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The escalating global allergy epidemic has emerged as a pressing and persistent challenge, exerting a profound impact on human health systems across centuries. This burgeoning predicament can be attributed to contemporary lifestyles, environmental influences, and genetic predispositions. The manifestation of allergy-related factors exhibits dynamic fluctuations contingent on temporal shifts, geographical distinctions, cultural variances, and diverse demographic strata. In this review, we present recent epidemiological insights derived from two distinct birth cohorts: the Japan Environment and Children's Study (JECS), encompassing the entirety of Japan, and the Tokyo Children's Health, Illness, and Development Study (T-Child Study) within Tokyo. Through this comprehensive review, we offer a comprehensive overview of the latest epidemiological discoveries stemming from these pivotal Japanese birth cohorts, thereby affording a unique opportunity to deliberate on imperative strategies for the optimal management of the allergy epidemic. [ABSTRACT FROM AUTHOR]

Background: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. Methods: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. Results: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36–0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01–4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. Conclusions: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to clarify the clinical characteristics and management of infants with suspected acute food protein–induced enterocolitis syndrome (FPIES) who presented to the pediatric emergency department (ED) before and after the guidelines were published. Methods: This was a retrospective cohort study. We classified the infants as "acute FPIES‐like symptoms" who were younger than 12 months of age and visited the pediatric ED of the National Center for Child Health and Development due to vomiting 1–4 h after food ingestion without any causative disease, such as infection. The medical records of those infants in 2015 and 2021 were reviewed. We used the nonparametric Mann–Whitney U test to compare two groups for continuous variables, whereas chi‐squared or Fisher's exact tests were used for nominal variables. Results: The number of infants with acute FPIES‐like symptoms was 15 (13%) in 2015 and 14 (15%) in 2021. The trigger foods were cow's milk or dairy products in half of the infants, and five as a result of ingestion of hen's eggs in 2021, compared to zero cases in 2015. Five in 2015 and 12 in 2021 required examination at the ED. Three in 2015 and six in 2021 met the diagnostic criteria for acute FPIES in the international consensus guidelines. The emergency physicians did not record at least four minor criteria for acute FPIES in seven in 2015 and five in 2021. No infants (0%) in 2015 and two (14%) in 2021 were referred to the allergy department by an emergency physician. Conclusions: Acute FPIES should be considered one of the differential diagnoses of vomiting, and pediatric medical staff should be aware of FPIES diagnostic criteria and appropriately refer suspected cases to a specialist. [ABSTRACT FROM AUTHOR]

Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood. This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles. The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels. The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins. [ABSTRACT FROM AUTHOR]

Applying urinary PGDM as a biomarker for OFC could improve the safety of the FA diagnostic procedure by preventing severe allergic reactions, such as anaphylaxis, during an OFC. Urinary prostaglandin D2 metabolite (PDGM) levels increased in children with acute allergic reactions to foods Urinary PGDM were also increased in children with indeterminate food challenge outcomes compared to non-reactors These preliminary data suggest that urinary PGDM might be a useful biomarker for food challenges To the Editor, Oral food challenge (OFC) is a gold standard diagnostic method for food allergy (FA).1 Positive or negative OFC results are judged by an experienced physician based on objective allergic signs without reference to accurate biomarkers. In summary, urinary PGDM is a novel, noninvasive biomarker for detecting immediate food-induced allergic reactions, including subtle allergic reactions. [Extracted from the article]

Background: The relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population. Methods: The cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates. Results: This study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls. Conclusions: Children with allergies mount and maintain a comparable immune response to the measles vaccine. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have reported that maternal asthma increases the risk of preterm birth. We hypothesized that inflammatory reactions caused by allergic diseases might affect the uterine environment and, subsequently, perinatal outcomes. The objective of this study was to examine the associations between allergic features among mothers and preterm pregnancy outcomes in a nationwide birth cohort. Methods: We analyzed data from pregnant women obtained from the Japanese Environment and Children's Study (JECS), a nationwide general birth cohort study. We used binomial and multinomial logistic regression models to examine the associations between maternal allergic features and preterm birth, threatened preterm labor (TPL), and preterm premature rupture of the membrane (PPROM). Results: A total of 97,683 pregnant women were included. Prevalence of preterm birth, TPL, and PPROM was 4.7, 19.6, and 1.2%, respectively. Maternal history of allergic diseases (asthma, allergic rhinitis, allergic conjunctivitis, food allergy, drug allergy, and contact dermatitis) increased the risk of TPL(adjusted odds ratio [aOR] = 1.11 [95% CI: 1.06–1.17], aOR = 1.12 [1.08–1.16], aOR = 1.10 [1.04–1.16], aOR = 1.17 [1.09–1.26], aOR = 1.35 [1.23–1.48], and aOR = 1.34 [1.20–1.49], respectively). Although some maternal allergic features showed a negative association with preterm birth, the variables affecting preterm birth differed according to the gestational age of the fetus (22–33 weeks vs. 34–36 weeks). There were no significant associations between maternal allergic features and PPROM. Conclusion: Maternal allergic disease, except atopic dermatitis, may increase the risk of TPL. Comorbidity of maternal allergic disorders and perinatal adverse outcomes require further investigation. [ABSTRACT FROM AUTHOR]

