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.

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.

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.

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.

Prenatal exposure to bisphenol-A is associated with Toll-like receptor-induced cytokine suppression in neonates.

BACKGROUND: Despite widespread human exposure to biphenol A (BPA), limited studies exist on the association of BPA with adverse health outcomes in young children. This study aims to investigate the effect of prenatal exposure to BPA on toll-like receptor-induced cytokine responses in neonates and its association with infectious diseases later in life. METHODS: Cord bloods were collected from 275 full-term neonates. Production of TNF-α, IL-6, and IL-10 were evaluated after stimulating mononuclear cells with toll-like receptor ligands (TLR1-4 and 7-8). Serum BPA concentrations were analyzed by enzyme-linked immunosorbent assay. Bacteria from nasopharyngeal specimens were identified with multiplex PCR and culture method. RESULT: Result showed significant association between cord BPA concentration and TLR3- and TLR4-stimulated TNF-α response (P = 0.001) and that of TLR78-stimulated IL-6 response (P = 0.03). Clinical analysis did not show prenatal BPA exposure to be correlated with infection or bacterial colonization during the first year of life. CONCLUSION: This is the first cohort study that indicated prenatal BPA exposure to play a part in TLR-related innate immune response of neonatal infants. However, despite an altered immune homeostasis, result did not show such exposure to be associated with increased risk of infection during early infancy.

Maternal Vitamin D Level Is Associated with Viral Toll-Like Receptor Triggered IL-10 Response but Not the Risk of Infectious Diseases in Infancy.

Reports on the effect of prenatal vitamin D status on fetal immune development and infectious diseases in childhood are limited. The aim of this study was to investigate the role of maternal and cord blood vitamin D level in TLR-related innate immunity and its effect on infectious outcome. Maternal and cord blood 25 (OH)D level were examined from 372 maternal-neonatal pairs and their correlation with TLR-triggered TNF-α, IL-6, and IL-10 response at birth was assessed. Clinical outcomes related to infection at 12 months of age were also evaluated. The result showed that 75% of the pregnant mothers and 75.8% of the neonates were vitamin deficient. There was a high correlation between maternal and cord 25(OH)D levels (r = 0.67, p < 0.001). Maternal vitamin D level was inversely correlated with IL-10 response to TLR3 (p = 0.004) and TLR7-8 stimulation (p = 0.006). However, none of the TLR-triggered cytokine productions were associated with cord 25(OH)D concentration. There was no relationship between maternal and cord blood vitamin D status with infectious diseases during infancy. In conclusion, our study had shown that maternal vitamin D, but not cord vitamin D level, was associated with viral TLR-triggered IL-10 response.

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.

Exclusive breastfeeding is associated with reduced cow's milk sensitization in early childhood.

BACKGROUND: Although breastfed infants have consistently been reported as having fewer infections and respiratory morbidity during infancy, none have reached a definitive conclusion as to whether breastfeeding is an effective strategy to prevent allergic diseases. This study aims to investigate the relationship between exclusive breastfeeding and sequential changes of several biomarkers of allergy, such as absolute eosinophil count, total IgE level, and specific IgE level during the first 3 yrs of life. METHODS: This is an unselected, population-based study that is part of a prospective birth cohort called the PATCH (Prediction of Allergy in Taiwanese Children). Blood analysis was performed at ages 6, 12, 18, 24, and 36 months. Clinical records of breastfeeding and detailed questionnaires regarding to allergic diseases were also obtained. RESULTS: Analysis comparing exclusive breastfeeding ≥4 months with those <4 months and those partially breastfed showed a decreased risk of sensitization toward cow's milk protein up to the age of 2 yr (adjusted OR for cow's milk sensitization at 12 months was 0.2 [95% CI, 0.07-0.5]), at 18 months of age it was 0.2 [95% CI, 0.07-0.5], and at 24 months of age it was 0.2 [95% CI, 0.04-0.7]). In addition, although not significant, children of the exclusive breastfeeding group showed a trend of lower absolute eosinophil counts than their counterparts at all ages, and a lower total IgE level at the age of 3 yr. CONCLUSIONS: Results of this study suggest that exclusive breastfeeding is associated with a reduced risk of cow's milk protein sensitization during early childhood.

Cytokine responses of TNF-α, IL-6, and IL-10 in G6PD-deficient infants.

