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Particulate matter (PM) exposure during pregnancy increases the risk of developing asthma in children. However, the placental mechanisms have yet to be elucidated. This study aims to evaluate the mechanisms associated with PM exposure during pregnancy and asthma susceptibility via placental epigenetic dysregulation. We analyzed data from two independent Korean birth cohorts (COCOA, 684 children; PSKC, 818 children). Physician-diagnosed current asthma and bronchial hyperresponsiveness (BHR) via methacholine challenge tests were evaluated at age seven. We estimated PM exposure with a diameter <10 μm (PM 10 ) during pregnancy using land-use regression models. We performed genome-wide methylation profiling in the placenta of 40 samples in the COCOA study and analyzed the gene expression levels. High PM 10 exposure during pregnancy increased the risk of developing current asthma and BHR in the COCOA study (aOR 2.36, 95% CI 1.06-5.22; aOR 2.14, 95% CI 1.40-3.27, respectively) and current asthma in the PSKC (aOR 2.62, 95% CI 1.35-5.09). The genes involved in neuronal differentiation and proliferation and Notch signaling pathways were significantly hypermethylated in children with high PM 10 -exposed asthma. The methylation and expression levels of eight genes (PAX6, REST, OLIG2, GLI1, ZBTB7A, NOTCH4, NOTCH1, and NOTCH3) in these pathways correlated with clinical parameters. This may effectively predict PM-related asthma through a prediction model using degrees of gene-based or CpG-based methylation (AUC = 0.96 and 0.93, respectively). PM 10 exposure during pregnancy impacts asthma development in offspring via placental DNA hypermethylation via neuronal differentiation and proliferation and Notch signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Environmental pollutants, particularly volatile organic compounds (VOCs), are associated with various diseases, including atopic dermatitis (AD). However, despite numerous studies on AD, there is a lack of research on the impact of various environmental exposures on mothers and infants. This study, therefore, investigated the effects of maternal exposure to specific VOCs (toluene, xylene, and benzene) on the expression of AD-related genes in mothers and their infants. RNA expression levels and DNA methylation patterns were analyzed to examine the correlation between environmental exposures and AD. A multi-omics approach integrating gene expression and methylation data was additionally employed to gain a broader understanding of the genetic impact of VOC exposure. Network analysis revealed significant changes in gene expression associated with AD. For example, maternal exposure to toluene resulted in the upregulation of AQP10, which is linked to keratinocyte dysfunction, and in infants, the genes IL31RA and CCL20 were notably affected, both of which play critical roles in immune response and skin barrier function. In mothers exposed to xylene, the histamine receptor gene HRH1 was identified as a key player in influencing AD through its role in skin barrier recovery, while infants exhibited consistent network responses with upregulation of IL31RA and downregulation of TIGIT, reflecting a shared response across different xylene isomers. Interestingly, infants exposed to xylene isomers displayed nearly identical gene network patterns, suggesting developmental resistance to diverse environmental factors. No significant gene changes were identified in the benzene-exposed group. These findings suggest that exposure to specific VOCs may have different effects on gene expression related to AD, highlighting the complexity of how environmental factors contribute to disease development.

Background: An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD., Objective: We sought to determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms on the basis of multiomics analyses., Methods: Latent class trajectory analysis was used to classify AD phenotypes in 2247 children who were followed until age 9 years from the COhort for Childhood Origin of Asthma and allergic diseases birth cohort study. Multiomics analyses (microbiome, metabolites, and gut epithelial cell transcriptome) using stool samples collected at age 6 months were performed to elucidate the underlying mechanisms of AD phenotypes., Results: Five AD phenotypes were classified as follows: never/infrequent, early-onset transient, intermediate transient, late-onset, and early-onset persistent. Early-onset persistent and late-onset phenotypes showed increased risks of food allergy and wheezing treatment ever, with bronchial hyperresponsiveness evident only in the early-onset persistent phenotype. Multiomics analyses revealed a significantly lower relative abundance of Ruminococcus gnavus and a decreased gut acetate level in the early-onset persistent phenotype, with potential associations to ACSS2, Janus kinase-signal transducer and activator of transcription signaling, and systemic T H 2 inflammation. The early-onset transient phenotype was associated with adenosine monophosphate-activated protein kinase (AMPK) and/or chemokine signaling regulation, whereas the late-onset phenotype was linked with IL-17 and barrier dysfunction., Conclusions: Multiomics profiling in early life may offer insights into different mechanisms underlying AD phenotypes in children., Competing Interests: Disclosure statement This study was funded by the Research Program of the Korea National Institute of Health, South Korea (grant nos. 2008-E33030-00, 2009-E33033-00, 2011-E33021-00, 2012-E33012-00, 2013-E51003-00, 2014-E51004-00, 2014-E51004-01, 2014-E51004-02, 2017-E67002-00, 2017-E67002-01, 2017-E67002-02, 2020E670200, 2020E670201, and 2020E670202) and by the National Research Foundation funded by the Korean government (Ministry of Science and Information and communication Technology, MSIT) (grant nos. 2017M3A9F3043834 and 2021R1A2C2095664). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: The combination therapy of leukotriene receptor antagonists and antihistamines may alleviate allergic rhinitis (AR) symptoms better than monotherapy. This study aimed to investigate the safety and efficacy of Monterizine ® , a fixed-dose combination of montelukast and levocetirizine, compared to montelukast monotherapy in pediatric patients with AR., Methods: One hundred seventy-six children aged 6 to 14 years with perennial AR symptoms were recruited. One hundred forty-seven subjects were randomized into 1 of 2 groups: the mont+levo group (fixed-dose combination of montelukast [5 mg] + levocetirizine [5 mg]) or the mont group (montelukast single agent [5 mg]). Study subjects took the treatment every evening for 4 weeks and recorded their daytime nasal symptom score (DNSS) and nighttime nasal symptom score (NNSS) in a diary every day. Adverse events (AEs) were also recorded, and patients were surveyed as to their overall satisfaction with the therapeutic product they received., Results: When DNSS and NNSS were assessed individually, daytime nasal congestion symptom scores decreased more in the mont+levo group during the 4-week treatment period than in the mont group ( P = 0.0341). The daytime rhinorrhea symptom scores also decreased more in the mont+levo group ( P = 0.0469). The nighttime nasal congestion score (severity when awake) decreased more in the mont+levo group than in the mont group ( P = 0.0381). Study subjects in the mont+levo group experienced a greater improvement in quality of life than subjects in the mont group ( P < 0.0001)., Conclusions: The combination therapy of montelukast and levocetirizine was more effective in reducing both daytime nasal symptoms (nasal congestion and rhinorrhea) and nighttime nasal symptoms (severity of nasal congestion when awake). With fewer AEs and higher overall satisfaction, combination therapy is recommended for pediatric patients with perennial AR., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Wheat allergy is one of the most prevalent allergens in Korea, decreasing quality of life and causing nutritional repercussions., Objective: We aimed to investigate the efficacy and safety of the home-based wheat oral immunotherapy (OIT) using wheat noodles in children with a wheat allergy., Methods: We conducted a retrospective study involving 72 children aged 3 to 17 years diagnosed with a wheat allergy. Patients received wheat OIT using wheat noodles (n = 50) and were compared with a historical control group (n = 22). Baseline characteristics, adverse events, and immunological changes were assessed. Predictors of successful desensitization were identified using logistic regression analysis., Results: Among 50 patients completing the up-dosing phase, 82.0% achieved desensitization to 2,400 mg of wheat protein, compared to 4.5% in the control group (p < 0.001). During the up-dosing period, the median number of adverse reactions per person was 2, and anaphylaxis occurred in 30.0% (15/50). However, there were no life-threatening adverse events. In multivariable analysis, the presence of asthma (adjusted odds ratio [aOR], 8.88; 95% confidence interval [CI], 1.10-71.97; p = 0.041) and a higher ratio of specific IgE (sIgE) to ω-5-gliadin and total IgE (aOR 19.09, 95%CI 1.21-300.80, p = 0.036) were significantly associated with treatment outcomes of wheat OIT., Conclusion: Our study showed the safety and efficacy of home-based wheat OIT using boiled noodles in Korean children with wheat allergies. Careful consideration is warranted for patients with elevated baseline sIgE to ω-5-gliadin to total IgE ratio and a history of asthma.

