Molecular sensitization patterns in birch pollen-sensitized Korean children according to the presence of oral allergy syndrome.

The profiles of sensitization based on component-resolved diagnosis (CRD) differ from region to region in populations sensitized to birch pollen. We investigated the endotypes of birch pollen-sensitized Korean children with allergic diseases using CRD and distinguished the endotypes of oral allergy syndrome (OAS) among them.Thirty-one birch pollen-sensitized children with allergic diseases were enrolled. Specific immunoglobulin E (IgE) to birch pollen and fruit including apple, peach, and kiwi were evaluated via skin prick tests and ImmunoCAP in all subjects. Sensitization profiles based on CRD were evaluated with the Immuno-solid-phase Allergen Chip for birch pollen-sensitization using birch pollen components (Bet v 1, Bet v 2, and Bet v 4), and for OAS using the allergen families pathogenesis-related class 10 proteins (PR-10), lipid transfer proteins, and profilin.All patients (n = 13) with OAS were sensitive to Bet v 1. However, 61% (11/18) of patients without OAS were sensitized to Bet v 1. The level of specific IgE to Bet v 1 was higher in patients with OAS than in those without OAS. All birch pollen-sensitized Korean children with OAS were sensitized to PR-10, and 69% (9/13) of them were mono-sensitized to PR-10. Among patients without OAS, 33% (6/18) were not sensitized to any of the allergen families.Birch pollen-sensitized Korean children with allergic diseases showed unique patterns of sensitization to Bet v 1, Bet v 2, and Bet v 4, and the sensitization profiles based on CRD were totally different according to the presence of OAS.

Leptin and urinary leukotriene E4 and 9α,11ß-prostaglandin F2 release after exercise challenge.

BACKGROUND: Leptin-related effects on inflammation and bronchial hyperresponsiveness (BHR) in the human airway have not been demonstrated. OBJECTIVES: To investigate the relationship between the levels of serum leptin and BHR and urinary leukotriene E4 (LTE4) and 9α,11ß-prostaglandin F2 (9α,11ß-PGF(2)) release after exercise challenge in asthmatic children. METHODS: Eighty-six prepubertal children between 6 and 10 years old were enrolled and divided into 4 groups: 19 obese asthmatic children, 25 normal-weight asthmatic children, 21 obese nonasthmatic children, and 21 healthy controls. We measured serum leptin levels and urinary LTE4 and 9α,11ß-PGF2 levels in children before and 30 minutes after the exercise challenge. RESULTS: Serum leptin levels were significantly higher in obese asthmatic children compared with normal-weight asthmatic children. Significant increases in urinary levels of LTE4 and 9α,11ß-PGF2 were observed in obese asthmatic children after the exercise challenge. Although smaller than in obese asthmatic children, significant increases in the urinary levels of LTE4 and 9α,11ß-PGF2 were also observed in the normal-weight. Asthmatic children Logarithmic serum leptin values were significantly associated with the logarithmic maximum percentage change in forced expiratory volume in 1 second, the logarithmic urinary LTE4 change, and the logarithmic urinary 9α,11ß-PGF2 change from baseline to after exercise in both obese and normal-weight asthmatic children. CONCLUSION: The serum levels of leptin were significantly associated with BHR and urinary LTE4 and 9α,11ß-PGF2 release induced by exercise challenge in asthmatic children.

Ratio of leukotriene e(4) to exhaled nitric oxide and the therapeutic response in children with exercise-induced bronchoconstriction.

PURPOSE: This study assessed the association between the ratio of leukotriene E(4) (LTE(4)) to fractional exhaled nitric oxide (FE(NO)) in the response of children with exercise-induced bronchoconstriction (EIB) enrolled in a therapeutic trial with montelukast or inhaled corticosteroid (fluticasone propionate [FP]). METHODS: Children aged 6 to 18 years with EIB were randomized in a 4-week, placebo-controlled, double-blinded trial with montelukast or FP. Before and after treatment, treadmill exercise challenges were performed. The LTE(4) levels in the induced sputum and urine and the FE(NO) levels were measured in subjects before and 30 minutes after the exercise challenges. The same tests were conducted after treatment. RESULTS: A total of 24 patients completed the study: 12 in the montelukast group and 12 in FP group. Both study groups displayed a similar postexercise maximum decrease in forced expiratory volume in one second (FEV1) before treatment as well as after treatment. However, there were significant differences in the magnitude of change between the two (Δ; -18.38±14.53% vs. -4.67±8.12% for the montelukast and FP groups, respectively; P=0.021). The Δ logarithmic sputum baseline and postexercise LTE(4)/FE(NO) ratio were significantly lower in the montelukast group than in the FP group (baseline; -0.09±0.21 vs. -0.024±0.03, P=0.045; postexercise, -0.61±0.33 vs. -0.11±0.28, P=0.023). CONCLUSIONS: These data indicate that the efficacy of montelukast for preventing a maximum decrease in FEV1 after exercise is significantly higher than that of FP, and the high LTE(4)/FE(NO) ratio is associated with a greater response to montelukast than to FP for EIB therapy. These results suggest that LTE(4) may play an important role in EIB.

