Disparities in pediatric anaphylaxis triggers and management across Asia.

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.

Initial updosing phase of oral immunotherapy improves quality of life and psychological burden in parents of children with food allergy.

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.

Skin biomarkers predict the development of food allergy in early life.

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.

Postpartum Maternal Anxiety Affects the Development of Food Allergy Through Dietary and Gut Microbial Diversity During Early Infancy.

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.

Validity and Reliability of the Korean Versions of the Food Allergy Quality of Life Questionnaire-Child Form and Teenager Form.

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 (ß = 0.736, P < 0.001), indicating construct validity. The K-FAQLQ-CF score was weakly associated with the K-PedsQL™ 4.0 score (ß = -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 (ß = 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.

Epigenetic Methylation Changes in Pregnant Women: Bisphenol Exposure and Atopic Dermatitis.

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.

Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

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.

Insights from the COCOA birth cohort: The origins of childhood allergic diseases and future perspectives.

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.

Practical issues of oral immunotherapy for egg or milk allergy.

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.

Psychological Distress and Perceived Burden in Parents of Korean Children With IgE-Mediated Food Allergy.

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 (ß = 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 (ß = 9.32; 95% CI, 2.97 to 15.68), cow's milk (CM) allergy (ß = 8.24; 95% CI, 2.04 to 14.44), soybean allergy (ß = 13.91; 95% CI, 1.62 to 26.20), higher anxiety (ß = 1.05; 95% CI, 0.07 to 1.41), higher depression (ß = 2.15; 95% CI, 1.61 to 2.69), and lower resilience (ß = -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.

Blood eosinophil related to maternal allergic rhinitis is associated with the incidence of allergic rhinitis in offspring: COCOA study.

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.

Alterations of Epidermal Lipid Profiles and Skin Microbiome in Children With Atopic Dermatitis.

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.

Associations of prenatal antibiotic exposure and delivery mode on childhood asthma inception.

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.

Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis.

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.

Quality of Life in Food Allergy: Validation of the Korean Version of the Food Allergy Quality of Life Questionnaire Parent Form (K-FAQLQ-PF) and Risk Factor Analysis.

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.

Staphylococcus aureus causes aberrant epidermal lipid composition and skin barrier dysfunction.

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)-1ß, 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-1ß, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA.

Phenotype of Atopic Dermatitis With Food Allergy Predicts Development of Childhood Asthma via Gut Wnt Signaling.

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/ß-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.

Maternal Posttraumatic Stress Symptoms and Psychological Burden in Mothers of Korean Children With Anaphylaxis.

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.

Multicenter Surveillance of Cystic Fibrosis in Korean Children.

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).