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.