Allergic rhino-conjunctivitis with pollen allergy has been prevalent worldwide and Pollen-food allergy syndrome (PFAS) refers to individuals with pollen allergy who develop oral allergy syndrome (OAS) on consuming fruits and vegetables. The prevalence of PFAS varies by region and that in Japanese adolescents remains to be elucidated. In this cross-sectional study, we examined the epidemiological characteristics of PFAS in a general population of Japanese adolescents according to pollen allergy, OAS, and IgE component sensitization. Participants comprised adolescents, at age 13 years, from a prospective birth cohort study in Japan. We administered questionnaires to collect information from parents regarding pollen allergy, PFAS and OAS at each child's age 13 years. ImmunoCAP ISAC was used to assess IgE component sensitization. Among 506 participants with a complete questionnaire and ISAC measurement results, 56.5% had a history of hay fever, 16.0% had a history of OAS, 51.0% had pollen allergy, and 11.7% had a history of PFAS; additionally, 72.7% were sensitized to one or more tree, grass, and/or weed allergens. The most common sensitization (95.7%) among adolescents with pollen allergy was to Japanese cedar (Cry j 1). The most common causal foods were kiwi and pineapple (both 39.0%). Knowledge levels about PFAS were poor among affected adolescents. We found a high prevalence of PFAS among adolescents in Japan. Although it affects approximately 1/10 adolescents in the general population, public awareness regarding PFAS is poor. Interventional strategies are needed to increase knowledge and to prevent PFAS in the general population. [ABSTRACT FROM AUTHOR]

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children's Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year. [ABSTRACT FROM AUTHOR]

Dear Editors, Skin barrier functions such as transepidermal water loss (TWEL), water content of the skin stratum corneum (WCSC), and thickness of the skin stratum corneum (TSSC) are recognized as being affected by skin diseases including atopic dermatitis (AD).1 The challenge of measuring TEWL is that its variables are typically affected by the environment. Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year. [Extracted from the article]

Background Although the beta-2 receptor agonist (B2 RA) is occasionally prescribed in the prenatal period for women with preterm labor, few studies have referred to the long-term effects of intrauterine exposure to B2 RA on fetus. We examined the association between intrauterine exposure to B2 RA and asthma in the offspring. Methods We obtained data from a hospital-based birth cohort study conducted in Tokyo, Japan. The outcomes of interest were three indicators, consisting of current wheeze, current asthma, and ever asthma at 5 years of age, based on the International Study of Asthma and Allergies in Childhood questionnaire. Logistic regression analysis was used to evaluate the association between intrauterine B2 RA exposure and outcomes. To evaluate dose-dependent risk, we categorized children into three groups according to both the cumulative dose and duration (days) and conducted trend analysis. Results Of 1158 children, 94 (8.1%) were exposed to B2 RA in utero, and 191 (16.5%), 111 (9.6%), and 168 (14.5%) children experienced current wheeze, current asthma, and ever asthma, respectively. After adjusting for confounders, we found an increased risk of current asthma caused by B2 RA exposure with an adjusted odds ratio of 2.04 (95% confidence interval: 1.02-4.05). Trend analysis showed that B2 RA exposure in utero was associated with a dose-dependent increased risk of current asthma in terms of both cumulative dose and duration ( P values for trend were .015 and .017, respectively). These results were similar to those for other outcome measures. Conclusion Exposure to B2 RA in utero could be a risk for childhood asthma. [ABSTRACT FROM AUTHOR]

• Five groups of cytokines/chemokines by using hierarchical clustering analysis in children. • CCL17 and CCL27 were observed in children with diagnosis of childhood AD. • Unsupervised machine learning identified three clusters of children based on cytokine/chemokine pattern. This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification. [ABSTRACT FROM AUTHOR]