The pathogenesis of atopic dermatitis (AD) is multifactorial, involving a dynamic interplay between genetic susceptibility, skin-barrier dysfunction, microbiome alterations, and immune dysregulation, whereas food allergy (FA) arises from the interplay of transcutaneous sensitization to food allergens and failure in the induction of oral tolerance. Skin epicutaneous sensitization is commonly involved in the development of AD and FA. Although clinical trials have been conducted to prevent AD or FA by applications of emollients on the skin after birth, the results are not consistent. For more effective preventive strategies, reliable biomarkers are required to identify high-risk individuals. Skin tape stripping (STS) is a non-invasive technique for identifying these biomarkers in the skin. By analyzing the stratum corneum collected via STS, researchers can gain molecular or cellular insights into the early pathogenesis and potential progression of AD and FA. This review aims to elucidate the critical aspects of AD and FA, underlying their pathogenesis, early manifestations, and STS's potential as a tool for identifying predictive non-invasive biomarkers in infants prior to onset of clinical disease., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children's health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer's, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.

Severe atopic dermatitis (AD) is not a localized cutaneous disease, but a systemic disease that often accompanies comorbidities. In this nationwide population-based study, we aimed to analyze the prevalence of severe AD and chronic systemic diseases in Koreans aged ≤ 20 years between 2011 and 2019 using the data from the Korean Health Insurance Review and Assessment Service. Total AD and severe AD were defined according to the International Classification of Diseases-10 code L20. In children aged 6-20 years, the prevalence of severe AD significantly increased from 0.02% in 2011 to 0.04% in 2019 ( P for trend < 0.001), with the ratio of severe AD to total AD increasing from 0.76% in 2011 to 1.10% in 2019 ( P for trend < 0.001). The prevalence rates of severe AD significantly increased between 2011 and 2019 in children aged 6-12 years ( P for trend < 0.05) and 13-18 years ( P for trend < 0.001). Severe AD was more frequently found in males than in females each year (all P < 0.001, from 2011 to 2019). During the period from 2011 to 2019, the prevalence rate of chronic systemic diseases was higher in subjects with severe AD than in those without AD ( P < 0.001) or with mild-to-moderate AD ( P < 0.001). In conclusion, our results suggest that the prevalence of severe AD is increasing in Korean children and adolescents and is higher in males and older age groups. Moreover, severe AD is associated with chronic systemic diseases. Therefore, more attention should be paid to managing severe AD., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Allergic rhinitis (AR) phenotypes in childhood are unclear., Objectives: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics., Methods: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype., Results: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response., Conclusions: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The epidemiology and management of anaphylaxis are not well-reported in Asia., Methods: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared., Results: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao., Conclusions: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Food allergy (FA) often occurs in early childhood with and without atopic dermatitis (AD). FA can be severe and even fatal. For primary prevention, it is important to find early biomarkers to predict the future onset of FA before any clinical manifestations., Objective: Our aim was to find early predictors of future onset of FA in the stratum corneum (SC)., Methods: Skin tape strips were collected from the forearm of newborns (n = 129) at age 2 months, before any signs of clinical FA or AD. Children were clinically monitored until they reached age 2 years to confirm the presence or absence of FA and AD. Skin tape strips were subjected to lipidomic analyses by liquid chromatography-tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay., Results: Overall, 9 of 129 infants (7.0%) developed FA alone and 9 of 129 infants (7.0%) developed FA concomitantly with AD. In the stratum corneum of children with future FA and concomitant AD and FA, absolute amounts of unsaturated (N24:1)(C18-sphingosine)ceramide and (N26:1)(C18-sphingosine)ceramide and their relative percentages within the molecular group were increased compared with the amounts and percentages in healthy children, with P values ranging from less than .01 to less than .05 according to ANOVA. The children with future AD had normal levels of these molecules. IL-33 level was upregulated in those infants with future FA but not in those with future AD, whereas thymic stromal lymphopoietin was upregulated in those with future AD but not in those with future FA. Logistic regression analysis revealed strong FA predicting power for the combination of dysregulated lipids and cytokines, with an odds ratio reaching 101.4 (95% CI = 5.4-1910.6)., Conclusion: Noninvasive skin tape strip analysis at age 2 months can identify infants at risk of FA in the future., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined., Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks., Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p  < 0.01) and maltose ( p  < 0.05 and p  < 0.01). Sleep disturbance was improved only in the FOS group ( p  < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p  < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p  < 0.01)., Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD., Competing Interests: SSa, SP, and KR were employed by Samyang Corporation. JB are employed by BioEleven Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Kang, Sa, Park, Ryu, Lee, Park, Kwon, Kim, Kim, Shin, Jang, Kim, Bae, Ahn, Liu and Kim.)

