IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation.

BACKGROUND: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. METHODS: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. RESULTS: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. CONCLUSION: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.

Serum high-mobility group box 1 protein level correlates with the lowest SaO2 in patients with sleep apnea: a preliminary study / Nível sérico da proteína de alta mobilidade do grupo Box-1 está associado à SaO2 mais baixa em pacientes com apneia do sono: um estudo preliminar

Abstract Introduction: Serum level of high-mobility group box 1 protein is reportedly correlated with the severity of obstructive sleep apnea. Objective: We tried to evaluate the possibility of using the serum high-mobility group box 1 protein level as a biologic marker in obstructive sleep apnea patients. Methods: We generated a chronic intermittent hypoxia murine model that reflected human obstructive sleep apnea. Obstructive sleep apnea patients who underwent polysomnography were prospectively enrolled. Serum samples were obtained from mice and obstructive sleep apnea patients, and the serum high-mobility group box1 protein level was measured by enzyme-linked immunosorbent assay. Results: Serum high-mobility group box 1 protein level was 56.16 ± 30.33 ng/mL in chronic intermittent hypoxia and 18.63 ± 6.20 ng/mL in control mice (p<0.05). The mean apnea-hypopnea index and respiratory disturbance index values of enrolled obstructive sleep apnea patients were 50.35 ± 27.96 and 51.56 ± 28.53, respectively, and the mean serum high-mobility group box 1 protein level was 30.13 ± 19.97 ng/mL. The apnea-hypopnea index and respiratory disturbance index were not significantly correlated with the serum high-mobility group box 1 protein level (p>0.05). Instead, this protein level was significantly correlated with lowest arterial oxygen concentration (SaO2) (p<0.05). Conclusion: High-mobility group box 1 protein may be involved in the pathogenesis of obstructive sleep apnea, and the possibility of this protein being a useful biologic marker in obstructive sleep apnea should be further evaluated.

Resumo Introdução: O nível sérico da proteína de alta mobilidade do grupo Box-1 está relacionado com a gravidade da apneia obstrutiva do sono. Objetivo: Avaliar o uso do nível sérico da proteína de alta mobilidade do grupo Box-1 como um marcador biológico em pacientes com apneia obstrutiva do sono. Método: Geramos um modelo murino de hipóxia intermitente crônica que imita a apneia obstrutiva do sono em humanos. Pacientes com apneia obstrutiva do sono que fizeram polissonografia foram incluídos prospectivamente. Amostras de soro foram obtidas de camundongos e pacientes com apneia obstrutiva do sono e o nível sérico da proteína de alta mobilidade do grupo Box-1 foi medido por enzyme-linked immunosorbent assay. Resultados: O nível sérico da proteína de alta mobilidade do grupo Box-1 foi 56,16 ± 30,33 ng/mL em hipóxia intermitente crônica e 18,63 ± 6,20 ng/mL em camundongos controle (p < 0,05). Os valores médios do índice de apneia-hipopneia e do índice de distúrbio respiratório nos pacientes com apneia obstrutiva do sono foram 50,35 ± 27,96 e 51,56 ± 28,53, respectivamente, e o nível médio da proteína de alta mobilidade do grupo Box-1 foi 30,13 ± 19,97 ng/mL. O índice de apneia-hipopneia e o índice de distúrbio respiratório não foram significantemente associados com o nível da proteína de alta mobilidade do grupo Box-1 p> 0,05). Em vez disso, esse nível de proteína foi significantemente associado com o valor mais baixo da concentração arterial de oxigênio (SaO2) (p <0,05). Conclusão: A proteína de alta mobilidade do grupo Box-1 pode estar envolvida na patogênese da apneia obstrutiva do sono e a possibilidade de que essa proteína possa ser um marcador biológico útil na apneia obstrutiva do sono deve ser avaliada mais detalhadamente.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study.

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5-15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

Clinical characteristics and etiologies of bronchiectasis in Korean children: A multicenter retrospective study.

