T-cell receptor diversity and allergen sensitivity in childhood asthma and atopic dermatitis.

BACKGROUND: Childhood allergies of asthma and atopic dermatitis (AD) involve an overactive T-cell immune response triggered by allergens. However, the impact of T-cell receptor (TCR) repertoires on allergen sensitization and their role in mediating different phenotypes of asthma and AD in early childhood remains unclear. METHODS: A total of 78 children, comprising 26 with asthma alone, 26 with AD alone, and 26 healthy controls (HC), were enrolled. TCR repertoire profiles were determined using a unique molecular identifier system for next-generation sequencing. Integrative analyses of their associations with allergen-specific IgE levels and allergies were performed. RESULTS: The diversity in TCR alpha variable region (TRAV) genes of TCR repertoires and complementarity determining region 3 (CDR3) clonality in TRAV/TRBV (beta) genes were significantly higher in children with AD compared with those with asthma and HC (p < .05). Compared with HC, the expression of TRAV13-1 and TRAV4 genes was significantly higher in both asthma and AD (p < .05), with a significant positive correlation with mite-specific IgE levels (p < .01). In contrast, TRBV7-9 gene expression was significantly lower in both asthma and AD (p < .01), with this gene showing a significant negative correlation with mite-specific IgE levels (p < .01). Furthermore, significantly higher TRAV8-3 gene expression, positively correlated with food-specific IgE levels, was found in children with AD compared with those with asthma (p < .05). CONCLUSION: Integrated TCR repertoires analysis provides clinical insights into the diverse TCR genes linked to antigen specificity, offering potential for precision immunotherapy in childhood allergies.

Phenotype-specific signatures of systems-level gut microbiome associated with childhood airway allergies.

BACKGROUND: Perturbation of gut symbiosis has been linked to childhood allergic diseases. However, the underlying host-microbe interaction connected with specific phenotypes is poorly understood. METHODS: To address this, integrative analyses of stool metagenomic and metabolomic profiles associated with IgE reactions in 56 children with mite-sensitized airway allergies (25 with rhinitis and 31 with asthma) and 28 nonallergic healthy controls were conducted. RESULTS: We noted a decrease in the number and abundance of gut microbiome-encoded carbohydrate-active enzyme (CAZyme) genes, accompanied with a reduction in species richness, in the asthmatic gut microflora but not in that from allergic rhinitis. Such loss of CAZymes was consistent with the observation that a CAZyme-linked decrease in fecal butyrate was found in asthmatics and negatively correlated with mite-specific IgE responses. Different from the CAZymes, we demonstrated an increase in α diversity at the virulome levels in asthmatic gut microbiota and identified phenotype-specific variations of gut virulome. Moreover, use of fecal metagenomic and metabolomic signatures resulted in distinct effects on differentiating rhinitis and asthma from nonallergic healthy controls. CONCLUSION: Overall, our integrative analyses reveal several signatures of systems-level gut microbiome in robust associations with fecal metabolites and disease phenotypes, which may be of etiological and diagnostic implications in childhood airway allergies.

Metabolomics analysis reveals molecular linkages for the impact of vitamin D on childhood allergic airway diseases.

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.

Metabolomics reveals microbial-derived metabolites associated with immunoglobulin E responses in filaggrin-related atopic dermatitis.

BACKGROUND: Filaggrin (FLG) gene mutation and immunoglobulin E (IgE)-mediated sensitization are the most important predictors of atopic dermatitis (AD). However, a metabolomics-based approach to address the metabolic impact of FLG mutations on allergic IgE responses for AD is still lacking. We, though, determine the relationships of metabolic profiles in AD with FLG mutations and allergic responses. METHODS: Eighty-one children with adolescent AD (n = 58) and healthy controls (n = 23) were prospectively enrolled. Mutations in the filaggrin gene were identified using whole-exome sequencing, and plasma metabolic profiles were determined using 1 H-nuclear magnetic resonance (NMR) spectroscopy. Integrative analyses of their associations related to total serum IgE levels were performed, and further metabolic functional pathways for AD were also assessed. RESULTS: Metabolites contributed to the separation between AD and controls were identified using the supervised partial least squares discriminant analysis (Q2 /R2  = 0.90, Ppermutation <0.001). Nitrogen and amino acid metabolisms for energy production, and microbe-related methane and propanoate metabolisms were significantly associated with AD compared with healthy controls (FDR-adjusted p < .05). Five of fifteen metabolites related to FLG mutations were positively correlated with total serum IgE levels. Among them, dimethylamine and isopropanol were strongly associated with methane metabolism and propanoate metabolism, respectively, in AD with FLG mutations (FDR-adjusted p < .01). CONCLUSION: A strong correlation of microbial-derived metabolites, dimethylamine and isopropanol, with FLG mutations and IgE allergic reactions provides the influence of host genetics on the microbiome to regulate susceptibility to allergic responses in the pathogenesis of AD.