G6PD-deficient adults are reported to be susceptible to severe infection, and decreased cytokine responses have been postulated as the underlying mechanism. However, investigating the association of G6PD deficiency and cytokine responses during infancy is lacking. The current study aims to determine whether cytokine responses of tumor necrosis factor ()-α, interleukins (IL)-6, and IL-10 are impaired in the G6PD-deficient infants. Upon agreements with informed consents, peripheral blood mononuclear cells (PBMCs) of enrolled infants were collected twice at 1 month and 1 year of age. PBMCs were then stimulated with toll-like receptor (TLR) agonists-including PAM3csk4 for TLR1-2, poly (I:C) for TLR3, and lipopolysaccharide for TLR4-to analyze the expression of TNF-α, IL-6, and IL-10. Males (P = .004) and phototherapy during neonatal period (P = .008) were more common among G6PD-deficient infants than G6PD-normal subjects. After the stimulation of TLR agonists, there was no significant difference in the expression of TNF-α, IL-6, and IL-10 between PBMCs of G6PD-deficient and -normal infants at both 1 month and 1 year of age. In conclusion, the clinical characteristics of G6PD-deficient infants are different from those of G6PD-normal subjects. The data suggest that the innate immune responses to TLR agonists in G6PD-deficient infants are not different from those of G6PD-normal infants.

The association between human milk fatty acid composition in mothers with an elevated body mass index and infant growth changes.

BACKGROUND & AIMS: Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life. METHODS: Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age. RESULTS: We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted ß = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories.

Cardiovascular-associated tracheobronchial obstruction in children.

Tracheobronchial compression of cardiovascular origin is an uncommon and frequently unrecognised cause of respiratory distress in children. The compression may be due to encircling vessels or dilated neighbouring cardiovascular structures. Bronchoscopy and detailed radiography, especially computed tomography and magnetic resonance imaging, are among the most powerful diagnostic tools. Few previous reports have addressed the relationship between bronchoscopic findings and underlying cardiovascular anomalies. The objective of this study was to correlate bronchoscopic and radiographic findings in children with cardiovascular-associated airway obstruction. A total of 41 patients were recruited for the study. Patients with airway obstruction were stratified on the basis of the aetiology of the cardiovascular structures and haemodynamics into an anatomy-associated group and a haemodynamics-associated group. In the anatomy-associated group, stenosis and malacia were found with comparable frequency on bronchoscopy, and the airway obstructions were mostly found in the trachea (71% of patients). In the haemodynamics-associated group, malacia was the most common bronchoscopic finding (85% of patients), and nearly all locations of airway involvement were in the airway below the carina (90% of patients). The tracheal compression was usually caused by aberrant systemic branching arteries in the anatomy-associated group. In the haemodynamics-associated group, the causal relationships varied. Tracheal compression was often caused by lesions of the main pulmonary artery and aorta, whereas obstruction of the right main bronchus was caused by lesions of the main pulmonary artery and right pulmonary artery. The causes of left main bronchus compression were more diverse. In summary, the bronchoscopic presentations and locations are quite different between these two groups.

Longitudinal investigation of pathogenic bacterial colonization in early childhood: Emphasis on the determinants of Moraxella catarrhalis colonization.

BACKGROUND: Moraxella catarrhalis is a common, potential pathogen colonizing the respiratory tract in children. However, there is little information regarding the determinants of M. catarrhalis colonization and disease development. METHODS: A population-based cohort study was conducted to collect nasopharyngeal swabs from children aged 1, 2, 4, 6, 12, 18, 24, 36, and 60 months for the detection of four common respiratory tract pathogens, including Staphylococcus aureus, M. catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae. Questionnaires on breastfeeding status were administered during each visit. RESULTS: A total of 921 children were enrolled between 2012 and 2018. S.aureus was the most common pathogen, although the rates declined during the initial 18 months of life; in contrast, the other three pathogens increased during the first 5 years of life. M. catarrhalis was the second most common colonizing pathogen in all age groups, with prevalence ranging from 0.8% (7/842) at one month to 20.4% (33/162) at 60 months of age. Breastfed children (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.35-0.92; P = 0.02) had a lower potential for M. catarrhalis carriage; however, infants with a longer duration of exclusive breastfeeding (OR: 1.12; 95% CI: 1.01-1.25; P = 0.04), especially >12 months of age, had a higher rate of M. catarrhalis carriage. CONCLUSION: Breastfeeding should be promoted because it may be correlated with a lower risk of M. catarrhalis carriage. However, an extended period of exclusive breastfeeding may be positively associated with M. catarrhalis colonization.

Introduction of Egg White and Yolk to Infant Diets and Early Childhood Atopic Dermatitis.

