Dae Jin Song

Allergic Diseases in Preschoolers Are Associated With Psychological and Behavioural Problems

Purpose The aim of the present study was to investigate the relationship between three major allergic diseases, asthma, allergic rhinitis (AR), and atopic dermatitis (AD), and psychological and behavioural problems in preschoolers based on a community survey. Methods A cross-sectional survey was conducted using a modified International Study of Asthma and Allergies in Childhood questionnaire to determine the prevalence of symptoms and diagnosed allergic diseases, and a Korean version of the Child Behaviour Checklist to assess internalizing, externalizing, and sleep problems among 780 preschoolers. Five-hundred and seventy-five preschoolers with valid data were included in this study. Results The prevalence of lifetime diagnosis and treatment in the past 12 months was 8.7% and 4.4% for asthma, 24.4% and 19.2% for AR, and 35.1% and 16.6% for AD, respectively. Scores for internalizing and sleep problems were significantly higher in those diagnosed with AR. Preschoolers who had been treated for AD in the past 12 months had higher attention problem and attention-deficit/hyperactivity disorder scores. Sleep problems were more severe in moderate to severe AD compared to control and mild AD groups, categorised according to SCOring index of AD. The severity of sleep problems correlated positively with the percentage of eosinophils in peripheral blood. Conclusions Psychological and behavioural problems differed among the three major allergic diseases, weaker association for asthma and stronger association for AR and AD. The results of this study may lead to the identification of potential underlying shared mechanisms common to allergic diseases and psychological and behavioural problems.

Additive Effect between IL-13 Polymorphism and Cesarean Section Delivery/Prenatal Antibiotics Use on Atopic Dermatitis: A Birth Cohort Study (COCOA)

Background Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act additively to promote the development of AD in infancy. Methods The Cohort for Childhood of Asthma and Allergic Diseases (COCOA) was selected from the general Korean population. A pediatric allergist assessed 412 infants for the presence of AD at 1 year of age. Their cord blood DNA was subjected to interleukin (IL)-13 (rs20541) and cluster-of-differentiation (CD)14 (rs2569190) genotype analysis. Results The combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (adjusted odds ratio, 5.70; 95% CI, 1.19–27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. There was a trend of interaction between IL-13 (rs20541) and delivery mode with respect to the subsequent risk of AD. (P for interaction = 0.039) Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had a lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05). Conclusion Cesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic predisposition.

Effect of paracetamol use on the modification of the development of asthma by reactive oxygen species genes.

BACKGROUND Recent studies have identified an increase in the prevalence of asthma associated with paracetamol use. OBJECTIVE To identify the relationship among asthma, biomarkers, genes, and paracetamol use in preschool children. METHODS We undertook a population-based, cross-sectional survey of 933 preschool children. Asthma status was classified according to medical history and asthmatic symptoms. History of paracetamol use in infancy was recorded. Impulse oscillometry, blood tests for eosinophils and total IgE, and genotyping of NAT2, Nrf2, and GSTP1 polymorphisms by TaqMan assay were conducted. RESULT Paracetamol use in infancy was associated with an increased risk of treatment for asthma within the previous 12 months. Paracetamol use together with a family history of asthma increased the risk of asthma diagnosis ever, current asthma, and treatment for asthma within the previous 12 months. Gene polymorphisms in NAT2 (rs4271002), Nrf2 (rd6726395), and GSTP1 (rd1695) increased the risk of treatment for asthma within the last 12 months. Eosinophils were significantly elevated in the group with paracetamol use and a family history of asthma; however, the serum total IgE level and IOS did not show any significant difference. CONCLUSION Paracetamol use in infancy was significantly associated with increased risk of asthma. The association is more significant in genetically susceptible children, related to antioxidant genes, and the effect may be mediated by eosinophilic inflammation.

Fraction of exhaled nitric oxide and wheezing phenotypes in preschool children.

Asthma is a chronic lower airway inflammatory disease. Nitric oxide is an inflammatory mediator produced endogenously in the airway. Previous studies have demonstrated that the fractional concentration of exhaled nitric oxide (FeNO) is increased in asthma.

Clinical Application of Exhaled Nitric Oxide Measurements in a Korean Population

Nitric oxide (NO) is a biologic mediator of various physiologic functions. Recent evidence suggests the clinical utility of fractional exhaled NO (FeNO) as a biomarker for assessing asthma and other respiratory diseases. FeNO methodologies have been recently standardized by international research groups and subsequently validated in several Korean population studies. Normal ranges for FeNO have been reported for various ethnic groups, and the clinical utility has been widely evaluated in asthma and various respiratory diseases. Based on current evidence including most of Korean population data, this position paper aims to introduce the methodological considerations, and provide the guidance for the proper clinical application of FeNO measurements in Korean populations.

Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)

Purpose Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. Methods The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. Results The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). Conclusion The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.