Levels of 15-HETE and TXB2 in exhaled breath condensates as markers for diagnosis of childhood asthma and its therapeutic outcome.

BACKGROUND: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B4 (LTB4 ), 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 LTB4 , the levels of exhaled 15-hydroxyeicosatetraenoic acid (15-HETE), but not thromboxane B2 (TXB2 ), 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, FEV1 (forced expiratory volume in the first second), and FeNO, while the 15-HETE/LTB4 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 (FEV1 , p < .001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p < .001) and reduced levels of TXB2 (p < .05) at convalescence, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and lipoxin A4 (LXA4 ) 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 TXB2 and increased levels of 15-HETE were prominent at convalescence.

Integration of metagenomics-metabolomics reveals specific signatures and functions of airway microbiota in mite-sensitized childhood asthma.

BACKGROUND: Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome. METHODS: To explore the functional capacity of asthmatic microbiome and its intricate connection with the host, we performed shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in a cohort of children with mite-sensitized asthma and non-asthmatic controls. RESULTS: We observed higher gene counts and sample-to-sample dissimilarities in asthmatic microbiomes, indicating a more heterogeneous community structure and functionality among the cases than in controls. Moreover, we identified airway microbial species linked to changes in circulating metabolites and IgE responses of the host, including a positive correlation between Prevotella sp oral taxon 306 and dimethylglycine that were both decreased in patients. Several control-enriched species (Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306) were inversely correlated with total and allergen-specific IgE levels. Genes related to microbial carbohydrate, amino acid, and lipid metabolism were differentially enriched, suggesting that changes in microbial metabolism may contribute to respiratory health in asthmatics. Pathway modules relevant to allergic responses were differentially abundant in asthmatic microbiome, such as enrichments for biofilm formation by Pseudomonas aeruginosa, membrane trafficking, histidine metabolism, and glycosaminoglycan degradation, and depletions for polycyclic aromatic hydrocarbon degradation. Further, we identified metagenomic and metabolomic markers (eg, Eubacterium sulci) to discriminate cases from the non-asthmatic controls. CONCLUSIONS: Our dual-omics data reveal the connections between respiratory microbes and circulating metabolites perturbed in mite-sensitized pediatric asthma, which may be of etiological and diagnostic implications.

Prenatal exposure to bisphenol - A is associated with dysregulated perinatal innate cytokine response and elevated cord IgE level: A population-based birth cohort study.

BACKGROUND: Reports on the relationship between prenatal exposure to bisphenol-A (BPA) and the development of childhood allergy have been conflicting. This study aimed to investigate the impact of prenatal BPA exposure on several objective outcomes such as cytokine profile, atopic sensitization, and infant lung function (ILF) tests in addition to clinical allergic symptoms. METHODS: A subset of 274 children from the PATCH cohort study with available cord BPA data were followed until 3 years of age. Total and specific IgE level and Toll-like receptor (TLR) stimulated cytokine production were assessed yearly since birth. ILF such as tidal volume, VmaxFRC, airway resistance and compliance were performed at least once before the age of 2 years. Allergic outcome was determined by questionnaires and physician's assessment. RESULTS: There was significant association between BPA concentration and IgE level in the cord blood (p < 0.01), but the correlation was no longer significant at ages 1 through 3 years. In addition, cord BPA concentration was associated with dysregulated TLR stimulated TNF-α and IL-6 production, but the correlation was significant only at birth. No relationship was found between cord BPA concentration and ILF measurements or allergic symptoms (wheezing, rhino-conjunctivitis, or eczema) throughout early childhood. CONCLUSION: Results showed that prenatal exposure to BPA was not associated with increased risk of childhood allergy or impaired ILF. However, with its impact on biomarkers for allergy such as alterations in perinatal cytokine profile and elevated cord IgE level, the potential role of prenatal BPA exposure on the development of allergy cannot be disregarded.