This study investigated whether the introduction of allergenic foods in infancy is associated with atopic dermatitis (AD) in early childhood. Information regarding parental allergic histories, the introduction of six possible allergenic foods (fruits, egg white, egg yolk, fish, shellfish, and peanuts), and physician-diagnosed AD was obtained using age-specific questionnaires (0-2 years). Immunoglobulin E, specific to 20 food allergens, was also quantified at 12 months of age. Logistic regression analyses were used to determine the association between individual food introduction and the outcomes of food sensitization and AD. We found AD development by 2 years of age was significantly related to a parental history of allergy (adjusted odds ratio (aOR) = 1.29) and not being introduced to egg white and yolk during infancy (aORs = 2.27 and 1.97, respectively). Stratified analyses revealed that the introduction of both egg white and yolk was negatively associated with AD by 2 years of age, especially for those children where both parents had allergic diseases (aOR = 0.10). In summary, the introduction of egg white and yolk to an infant's diet may be a modifiable factor in reducing the risk of physician-diagnosed AD by 2 years of age, which may be particularly important for infants where both parents have allergies.

Longitudinal analysis of the impact of smoking exposure on atopic indices and allergies in early childhood.

Background: Exposure to smoking is recognized as a health hazard; however, a longitudinal analysis of the impact of smoking exposure in families on the allergic reactions related to childhood atopic diseases has not been well addressed. Methods: Children who completed a three-year follow-up period from the birth cohort were included in this study. The history of smoking exposure was recorded, and the urine cotinine levels were measured at 1 and 6 months, and 1, 2, and 3 years of age. Specific IgE levels against food and mite allergens were measured at age 6 months, and 1, 2, and 3 years. Their relevance to family smoking exposure and the subsequent development of atopic diseases was also analyzed. This study was approved by the Ethics Committee of Chang Gung Memorial Hospital (No. 102-1842C). Results: A total of 198 infants were enrolled in this study. The prevalence of passive smoking exposure among these children was as high as 45%. The urine cotinine levels were significantly higher in children with history of smoking exposure (P < 0.001). At 6 months of age, the food-specific IgE levels and the prevalence of eczema were significantly higher in children with smoking exposure than in those without smoking exposure (P < 0.05). By contrast, the urine cotinine levels were significantly higher in children with IgE sensitization (>100 kU/L, P < 0.05) at 3 years of age, which was also significantly associated with a higher prevalence of allergic rhinitis and development of asthma (P < 0.01). Conclusion: Family smoking exposure appears to be strongly associated with food sensitization in infancy and with IgE production in later childhood. This could potentially increase the susceptibility of developing infantile eczema and subsequent childhood airway allergies.

The respiratory impacts of air pollution in children: Global and domestic (Taiwan) situation.

Air pollution is a global issue that threatens the health of human beings. Epidemiologic reports have shown air pollution exposures to result in millions of deaths annually. Infancy and childhood, the period of organ and lung development, is most susceptible to these environmental hazards; as a result, the risks of respiratory diseases are increased after air pollution exposure. These pollutants can originate from indoor and ambient environment, presenting as vapor or particles, and differ in chemical compositions. This review will give brief introduction to various major pollutants and their origin, as well the correlation with respiratory diseases after exposure. We will also present several current facts in domestic area (Taiwan), regarding the status of local air-pollution, and discuss its impacts on pediatric respiratory health. This report will provide useful information for clinicians and offer advice for policy makers to develop public health guidelines of pollution control and prevention.

Association between Serum Zinc and Toll-like-Receptor- Related Innate Immunity and Infectious Diseases in Well-Nourished Children with a Low Prevalence of Zinc Deficiency: A Prospective Cohort Study.

Existing reports focus on zinc-associated immunity and infection in malnourished children; however, whether zinc also plays an important role in the immune homeostasis of the non-zinc-deficient population remained unknown. This study aimed to investigate the association between zinc status and toll-like receptor (TLR)-related innate immunity and infectious outcome in well-nourished children. A total of 961 blood samples were collected from 1 through 5 years of age. Serum zinc was analyzed, and mononuclear cells isolated to assess TNF-α, IL-6, and IL-10 production by ELISA after stimulation with TLR ligands. Childhood infections were analyzed as binary outcomes with logistic regression. The prevalence of zinc deficiency was 1.4-9.6% throughout the first 5 years. There was significant association between zinc and TLR-stimulated cytokine responses. Higher serum zinc was associated with decreased risk of ever having pneumonia (aOR: 0.94; 95% CI: 0.90, 0.99) at 3 years, and enterocolitis (aOR: 0.96; 95% CI: 0.93, 0.99) at 5 years. Serum zinc was lower in children who have had pneumonia before 3 years of age (72.6 ± 9 vs. 81.9 ± 13 µg/dL), and enterocolitis before 5 years (89.3 ± 12 vs. 95.5 ± 13 µg/dL). We emphasize the importance of maintaining optimal serum zinc in the young population.