Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide in children with asthma.

OBJECTIVE: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and obstruction. AHR to stimuli that indirectly cause bronchial smooth muscle (BSM) contractions via release of endogenous mediators is thought to better reflect airway inflammation than AHR to stimuli that act directly on BSM. Fractional exhaled nitric oxide (FeNO) is a useful parameter for noninvasive clinical airway inflammation assessments. Accordingly, this study aimed to examine the relationships of mannitol and methacholine challenge test outcomes with FeNO and the influence of inhaled corticosteroid treatment in children with asthma. METHODS: One hundred thirty-four asthmatic children (89 males; ages: 5-17 years, median: 9 years) underwent spirometry, FeNO measurement, serum total/specific IgE testing, and blood eosinophil count. All subjects were challenged with mannitol dry powder (MDP; AridolH, Pharmaxis, Australia) and methacholine at 7-day intervals. Data of steroid-treated and steroid-naïve children were compared. RESULTS: Positive responses to MDP and methacholine challenge tests were observed in 74.6% and 67.2% of total subject group, respectively, and 72 children had positive response to both challenge tests. The median FeNO level, response-dose ratio (RDR) of PC20 methacholine, and RDR of PD15 MDP were significantly higher in the steroid-treated group than in the steroid-naïve group (p < 0.001, 0.226, and 0.004, respectively). FeNO levels associated significantly with PD15 MDP and RDR PD15 MDP in total subject populations (p = 0.016 and 0.003, respectively); however, a significant correlation between FeNO and RDR PD15 MDP was observed only in the steroid-naïve group. CONCLUSIONS: Compared with AHR to methacholine, AHR to MDP more closely reflected the level of FeNO in steroid-naïve asthmatic children.

Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: We aimed to systematically review observational studies investigating the relationship between vitamin D levels and allergic rhinitis (AR). METHODS: Studies were selected if they evaluated the relationship between vitamin D levels and AR, and included studies that evaluated other allergic conditions if those studies also contained data on AR. We assessed the incidence and prevalence of AR according to vitamin D levels and compared vitamin D levels in patients with AR to levels in controls. RESULTS: Nineteen studies were selected. Of these, only seven focused solely on AR; 10 studies evaluated the other allergic diseases as well as AR; and two studies evaluated asthma primarily, but also included data on patients with AR. The pooled odds ratios (ORs) for the incidence of AR according to vitamin D levels were not statistically significant for either children or adults. Lower vitamin D levels were associated with a higher AR prevalence only in children (pooled OR [95% confidence interval (CI)], 0.75 [0.58, 0.98]). The pooled mean vitamin D level in patients with AR was lower than that of controls only in children (pooled means difference [95% CI], -7.63 [-13.08, -2.18]). CONCLUSIONS: Prior vitamin D levels were not related to developing AR, but lower vitamin D levels were associated with a higher AR prevalence only in children. There is insufficient evidence to support vitamin D supplementation for AR prevention. However, physicians should consider evaluating patients for vitamin D deficiency during AR management, especially in children.

Serum clusterin level in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a marker to assess inflammatory diseases. The clusterin levels in AD have not been evaluated thus far. OBJECTIVE: We evaluated serum clusterin levels in children with AD and assessed the relationship between serum clusterin levels and the severity of AD. METHOD: The study enrolled a total 140 children, of whom 100 had AD (n = 100) and 40 were healthy (n = 40). The severity of AD was scored by using the SCORing Atopic Dermatitis (SCORAD). Total serum immunoglobulin E and specific immunoglobulin E levels against egg whites, cow's milk, peanuts, soybeans, wheat, and Dermatophagoides farinae were measured. Clusterin levels in serum were measured by enzyme-linked immunosorbent assay. RESULTS: The mean (interquartile range) age of the children was 5.1 years (1.3-8.4 years), and 92 (69.3%) of the children were boys. The mean (standard deviation) SCORAD index was 50.4 ± 17. The mean (standard deviation) clusterin level of children with AD was higher than that in the healthy control group children (148.13 ± 4.3 pg/mL versus 144.85 ± 5.1 pg/mL; p = 0.001). Serum clusterin levels were correlated with the SCORAD index (r = 0.327, p = 0.002). CONCLUSIONS: The serum clusterin level was higher in children with AD than in the healthy control group and increased with the severity of AD. Serum clusterin may be a candidate molecule that reflects AD and its severity.