Metabolomics Reveals Anaerobic Bacterial Fermentation and Hypoxanthine Accumulation for Fibrinous Pleural Effusions in Children with Pneumonia.

Fibrin formation in infectious parapneumonic effusion (IPE) characterizes complicated parapneumonic effusion and is important for providing guidelines for the management of IPEs that require aggressive interventions. We aim to identify metabolic mechanisms associated with bacterial invasion, inflammatory cytokines, and biochemical markers in cases of fibrinous infectious pleural effusions in children with pneumonia. Pleural fluid metabolites were determined by 1H nuclear magnetic resonance spectroscopy. Metabolites that contributed to the separation between fibrinous and nonfibrinous IPEs were identified using supervised partial least squares discriminant analysis ( Q2/ R2 = 0.84; Ppermutation < 0.01). IL-1ß in the inflammatory cytokines and glucose in the biochemical markers were significantly correlated with 11 and 9 pleural fluid metabolites, respectively, and exhibited significant overlaps. Four metabolites, including glucose, lactic acid, 3-hydroxybutyric acid, and hypoxanthine, were significantly correlated with plasminogen activator inhibitor type 1 in the fibrinolytic system enzymes. Metabolic pathway analysis revealed that anaerobic bacterial fermentation with increased lactic acid and butyric acid via glucose consumption and adenosine triphosphate hydrolysis with increased hypoxanthine appeared to be associated with fibrinous IPE. Our results demonstrate that an increase in lactic acid anaerobic fermentation and hypoxanthine accumulation under hypoxic conditions are associated with fibrin formation in IPE, representing advanced pleural inflammatory progress in children with pneumonia.

Metabolomic biomarkers in cervicovaginal fluid for detecting endometrial cancer through nuclear magnetic resonance spectroscopy.

INTRODUCTION: Endometrial cancer (EC) is one of the most common gynecologic neoplasms in developed countries but lacks screening biomarkers. OBJECTIVES: We aim to identify and validate metabolomic biomarkers in cervicovaginal fluid (CVF) for detecting EC through nuclear magnetic resonance (NMR) spectroscopy. METHODS: We screened 100 women with suspicion of EC and benign gynecological conditions, and randomized them into the training and independent testing datasets using a 5:1 study design. CVF samples were analyzed using a 600-MHz NMR spectrometer equipped with a cryoprobe. Four machine learning algorithms-support vector machine (SVM), partial least squares discriminant analysis (PLS-DA), random forest (RF), and logistic regression (LR), were applied to develop the model for identifying metabolomic biomarkers in cervicovaginal fluid for EC detection. RESULTS: A total of 54 women were eligible for the final analysis, with 21 EC and 33 non-EC. From 29 identified metabolites in cervicovaginal fluid samples, the top-ranking metabolites chosen through SVM, RF and PLS-DA which existed in independent metabolic pathways, i.e. phosphocholine, malate, and asparagine, were selected to build the prediction model. The SVM, PLS-DA, RF, and LR methods all yielded area under the curve values between 0.88 and 0.92 in the training dataset. In the testing dataset, the SVM and RF methods yielded the highest accuracy of 0.78 and the specificity of 0.75 and 0.80, respectively. CONCLUSION: Phosphocholine, asparagine, and malate from cervicovaginal fluid, which were identified and independently validated through models built using machine learning algorithms, are promising metabolomic biomarkers for the detection of EC using NMR spectroscopy.

Gut microbial-derived butyrate is inversely associated with IgE responses to allergens in childhood asthma.