Purpose: We aimed to investigate the mediating factors between maternal anxiety and the development of food allergy (FA) in children until 2 years from birth., Methods: In this longitudinal cohort of 122 mother-child dyads from pregnancy to 24 months of age, we regularly surveyed maternal psychological states, infant feeding data, and allergic symptoms and collected stool samples at 6 months of age for microbiome analysis. Considering the temporal order of data collection, we investigated serial mediating effects and indirect effects among maternal anxiety, dietary diversity (DD), gut microbial diversity, and FA using structural equation modeling., Results: Among the 122 infants, 15 (12.3%) were diagnosed with FA. Increased maternal anxiety between 3 and 6 months after delivery was associated with a lower DD score. Infants with low DD at 4 months showed low gut microbial richness, which was associated with FA development. When the infants were grouped into 4 subtypes, using consensus clustering of 13 gut bacteria significantly associated with maternal anxiety and DD, Prevotella , Eubacterium , Clostridiales and Lachnospiraceae were more abundant in the group with lower FA occurrence., Conclusions: Postpartum maternal anxiety, mediated by reduced DD and gut microbial diversity, may be a risk factor for the development of FA in infants during the first 2 years of life., Competing Interests: There are no financial or other issues that might lead to a conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.

We aimed to assess the validity and reliability of the Korean versions of the Food Allergy Quality of Life Questionnaire-Child Form (K-FAQLQ-CF) and the Food Allergy Quality of Life Questionnaire-Teenager Form (K-FAQLQ-TF). Patients aged 8-17 years with food allergy (FA) were enrolled and completed the Korean versions of the questionnaires, including the K-FAQLQ-CF, the Food Allergy Independent Measure-Child Form (K-FAIM-CF), and the Pediatric Quality of Life Inventory™ (K-PedsQL™ 4.0) for children and the K-FAQLQ-TF, the Food Allergy Independent Measure-Teenager Form (K-FAIM-TF), and the K-PedsQL™ 4.0 for adolescents. We enrolled 56 children and 23 adolescents in this study. The K-FAQLQ-CF showed a good internal consistency (Cronbach's α coefficient = 0.969) and an excellent test-retest reliability (intraclass correlation coefficient = 0.914, P = 0.011). There was a moderate correlation between the K-FAQLQ-CF and K-FAIM-CF scores (β = 0.736, P < 0.001), indicating construct validity. The K-FAQLQ-CF score was weakly associated with the K-PedsQL™ 4.0 score (β = -0.289, P = 0.031), verifying convergent and discriminant validities. The K-FAQLQ-TF also showed a good internal consistency (Cronbach's α coefficient = 0.966) and test-retest reliability (intraclass correlation coefficient = 0.974, P = 0.005). Construct validity was also established by a moderate correlation with the K-FAIM-TF (β = 0.699, P < 0.001). Our results suggest that the K-FAQLQ-CF and K-FAQLQ-TF are valid and reliable tools to evaluate the quality of life of children and adolescents with FA in Korea., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Oral immunotherapy (OIT) has been recommended to reduce parental burden related to strict allergen avoidance and induce desensitization and immune tolerance for patients with long-lasting allergies to hen's eggs (HE) or cow's milk (CM). OIT should be monitored by pediatric allergists specializing in OIT and oral food challenge tests to manage allergic reactions. Although a previous history of anaphylaxis or multiple food allergies is not a contraindication to OIT, it is contraindicated if the patient has uncontrolled asthma, a malignancy, active systemic autoimmune disorders, or diseases requiring treatment with beta-blockers. A variety of OIT protocols have been de veloped to ensure better outcomes and safe up-dosing, including adjunctive therapies with biologics. This review provides insight into the practical issues of various immunotherapy options for children with HE or CM allergies.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches-proteomics, transcriptomics, and metabolomics-we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Food allergy (FA) can have a profound effect on quality of life (QoL), stress, and anxiety in the family. We aimed to validate the Korean version of the Food Allergy Quality of Life-Parental Burden (FAQL-PB) and identify factors related to the parental psychosocial burden of caring for children with FAs., Methods: Parents of children aged between 6 months and 17 years with immunoglobulin E (IgE)-mediated FAs from the Pediatric Allergy Department of five university hospitals in Korea were enrolled in the study. Parents were asked to complete the FAQL-PB, Food Allergy Independent Measure-Parent Form (FAIM-PF), Child Health Questionnaire-Parents Form 28 (CHQ-PF28), Beck's Anxiety Inventory, Connor-Davidson Resilience Scale, and Patient Health Questionnaire-9 for depression. Statistical analyses included internal consistency, test-retest reliability, concurrent validity, discriminative validity, and logistic regression analyses., Results: A total of 190 parents were enrolled. Social activity limitation was the item with the highest FAQL-PB scores. The Cronbach's α for each item was higher than 0.8. The test-retest reliability was good (intra-class correlation coefficient, 0.716; 95% confidence interval [CI], 0.100-0.935). An increase in the FAQL-PB was significantly associated with an increase in the FAIM-PF (β = 0.765, P < 0.001) (concurrent validity). There was a positive correlation between parental burden, anxiety, and depression, while resilience was inversely correlated with parental burden (all P < 0.001). The total FAQL-PB score in parents of children who had experienced anaphylaxis was significantly higher than that in parents of children who did not experience it ( P = 0.008). When adjusting for age, sex, and underlying diseases, anaphylaxis (β = 9.32; 95% CI, 2.97 to 15.68), cow's milk (CM) allergy (β = 8.24; 95% CI, 2.04 to 14.44), soybean allergy (β = 13.91; 95% CI, 1.62 to 26.20), higher anxiety (β = 1.05; 95% CI, 0.07 to 1.41), higher depression (β = 2.15; 95% CI, 1.61 to 2.69), and lower resilience (β = -0.42; 95% CI, -0.61 to -0.2) were significantly associated with greater parental burden in children with IgE-mediated FAs., Conclusion: FAQL-PB is a reliable and valid tool for use in Korea. Anaphylaxis, CM or soybean allergies, more anxiety and depression symptoms, and lower resilience are associated with poorer QoL in parents of children with FAs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Objective: The identification of allergic rhinitis (AR) in early life is important for the target of intervention. AR is caused by various environmental factors, including house dust mites. We investigated the relationship between the Dermatophagoides farinae (Der f)-IgE and eosinophil in mothers with AR at delivery and the eosinophil levels and AR incidence in children., Methods: The study participants were 983 mother-child pairs from the COhort for Childhood Origin of Asthma and Allergic Diseases. AR was diagnosed by a doctor at delivery in mother and at 3 years of age in offspring. The association between eosinophil level and AR was assessed using logistic regression analysis., Results: The Der f-IgE level in mother having AR at delivery was associated with the mother's eosinophil level, and the mother's eosinophil level was associated with the child's eosinophil level both at age 1 and 3. The risk of AR at age 3 in children was increased according to increased eosinophil levels in mothers at delivery and in children both aged 1 and 3 years (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 2.57 [1.14-5.78], 2.28 [1.02-5.13], respectively). The risk of childhood AR at the age of 3 is increased when both mothers and children have high eosiniophils (aOR and 95% CI: 2.62 [1.01-6.79], 1.37 [0.98-1.91])., Conclusions: Der f-IgE in mothers at delivery was related to eosinophil levels in mothers with AR and higher level of eosinophils in both mother and children was associated with the increased risk of AR incidence at the first 3 years of life of children., (© 2023. The Author(s).)

