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.

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.

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.

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.

Potential Effects of Low-Level Toluene Exposure on the Nervous System of Mothers and Infants.

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.

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.

Home-based up-dosing of wheat oral immunotherapy: Real-world effectiveness and predictive factor analysis.

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.

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.

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.

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.

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.

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.

Food allergy in early childhood increases the risk of oral allergy syndrome in schoolchildren: A birth cohort study.

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.

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity.

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.

Natural Course and Prognostic Factors of Immediate-Type Peanut Allergy in Children.

BACKGROUND: Predicting food allergy resolution is essential to minimize the number of restricted foods in children. However, there have been no studies on the natural history of peanut allergy (PA) in Korea. OBJECTIVE: This study aimed to evaluate the natural course and prognostic factors of immediate-type PA in children till the age of 10 years. METHODS: We retrospectively collected data of 122 children who developed PA before 60 months of age from 3 tertiary hospitals in Korea. Diagnosis and resolution of PA was defined as an oral food challenge test or a convincing history of symptoms within 2 h after peanut ingestion. The prognostic factors for resolution of PA were identified using the Cox proportional hazard model. RESULTS: The median (interquartile range) age at diagnosis was 2.0 (1.3-3.0) years. Among the 122 children, PA resolved in 18 (14.8%) children. The level of peanut-specific IgE (sIgE) at diagnosis in the persistence group was significantly higher than that in the resolution group (p = 0.026). The probabilities of resolution of PA were 10.3% and 32.8% at the ages of 6 and 10 years, respectively. A peanut-sIgE level ≥1 kU/L at diagnosis was significantly associated with persistent PA (hazard ratio, 5.99; 95% confidence interval, 1.89-18.87). CONCLUSIONS: Only 10.3% of our patients had a probability of developing spontaneous resolution of PA by 6 years of age. Peanut-sIgE levels ≥1 kU/L at diagnosis were associated with the persistence of PA.

Dog Ownership in Early Life Increased the Risk of Nonatopic Asthma in Children.

BACKGROUND: It is still debatable whether dog ownership during early childhood is a risk factor for the development of allergic diseases. OBJECTIVE: We investigated the association of dog ownership in early life with sensitization and asthma in childhood. METHODS: Data from the Cohort for Childhood Origin of Asthma and Allergic diseases were used to investigate the association between dog ownership at any time from pregnancy to 1 year of age and sensitization to aeroallergens at 3 and 7 years old, bronchial hyperresponsiveness (BHR), and asthma at 7 years old. We analyzed the cytokine levels in cord blood (CB) and indoor environmental measurement concentrations in the mother's residence obtained at 36 weeks of pregnancy. RESULTS: Sensitization to dogs at age 3 and 7 did not differ between dog ownership and nonownership, but dog ownership during early life decreased the risk of sensitization to aeroallergens at age 7 (aOR = 0.44, 95% CI 0.21-0.90). Dog ownership significantly increased the risk of nonatopic BHR (aOR = 2.86; 95% CI 1.32-6.21). In addition, dog ownership was associated with asthma, especially nonatopic asthma at 7 years old (aOR = 2.73, 95% CI 1.02-7.32; aOR = 7.05, 95% CI 1.85-26.90, respectively). There were no significant differences in the concentrations of IL-13 or interferon-γ in CB or indoor environmental measurements according to dog ownership during pregnancy. CONCLUSION: Early-life dog exposure in this birth cohort has been shown to reduce atopy but increase the risk of nonatopic BHR and nonatopic asthma at 7 years old.

Effect of early-life antibiotic exposure and IL-13 polymorphism on atopic dermatitis phenotype.

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.

Mid-pregnancy PM2.5 exposure affects sex-specific growth trajectories via ARRDC3 methylation.

Prenatal particulate matter <2.5 µm (PM2.5) 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 PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 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 PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.

Effect of prenatal phthalate exposure on childhood atopic dermatitis: A systematic review and meta-analysis.

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.