BACKGROUND: A comprehensive metabolomics-based approach to address the impact of specific gut microbiota on allergen sensitization for childhood rhinitis and asthma is still lacking. METHODS: Eighty-five children with rhinitis (n = 27) and with asthma (n = 34) and healthy controls (n = 24) were enrolled. Fecal metabolomic analysis with 1 H-nuclear magnetic resonance (NMR) spectroscopy and microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for allergic rhinitis and asthma was also assessed. RESULTS: Amino acid, ß-alanine, and butanoate were the predominant metabolic pathways in the gut. Among them, amino acid metabolism was negatively correlated with the phylum Firmicutes, which was significantly reduced in children with rhinitis and asthma. Levels of histidine and butyrate metabolites were significantly reduced in children with rhinitis (P = 0.029) and asthma (P = 0.009), respectively. In children with asthma, a reduction in butyrate-producing bacteria, including Faecalibacterium and Roseburia spp., and an increase in Clostridium spp. were negatively correlated with fecal amino acids and butyrate, respectively (P < 0.01). Increased Escherichia spp. accompanied by increased ß-alanine and 4-hydroxybutyrate appeared to reduce butyrate production. Low fecal butyrate was significantly associated with increased total serum and mite allergen-specific IgE levels in children with asthma (P < 0.05). CONCLUSION: A reduced fecal butyrate is associated with increased mite-specific IgE levels and the risk of asthma in early childhood. Fecal ß-alanine could be a specific biomarker connecting the metabolic dysbiosis of gut microbiota, Clostridium and Escherichia spp., in childhood asthma.

Association of maternal allergy with human milk soluble CD14 and fatty acids, and early childhood atopic dermatitis.

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.

Longitudinal vitamin D deficiency is inversely related to mite sensitization in early childhood.

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.

Longitudinal urinary metabolomic profiling reveals metabolites for asthma development in early childhood.

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.

Introduction of various allergenic foods during infancy reduces risk of IgE sensitization at 12 months of age: a birth cohort study.

BackgroundIn this study, we aimed to determine whether introducing various allergenic foods during infancy is associated with IgE sensitization at 12 months of age.MethodsDetailed information on feeding practices regarding six possible allergenic foods (fruits, egg white, egg yolk, fish, shellfish, and peanuts) was obtained by administering age-specific questionnaires to parents of infants at ages 6 and 12 months. Fecal secretory IgA (sIgA), fecal eosinophil cationic protein (ECP), and serum levels of total IgE and IgE specific to 20 foods, and IgE specific to 20 inhalant allergens were also quantified at 12 months of age.ResultsAt 12 months of age, infants with IgE sensitization had been introduced to fewer allergenic food items during infancy (3.2±1.4 vs. 3.7±1.3 items). Compared with infants who were given 0-2 allergenic food items, infants introduced to 3-4 or ≥5 allergenic food items showed a significantly lower risk of IgE sensitization (odds ratios (ORs) 0.62 and 0.61, respectively) and lower total IgE levels. In addition, non-introduction of egg white or egg yolk was significantly related to IgE sensitization (ORs 1.41 and 1.26, respectively).ConclusionIncreasing the diversity of allergenic foods in infancy, including fruits, egg white, egg yolk, fish, shellfish, and peanuts, may protect infants from IgE sensitization at 12 months of age.

Cord Blood Soluble CD14 Predicts Wheeze and Prolonged Cough in Young Children: The PATCH Study.

BACKGROUND: Soluble cluster of differentiation 14 (sCD14) plays a role in the development and manifestation of atopic symptoms, although the results of previous studies have been inconclusive. The aim of this study is to evaluate the practical use of sCD14 as a predictive biomarker of allergy in young children. METHODS: Children aged 0-1 year from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Cord blood sCD14 concentrations were measured. Pediatrician evaluation and questionnaire interviews were performed periodically until 1 year of age to determine the children's allergic and respiratory symptoms. RESULTS: Two hundred and six 1-year-old subjects were enrolled. Wheeze was positively associated with cord blood sCD14, a family member with asthma and parental smoking. Prolonged cough was associated with cord blood sCD14, older maternal age and more siblings. In the multivariate logistic regression analysis, cord blood sCD14 was the only independent predictive biomarker for wheeze and prolonged cough by 1 year of age. Every 100-ng/ml increase in cord blood sCD14 resulted in a 1.56-fold higher risk of developing wheeze and a 1.62-fold higher risk of prolonged cough in children by 1 year of age. CONCLUSIONS: Cord blood sCD14 may be a useful biomarker for predicting infant wheeze and prolonged cough by 1 year of age.

Maternal vitamin D levels are inversely related to allergic sensitization and atopic diseases in early childhood.

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.

Serum 25-hydroxyvitamin D levels in relation to lung function and exhaled nitric oxide in children.