Genome-wide association study of recalcitrant atopic dermatitis in Korean children.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. OBJECTIVE: We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. METHODS: Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. RESULTS: SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10(-8)). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10(-6), including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. CONCLUSION: Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.

The association between platelet count and metabolic syndrome in children and adolescents.

UNLABELLED: The goal of this study was to evaluate the association between platelet count and metabolic syndrome (MetS) in children and adolescents in Korea. This study included data from 2228 subjects (1201 boys and 1027 girls) who participated in the 2010-2012 Korean National Health and Nutrition Examination Survey (KNHANES-V). We used the modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria to define MetS. Odds ratios (95% confidence intervals [CIs]) for MetS were calculated with a multiple logistic regression analysis after adjusting for confounding factors across platelet count quartiles. The overall prevalence of MetS according to the modified NCEP-ATP III criteria was 4.9% (± 0.7%) in boys and 5.7% (± 0.9%) in girls. The prevalence of MetS significantly increased with increasing platelet quartiles in both boys and girls. In a multiple logistic regression analysis, the adjusted ORs (95% CIs) for the highest vs. the lowest quartile were 5.03 (1.30-19.48) in boys and 4.08 (1.20-13.93) in girls after adjusting for age and total cholesterol. CONCLUSIONS: Higher platelet count was associated with increased prevalence and risk of MetS in children and adolescents.

Relationship between serum γ-glutamyltransferase level and leukocyte count in Korean children and adolescents.

BACKGROUND: Elevated γ-glutamyltransferase (GGT) is an important risk factor for cardiometabolic diseases, which may result from chronic low-grade inflammation. Leukocyte count is widely considered a marker of inflammation and is also an independent predictor of cardiometabolic diseases. This study aimed to determine the relationship between GGT and leukocyte count in a representative sample of Korean children and adolescents. METHODS: A nationwide cross-sectional study was conducted to examine the relationship between GGT and leukocyte count in 830 boys and 714 girls (aged 10-18 years), using data from the 2010-2012 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) for high leukocyte count (≥ 75th percentile) were calculated across GGT quartiles using multiple logistic regression analyses. RESULTS: Leukocyte count gradually increased in accordance with serum GGT quartiles in both boys and girls (all p-values < 0.001). The OR (95% CI) for high leukocyte of the highest GGT quartile was 2.19 (1.05-4.58) for boys and 2.36 (1.13-4.93) for girls after adjusting for age, BMI, blood pressure, total cholesterol, triglyceride, physical activity, household income, and residential area. Similarly, these positive associations were observed in multiple logistic regression analysis using log2-transformed serum GGT as a continuous variable. CONCLUSIONS: The present study demonstrates a positive relationship between serum GGT and leukocyte count. These findings indicate that serum GGT may be closely related with subclinical low-grade inflammation in children and adolescents.

Effect of breastfeeding on lung function in asthmatic children.

Effect of breastfeeding on the protective effect on asthma has been studied extensively but remains controversial. Studies regarding the effect of breastfeeding on lung function have also been conflicting. The aim of this study was to determine the influence of breastfeeding on lung function in asthmatic children. We included 555 patients who visited Severance Children's Hospital Allergy Clinic with asthma. Pulmonary function, its bronchodilator response (BDR), fractional nitric oxide, and sputum eosinophils were measured. Parents completed questionnaires with information on feeding practices, family history of allergic disease, exposure to tobacco smoke, and presence of pets. Breastfeeding duration was categorized as not breastfed, breastfed <6 months, and breastfed ≥6 months. Within the asthma group, we stratified by atopic sensitization. We also investigated whether exclusivity of breastfeeding had any modifying effect on lung function. In the asthma group, ratio of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) significantly increased according to breastfeeding duration: 86.6 ± 8.7 for not breastfed group, 87.2 ± 8.6 for <6 months group, and 88.8 ± 7.7 for ≥6 months group. Within asthma group, only the nonatopic subjects showed a significant increase of FEV1/FVC, maximal midexpiratory flow, and decrease of maximal response to BD according to breastfeeding duration. Increase in FEV1/FVC was seen in the exclusive breastfeeding for ≥6 months group compared with those partially breastfed but FVC was significantly lower in those exclusively breastfed <6 months group compared with those partially breastfed. BDR decreased with breastfeeding duration in the nonatopic asthma group. In conclusion, longer duration of breastfeeding appears to have a favorable effect on lung function in asthmatic children, especially in nonatopic subjects.