BACKGROUND: Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children. METHODS: We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017 at 28 secondary or tertiary hospitals in South Korea. RESULTS: A total of 387 cases were enrolled. The mean age at diagnosis was 9.2 ±â€¯5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1 s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency. CONCLUSIONS: Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.

Representative levels of blood lead, mercury, and urinary cadmium in youth: Korean Environmental Health Survey in Children and Adolescents (KorEHS-C), 2012-2014.

BACKGROUND: This study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3-18 year-old Korean children and adolescents. MATERIALS AND METHODS: We used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012-2014 and identified 2388 children and adolescents aged 3-18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father's education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times. RESULTS: The median levels of blood lead and mercury, as well as urinary cadmium were 1.23µg/dL, 1.80µg/L, and 0.40µg/L (95% CIs, 1.21-1.25, 1.77-1.83, and 0.39-0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010. CONCLUSION: Sociodemographic factors, including age, sex, and father's education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population.

Efficacy of pamidronate in pediatric osteosarcoma patients with low bone mineral density.

PURPOSE: Most surviving pediatric osteosarcoma patients experience osteoporosis, bone pain, and pathologic fracture during and after therapy. The aim of this study was to evaluate the efficacy and side effects of pamidronate therapy in these patients. METHODS: Nine osteosarcoma patients (12.8±1.6 years of age; 5 boys and 4 girls) who had a history of nontraumatic fracture or severe pain after completing chemotherapy were included. Intravenous pamidronate (1.5 mg/kg) was given every 6 weeks for 4 to 6 cycles. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry. Clinical outcomes including acute side effects were also evaluated. RESULTS: After pamidronate treatments, all patients experienced decreased pain. Seven of 9 patients could walk without a crutch. The BMD of lumbar spine was increased by 0.108±0.062 mg/cm(2) after 8.4±1.0 months (n=8, P=0.017) and the mean z-score improved from -2.14±0.94 to -1.76±0.95 (P=0.161). Six patients (67%) had an acute-phase reaction, and 2 patients had symptomatic hypocalcemia. CONCLUSION: Pamidronate appears to be safe and effective for the treatment of osteosarcoma in children with low BMD and bone pain.

Tuberculosis-associated hemophagocytic lymphohistiocytosis in adolescent diagnosed by polymerase chain reaction.

We present a case of tuberculosis-associated hemophagocytic lymphohistiocytosis in a 14-year-old girl. The patient presented with weight loss, malaise, fatigue, prolonged fever, and generalized lymphadenopathy. Laboratory investigation revealed pancytopenia (white blood cells, 2,020 cells/µL; hemoglobin, 10.2 g/dL; platelets, 52,000 cells/µL), hypertriglyceridemia (229 mg/dL), and hyperferritinemia (1,420 ng/mL). Bone marrow biopsy showed a hypocellular bone marrow with a large numbers of histiocytes and marked hemophagocytosis; based on these findings, she was diagnosed with hemophagocytic lymphohistiocytosis. Polymerase chain reaction (PCR) with both the bone marrow aspiration and sputum samples revealed the presence of Mycobacterium tuberculosis. Antitubercular therapy with immune modulation therapy including dexamethasone and intravenous immunoglobulin was initiated. The results of all laboratory tests including bone marrow biopsy and PCR with both the bone marrow aspiration and sputum samples were normalized after treatment. Thus, early bone marrow biopsy and the use of techniques such as PCR can avoid delays in diagnosis and improve the survival rates of patients with tuberculosis-associated hemophagocytic lymphohistiocytosis.

Modification of additive effect between vitamins and ETS on childhood asthma risk according to GSTP1 polymorphism: a cross -sectional study.