Changes in sensitization rate to weed allergens in children with increased weeds pollen counts in Seoul metropolitan area.

The prevalence of allergic diseases in children has increased for several decades. We evaluated the correlation between pollen count of weeds and their sensitization rate in Seoul, 1997-2009. Airborne particles carrying allergens were collected daily from 3 stations around Seoul. Skin prick tests to pollen were performed on children with allergic diseases. Ragweed pollen gradually increased between 1999 and 2005, decreased after 2005 and plateaued until 2009 (peak counts, 67 in 2003, 145 in 2005 and 83 grains/m(3)/day in 2007). Japanese hop pollen increased between 2002 and 2009 (peak counts, 212 in 2006 and 492 grains/m(3)/day in 2009). Sensitization rates to weed pollen, especially ragweed and Japanese hop in children with allergic diseases, increased annually (ragweed, 2.2% in 2000 and 2.8% in 2002; Japanese hop, 1.4% in 2000 and 1.9% in 2002). The age for sensitization to pollen gradually became younger since 2000 (4 to 6 yr of age, 3.5% in 1997 and 6.2% in 2009; 7 to 9 yr of age, 4.2% in 1997 and 6.4% in 2009). In conclusion, sensitization rates for weed pollens increase in Korean children given increasing pollen counts of ragweed and Japanese hop.

Mycoplasma pneumoniae Infection Affects the Serum Levels of Vascular Endothelial Growth Factor and Interleukin-5 in Atopic Children.

PURPOSE: Previous studies have outlined mechanisms by which Mycoplasma pneumonia (M. pneumonia) infection may promote allergic lung inflammation and airway remodeling, and increasing evidence from human studies suggests that atypical bacterial infections contribute to asthma exacerbation, chronic asthma, and disease severity with changes in cytokine expression. The present study evaluated changes in serum levels of vascular endothelial growth factor (VEGF) and interleukin (IL)-5 in atopic children with Mycoplasma pneumoniae pneumonia. METHODS: We recruited a total of 72 children with pneumonia. The patients were divided into 4 groups: atopic children with M. pneumonia pneumonia (group I, n=24), non-atopic children with M. pneumonia pneumonia (group II, n=23), atopic children with viral pneumonia (group III, n=13), and non-atopic children with viral pneumonia (group IV, n=12). Serum levels of IL-5, IL-13, VEGF, and tumor necrosis factor-α were measured at admission and at recovery using enzyme-linked immunosorbent assays. RESULTS: Serum levels of VEGF and IL-5 were elevated in group I compared with the other groups at both admission phase and clinical recovery phase. In group I, serum levels of VEGF and IL-5 were higher at recovery phase than at admission phase (VEGF: 1,102.2±569.4 vs. 874.9±589.9 pg/mL, respectively; IL-5: 150.5±63.9 vs. 120.2±46.7 pg/mL, respectively). CONCLUSIONS: The serum levels of VEGF and IL-5 were more increased in atopic children with M. pneumonia pneumonia than in the other groups. In this group, the serum levels of VEGF and IL-5 were more increased at recovery phase than at admission phase. The results of this study suggest that increases in VEGF and IL-5 may contribute to the development of hypersensitivity during M. pneumonia infection. These cytokines may act through their respective pro-inflammatory pathways to aggravate the allergic status and induce airway hypersensitivity during M. pneumonia pneumonia in atopic children.

The revised edition of korean calendar for allergenic pollens.

