Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department.

BACKGROUND: Croup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited. The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). POPULATION AND METHOD: Patients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. RESULT: In total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842-0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711-0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. CONCLUSION: NLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

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.

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.

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 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.

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.

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.

In-hospital care of children with COVID-19.

Children have been reported to be less affected and to have milder severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults during the coronavirus disease 2019 (COVID-19) pandemic. However, children, and particularly those with underlying disorders, are still likely to develop critical illnesses. In the case of SARS-CoV-2 infection, most previous studies have focused on adult patients. To aid in the knowledge of in-hospital care of children with COVID-19, this study presents an expert review of the literature, including the management of respiratory distress or failure, extracorporeal membrane oxygenation (ECMO), multisystem inflammatory syndrome in children (MIS-C), hemodynamic and other organ support, pharmaceutical therapies (anti-viral drugs, anti-inflammatory or antithrombotic therapies) and management of cardiopulmonary arrest.

Early postnatal and concurrent exposure to metals and neurobehavioral outcomes at 5 years: Associations with individual environmental exposures and mixtures.

BACKGROUND: Little is known about the effect of postnatal exposure to heavy metals on children's behavior problems. This study aimed to investigate the association between metal exposure during different stages of postnatal life and neurobehavioral outcomes in preschool children. METHODS: Urinary concentrations of six metals (arsenic, cadmium, chromium, lead, manganese, and vanadium) were measured using inductively coupled plasma mass spectrometry in 220 participants at two time points: before 1 year and at 5 years of age. Mothers completed the Child Behavior Checklist when the children were 5 years old. Multivariable linear and logistic regression analyses were used to evaluate the association between metal concentrations and behavioral outcomes. We employed Bayesian kernel machine regression (BKMR) to assess possible joint effects and potential interactions between metal mixtures and behavioral outcomes. RESULTS: Concentrations of urinary arsenic (As) in infants were associated with higher scores for anxious/shy behavior problems (ß ranging from 0.03 to 0.23). Further analyses showed that As exposure increased the odds of scores falling into the borderline or clinical range on anxious/depressed, affective, and pervasive developmental problems (ORs: 2.45-3.40). Stratification by sex indicated significance in girls but not in boys. BKMR analysis showed that, among the metal mixtures, As displayed a major effect on behavior scores. Concentrations of urinary cadmium in infants were also associated with higher behavioral scores but did not increase the risk of clinical problems. A cross-sectional survey in 5-year-olds did not show a significant association between concurrent metal exposure and behavioral outcome. CONCLUSION: Our results showed that exposure to As and Cd during infancy was associated with emotional problems in children. The effect of arsenic exposure was more pronounced among female infants. We suggest reducing exposure to toxic metals during early postnatal life to prevent behavioral problems in children."

Macrolide-resistant Mycoplasma pneumoniae in children in Taiwan.

The aim of this study was to estimate the prevalence of macrolide-resistant Mycoplasma pneumoniae in Taiwan and to compare the clinical courses of pediatric patients with macrolide-resistant (MR) M. pneumoniae and macrolide-susceptible (MS) M. pneumoniae infection. Patients were among the children admitted to Chang Gung Children's Hospital with mycoplasmal pneumonia between February and December 2011. Detection for macrolide resistance was performed after informed consent was obtained. We retrospectively reviewed medical records and compared the clinical courses of two groups of patients of 73 children enrolled into our study. The rate of macrolide resistance in M. pneumoniae was 12.3 %. Longer hospital stay was observed in the MR patients than MS patients [median, 7 days vs. 5 days (P = 0.019)]. Clinical features or radiographic or laboratory findings are not helpful to differentiate MR from MS mycoplasmal pneumonia. Early diagnosis of MR mycoplasmal pneumonia is crucial for the best management of these patients and obviates the need for extensive etiological searches of these nonresponding cases.

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.