IgE reactivity to carbohydrate moieties of glycoproteins in wheat allergy.

Carbohydrate moieties of different glycoproteins, such as cross-reactive carbohydrate determinants (CCDs) and galactose α-1,3-galactose, can induce IgE reactivity with varied clinical significance. In this study, the possible participation of glycan from wheat gliadin, with respect to its IgE-binding capacity, was investigated in children with food allergies to wheat. Total IgE and wheat-specific IgE quantification, documentation of history, and/or oral food challenge (OFC) were performed for 52 children. Subjects with positive wheat-specific IgE were characterized as the symptomatic group, never-exposed group, or asymptomatic group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and glycan detection in gliadin were performed. IgE binding to gliadin and deglycosylated gliadin was measured by immunoblotting and ELISA. Gliadin-specific IgE was detected and correlated with wheat-specific IgE in the symptomatic, never-exposed, and asymptomatic groups. The glycan range overlapped significantly with the gliadin range. Deglycosylation of gliadin reduced the allergenicity of gliadin. In gliadin, the allergenicity of the glycan portion was greater in the symptomatic group than in the never-exposed and asymptomatic groups. We conclude that N-glycan in gliadin might exhibit allergenicity as a possible carbohydrate epitope in wheat allergy in children.

Modulation of IL-8 boosted by Mycoplasma pneumoniae lysate in human airway epithelial cells.

Mycoplasma pneumoniae, a major cause of community-acquired pneumonia, has been recognized as a trigger for asthma inception and exacerbation. The epithelial cells on the respiratory tract parasitized by M. pneumoniae exhibit a number of cytopathic effects as a result of local inflammation and stimulated host immune response. We investigated the interactions of signaling molecules regulating the release of IL-8 by the direct stimulation of M. pneumoniae lysate (MPL) in human airway epithelial cells. In human airway epithelial cells, MPL-induced IL-8 proteins were decreased by monoclonal anti-TLR2 antibody in a dose-dependent fashion, and significantly blocked by siRNA TLR2. The pharmacologic inhibitors of ERK, U0126 and PD98059, effectively reduced IL-8 expression and the active forms of ERK signaling molecules, as detected by anti-phosphorylated p44/42 antibody. The region spanning from -132 to +41 in the IL-8 promoter demonstrated the highest luciferase activity against MPL and the mutations of NF-κB and NF-IL6 entirely diminished the activity. After investigating transfections of the NF-κB and NF-IL6 reporter vectors, NF-IL6 activation was significantly induced by MPL stimulation, which was considerably decreased by U0126 and monoclonal anti-TLR2 antibody. These results indicate that MPL-induced IL-8 increase is transcriptionally regulated by NF-IL6 more than by NF-κB. Additionally, the activation of NF-IL6 is influenced by TLR2 and ERK signaling pathways in airway epithelial cells.

Association of genetic variation in chitotriosidase with atopy in Korean children.

BACKGROUND: The atopic diseases, which are the most common chronic diseases of childhood, are complex genetic diseases that involve the contribution of multiple genetic factors to disease pathophysiology. Chitotriosidase is involved in innate immunity, but the association of chitotriosidase with allergic diseases remains unclear. OBJECTIVE: To examine the contribution of genetic variation of the chitotriosidase-encoding gene CHIT1 to atopic phenotypes in a Korean cohort of children. METHODS: We identified CHIT1 variations in a Korean population and conducted association analyses using 295 atopic and 242 nonatopic children. An independent replication study was performed using DNA samples from 148 atopic and 243 nonatopic children. All children were unrelated. We performed Western blot analysis in each genotype in vitro to see whether the CHIT1 A442G variation affects the final protein expression levels. RESULTS: In the case-control association analysis, atopy was significantly associated with a single A442G (rs1065761) polymorphism in CHIT1 (odds ratio = 1.32, P = .01). Children with the c.442G risk allele had significantly higher blood eosinophils (P = .001), total serum IgE (P = .007), and eosinophil cationic protein (P = .02) levels. The results of the replication stage analysis confirmed a significant association between the A442G polymorphism and childhood atopy. The joint analysis of the exploratory and replication studies displayed a stronger significant association. The relative protein expression levels of chitotriosidase were significantly higher in both cell lysate and media with the G transfection compared with the wild type. CONCLUSION: These results indicate that the nonsynonymous A442G polymorphism in CHIT1 is associated with risk of atopy.