The old calendar of pollens did not reflect current pollen distribution and concentrations that can be influenced by changes of weather and environment of each region in South Korea. A new pollen calendar of allergenic pollens was made based on the data on pollen concentrations obtained in eight regions nationwide between 1997 and 2009. The distribution of pollen was assessed every day at 8 areas (Seoul, Guri, Busan, Daegu, Jeonju, Kwangju, Kangneung, and Jeju) for 12 years between July 1, 1997 and June 30, 2009. Pollens were collected by using Burkard 7-day sampler (Burkard Manufacturing Co Ltd, UK). Pollens which were stained with Calberla's fuchsin staining solution were identified and counted. Pine became the highest pollen in May, and the pollen concentrations of oak and birch also became high. Ragweed appeared in the middle of August and showed the highest pollen concentration in the middles of September. Japanese hop showed a high concentration between the middle of August and the end of September, and mugwort appeared in the middles of August and its concentration increased up until early September. In Kangneung, birch appeared earlier, pine showed a higher pollen concentration than in the other areas. In Daegu, Oriental thuja and alder produced a large concentration of pollens. Pine produced a large concentration of pollens between the middle of April and the end of May. Weeds showed higher concentrations in September and mugwort appeared earlier than ragweed. In Busan the time of flowering is relatively early, and alder and Oriental thuja appeared earliest among all areas. In Kwangju, Oriental thuja and hazelnut appeared in early February. Japanese cedar showed the highest pollen concentration in March in Jeju. In conclusion, update information on pollen calendar in South Korea should be provided for allergic patients through the website to manage and prevent the pollinosis.

Serum leptin and adiponectin levels correlate with exercise-induced bronchoconstriction in children with asthma.

BACKGROUND: Exercise-induced bronchoconstriction (EIB), a form of bronchial hyperresponsiveness (BHR), is common in children with asthma or obesity. Epidemiological studies have shown that asthma and obesity are increasing in parallel, but obesity- and adipokine-related effects on inflammation and BHR have not yet been demonstrated in the human airway. OBJECTIVE: To address the relationship between leptin and adiponectin and EIB in children with asthma. METHODS: Eighty-five prepubertal children between the ages of 6 and 10 years were included in our study. They comprised obese with asthma (n = 19), normal weight with asthma (n = 23), obese without asthma (n = 23), and healthy (n = 20). We measured serum leptin and adiponectin levels. We also performed pulmonary function tests: baseline, postbronchodilator inhalation, methacholine inhalation, and exercise. The area under the forced expiratory volume in 1 second (FEV(1))-time curve quantified the severity of EIB over a 20-minute period after exercise (AUC(20)). RESULTS: The obese children had significantly elevated levels of leptin and reduced levels of adiponectin. The maximum decreases in %FEV(1) and AUC(20) after exercise were positively correlated with leptin levels and negatively with serum adiponectin levels in children with asthma. The odds for having EIB were incrementally and significantly higher for children with higher levels of serum leptin. CONCLUSIONS: Levels of the adipocyte-derived hormones leptin and adiponectin are significantly correlated with BHR induced by exercise challenge in children with asthma. Further studies are needed to elucidate whether the changes in leptin and adiponectin levels bear a causal relationship to the EIB/BHR.

Long-term Efficacy of Intravenous Immunoglobulin Therapy for Moderate to Severe Childhood Atopic Dermatitis.

PURPOSE: The present study investigates the long-term effects of intravenous immunoglobulin (IVIg) therapy for the treatment of moderate to severe childhood atopic dermatitis (AD). Previous research indicates that IVIg can treat severe AD; however, the effectiveness of IVIg has not been confirmed in prospective, blinded clinical trials. METHODS: Forty eligible children with moderate to severe AD, as defined by the criteria of Hanifin and Rajka, were enrolled in a randomized, placebo-controlled study. After the completion of an initial screening visit (V0), the patients were randomly allocated into therapy (n=30) and control (n=10) groups (V1). Thirty children were each treated with three injections of 2.0 g/kg IVIg at 1-month intervals over a 12-week period. Ten children were treated with placebo. Assessments were conducted after each injection (V2, V3, and V4) and at 3 (V5) and 6 months (V6) after completed treatment. RESULTS: The disease severity index was significantly decreased at V5 compared with the value at V1 (P<0.05). There were no significant changes in the total IgE level or total eosinophil count in peripheral blood at the last injection (V4) compared with the value at V1. The interleukin (IL)-5/interferon (IFN)-γ ratio was assessed in T-helper 1 (Th1) and Th2 cells. The ratio significantly decreased between V1 and V5, after which it increased, such that the ratio at V6 was not significantly different from that at V1. Compared with the level at V1, the intercellular cell adhesion molecule-1 level at V4 did not differ significantly, but the level at V5 was lower. CONCLUSIONS: This study suggests that IVIg therapy may clinically improve AD in patients after 3 months of therapy, but the improvement may decline by 6 months after therapy.

Antibiotic-induced severe neutropenia with multidrug-dependent antineutrophil antibodies developed in a child with Streptococcus pneumoniae infection.

Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.