Background: Prenatal antibiotic exposure and delivery mode may affect the gut microbiome in early life and influence the development of childhood asthma, but the combined effect of these 2 factors is unknown., Objective: To identify the individual and combined effects of prenatal antibiotic exposure and delivery mode on the development of asthma in children and the potential mechanisms underlying these associations., Methods: A total of 789 children from the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study were enrolled. Asthma was defined as a physician-confirmed diagnosis with asthma symptoms in the previous 12 months at age 7 years. Information on prenatal antibiotic exposure was obtained by mothers using a questionnaire. Logistic regression analysis was used. Gut microbiota analysis using 16S rRNA gene sequencing of fecal specimens obtained at 6 months was undertaken for 207 infants., Results: Prenatal antibiotic exposure and cesarean section delivery (adjusted odds ratio [aOR], 95% confidence interval [CI], 5.70 [1.25-22.81] and 1.57 [1.36-6.14], respectively) were associated with childhood asthma, especially synergistically when compared with the vaginal delivery-prenatal antibiotic exposure reference group (aOR, 7.35; 95% CI, 3.46-39.61; Interaction P = .03). Prenatal antibiotic exposure was associated with childhood asthma with aORs 21.79 and 27.03 for 1 and 2 or more exposures, respectively. Considerable small-airway dysfunction (R5-R20 in impulse oscillometry) was observed with prenatal antibiotic exposure and cesarean section delivery, compared with those with spontaneous delivery without prenatal antibiotic exposure. There was no significant difference in the diversity of gut microbiota among the 4 groups. However, the relative abundance of Clostridium was significantly increased in infants with prenatal antibiotic exposure and delivered by means of cesarean section., Conclusion: Prenatal antibiotic exposure and delivery mode might modulate asthma development in children and small-airway dysfunction, potentially through early-life gut microbiota alterations., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction., Methods: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures., Results: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N-16:0 NS-CER], sphingomyelins [16:0-18:0 SM]), and lysophosphatidylcholines [16:0-18:0 LPC], but significantly reduced the proportion of corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA-colonized AD skin. S. aureus indirectly through interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin., Conclusion: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus-induced IL-1β, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Atopic dermatitis (AD) commonly occurs in children and can progress into severe phenotypes or atopic march, causing significant impairment in quality of life. It is important to find early biomarkers of future onset of AD before any clinical manifestations., Objective: We sought to find early predictors of future onset of AD in skin stratum corneum (SC)., Methods: Skin tape strips were collected from the forearm of newborns (n = 111) with and without family history of atopic diseases at the age of 2 months before any signs of clinical AD. Children were clinically monitored until they reached age 2 years to ensure the presence or absence of AD. Skin tape strips were subjected to lipidomic analyses by the liquid chromatography electrospray ionization tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay., Results: Overall, 22 of 74 (29.7%) and 5 of 37 (13.5%) infants developed AD in the risk group and the control group, respectively. In the SC of future AD children, protein-bound ceramides were decreased (P < .001), whereas unsaturated sphingomyelin species (P < .0001) and "short-chain" nonhydroxy fatty acid sphingosine and alpha-hydroxy fatty acid sphingosine ceramides were elevated (P < .01 and .05, respectively) as compared with healthy children. Thymic stromal lymphopoietin and IL-13 levels were increased in the SC of future AD subjects (by 74.5% and 78.3%, P = .0022 and P < .0001, respectively). Multivariable logistic regression analysis revealed strong AD predicting power of the combination of family history, type 2 cytokines, and dysregulated lipids, with an odds ratio reaching 54.0 (95% CI, 9.2-317.5)., Conclusions: Noninvasive skin tape strip analysis at age 2 months can identify asymptomatic children at risk of future AD development with a high probability., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to investigate epidermal lipid profiles and their association with skin microbiome compositions in children with atopic dermatitis (AD)., Methods: Specimens were obtained by skin tape stripping from 27 children with AD and 18 healthy subjects matched for age and sex. Proteins and lipids of stratum corneum samples from nonlesional and lesional skin of AD patients and normal subjects were quantified by liquid chromatography tandem mass spectrometry. Skin microbiome profiles were analyzed using bacterial 16S rRNA sequencing., Results: Ceramides with nonhydroxy fatty acids (FAs) and C18 sphingosine as their sphingoid base (C18-NS-CERs) N-acylated with C16, C18 and C22 FAs, sphingomyelin (SM) N-acylated with C18 FAs, and lysophosphatidylcholine (LPC) with C16 FAs were increased in AD lesional skin compared to those in AD nonlesional skin and that of control subjects (all P < 0.01). SMs N-acylated with C16 FAs were increased in AD lesional skin compared to control subjects ( P < 0.05). The ratio of NS-CERs with long-chain fatty acids (LCFAs) to short-chain fatty acids (SCFAs) (C24-32:C14-22), the ratio of LPC with LCFAs to SCFAs (C24-30:C16-22) as well as the ratio of total esterified omega-hydroxy ceramides to total NS-CERs were negatively correlated with transepidermal water loss (rho coefficients = -0.738, -0.528, and -0.489, respectively; all P < 0.001). The proportions of Firmicutes and Staphylococcus were positively correlated to SCFAs including NS ceramides (C14-22), SMs (C17-18), and LPCs (C16), while the proportions of Actinobacteria, Proteobacteria, Bacteroidetes, Corynebacterium, Enhydrobacteria , and Micrococcus were negatively correlated to these SCFAs., Conclusions: Our results suggest that pediatric AD skin shows aberrant lipid profiles, and these alterations are associated with skin microbial dysbiosis and cutaneous barrier dysfunction., Competing Interests: Dr. Leung has consulted for Regeneron, Sanofi, Novartis and Genzyme. Dr. Berdyshev has research contracts from LEO Pharmaceutical and Sanofi., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: This study aimed to evaluate the reliability and validity of the Korean version of the Food Allergy Quality of Life Questionnaire-Parent Form (K-FAQLQ-PF) and to identify clinical characteristics related to low quality of life (QoL) in Korean children with food allergy (FA)., Methods: Parents of 0-12-year-old patients with FA were enrolled. The English version of FAQLQ-PF was translated into Korean. Construct validation was confirmed by the Food Allergy Independent Measure-Parent Form (FAIM-PF) and