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Background: Several studies have reported the relevance between serum vitamin D and allergic immunoglobulin E (IgE) responses and atopic diseases. However, a metabolomics-based approach to the impacts of vitamin D on allergic reactions remains unclear., Methods: A total of 111 children completed a 3-year follow-up were enrolled and classified based on longitudinal vitamin D status (≥ 30 ng/ml, n = 54; 20-29.9 ng/ml, n = 41; <20 ng/ml, n = 16). Urinary metabolomic profiling was performed using 1 H-Nuclear magnetic resonance (NMR) spectroscopy at age 3. Integrative analyses of their associations related to vitamin D levels, atopic indices, and allergies were performed, and their roles in functional metabolic pathways were also assessed., Results: Six and five metabolites were identified to be significantly associated with vitamin D status and atopic diseases, respectively (FDR-adjusted p-value <.05). A further correlation analysis revealed that vitamin D-associated 3-hydroxyisobutyric acid and glutamine were positively correlated with atopic disease-associated succinic acid and alanine, respectively. Furthermore, hippuric acid was negatively correlated with atopic disease-associated formic acid, which was positively correlated with vitamin D level (p < .01). Absolute eosinophil count (AEC) was positively correlated with serum D. pteronyssinus- and D. farinae-specific IgE level (p < .01) but negatively correlated with vitamin D level (p < .05). Amino acid metabolisms were significantly associated with vitamin D related to childhood allergies., Conclusion: Integrative metabolomic analysis provides the link of vitamin D-associated metabolites with the gut microbiome and immunoallergic reactions related to childhood allergies., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B 4 (LTB 4 ), characterizes childhood asthma. While fractional exhaled nitric oxide (FeNO) has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment., Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA., Results: In addition to those previously reported, including LTB 4 , the levels of exhaled 15-hydroxyeicosatetraenoic acid (15-HETE), but not thromboxane B 2 (TXB 2 ), showed significant difference between asthmatics (N = 318) and healthy controls (N = 97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver operating characteristic (ROC) curve analyses revealed similar distinguishing power for the levels of 15-HETE, FEV 1 (forced expiratory volume in the first second), and FeNO, while the 15-HETE/LTB 4 ratio was significantly lower in subjects with asthma as compared to that of healthy controls (p < 0.0001). Analysis of asthmatics (N = 75) during exacerbation and convalescence showed significant improvement in lung function (FEV 1 , p < .001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p < .001) and reduced levels of TXB 2 (p < .05) at convalescence, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB 4 and lipoxin A 4 (LXA 4 ) at convalescence were noted only in those at the top 30 percentile during exacerbation., Conclusion: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB 2 and increased levels of 15-HETE were prominent at convalescence., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: This study aimed to investigate whether maternal allergy is associated with soluble CD14 (sCD14) and fatty acid composition in different stages of lactation and the onset of atopic dermatitis (AD) in early childhood., Methods: In total, 443 mother-child groups (445 children) were enrolled in the Prediction of Allergies in Taiwanese Children birth cohort study. Colostrum and mature milk at 2 months postpartum (2-month HM) were collected from lactating mothers. Information regarding parental allergy histories and physician-diagnosed atopic diseases was obtained using age-specific questionnaires (0-2 years). We compared sCD14 levels and the composition of 30 fatty acids in the colostrum and 2-month HM, respectively, between allergic and non-allergic mothers and between children with and without AD by the age of 2 years., Results: In total, 185 (41.8%) mothers presented with allergies, and 154 (34.6%) children had physician-diagnosed AD by the age of 2 years. Both in the colostrum and 2-month HM of 289 lactating mothers, sCD14 levels were significantly lower in allergic mothers whose children presented with AD compared with children who did not (P = 0.015 and 0.044, respectively). Among the children with AD who were born to non-allergic mothers, sCD14 levels were lower. However, the result was not statistically significant (P = 0.376 and 0.264, respectively). Our data revealed the lack of associations between fatty acid composition and AD (P > 0.05)., Conclusion: Decreased sCD14 levels in the colostrum and 2-month HM were associated with AD at 2 years of age, particularly among children born to mothers with allergies., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Several metabolites and altered metabolic pathways have been reported to be associated with asthma. However, longitudinal analysis of the dynamics of metabolites contributing to the development of asthma has not yet been fully clarified., Methods: We sought to identify the metabolic mechanisms underlying asthma development in early childhood. Thirty children with asthma and paired healthy controls from a prospective birth cohort were enrolled. Time series analysis of urinary metabolites collected at ages 1, 2, 3, and 4 years was assessed using 1 H nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA). Metabolites identified were studied in relation to changes over time in a linear mixed model for repeated measures., Results: A total of 172 urine samples collected from the enrolled children were analyzed. Urinary metabolomics identified four metabolites significantly associated with childhood asthma development, with longitudinal analysis. Among them, dimethylamine, a metabolite produced by intestinal bacteria, appeared to shift from higher to lower level during asthma development. A persistent lower level of 1-methylnicotinamide and allantoin was found in children with asthma, with a peak difference at age 3 years (P = .032 and P = .021, respectively). Furthermore, a significant inverse correlation was found between allantoin and house dust mite sensitization (Spearman's r = -.297 P = .035)., Conclusions: Longitudinal urinary metabolomic profiling provides a link of microbe-environment interactions in the development of childhood asthma. 