BACKGROUND: Asthma is characterized by airway inflammation, and bronchial airways are particularly susceptible to oxidant-induced tissue damage. OBJECTIVE: To investigate the effect of dietary antioxidant intake and environmental tobacco smoke (ETS) on the risk of childhood asthma according to genotypes susceptible to airway diseases. METHODS: This cross-sectional study included 1124 elementary school children aged 7-12 years old. Asthma symptoms and smoking history were measured using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Intake of vitamin A (including retinol and ß-carotene), C, and E was measured by a semi-quantitative food frequency questionnaire (FFQ). GSTP1 polymorphisms were genotyped from peripheral blood samples. RESULTS: ETS was significantly associated with presence of asthma symptoms (adjusted odds ratio [aOR], 2.48; 95 % confidence interval [CI], 1.29-4.76) and diagnosis (aOR, 1.91; 95 % CI, 1.19-3.06). Dietary antioxidant intake was not associated with asthma symptoms, although ETS plus low vitamin A intake showed a significant positive association with asthma diagnosis (aOR, 2.23; 95 % CI, 1.10-4.54). Children with AA at nucleotide 1695 in GSTP1 who had been exposed to ETS and a low vitamin A intake have an increased risk of asthma diagnosis (aOR, 4.44; 95 % CI,1.58-12.52) compared with children who had not been exposed to the two risk factors. However, ETS exposure and low vitamin A intake did not significantly increase odds of asthma diagnosis in children with AG or GG genotypes. CONCLUSION: Low vitamin A intake and ETS exposure may increase oxidative stress and thereby risk for childhood asthma. These relationships may be modified by gene susceptibility alleles of GSTP1.

Bone mineral density change during adjuvant chemotherapy in pediatric osteosarcoma.

PURPOSE: Osteoporosis is currently receiving particular attention as a sequela in survivors of childhood osteosarcoma. The aim of this study was to evaluate bone mineral density (BMD) changes during methotrexate-based chemotherapy in children and adolescents with osteosarcoma. METHODS: Nine patients with osteosarcoma were included in this retrospective study and compared with eight healthy controls. BMD of the lumbar spine and unaffected femur neck of patients was serially measured by dual-energy x-ray absorptiometry (DXA) before and just after chemotherapy and compared with controls. RESULTS: Four patients (44%) showed decreased lumbar spine BMD and seven patients (78%) showed decreased femur neck BMD, while all controls showed increased lumbar and femur BMD (P=0.024 and P=0.023). The femur neck BMD z-scores decreased from -0.49±1.14 to -1.63±1.50 (P=0.032). At the end of therapy, five patients (56%) showed femur neck BMD z-scores below -2.0. CONCLUSION: The bone metabolism is disturbed during therapy in children with osteosarcoma, resulting in a reduced BMD with respect to healthy controls. Since a reduced BMD predisposes to osteoporosis, specific attention and therapeutic interventions should be considered.

Prenatal Particulate Matter/Tobacco Smoke Increases Infants' Respiratory Infections: COCOA Study.

PURPOSE: To investigate whether prenatal exposure to indoor fine particulate matter (PM2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects. METHODS: The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician's diagnosis. Indoor PM2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis. RESULTS: Prenatal exposure to indoor PM2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM2.5 and ETS exposure were not found for upper RTIs. CONCLUSIONS: Prenatal exposure to both indoor PM2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.

The Association of Lung Function, Bronchial Hyperresponsiveness, and Exhaled Nitric Oxide Differs Between Atopic and Non-atopic Asthma in Children.

PURPOSE: Although many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA. METHODS: One hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured. RESULTS: The AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only. CONCLUSIONS: These findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR.

Low vitamin D levels are associated with both iron deficiency and anemia in children and adolescents.