the Child Health Questionnaire Parent Form 28 (CHQ-PF28). Logistic regression analyses were used to evaluate associations between potential risk factors and QoL outcomes., Results: A total of 182 patients with a median age of 5.0 years were enrolled in the study. Cronbach's α coefficient values indicating internal consistency were higher than 0.8. Intraclass correlation coefficient values for test-retest reliability were good for all age groups ( r > 0.6). Total K-FAQLQ-PF scores were positively correlated with the FAIM-PF ( r = 0.56, P < 0.05) and were negatively correlated with the parental impact-emotional domain in the CHQ-PF28 ( r = -0.44, P < 0.05). In multivariable logistic regression analysis, low QoL was significantly associated with female sex (adjusted odds ratio [aOR], 2.07; 95% confidence interval [CI], 1.03-4.18), age ≥ 5 years (aOR, 2.84; 95% CI, 1.31-6.16), FA diagnosis before the age of 3 years (aOR, 3.96; 95% CI, 1.13-13.93), the presence of atopic dermatitis (aOR, 2.21; 95% CI, 1.07-4.57), and residence in non-metropolitan areas (aOR, 3.44; 95% CI, 1.73-6.85)., Conclusions: According to parental perceptions, the K-FAQLQ-PF is a valid and reliable tool to assess psychosocial QoL in Korean children with FAs. Age, sex, residential area, and comorbid AD can affect the QoL of pediatric patients with FA., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a wide spectrum of clinical phenotype. However, specific description of phenotypes of AD depending on the comorbidities in early childhood is lacking. This study aimed to investigate whether the AD phenotype in early childhood is related to childhood asthma and to elucidate the mechanisms involved., Methods: Data on the first 3 years of life were collected prospectively from 1,699 children in the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). We applied an unsupervised latent class analysis to the following five factors: food sensitization, inhalant sensitization, food allergy (FA), AD, and recurrent wheezing. The risks of developing FA, AD, allergic rhinitis (AR), and asthma in children aged 5-7 years were evaluated. Colonocyte transcriptome and ingenuity pathway analysis were performed., Results: Four phenotypes were identified; no allergic diseases (78.4%), AD without sensitization (16.4%), FA with AD (2.9%), and AD with sensitization (7.8%). The FA with AD had the highest risk for FA, AR, and asthma and the highest cord blood immunoglobulin E (IgE) levels. In AD without sensitization and with sensitization, scoring of AD (SCORAD) in early childhood was higher than in FA with AD. Canonical pathway analysis with the colonocyte transcriptome revealed that the key pathway in FA with AD was 'Wnt/β-catenin Signaling.' The relative abundance of Wnt6 mRNA was positively correlated with food-specific IgE levels at 1 and 3 years., Conclusions: When FA is present in various phenotypes of AD at early life, regardless of severity of eczema, it may be associated with gut Wnt signaling and later development of asthma., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: Anaphylaxis is a severe allergic reaction that is potentially life-threatening, but post-traumatic stress symptoms (PTSS) in the caregivers of children with anaphylaxis have not been evaluated. This study aimed to investigate the psychological burden on mothers of children with recent anaphylaxis., Methods: A total of 188 children with recent anaphylaxis was recruited from 13 hospitals in Korea. Validated questionnaires, including the Korean versions of the Beck Anxiety Inventory (K-BAI), the Beck Depression Inventory (K-BDI), and the Impact of Event Scale Revised-Korean version (IES-R-K), were used to evaluate maternal anxiety, depression, and PTSS., Results: The median ages of children and their mothers were 4 and 36 years, respectively. PTSS (IES-R-K ≥ 25) were identified in 56.9% of mothers, and 57.9% of them showed severe PTSS. The proportions of mothers who had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17) were 18.6% and 33.0%, respectively. Multivariable logistic regression analysis indicated that the patient's history of asthma (adjusted odds ratio [aOR], 5.46; 95% CI, 1.17-25.59) and the presence of central nervous symptoms (aOR, 3.27; 95% CI, 1.07-9.96) were associated with PTSS. Age of 2 or older (aOR, 2.87; 95% CI, 1.10-7.52) and eggs, milk, or wheat as the cause of anaphylaxis (aOR, 2.87; 95% CI, 1.10-7.52) increased the risk of severe PTSS., Conclusions: The rate of PTSS among mothers of children with recent anaphylaxis was high at 56.9%. Clinicians who care for pediatric anaphylaxis patients should be aware of the psychological burden on their caregivers., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, is rare among non-Caucasians. We aimed to identify the clinical features and CFTR mutations in Korean children., Methods: We included 18 pediatric patients with CF diagnosed using sweat chloride test or genetic analysis for 30 years. HEK293 cells were transfected with wild-type CFTR , ΔF508- CFTR , and L441P- CFTR mutant plasmids for 24 hours and treated with CFTR correctors (VX809 and VX661)., Results: The median age at diagnosis was 9.2 years. Eleven patients had growth retardation, and 6 had a respiratory failure at diagnosis. Genetic analysis was used for all patients, while sweat testing was for 8 patients. At diagnosis, the median z scores of forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, and forced expiratory flow at 25%-75% of forced vital capacity were -3.61 (-5.78, 1.78), -3.38 (-4.40, -0.60), and -4.45 (-5.78, 0.54), respectively. Two patients were treated with dornase alfa and only one with CFTR modulator. Patients were followed up for 3.7 years as a median. Four patients died at 10.6 years, with 4.2 years of post-diagnosis survival. The most common mutation was exon 16-17b deletion (19.4%). Among 11 single nucleotide variants, c.1322T>C (p.Leu441Pro, L441P) was detected in 4 patients. In the functional assay, L441P-CFTR correction was well restored by CFTR correctors compared with ΔF508., Conclusions: CF is extremely rare in Korean children and is caused by different mutations from those commonly observed in Caucasians. Early diagnosis and treatment availability may improve outcomes. CFTR modulators may be effective for Asian patients with rare CFTR mutations, c.1322T>C (p.Leu441Pro)., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: The beneficial effects of a combination therapy using Bifidobacterium longum and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated., Methods: Gene expressions of interleukin (IL)-4 and IL-13 from peripheral blood mononuclear cells and fecal abundance of B . longum from 12-month-old infants were evaluated. Human primary epidermal keratinocytes (HEKs) and hairless mice were treated with B. longum , GOS, B. longum -derived extracellular vesicles (BLEVs), dinitrochlorobenzene (DNCB), or a synbiotic mixture of B . longum and GOS. Expression of epidermal barrier proteins and cytokines as well as serum immunoglobulin E (IgE) levels were analyzed in HEKs and mice. Dermatitis scores, transepidermal water loss (TEWL), epidermal thickness, and fecal