Sui-Ling Liao

Suboptimal Vitamin D Status in a Population-Based Study of Asian Children: Prevalence and Relation to Allergic Diseases and Atopy

Background New evidence shows high prevalence of vitamin D deficiency in many countries and some studies suggest a possible link between vitamin D status and allergic diseases. The objectives of this study were to determine the prevalence of suboptimal vitamin D status in a population sample of Asian children and to investigate the relationship of vitamin D status with allergic diseases and atopy. Methods Children aged 5–18 years (N = 1315) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were evaluated using questionnaires, anthropometric measurements, and serum levels of 25-hydroxyvitamin D [25(OH)D] and total and specific immunoglobulin E (IgE). Results The mean concentration of serum 25(OH)D was 20.4 ng/mL (SD: 7.1 ng/mL). Vitamin D deficiency (defined as serum 25(OH)D<20 ng/mL) was present in 670 subjects (51.0%), while vitamin D insufficiency (defined as serum 25(OH)D<30 ng/mL) was observed in 1187 subjects (90.3%). Older age (P<0.001), female gender (P<0.001), higher body mass index (P = 0.001), winter and spring seasons (compared to summer; P both<0.001), and passive smoking (P = 0.011) were independently associated with low serum 25(OH)D levels. After adjusting for potential confounders, serum 25(OH)D status had no association with asthma, rhinitis, eczema, atopy, or total serum IgE (all P>0.05). Conclusions Low serum 25(OH)D levels are remarkably common in this population sample of Asian children, suggesting that millions of children living in Taiwan may have suboptimal levels of vitamin D, which should be a matter of public health concern. Our results provides epidemiological evidence against the association of vitamin D status with various allergic diseases and atopy in Asian children.

Maturation of Toll-like receptor 1-4 responsiveness during early life.

BACKGROUND Toll-like receptors (TLRs) are part of the highly conserved components of the innate immune system, and have been investigated extensively; however, little is known about TLR function during early postnatal life, a critical period for immune maturation. AIMS In order to achieve a more complete understanding of the ontogeny of immune system during the first years of life, our study investigated age-matched TLR1-4 responsiveness at several time points up to the age of two years. STUDY DESIGN Mononuclear cells were isolated from cord blood (n=150) and peripheral blood from infants at 6 (n=68), 12 (n=75), and 24 (n=74)months of age, and from 50 adults. Cells were stimulated with Toll-like receptor ligands (TLR1-4) and phytohemagglutinin (PHA). Stimulated cells were assessed for their production of the cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and for TLR4 gene expression. RESULTS Our results suggested that cord response of IL-6 and TNF-α was not affected by allergic background. In addition, neonatal mononuclear cell had enhanced IL-6 production upon TLR1, 2, and 4 stimulations as compared to those of young children and adults. Nevertheless, after 6 months of age, the level remained comparable throughout the first two years of life. While TNF-α response to all TLR stimulations remained fairly similar during early life. This cytokine pattern closely paralleled our findings for TLR4 mRNA expression, and longitudinal cytokine changes within the same individual. CONCLUSIONS Our findings provided additional information to the understanding of immune development during early life, and offered stronger evidence of neonatal innate immunity being capable of responding adequately to TLR stimulation.

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

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.

Value of Lung Ultrasonography in the Diagnosis and Outcome Prediction of Pediatric Community-Acquired Pneumonia with Necrotizing Change.

Background Lung ultrasonography has been advocated in diagnosing pediatric community-acquired pneumonia. However, its function in identifying necrotizing pneumonia, a complication, has not been explored. This study investigated the value of lung ultrasonography in diagnosing pediatric necrotizing pneumonia and its role in predicting clinical outcomes. Methods We retrospectively reviewed 236 children with community-acquired pneumonia who were evaluated using lung ultrasonography within 2–3 days after admission. The ultrasonographic features assessed included lung perfusion, the presence of hypoechoic lesions, and the amount of pleural effusion. Chest computed tomography was also performed in 96 patients as clinically indicated. Detailed records of clinical information were obtained. Results Our results showed a high correlation between the degree of impaired perfusion in ultrasonography and the severity of necrosis in computed tomography (r = 0.704). The degree of impaired perfusion can favorably be used to predict massive necrosis in computed tomography (area under the receiver operating characteristic curve, 0.908). The characteristics of impaired perfusion and hypoechoic lesions in ultrasonography were associated with an increased risk of pneumatocele formation (odds ratio (OR), 10.11; 95% CI, 2.95–34.64) and the subsequent requirement for surgical lung resection (OR, 8.28; 95% CI, 1.86–36.93). Furthermore, a longer hospital stay would be expected if moderate-to-massive pleural effusion was observed in addition to impaired perfusion in ultrasonography (OR, 3.08; 95% CI, 1.15–8.29). Conclusion Lung ultrasonography is favorably correlated with chest computed tomography in the diagnosis of necrotizing pneumonia, especially regarding massive necrosis of the lung. Because it is a simple and reliable imaging tool that is valuable in predicting clinical outcomes, we suggest that ultrasonography be applied as a surrogate for computed tomography for the early detection of severe necrotizing pneumonia in children.