Association between eosinophilic airway inflammation and persistent airflow limitation.

OBJECTIVE: We aimed to evaluate the association between eosinophilic inflammation in induced sputum and pulmonary function and persistent airflow limitation in children. METHODS: A total of 92 asthmatic children and 72 controls were enrolled in this study. Eosinophil count (%) and eosinophil cationic protein (ECP) levels were measured in induced sputum. We performed spirometry and a methacholine challenge test, and measured total eosinophil count, total serum IgE, and serum ECP in all subjects. RESULTS: Asthmatic children had significantly higher levels of sputum eosinophils (9% vs. 0%; P < 0.001) and sputum ECP (2.3 ± 0.7 vs. 1.6 ± 0.6 log µg/L, p < .001) than controls. Sputum ECP levels showed a significant negative correlation with post-bronchodilator (post-BD) FEV(1) (r = -0.307; p = .001) and post-BD FEV(1)/FVC (r = -0.286; p = .002), whereas sputum eosinophils showed no correlation with post-BD FEV(1) and post-BD FEV(1)/FVC. However, no significant differences in sputum ECP and sputum eosinophil counts were observed in asthmatic children with and without persistent airflow limitation. CONCLUSIONS: Our findings suggest that sputum eosinophilic inflammation, especially ECP, is associated with pulmonary function and persistent airflow limitation, which is manifested by low post-BD FEV(1)/FVC.

Clinical characteristics of eosinophilic and noneosinophilic asthma in children.

AIM: Asthma is a heterogeneous and complex chronic inflammatory disease of the airways. Asthma can be classified as eosinophilic asthma (EA) or noneosinophilic asthma (NEA). We investigated whether children with EA manifest different clinical characteristics than those with NEA. METHODS: We enrolled 288 steroid-naive asthmatic children and classified them, based on the cell counts in induced sputum, into EA (158 children) and NEA (89 children) groups. RESULTS: No significant differences were observed between the groups with regard to age, sex, family history of atopy, secondary smoking or asthma exacerbations. Moderate-to-severe asthma was more frequent in the EA group than in the NEA group. Blood eosinophil counts and serum eosinophil cationic protein were higher in EA patients than in NEA patients. The forced expiratory volume in 1 sec was lower in children with EA than in those with NEA (% of predicted value, 88.6 ± 18.5 vs. 93.6 ± 15.6, p < 0.05). The sputum eosinophil (in EA) and neutrophil (in NEA) counts increased with increasing asthma severity. CONCLUSION: Airway inflammation, especially eosinophilic inflammation, was associated with asthma severity and reduced pulmonary function in children.

Avoidable causes of delayed enteral nutrition in critically ill children.

To evaluate the incidence of delayed enteral nutrition (EN) and identify avoidable causes of delay, we retrospectively reviewed medical records of 200 children (median age [range]; 37.5 [1-216] months) who stayed in the intensive care unit (ICU) for a minimum of 3 days. Among 200 children, 115 received EN following ICU admission with a median time of EN initiation of 5 days after admission. Of these, only 22 patients achieved the estimated energy requirement. A significant decrease in the final z score of weight for age from the initial assessment was observed in the non-EN group only (-1.3±2.17 to -1.57±2.35, P<0.001). More survivors than non-survivors received EN during their ICU stay (61.2% vs 30.0%, P=0.001) and received EN within 72 hr of ICU admission (19.8% vs 3.3%, P=0.033). The most common reason for delayed EN was gastrointestinal (GI) bleeding, followed by altered GI motility and hemodynamic instability. Only eight cases of GI bleeding and one case of altered GI motility were diagnosed as active GI bleeding and ileus, respectively. This study showed that the strategies to reduce avoidable withholding EN are necessary to improve the nutrition status of critically ill children.