B. longum abundance were evaluated in mice., Results: Fecal abundance of B . longum was negatively correlated with blood IL-13 expression in infants. B. longum or BLEVs increased expression of filaggrin ( FLG ) and loricrin ( LOR ) in HEKs. B . longum increased the efficacy of GOS to upregulate FLG and LOR expressions in HEKs. Oral administration of GOS increased fecal abundance of B . longum in mice. Oral administration of B . longum attenuated DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, and deficiency of epidermal barrier proteins. Moreover, the combination of B. longum and GOS showed greater effects to improve DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, serum IgE levels, IL-4 over-expression, and the deficiency of epidermal barrier proteins than the administration of B. longum alone., Conclusions: B. longum and GOS improve DNCB-induced skin barrier dysfunction and AD-like skin., Competing Interests: Youngbae Noh, Sangjong Kim, and Phyrim Lee are employed by Lotte R&D Center. The other authors declare that there are no potential conflicts of interests with respect to the authorship and/or publication of this article., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose of Review: Endotypes are clinically relevant phenotypes that can be explained by molecular mechanisms, and are defined to predict the development, progression, prognosis and responses to treatment on the individual level. This review summarizes atopic dermatitis phenotypes, endotypes and their potential application for personalized medicine., Recent Findings: Atopic dermatitis can be classified into several phenotypes according to disease courses that likely have common pathophysiology. The genotype is important to define endotypes, but the value of genotype alone remains somewhat limited in most atopic dermatitis patients. Recent studies have demonstrated that atopic dermatitis phenotypes according to ethnicity or age can be classified into endotypes based on the dominant immunologic markers, that is TH1/TH2/TH17/TH22 cells. Newly developed biologic agents targeting specific cytokines show therapeutic potential in a personalized medicine approach., Summary: Cytokine-based endotypes in different age groups or ethnic groups have contributed to expanding our understanding of atopic dermatitis. Recent biologics or small molecules can be used for more personalized treatment of atopic dermatitis. Further research using integrated multiomic analysis is needed to define a more detailed classification of endotypes and provide endotype-driven targeted therapies for personalized medicine., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The level of pollen in Korea has increased over recent decades. Research suggests that oral allergy syndrome (OAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of OAS in children aged 6-10 years from a general-population-based birth cohort., Methods: We analyzed 930 children from the cohort for childhood origin of asthma and allergic diseases (COCOA). Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for the general population of children aged 3 and 7 years., Results: Of the 930 eligible children, 44 (4.7%) aged 6-10 years were diagnosed with OAS. The mean age at onset was 6.74 years. OAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. OAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy until the age of 3 years increased the risk of OAS (aOR 2.971, 95% CI: 1.159-7.615)., Conclusion: Food allergy and food sensitization in early childhood were associated with OAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of OAS., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea., Methods: AD patients aged 6-18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient's allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2-5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups., Results: A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma ( P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group ( P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group ( P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD ( P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life ( P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group., Conclusion: This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

This study aimed to explore time trends in the prevalence of atopic dermatitis (AD) according to age in Korean children. We observed changes in the estimated annual prevalence of AD using data from the Korean National Health Insurance Service (NHIS) and Statistics Korea between 2003 and 2018. In each year, the highest prevalence was evident among children aged 12 to 23 months, and then the prevalence decreased with age. The annual prevalence of AD in Korean children under the age of 18 slightly increased from 4.0% in 2003 to 4.5% in 2018. During this period, the prevalence in children aged 6 to 18 years increased from 1.9% in 2003 to 3.1% in 2018, while that of infants aged less than 24 months substantially decreased. Among children who were born in 1991, 1997, 2000, 2003 and 2006, the slopes of decreasing trend lines over age 6 were similar. Comparing children born in 2009 and 2012 with those born before 2006, the more recent the birth year, the higher the prevalence of AD over age 6. In conclusion, time trends of the annual prevalence of AD in Korean children from 2003 through 2018 were different according to age group. These results suggest that AD development during infancy is decreasing whereas either a late-onset AD or early-onset, persistent phenotype is likely to increase. Different strategies according to age are required for more effective prevention and treatment of AD in Korean children., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Air pollution may influence prenatal maternal stress, but research evidence is scarce. Using data from a prospective cohort study conducted on pregnant women (n = 2153), we explored the association between air pollution and perceived stress, which was assessed using the 14-item Perceived Stress Scale (PSS), among pregnant women. Average exposures to particulate matter with an aerodynamic diameter of < 2.5 µm (PM 2.5 ) or < 10 µm (PM 10 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) for each trimester and the entire pregnancy were estimated at maternal residential addresses using land-use regression models. Linear regression models were applied to estimate associations between PSS scores and exposures to each air pollutant. After adjustment for potential confounders, interquartile-range (IQR) increases in whole pregnancy exposures to PM 2.5 , PM 10 , and O 3 in the third trimester were associated with 0.37 (95% confidence interval [CI] 0.01, 0.74), 0.54 (95% CI 0.11, 0.97), and 0.30 (95% CI 0.07, 0.54) point increases in prenatal PSS scores, respectively. Furthermore, these associations were more evident in women with child-bearing age and a lower level of education. Also, the association between PSS scores and PM 10 was stronger in the spring. Our findings support the relationship between air pollution and prenatal maternal stress., (© 2021. The Author(s).)

