Jung Yeon Shim

TGF‐β effects on airway smooth muscle cell proliferation, VEGF release and signal transduction pathways

Background and objective:  Airway smooth muscle (ASM) cell hyperplasia is a key feature of airway remodelling. Mitogen‐activated protein kinase (MAPK) and phosphoinositide 3‐kinase (PI3K) are key components in signal transduction associated with cell proliferation; MAPK consists of the extracellular signal‐regulated kinase (ERK), p38MAPK and c‐Jun NH2‐terminal kinase (JNK). The effect of transforming growth factor (TGF)‐β on the proliferation of ASM cells, the release of vascular endothelial growth factor (VEGF) by ASM cells and relevant signal transduction pathways were investigated.

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.

Clinical Significance of Serum Procalcitonin in Patients with Community-acquired Lobar Pneumonia

BACKGROUND Community-acquired pneumonia (CAP) is a common respiratory disorder in children, which necessitates hospitalization. Bacterial pneumonia, especially lobar pneumonia and parapneumonic effusions, is associated with considerably severe clinical course and extensive alveolar infiltrates. Serum procalcitonin (PCT) level has been used to distinguish bacterial from viral infections, but its usefulness is disputed. The diagnostic accuracy and usefulness of PCT, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count were determined by comparing their values in the patients with CAP with those in healthy controls. METHODS The serum PCT levels, as well as CRP level, ESR, and WBC counts, were measured in 76 hospitalized patients with CAP (lobar pneumonia, 16; bronchopneumonia, 60) and 18 healthy controls. Serum PCT level was measured using VIDAS BRAHMS PCT (Biomerieux, France), and ROC curve analysis was performed to evaluate its diagnostic accuracy. RESULTS Serum PCT levels were higher in the patients with CAP than in healthy controls, especially in the patients with lobar pneumonia than in those with bronchopneumonia. Serum CRP level was also significantly elevated in the patients with CAP, especially in those with lobar pneumonia. The diagnostic accuracy of serum PCT level for the diagnosis of lobar pneumonia was better than those of serum CRP level and ESR. The serum PCT level was significantly correlated with the CRP level, ESR, and WBC count. CONCLUSIONS Serum PCT level was a better marker than CRP level or ESR for the diagnosis of lobar pneumonia in children with CAP.

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.

Serum vascular endothelial growth factor in pediatric patients with community-acquired pneumonia and pleural effusion.

This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion.

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.

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.

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.