Prognostic usefulness of eosinopenia in the pediatric intensive care unit.

Eosinopenia, a biomarker for infection, has recently been shown to be a predictor of adult mortality in the intensive care unit (ICU). Our study assessed the usefulness of eosinopenia as a mortality and an infection biomarker in the pediatric ICU (PICU). We compared the PICU mortality scores, eosinophil count and percentage at ICU admission between children who survived and those who did not survive and between children with infection and those without infection. A total of 150 patients were evaluated. The initial eosinophil count and percentage were significantly lower in the group that did not survive when compared to those that did survive (P < 0.001; P < 0.001). However, there was no significant difference in the eosinophil count and percentage seen in patients with and without infection. Eosinopenia, defined as an eosinophil count < 15 cells/µL and an eosinophil percentage < 0.25%, (hazard ratio [HR]: 2.96; P = 0.008) along with a Pediatric Index of Mortality (PIM) 2 (HR: 1.03; P = 0.004) were both determined to be independent predictors of mortality in the PICU. The presence of eosinopenia at the ICU admission can be a useful biomarker for mortality in children, but is not useful as a biomarker for infection.

Involvement of the MAPK and PI3K pathways in chitinase 3-like 1-regulated hyperoxia-induced airway epithelial cell death.

BACKGROUND: Exposure to 100% oxygen causes hyperoxic acute lung injury characterized by cell death and injury of alveolar epithelial cells. Recently, the role of chitinase 3-like 1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, in oxidative stress was demonstrated in murine models. High levels of serum CHI3L1 have been associated with various diseases of the lung, such as asthma, chronic obstructive pulmonary disease, and cancer. However, the role of CHI3L1 in human airway epithelial cells undergoing oxidative stress remains unknown. In addition, the signaling pathways associated with CHI3L1 in this process are poorly understood. PURPOSE: In this study, we demonstrate the role of CHI3L1, along with the MAPK and PI3K signaling pathways, in hyperoxia-exposed airway epithelial cells. METHOD: The human airway epithelial cell line, BEAS-2B, was exposed to >95% oxygen (hyperoxia) for up to 72h. Hyperoxia-induced cell death was determined by assessing cell viability, Annexin-V FITC staining, caspase-3 and -7 expression, and electron microscopy. CHI3L1 knockdown and overexpression studies were conducted in BEAS-2B cells to examine the role of CHI3L1 in hyperoxia-induced apoptosis. Activation of the MAPK and PI3K pathways was also investigated to determine the role of these signaling cascades in this process. RESULTS: Hyperoxia exposure increased CHI3L1 expression and apoptosis in a time-dependent manner. CHI3L1 knockdown protected cells from hyperoxia-induced apoptosis. In contrast, CHI3L1 overexpression promoted cell death after hyperoxia exposure. Finally, phosphorylation of ERK1/2, p38, and Akt were affected by CHI3L1 knockdown. CONCLUSION: This study indicates that CHI3L1 is involved in hyperoxia-induced cell death, suggesting that CHI3L1 may be one of several cell death regulators influencing the MAPK and PI3K pathways during oxidative stress in human airway epithelial cells.

A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children.

BACKGROUND: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. OBJECTIVE: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. METHODS: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. RESULTS: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P = .001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P = .004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P = .01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. CONCLUSIONS: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.

Patterns of psychosocial adaptation and allergic disorders in Korean schoolchildren.

BACKGROUND: To date, there is little evidence to support an association between symptoms of pediatric allergic disorders and psychosocial factors in the general population, particularly in Asian countries. The current study aims to investigate the relationship between psychosocial factors and symptoms of allergic disorders and to investigate the association between behavior problems and biomarkers of atopy. METHODS: A cross-sectional survey of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the Korean version of the Child Behavior Checklist (CBCL) was conducted from one elementary school in Seoul, Korea. Skin prick tests for 18 major allergens were also performed. RESULTS: A total of 780 children with valid CBCL surveys were included in the study. Externalizing problems were significantly larger in children with asthmatic symptoms, while internalizing problems were significantly larger in children with symptoms of both asthma and allergic rhinitis. Social adaptations were significantly lower in children with symptoms of allergic rhinitis and atopic dermatitis. Boys with more positive allergens via the skin prick tests showed larger internalizing problems. CONCLUSIONS: While school children with allergic symptoms have been reported to have more difficulties with psychosocial adaptation, the patterns of psychosocial problems varied somewhat according to the types of atopic disorder. There was a positive relationship between atopy and behavior problems, especially in boys.