We aimed to investigate associations of dietary diversity (DD) with gut microbial diversity and the development of hen's egg allergy (HEA) in infants. We enrolled 68 infants in a high-risk group and 32 infants in a control group based on a family history of allergic diseases. All infants were followed from birth until 12 months of age. We collected infant feeding data, and DD was defined using 3 measures: the World Health Organization definition of minimum DD, food group diversity, and food allergen diversity. Gut microbiome profiles and expression of cytokines were evaluated by bacterial 16S rRNA sequencing and real-time reverse transcriptase-polymerase chain reaction. High DD scores at 3 and 4 months were associated with a lower risk of developing HEA in the high-risk group, but not in the control group. In the high-risk group, high DD scores at 3, 4, and 5 months of age were associated with an increase in Chao1 index at 6 months. We found that the gene expression of IL-4, IL-5, IL-6, and IL-8 were higher among infants who had lower DD scores compared to those who had higher DD scores in high-risk infants. Additionally, high-risk infants with a higher FAD score at 5 months of age showed a reduced gene expression of IL-13. Increasing DD within 6 months of life may increase gut microbial diversity, and thus reduce the development of HEA in infants with a family history of allergic diseases., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2022. The Korean Association of Immunologists.)

This study aimed to investigate the short-term effect of exposure to indoor fine particulate matter (PM 2.5 ) on atopic dermatitis (AD) symptoms in children. Sixty-four children (40 boys and 24 girls) with moderate-to-severe AD, aged under 18 years were enrolled in the study. They were followed up from February 2019 through November 2020. Exposure to indoor PM 2.5 in each household of the enrolled children and their AD symptoms were measured daily. The generalized linear mixed model was utilized for statistical analysis. Subdivision analysis was performed by stratifying the patients by age, sex, season, severity, the presence of family allergic diseases, sensitization, and indoor environment conditions including temperature and relative humidity. A total of 9,321 person-days of AD symptom data were collected. The average PM 2.5 concentration was 28.7 ± 24.3 µg/m 3 , with the highest value in winter (47.1 ± 29.6 µg/m 3 ). The overall effect of PM 2.5 on AD symptoms was not statistically significant. However, an increase of 10 µg/m 3 in indoor PM 2.5 concentration increased AD symptom scores by 16.5% (95% CI: 6.5, 27.5) in spring and12.6% (95% CI: 4.3, 21.5) in winter, 6.7% (95% CI: 2.3, 11.3) at indoor temperatures of <25.5 °C, and by 15.0% (95% CI: 3.5, 27.7) with no use of an air purifier. The harmful effect of PM 2.5 in boys, in children aged ≥6 years, and in children with inhalant allergen sensitization was significant, showing an increase in AD symptoms of 4.9% (95% CI: 1.4, 8.6), 12.0% (95% CI: 5.3, 19.1), and 7.0% (95% CI: 1.9, 12.3) per 10 µg/m 3 of PM 2.5 , respectively. Furthermore, children with inhalant allergen sensitization plus severe symptoms (SCORing Atopic Dermatitis, SCORAD ≥ 30.7, median value) showed more harmful effects from exposure to PM 2.5 (15.7% (95% CI: 4.5, 28.1) increase in AD symptom scores per 10 µg/m 3 of PM 2.5 increase). Indoor exposure to PM 2.5 exacerbated AD symptoms in children in spring, winter, and at indoor temperatures of < 25.5 °C. In particular, this harmful effect was prominent in children with inhalant allergen sensitization and severe symptoms. Minimizing exposure to indoor PM 2.5 is needed for the proper management of AD.

Background: The prevalence of atopic dermatitis (AD) is increasing worldwide. Prenatal particulate matter with an aerodynamic diameter <2.5 μm (PM 2.5 ) and maternal anxiety during pregnancy has been suggested as a potential causes of AD. This study investigated the effects of prenatal PM 2.5 and maternal anxiety on AD and identified the critical period of PM 2.5 exposure for AD in infants., Methods: This study included 802 children from the COCOA birth cohort study with follow-up data at 1 year of age. PM 2.5 was estimated by land-use regression models and prenatal anxiety was measured with a questionnaire. AD was diagnosed by doctor at 1 year of age. Logistic regression analysis and Bayesian distributed lag interaction models were applied., Results: Higher PM 2.5 during the first trimester of pregnancy, higher prenatal maternal anxiety, and male gender were associated with AD at 1 year of age (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 1.86 [1.08-3.19], 1.58 [1.01-2.47], and 1.54 [1.01-2.36], respectively). Higher PM 2.5 during the first trimester and higher maternal anxiety during pregnancy showed an additive effect on the risk of AD (aOR: 3.13; 95% CI: 1.56-6.28). Among boys exposed to higher maternal anxiety during pregnancy, gestational weeks 5-8 were the critical period of PM 2.5 exposure for the development of AD., Conclusions: Higher PM 2.5 exposure during gestational weeks 5-8 increased the probability of AD in infancy, especially in boys with higher maternal anxiety. Avoiding PM 2.5 exposure and maternal anxiety from the first trimester may prevent infant AD., Competing Interests: The authors acknowledge that there is no conflict of interest to declare., (© 2021 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background and Objective: Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children., Methods: Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low (<-2), normal (≥-2 and ≤2), and high (>2) BMI z score groups., Results: Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups., Conclusion: GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research., (© 2021 Wiley Periodicals LLC.)