1-Methylnicotinamide and allantoin may participate in allergic reactions in response to allergen exposure, potentially serving as specific biomarkers for asthma., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: There are few studies addressing the longitudinal analysis of vitamin D deficiency and its impact on the development of atopic diseases in early childhood., Methods: We investigated 155 children who regularly followed up at our clinic for 5 years as subjects enrolled in a birth cohort study. The pattern of vitamin D levels from birth to 5 years of age was clustered using K-means method in R software. Absolute eosinophil count (AEC), and total serum and specific immunoglobulin E antibodies against food (egg white, milk, and wheat) and inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farina, and Cladosporium herbarum) were measured at 1.5, 3, 4 and 5 years of age., Results: A total of 137 children with serum samples obtained over at least 3 time points during the follow-up period were recruited. Using K-means clustering, the dynamic changes in vitamin D levels were significantly stratified into 3 clusters (cluster A, ≥30 ng/mL, n = 61; cluster B, 20-29.9 ng/mL, n = 53; cluster C, <20 ng/mL, n = 23). Despite no statistical association with atopic diseases, a persistent vitamin D deficiency appeared to be associated with eosinophilia at age 3, and total serum and mite-specific immunoglobulin E (IgE) levels at age 4. Furthermore, an associated higher prevalence of mite sensitization at age 4 was significantly associated with the risk of allergic rhinitis and asthma., Conclusions: Vitamin D deficiency is inversely associated with AEC and mite-specific IgE levels, which may potentially increase susceptibility to develop allergies including rhinitis and asthma in early childhood., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: There are few studies addressing the impact of maternal vitamin D status on the vitamin D levels in offspring, their sensitization to common allergens and atopic disease development., Methods: Children aged 0 through 4 yr from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Time series of serum 25-hydroxyvitamin D (25(OH)D) levels were measured in maternal blood before delivery, cord blood, and at age 1.5, 3, and 4 using an electrochemiluminescence-based assay. Specific IgE antibodies against food and inhalant allergens were measured at 6 months, and 1, 1.5, 2, 3, and 4 yr of age., Results: A total of 164 mother-child pairs from a birth cohort were recruited in this study. The mean levels of maternal 25(OH)D were 23.2 ± 7.7 ng/ml with a high (up to 80%) prevalence of insufficient vitamin D status (< 30 ng/ml). A significant correlation was seen between maternal and cord blood 25(OH)D levels (p < 0.001), and a persistent lower 25(OH)D level was found in children born to mothers with deficient 25(OH)D levels. Deficient maternal 25(OH)D levels (<20 ng/ml) appeared to be associated with a higher prevalence of allergen sensitization before age 2. Higher maternal 25(OH)D levels were significantly associated with lower risk of eczema (OR 0.12; 95% CI 0.02-0.63; p = 0.012) and asthma (OR 0.22; 95% CI 0.06-0.92; p = 0.038) at age 4., Conclusions: Low maternal 25(OH)D levels appear not only to be associated with an increase in the prevalence of allergic sensitization but also the risk of eczema and asthma in early childhood., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The association between vitamin D status at birth and allergen sensitizations is uncertain. The aim of this study was to investigate the relationship between cord blood vitamin D status with allergen sensitizations and the development of atopic diseases in early childhood., Methods: Children aged 0 through 4 yr from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Serum levels of 25-hydroxyvitamin D (25(OH)D) in cord blood were measured by a new automated electrochemiluminescence-based assay. Specific IgE antibodies against food and inhalant allergens were measured at 6 months, and 1, 1.5, 2, 3, and 4 yr of age., Results: A total of 186 children were regular followed up at clinics for a 4-yr follow-up period. The mean level of cord blood 25(OH)D was 23.8 ± 9.5 ng/ml with a high prevalence of low vitamin D status (<20 ng/ml) at birth (42%). There was a tendency of low cord blood 25(OH)D levels being associated with higher risk of food sensitization throughout childhood. Cord blood 25(OH)D levels were inversely associated with the risk of milk sensitization at age 2, at which age a higher prevalence of milk sensitization was significantly associated with the risk of allergic rhinitis, and asthma development at age 4., Conclusions: Low cord blood vitamin D levels appear to be associated with increased milk sensitization but not with asthma, eczema, or allergic rhinitis in early childhood., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)