Metabolomics Reveals Dynamic Metabolic Changes Associated with Age in Early Childhood

Objectives A detailed understanding of the metabolic processes governing rapid growth in early life is still lacking. The aim of this study was to investigate the age-related metabolic changes in healthy children throughout early childhood. Methods Healthy children from a birth cohort were enrolled in this study from birth through 4 years of age. Urinary metabolites were assessed at 6 months, and 1, 2, 3, and 4 yr of age by using 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis including principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). Metabolic pathway analysis was performed using the MetPA web tool. Results A total of 105 urine samples from 30 healthy children were collected and analyzed. Metabolites contributing to the discrimination between age groups were identified by using supervised PLS-DA (Q2 = 0.60; R2 = 0.66). A significantly higher urinary trimethylamine N-oxide (TMAO) and betaine level was found in children aged 6 months. Urinary glycine and glutamine levels declined significantly after 6 months of age and there was a concomitant compensatory increase in urinary creatine and creatinine. Metabolic pathway analysis using MetPA revealed similar nitrogen metabolism associated energy production across all ages assessed. Pathways associated with amino acid metabolism were significantly different between infants aged 6 months and 1 year, whereas pathways associated with carbohydrate metabolism were significantly different between children at ages 2 and 3 years. Conclusions Urine metabolomics ideally represents dynamic metabolic changes across age. Urinary metabolic profiles change significantly within the first year of life, which can potentially provide crucial information about infant nutrition and growth.

Multiplexed immunoglobulin E sensitization in relation to exhaled nitric oxide in a population sample of children

This study investigated the relationship between the specific immunoglobulin E (IgE) profile for 40 allergens using a novel microarray technique (BioIC) and fraction of exhaled nitric oxide (FeNO) in a population sample of 1321 children. Significant positive associations were found between FeNO and sensitization to mites (P < 0.001), animals (P = 0.001), cockroaches (P < 0.001), and foods (P = 0.042), and furthermore, between FeNO and the number of sensitizations (all P < 0.05) or the sum of specific IgE (all P ≤ 0.01) against the aforementioned allergen categories. Specifically, sensitization to the following allergens was significantly related to higher FeNO: Dermatophagoides pteronyssinus, Dermatophagoides farina, Blomia tropicalis, cat, German cockroach, Oriental cockroach, codfish, crab, shrimp, and cheese (all P ≤ 0.01). In conclusion, IgE sensitization to mites, pets, cockroaches, seafood, and cheese, respectively, is significantly associated with elevated FeNO levels in a dose‐dependent fashion in children. Our results provide new evidence that sensitization to certain food allergens may contribute to prompt inflammation in the airways.

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.

Tobacco smoke exposure and multiplexed immunoglobulin E sensitization in children: a population‐based study

Although there is evidence that exposure to tobacco smoke is harmful to childrens respiratory health, the effects of tobacco smoke exposure on the regulation of immunoglobulin E (IgE)‐mediated immune responses to specific allergens remain unclear. This study aimed to investigate the relationship between objectively assessed tobacco smoke exposure and specific IgE profiles for a broad spectrum of allergens in a population setting.

Obesity disproportionately impacts lung volumes, airflow and exhaled nitric oxide in children

Background The current literature focusing on the effect of obesity and overweight on lung function and fraction of exhaled nitric oxide (FeNO) in children, particularly among healthy children of non-European descent, remains controversial. Furthermore, whether the relationship of obesity and overweight with lung function and FeNO in children is modified by atopy is unclear. The objective of this study was to examine the effect of excess weight on lung function parameters and FeNO among Asian children, with a particular focus on exploring the potential effect modification by atopy. Methods We investigated the effect of excess weight on lung function and FeNO in a population sample of 1,717 children aged 5 to 18 years and explored the potential modifying effect of atopy. Results There were positive associations of body mass index (BMI) z-score with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and forced expiratory flow at 25–75% (FEF25-75) (all P<0.001), after controlling for confounders. The beta coefficient for FEV1 (0.084) was smaller than that for FVC (0.111). In contrast, a negative association was found between BMI z-score and FEV1/FVC ratio (P<0.001) and FeNO (P = 0.03). A consistent pattern of association for lung function variables was observed when stratifying by atopy. There was a negative association of BMI z-score with FeNO in atopic subjects (P = 0.006), but not in non-atopic subjects (P = 0.46). Conclusions Excess weight disproportionately impacts lung volumes and airflow in children from the general population, independent of atopic status. Excess weight inversely affects FeNO in atopic but not in non-atopic children.