Background: Although atopic dermatitis (AD) is associated with certain gene variants, the rapidly increasing incidence of AD suggests that environmental factors contribute to disease development. In this study, we investigated the association of AD incidence and phenotype with antibiotic exposure within 6 months of age, considering the dose administered and genetic risk., Methods: This study included 1637 children from the COCOA cohort. Pediatric allergists assessed the presence of AD at each visit and obtained information about antibiotic exposure for more than 3 days. IL-13 (rs20541) polymorphism was genotyped by the TaqMan method. We stratified the AD phenotypes into four groups and used multinomial logistic regression models for analysis., Results: Antibiotic exposure within 6 months of age was found to increase the risk of AD within 3 years of life (aOR = 1.40; 95% CI, 1.09-1.81) in dose-dependent manner. Antibiotic exposure more than twice increased the risk of the early-persistent AD phenotype (aOR = 2.50; 95% CI, 1.35-4.63). There was a weak interaction between genetic polymorphisms and environmental factors on the development of AD (p for interaction = 0.06). Children with the IL-13 (rs20541) GA + AA genotype have a higher risk of the early-persistent AD phenotype when exposed to antibiotics more than twice than those with the IL-13 (rs20541) GG genotype and without exposure to antibiotics (aOR = 4.73; 95% CI, 2.01-11.14)., Conclusion: Antibiotic exposure within 6 months was related to the incidence of early-persistent AD and a dose-dependent increase in the incidence of AD in childhood, whose effect was modified by the IL-13 (rs20541) genotype., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Oral immunotherapy (OIT) has emerged to build sustained unresponsiveness or tolerance in patients with egg allergy. However, it is important to increase compliance and ensure safety because OIT requires an extended period of time and has a risk of side effects like anaphylaxis. We aimed to show the feasibility and safety of OIT during the build-up phase using a home-based, up-dosing method in children with egg allergy. Sixteen patients aged 4 to 12 years with egg allergy were enrolled. Patients increased the dose of boiled egg white (EW) by 5% per day at home and 25% per month at the hospital, with a target dose of 40 g of boiled EW (4.0 g of EW proteins). A historical control group (n = 16) was matched for age, sex, and clinical characteristics for comparisons with the OIT group. Oral food challenge (OFC) tests were performed after completing the build-up phase. In the OIT group, 93.8% (15/16) of patients achieved desensitization, with only 1 patient discontinuing OIT before the maintenance phase due to repeated allergic reactions. Mild allergic reactions and anaphylaxis occurred in 12 (75.0%) and 2 patients (12.5%), respectively. However, there were no significant adverse reactions such as serious anxiety or life-threatening events that required discontinuation of treatment. On the contrary, only 1 patient (6.3%) in the control group passed an OFC of 40 g of boiled EW during the same period ( P < 0.001). Our results suggest that home-based up-dosing protocols using boiled eggs may be safe and feasible for the build-up phase of OIT in children with egg allergy., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Prenatal particulate matter <2.5 μm (PM 2.5 ) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM 2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM 2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM 2.5 levels and birth weight (BW). PM 2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM 2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM 2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM 2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM 2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM 2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Air pollution is associated with depressive and anxiety symptoms in the general population. However, this relationship among pregnant women remains largely unknown., Objective: To evaluate the association between pregnancy air pollution exposure and maternal depressive and anxiety symptoms during the third trimester assessed using the Center for Epidemiologic Studies-Depression and State-Trait Anxiety Inventory scales, respectively., Methods: We analyzed 1481 pregnant women from a cohort study in Seoul. Maternal exposure to particulate matter with an aerodynamic diameter <2.5 μm (PM 2.5 ) and <10 μm (PM 10 ), as well as to nitrogen dioxide (NO 2 ) and ozone (O 3 ) for each trimester and the entire pregnancy was assessed at participant's residential address by land use regression models. We estimated the relative risk (RR) and corresponding confidence interval (CI) of the depressive and anxiety symptoms associated with an interquartile range (IQR) increase in PM 2.5 , PM 10 , NO 2 , and O 3 using modified Poisson regression., Results: In single-pollutant models, an IQR increase in PM 2.5 , PM 10 , and NO 2 during the second trimester was associated with an increased risk of depressive symptoms (PM 2.5 RR = 1.15, 95% CI: 1.04, 1.27; PM 10 RR = 1.13, 95% CI: 1.04, 1.23; NO 2 RR = 1.15, 95% CI: 1.03, 1.29) after adjusting for relevant covariates. Similarly, an IQR increase in O 3 during the third trimester was associated with an increased risk of depressive symptoms (RR = 1.09, 95% CI: 1.01, 1.18), while the IQR increase in O 3 during the first trimester was associated with a decreased risk (RR = 0.89, 95% CI: 0.82, 0.96). Exposure to PM 2.5 , PM 10 , and NO 2 during the second trimester was significantly associated with anxiety symptoms. The associations with PM 2.5 and O 3 in single-and multi-pollutant models were consistent., Conclusions: Our findings indicate that increased levels of particulate matter, NO 2 , and O 3 during pregnancy may elevate the risk of depression or anxiety in pregnant women., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: The association between prenatal exposure to phthalate and childhood atopic dermatitis (AD) has previously been investigated; however, the results are inconsistent. Objective: We aimed to perform a systematic review and meta-analysis of birth cohort studies to investigate whether prenatal exposure to phthalate increases the risk of developing AD in children. Methods: We performed an electronic search of medical literature data bases. Studies were critically appraised, and a meta-analysis was performed. Results: Among 129 articles identified, 11 studies met the eligibility criteria. Included studies originated from Europe (n = 5), the United States (n = 4), and Asia ( n = 2). The study sample size ranged from 147 to 1024 mother-child pairs. Quality assessment by using the Newcastle-Ottawa scale of all the studies had scores of ≥6. A meta-analysis of data from eight selected studies suggested that monobenzyl phthalate (MBzP) exposure was significantly associated with the risk of AD development (odds ratio 1.16 [95% confidence interval, 1.04-1.31]; I² = 17.36%). However, AD development was not associated with other phthalate metabolites, such as mono-(2-ethylhexyl) phthalate, monoethyl phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, and the sum of di-[2-ethylhexyl] phthalate on the development of AD (all p values were > 0.05). Conclusion: Our meta-analysis suggested that prenatal exposure to phthalates may be associated with the development of childhood AD. However, further research is needed because only MBzP showed statistical significance and the number of articles in the literature is still insufficient.

Purpose: Interleukin (IL)-17 variants and perturbations in the gut microbiota may influence the development of atopic dermatitis (AD). However, unifying principles for variants of host and microbe interaction remains unclear. We sought to investigate whether IL-17 variants and gut microbiota affect the development of AD in infancy., Methods: Composition of the gut microbiota was analyzed in fecal samples from 99 normal healthy and 61 AD infants at 6 months of age. The associations between total immunoglobulin E (IgE), the scoring atopic dermatitis (SCORAD), short-chain fatty acids, transcriptome and functional profile of the gut measured in these subjects and Streptococcus were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and Streptococcus mitis ., Results: In this study, Streptococcus was enriched in infants with AD and was higher in those with the GA + AA of IL-17 (rs2275913) variant. Streptococcus was positively correlated with IgE and SCORAD in infants with AD and GA + AA of IL-17 . Butyrate and valerate were negatively correlated with Streptococcus and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of Clostridium were decreased compared with normal and GG. In transcriptome analysis, lactate dehydrogenase A-like 6B was higher in infants with AD compared with healthy infants. IL-6 and IL-8 were increased in IL-17 and/or S. mitis -stimulated HIEC-6 cells., Conclusions: These findings suggest that increased Streptococcus and A allele of IL-17 (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)