Phenotypic and genotypic correction of WASP gene mutation in Wiskott-Aldrich syndrome by unrelated cord blood stem cell transplantation.

We present two cases of Wiskott-Aldrich syndrome (WAS), in which nonsense mutations in the WASP gene were corrected phenotypically as well as genotypically by unrelated cord blood stem cell transplantation (CBSCT). Two male patients were diagnosed with WAS at the age of 5-month and 3-month and each received unrelated CBSCT at 16-month and 20-month of age, respectively. The infused cord blood (CB) units had 4/6 and 5/6 HLA matches and the infusion doses of total nucleated cells (TNC) and CD34+ cells were 6.24x10(7)/kg and 5.08x10(7)/kg for TNC and 1.33x10(5)/kg and 4.8x10(5)/kg for CD34+ cells, for UPN1 and UPN2, respectively. Complete donor cell chimerism was documented by variable number tandem repeat (VNTR) with neutrophil engraftment on days 31 and 13 and platelets on days 58 and 50, respectively. Immunologic reconstitution demonstrated that CBSCT resulted in consistent and stable T-, B-, and NK-cell development. Flow cytometric analysis for immunologic markers and sequence analysis of the WASP gene mutation revealed a normal pattern after CBSCT. These cases demonstrate that CBs can be an important source of stem cells for the phenotypical and genotypical correction of genetic diseases such as WAS.

Nicotine inhibits bFGF-induced neurite outgrowth through suppression of NO synthesis in H19-7 cells.

NO (Nitric oxide) has been known as a biological signaling molecule that can function as a beneficial agent in physiologically essential functions such as differentiation or neurotransmission. In this study, we elucidated how nicotine inhibits neuronal differentiation induced by the basic fibroblast growth factor (bFGF) in hippocampal cell line, H19-7 cells, because nicotine is one of the key neuroregulatory components. Treatment of H19-7 cells with bFGF increased NO production through upregulated iNOS/ nNOS expression, and also increased expressions of neuronal markers such as brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and Neuro-D. Pretreatment of the cells with nicotine decreased iNOS promoter activity as well as iNOS/nNOS expression induced by bFGF, resulting in decreased NO production. Nicotine also suppressed expressions of BDNF, NT3 and Neuro-D, resulting in decreased bFGF-induced neurite outgrowth. These results indicate that nicotine inhibits bFGF-induced neuronal differentiation in H19-7 cells through inhibition of NO formation by suppressing iNOS/nNOS expressions.

High body mass index and dietary pattern are associated with childhood asthma.

The increasing prevalence of asthma has coincided with an increase of body mass index (BMI) in both children and adults. We investigated the relationship between BMI and the symptom prevalence of asthma and the possible influences of dietary pattern. This was a community-based, cross-sectional study of 24,260 school children aged 6-12 years. Prevalences of asthma and potential confounding factors were assessed using a Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire which was completed by parents. We analyzed the relationship between BMI and symptoms of asthma and the possible influences of dietary pattern. A significant positive association between high BMI and previous 12-month prevalence of wheeze remained in boys (adjusted odds ratio, 1.610; 95% confidence interval, 1.274-2.033) but not in girls. In addition, there were significant associations between high BMI and lifetime prevalence of wheeze, previous 12-month wheeze, exercise-induced wheeze, diagnosis, and treatment of asthma. There were significant associations between high BMI and previous 12-month wheeze regardless of breast-milk feeding or whole-milk feeding. Frequent intake of fresh seafood, fresh fruits, and vegetables was associated with reduced prevalence of current asthma symptoms and was also associated with decreased BMI. These results indicate that BMI may be an independent risk factor for the development of asthma symptoms in boys. Intake of fresh seafood, fresh fruit, and vegetables, which may be associated with decreased BMI, may contribute to protect against the development of asthma symptoms in Korean elementary schoolchildren.

Urine leukotriene E and eosinophil cationic protein in nasopharyngeal aspiration from young wheezy children.