BACKGROUND: We aimed to examine the association between vitamin D deficiency and anemia in a nationally representative sample of Korean children and adolescents. METHODS: Cross-sectional data on 2526 children and adolescents aged 10-20 years from the Korea National Health and Nutrition Examination Survey-V (2010-2012) were used. Anemia was defined according to specifications of the World Health Organization. Iron deficiency was defined as serum ferritin level of <12 ng/mL and transferrin saturation (TSAT) <16%. RESULTS: The prevalence of vitamin D deficiency in Korean children and adolescents was high especially in female (35.7% vs. 50.9%, P < 0.001). The prevalence of anemia was also higher in female (1.1% vs. 6.8%; P < 0.001). In logistic regression, risk factors for anemia were female sex, old age, post-menarche, low household income, vitamin D deficiency, and iron deficiency. The Odds Ratio for anemia, iron deficiency and iron deficiency anemia (IDA) in subjects with vitamin D deficiency (<15 ng/mL) were 1.81(95% CI, 1.13-2.88), 1.94(95% CI, 1.27-2.97), and 2.26 (95% CI, 1.20-4.24) after controlling for other risk factors. However, after examining the sexes separately, only female subjects showed statistical significance. After further controlling for iron deficiency, the risk of anemia was not significant (P = 0.261). CONCLUSIONS: Vitamin D deficiency is associated with increased risk of anemia, especially iron deficiency anemia, in healthy female children and adolescents. However, the association is attenuated after adjustment for iron deficiency. Further studies are needed to determine whether vitamin D deficiency is the cause of anemia, or bystander of nutritional deficiency which cause iron deficiency.

The hemoglobin values of Korean adolescents show distinctive characteristics in comparison to those of Caucasians and African Americans.

BACKGROUND: Hematologic reference values vary by ethnicity. We aimed to determine reference values of hemoglobin (Hb) for Korean adolescents. METHODS: Using data from the 5th Korean National Health and Nutrition Examination Survey (KNHANES), we obtained reference values for Hb in adolescents aged 10-20 years. RESULTS: Among 2,526 subjects recruited, 330 were excluded due to chronic diseases (9 congenital heart disease, 6 epilepsy, and 1 thyroid disease) or abnormal laboratory values (253 subjects with Fe/TIBC <16%, 103 subjects with MCV <80 fl). Accordingly, data from 2,196 subjects (male = 1,196 and female = 1,000) were analyzed and age- and gender-stratified means and percentile values of Hb were obtained. Pertinent findings observed in the current study were: (i) Hb levels in Korean male were similar to those of non-Hispanic Caucasians; (ii) Hb values in females were similar to those of non-Hispanic Caucasians until age of 15, and thereafter were slightly lower. Prevalence of anemia according to WHO criteria and our own criteria (Hb levels <2 standard deviations of age- and gender-specific values) in total sample was 3.5% (88/2,526) and 3.8% (97/2,526), respectively. Anemia was more prevalent in female in comparison with male (6.5% vs. 1.0%, P < 0.001). CONCLUSIONS: Our results could be used as a national reference standard to correctly classify a large population sample. Further studies are necessary to determine reference Hb values for children younger than 10 years and identify genetic variations associated with distinctive characteristics observed in this study.

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BACKGROUND: This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. METHODS/DESIGN: The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child's neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child's genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child's exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child's neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child's microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures. DISCUSSION: The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.

Giant juvenile fibroadenoma of the breast: a case report and brief literature review.

A girl (age, 12 years 11 months) consulted the pediatric endocrinology clinic because of a rapidly growing right breast mass over 13 cm observed during the preceding 3 months. A surgical excision was performed, and the mass was diagnosed as a giant juvenile fibroadenoma. Giant juvenile fibroadenomas are rare, usually occurring between 10 and 18 years of age, and characterized by massive and rapid enlargement of an encapsulated mass. The etiology is believed to be an end-organ hypersensitivity to normal levels of estrogen. We report a case of giant juvenile fibroadenoma and present a review of the diagnostic workup and management of a large breast tumor during adolescence.

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.

Toxic inhalational injury-associated interstitial lung disease in children.

Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment.

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 ß-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, ß-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.

Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma.

PURPOSE: Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma. METHODS: The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed. RESULTS: The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r(2)=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively). CONCLUSIONS: Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.