Involvement of IL-10 gene promoter polymorphisms in the susceptibility for childhood asthma.

Asthma and atopy have a complex background that may result from the interaction of genes and the environment. Interleukin (IL)-10 is known to play various roles in immune-regulating and anti-inflammatory responses. The aim of this study was to evaluate the possible effect of the IL-10 promoter polymorphisms on susceptibility to childhood asthma. We recruited 333 patients with atopic asthma, 55 with nonatopic asthma, and 248 normal controls. We performed a genetic association study of three genetic polymorphisms (IL-10 -1082A>G, IL-10 -819T>C, and IL-10 -592A>C) of the IL-10 promoter. There was no difference between atopic asthma, nonatopic asthma, and normal controls with respect to allele, genotype, or haplotype frequencies of these IL-10 polymorphisms. However, the -1082A>G polymorphism and ATA haplotype in the IL-10 promoter gene were associated with airway hyper responsiveness (AHR) and the -819T>C, -592A>C, and ATA and ACC haplotypes were also shown to be related to serum eosinophil cationic protein (ECP). Our results suggest that the polymorphisms within the IL-10 promoter may have a disease-modifying effect in the asthmatic airway.

5-Lipoxygenase-activating protein (FLAP) inhibitor MK-0591 prevents aberrant alveolarization in newborn mice exposed to 85% oxygen in a dose- and time-dependent manner.

Bronchopulmonary dysplasia is characterized by prolonged oxygen dependency due to compromised gas-exchange capability. This is attributable mainly to inadequate and aberrant alveolarization resulting from insults like hyperoxia. Leukotrienes are associated with hyperoxia-induced inhibition of alveolarization. We hypothesized that a 5-lipoxygenase-activating protein (FLAP) inhibitor given while newborn mice were exposed to 85% oxygen would prevent aberrant alveolarization in a dose- and time-dependent manner. Newborn mice were exposed to either room air or hyperoxia for 14 days. Pups were treated with either vehicle or MK-0591 10, 20, or 40 mg/kg subcutaneously daily for days 1-4, 5-9, or 10-14. On day 14, the lungs were inflated, fixed, and stained for histopathological and morphometric analyses. Hyperoxia groups treated with MK-0591 20 or 40 mg/kg during days P1-P4 or P10-P14 showed alveolarization that resembled that of room air controls while untreated hyperoxia groups showed definite evidence of aberrant alveolarization but no inflammation. In a hyperoxia-exposed newborn mice model, a FLAP inhibitor given during critical window periods may prevent aberration of alveolarization in a dose- and time-dependent manner.

Prevalence of allergic diseases among Korean school-age children: a nationwide cross-sectional questionnaire study.

The purpose of this study was to investigate the nationwide prevalence of childhood asthma, eczema and other allergic diseases in Korean school-age children (8-11 yr old) and to assess the difference between residential areas. Among 6,279 elementary schools, 427 schools were randomly selected according to residential area (metropolitan, provincial, rural, and industrial area) by the cluster sampling method. Parents of students completed a modified Korean version of a questionnaire formulated by the International Study of Asthma and Allergies in Childhood (ISAAC). Among 50,200 subjects, 31,026 (61.8%) responded, and 30,893 (99.6%) were analyzed. The 12-month prevalence of wheeze, flexural rash, and allergic rhinitis symptoms were 4.8%, 15.3%, and 32.9%, respectively. The prevalence of diagnosis of allergic diseases in boys was higher than that in girls, with the exception of eczema. In both boys and girls, the difference of the prevalence of allergic diseases among industrial, metropolitan and provincial areas was not statistically significant, but the differences between rural area and other areas were significant. Our results support the importance of contextual effect associated with residential area as causative agents of allergic diseases among Korean school-age children.