Reference Values of Impulse Oscillometry and Its Utility in the Diagnosis of Asthma in Young Korean Children

Aims. The aims of this study were (1) to determine the reference values for impulse oscillometry (IOS) and (2) to apply them to the evaluation of asthma in the general population of young Korean children. Methods. We performed a questionnaire survey and IOS measurements in 390 children aged 3–7 years in Seoul and Gyeonggi province, Korea, from July to August 2010. IOS measurements included respiratory resistance (Rrs) and respiratory reactance (Xrs) at 5, 10, 15, 20, 25, and 35 Hz, respiratory impedance (Zrs), and resonance frequency (RF) before and 15 min after inhalation of 200 μg salbutamol. To determine the reference values for IOS, 161 children defined as healthy controls were assessed. Results. The IOS measurements were presented as means and standard deviations. The reference equations for IOS variables were determined by multiple linear regression analysis taking into account their height, weight, and age (R5 = 2.242 – 0.008 × height (cm) – 0.005 × age (months), coefficients of determination (R2) = 0.213). Height had the greatest correlation with IOS variables, similar to previous studies. Positive airway obstruction was defined as R5 greater than the 95th percentile of predicted R5 from the reference equation. There was a higher percentage of children with positive airway obstruction in children with asthma than in healthy controls (27.3% vs. 6.2%). Multivariate logistic regression analysis indicated that positive airway obstruction was a significant risk factor for the diagnosis of asthma (adjusted odds ratio (aOR), 6.245; 95% confidence interval (CI), 2.270–17.175). Conclusion. This study provided reference values for IOS in young Korean children and applied the reference values to evaluate children with asthma. We suggest the 95th percentile of predicted R5 as a cut-off value for positive airway obstruction, which may increase the risk for diagnosis of asthma.

Association of Antioxidants With Allergic Rhinitis in Children From Seoul

Purpose The prevalence of allergic diseases has risen over the last few decades. Many factors, including environmental factors such as those related to diet, have been considered. Among dietary factors, intake of antioxidant-related nutrients has been associated with the risk of allergic disease. We investigated the association of antioxidant nutritional status with allergic rhinitis (AR) in Korean schoolchildren aged 6-12 years. Methods Subjects were 4,554 children in Seoul, Korea. The risk of allergic disease was measured using the Korean version of the International Study of Asthma and Allergies in Childhood, and dietary intake was measured by a semi-quantitative food frequency questionnaire. Intake of vitamins A (including retinol and β-carotene), C, and E was used in the analysis. Results Vitamin C intake was negatively associated with an increased risk of current symptoms (adjusted odds ratio, 0.886; 95% confidence interval, 0.806-0.973). There was no association between AR and intake of vitamin A, retinol, β-carotene, or vitamin E. Total serum IgE level and sensitization to allergen did not differ according to nutrient intake. Conclusions The group of children with increased vitamin C consumption had fewer AR symptoms, despite the lack of a difference in total serum IgE level or allergen sensitization. These findings suggest that nutrient intake, especially that of vitamin C, influences AR symptoms.

Predictive value of C-reactive protein in response to macrolides in children with macrolide-resistant Mycoplasma pneumoniae pneumonia

Purpose The prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) has increased worldwide. The aim of this study was to estimate the proportion of MRMP in a tertiary hospital in Korea, and to find potential laboratory markers that could be used to predict the efficacy of macrolides in children with MRMP pneumonia. Methods A total of 95 patients with M. pneumoniae pneumonia were enrolled in this study. Detection of MRMP was based on the results of specific point mutations in domain V of the 23S rRNA gene. The medical records of these patients were reviewed retrospectively and the clinical course and laboratory data were compared. Results The proportion of patients with MRMP was 51.6% and all MRMP isolates had the A2063G point mutation. The MRMP group had longer hospital stay and febrile period after initiation of macrolides. The levels of serum C-reactive protein (CRP) and interleukin-18 in nasopharyngeal aspirate were significantly higher in patients who did not respond to macrolide treatment. CRP was the only significant factor in predicting the efficacy of macrolides in patients with MRMP pneumonia. The area under the curve for CRP was 0.69 in receiver operating characteristic curve analysis, indicating reasonable discriminative power, and the optimal cutoff value was 40.7 mg/L. Conclusion The proportion of patients with MRMP was high, suggesting that the prevalence of MRMP is rising rapidly in Korea. Serum CRP could be a useful marker for predicting the efficacy of macrolides and helping clinicians make better clinical decisions in children with MRMP pneumonia.

The relationship between asthma and bronchiolitis is modified by TLR4, CD14, and IL-13 polymorphisms.

Asthma is a complex genetic disorder that is associated with both genetic and environmental factors. The aim of study was to investigate the combined effect of toll‐like receptor 4 (TLR4), cluster of differentiation 14 (CD14), and interleukin‐13 (IL‐13) polymorphisms and bronchiolitis in the development of childhood asthma.