults, which was lower than 20.5% in other European studies conducted
in adolescents and adults with AR, or 23.0% in children with risk
factors.13,15 A Japanese study in the general
population also reported that 11.7% of adolescents had PFAS, and 22.9%
with pollen allergy had PFAS.14 Thus, the lower
prevalence of PFAS (4.7%) in this study likely results from the general
population and younger age of the participants compared with other
studies.
Most studies on PFAS were cross-sectional observational studies
intending to identify an association between PFAS and other risk
factors. In an Italian study on pollen-induced AR, longer AR duration
was associated with PFAS.21 Additionally, the
prevalence of asthma was significantly higher in patients with
birch-sensitization and PFAS than in those without PFAS. There was also
no significant difference in the prevalence of other allergic diseases
such as AD rhinoconjunctivitis according to the presence of
PFAS.16 These studies analyzed the comorbidities at
the time of investigation; therefore, it is difficult to determine the
relationship between PFAS and sensitization or allergic diseases in
early childhood. In this study, children were followed-up longitudinally
from birth so that the association between the development of PFAS and
allergic conditions could be thoroughly assessed. There were significant
differences in AD, food sensitization, and food allergy in early
childhood between the PFAS and non-PFAS groups. In particular, food
sensitization and food allergy in early schoolchildren with AR remained
significant risk factors for PFAS. These findings suggest that AR
children with food allergy in early childhood are more susceptible to
PFAS than AR children without food allergy history. Therefore,
monitoring PFAS symptoms is necessary in children with a history of food
allergy or sensitization in early childhood.
Class II food allergens are the primary concern in children with PFAS.
The food allergen itself is not typically the primary sensitizer, as
observed in class I food allergens.12 In general,
class I food allergens are stable in heat and during
digestion,12 allowing them to retain their
immunoglobulin E (IgE)-binding conformation, potentially leading to an
increased ability to sensitize and a higher incidence of severe systemic
reactions.12 In this study, sensitization to class I
food allergens in early childhood and a history of food allergy were
proven risk factors for school-age PFAS. Additionally, despite the
varying characteristics of food antigens and sensitization pathways,
mucosal immunity defects may be associated with food allergy and PFAS.
Further research is needed to elucidate the mechanisms of PFAS.
The age at which food reactions
begin, including PFAS, has been reported to be 25 years in a single
study conducted on adults using questionnaires in the
UK.23 In this study, the mean age of onset of PFAS was
6.74 years (3–10 years). Therefore, monitoring for PFAS is necessary in
children aged under 6 years.
Kiwi, peach, tomato, and watermelon were the common causative foods in
this study, which are associated with birch antigens (Bet V1 and Bet
V2), the most common cause of pollen sensitization.24Another Korean study revealed that apple, peach, and kiwi were common
causative foods for children aged 2–6 years with AD and birch
sensitization.25 In Western countries, 60–90% of
patients with pollinosis exhibit PFAS symptoms;26,27however, they were observed in only 41.7% of patients with pollinosis
in a Korean multicenter study,9 and 19.1% of children
in this study. In Western countries, pollinosis from Poaceae, such as
birch and timothy grass, and Asteraceae, such as ragweed and mugwort,
are common given their cross-reactions with many foods. The incidence of
PFAS varies depending on the environment, plant cultivation
circumstances, ethnic groups, and regional
differences,7 suggesting the difference in prevalence
between Korea and Western countries.
This study had several limitations. First, the number of children with
PFAS in this general population-based cohort study was relatively small
compared with other high-risk population studies. Second, PFAS was
diagnosed using a questionnaire and physician’s diagnosis, and a food
provocation test was not performed. However, PFAS was diagnosed through
reference of detailed medical history noted by pediatric allergists.
Despite these limitations, this study is the first to investigate PFAS
prevalence in young children in the general population. Moreover, as a
birth cohort study, longitudinal analysis was possible based on
acquisition of various clinical data before the development of PFAS.
Novel associations between PFAS and FA or food sensitization have been
revealed, and further studies are warranted to expand on this new
perspective on PFAS.
In conclusion, PFAS occurs in 4.73% of children aged 6–10 years, and
the most common causative food is fruit, especially kiwi. The risk of
developing PFAS in schoolchildren increased in the presence of food
allergy or food sensitization in early childhood. Further studies to
investigate the association of food allergy in early childhood with the
development of PFAS is required.