OBJECTIVE: To investigate the relationship of vitamin D status with lung function and fraction of exhaled nitric oxide (FeNO) in a population sample of children. STUDY DESIGN: A total of 1315 children aged 5-18 years were evaluated using serum 25-hydroxyvitamin D [25(OH)D] levels, spirometry, a single-breath online FeNO measurement, and questionnaires. RESULTS: After adjusting for confounders, the mean forced vital capacity was 53.4 mL (SE, 26.5 mL; P = .045), and the mean forced expiratory volume in 1 second was 48.2 mL (SE, 23.6 mL; P = .042) lower for children with insufficient serum 25(OH)D levels (20-29.9 ng/mL) compared with those with sufficient 25(OH)D levels (≥30 ng/mL). The mean difference between children with deficient (<20 ng/mL) and sufficient levels of serum 25(OH)D was 81.9 mL (SE, 26.7 mL; P = .002) for forced vital capacity and 55.2 mL (SE, 23.7 mL; P = .020) for forced expiratory volume in 1 second. There was no significant association between serum 25(OH)D levels and FeNO after adjusting for confounders. CONCLUSIONS: Our results demonstrate a significant relationship between insufficient serum vitamin D levels and worse lung function in children in the community with a suggested dose-response effect. Our findings also suggest that vitamin D status is not a significant determinant of FeNO in children in the general population.

Low cord blood vitamin D levels are associated with increased milk sensitization in early childhood.

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.

Factors associated with proceeding to surgical intervention and recurrence of primary spontaneous pneumothorax in adolescent patients.

UNLABELLED: Primary spontaneous pneumothorax (PSP) is not uncommon, and its recurrence is often a challenging clinical problem. Surgical management and predisposing factors for the recurrence of PSP, however, have not yet been well elucidated in adolescent patients. The major aim of this study was to investigate factors associated with proceeding to surgical intervention and recurrence of PSP in adolescents. Two hundred and nineteen episodes of PSP in 171 adolescent patients were retrospectively reviewed. The clinical and radiological spectrum of PSP and factors for proceeding to surgical intervention were assessed in these 171 patients. Risk factors for the recurrence of PSP were further analyzed in 128 patients with first attack of PSP. The male-to-female ratio of the 171 PSP patients was 9:1, and the mean age was 17.6 ± 1.5 years. The median body mass index (BMI) percentile was 11 (range 2-31), and 45 (34 %) patients had underweight BMI. The incidence of recurrent PSP was high with a total recurrence rate of 21 %. Ipsilateral recurrence rate of PSP after video-assisted thoracoscopic surgery (VATS) was much less than that of the conservative treatment (4 vs. 18 %). A large-size pneumothorax with a persistent air leak was the most significant factor for proceeding to VATS surgery (P = 0.001). In addition, it was a significant factor influencing the recurrence of PSP (P = 0.014). Other factors that did not significantly affect the recurrence rate were BMI, smoking status, and the number of bullae. CONCLUSION: Adolescent PSP has a high recurrence rate of 21 % after a 2-year follow-up. A large-size pneumothorax with a persistent air leak may not only lead to surgical intervention but also the risk of a recurrence of PSP. The initial size of pneumothorax may not only guide the management process but also predict the risk of a recurrence in adolescent patients with PSP.

Vitamin D level is inversely related to allergen sensitization for risking atopic dermatitis in early childhood.

Background: There are few studies concerning the impact of serum vitamin D status on the risk of allergen sensitization and atopic dermatitis (AD) during early childhood. Method: Children with AD and age-matched healthy controls (HC) were prospectively enrolled at age 0.5, 2, and 4 years. Serum 25-hydroxyvitamin D (25[OH]D) level was measured using Elecsys Vitamin D Total assay. The study utilized the ImmunoCAP assay to analyze specific IgE for food and inhalant allergens, along with total serum IgE levels. It explored the connection between vitamin D levels and allergen sensitization, as well as their influence on AD at different ages. Results: A total of 222 children including 95 (59 AD and 36 HC), 66 (37 AD and 29 HC), and 61 (32 AD and 29 HC) children were classified at age 0.5, 2, and 4 years, respectively. In children with AD, there was a significantly lower vitamin D level at age 2 and 4, but a significantly higher prevalence of food and mite sensitization at all ages in comparison with HC (P < 0.001). Vitamin D level was found to be inversely related to the prevalence of allergen sensitization at age 4 (P < 0.05). However, vitamin D level appeared to have high importance for allergen sensitization at all ages and AD at age 2 and 4 years. Conclusion: Vitamin D deficiency is strongly associated with heightened prevalence of allergen sensitization, potentially increasing the susceptibility to AD in early childhood.