Respiratory syncytial virus (RSV) infection is a risk factor for the development of asthma. It is very hard to distinguish bronchiolitis with respiratory virus infection from allergic asthma at first wheezing attack in early childhood. To distinguish wheezing children with RSV bronchiolitis from asthmatic children, we measured leukotriene E(4)(LTE(4)) in urine and ECP in nasopharyngeal aspiration (NPA) at first day of admission with wheezing attack. Thirty-two non-atopic children younger than the age of 3 yr with RSV induced bronchiolitis, 35 atopic asthmatic children with/without respiratory viral infection, and 23 children who exhibited no evidence of atopy, asthma, or virus infections as controls were selected in this study. We measured urinary LTE(4) and ECP level in NPA from subjects. Urinary LTE(4) concentrations in children with asthma were significantly higher than urinary LTE(4) in bronchiolitis and in controls (240.8 +/- 129.8 vs. 162.8 +/- 73.9 vs. 85.1 +/- 31.6 pg/ml). Children with RSV infection demonstrated higher urinary LTE(4) levels compared to children without RSV infection among asthmatic children. ECP in NPA was significantly correlated with urinary LTE(4) (r = 0.57, p < 0.01) in children entered this study who had detectable levels for both LTE(4) and ECP. In summary, Urinary LTE(4) concentrations may be suggested to useful mediators for differential diagnosis of wheezy diseases in early childhood. RSV infection also is associated with synergizing LT biosynthesis and this study demonstrated ECP in NPA was significantly correlated with urinary LTE(4) and may suggest that cysteinyl leukotriene initiate the production of ECP in early childhood, which could contribute to the development of wheeze.

Der f 2 activates phospholipase D in human T lymphocytes from Dermatophagoides farinae specific allergic individuals: involvement of protein kinase C-alpha.

The major house-dust mite allergen, Der f 2, stimulates the phospholipase D (PLD) in T lymphocytes from Dermatophagoides farinae specific allergic individuals. PLD activity increased more than two-fold in T cells from allergic patients compared with those cells from normal controls with maximal responses within 30 min after exposure of Der f 2. A well-known PLD activator PKC-alpha was found to be translocated to membrane from cytosol in Der f 2-treated T cells from Dermatophagoides farinae specific allergic individuals. Down-regulation of PKC-alpha with phorbol myristate acetate pretreatment for 24 h abolished Der f 2-induced PLD activation. Ro 320432, PKC inhibitor also reduced the effects of Der f 2-induced PLD activation suggesting that PKC-alpha acts as upstream activator of PLD in Der f 2-treated T cells. Taken together, the present data suggest that Der f 2 can stimulate PLD activity through the PKC-alpha activation in T cells from Dermatophagoides farinae allergic individuals.

Interleukin-6, interleukin-8, interleukin-11, and interferon-gamma levels in nasopharyngeal aspirates from wheezing children with respiratory syncytial virus or influenza A virus infection.

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)-6, IL-8, IL-11, and interferon-gamma (IFN-gamma) levels in nasopharyngeal aspirates (NPA) from non-asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL-11 in NPA from asthmatic children were significantly higher than those from non-asthmatic children with RSV infection, and RSV infection enhanced the IL-11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL-6 than that of children with IFAV infection. There was little difference in the IL-8 and IFN-gamma levels between asthmatic and non-asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL-11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL-6 production in RSV infection compared with IFAV infection.

The effect of disodium cromoglycate, budesonide, and cyclosporin A on interleukin-4, interleukin-5, and interleukin-13 secretions in Der p I-stimulated T cells from house dust mite-sensitive atopic and nonatopic individuals.

Disodium cromoglycate (DSCG), budesonide, and cyclosporin A (CsA) were the well-known immunomodulators for the allergic and immunologic diseases clinically. In this study, we evaluated the characteristics of inhibition on cytokine synthesis of Der p I-stimulated T cells by the same inhibiting concentrations of DSCG, budesonide, and CsA in house-dust mite antigen (Der p I)-specific atopic and nonatopic healthy individuals. Seven house dust mite allergen specific patients were recruited for this study. Seven healthy volunteers were included on the basis of negative allergic manifestations and low serum immunoglobulin E values. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of recombinant interleukin (rIL)-2 with or without budesonide, DSCG, CsA, and Der p I for 48 hours. Cells were stained with anti-CD4 fluorescein isothiocyanate-conjugated monoclonal antibody, and then anti-human IL-4 phycoerythrin, IL-5, or IL-13 monoclonal antibody, respectively, was added to both blocked and stained samples. Incubation of PBMC from atopics with each immunomodulator and Der p I resulted in the reduction of IL-4 secretion compared with Der p I alone stimulation. However, IL-4 secretion in PBMC from nonatopics was not reduced with DSCG and Der p I stimulation. IL-4, IL-5, and IL-13 secretions of PBMC from atopics were significantly decreased after incubation with each immunomodulator and Der p I, compared with after incubation with Der p I alone. These results might be considered to show either that DSCG has a selective inhibiting effect on cytokine production in T cells from atopics or is a weak inhibitor of cytokine secretions compared with budesonide and CsA at even strength for the inhibition of lymphocyte proliferation in normal, healthy individuals.