Biomedical subjects
Publications and source records attributed to Kyu-Earn Kim.
The present study evaluated the possible role of interleukin (IL)-10 promoter polymorphisms in children with atopic dermatitis (AD). IL-10 promoter polymorphisms are associated with the phenotype of AD in children.
A peritonsillar abscess is one of the most commonly occurring deep space infections of the head and neck in adults and children. A peritonsillar abscess that appears in newborns, however, is extremely rare. The treatment of a peritonsillar abscess requires both the selection of appropriate antibiotics and the best procedure to remove the abscessed material. We report a case of a peritonsillar abscess in a 40-day-old infant who was treated with antibiotic therapy alone.
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.
Monosensitization differs both immunologically and clinically from polysensitization, and specific immunotherapy is more effective in patients sensitized only to a single pollen than in multiple-pollen sensitized patients. To further examine the differences between monosensitized and polysensitized allergies, allergic indices were examined in 68 monosensitized and 62 polysensitized patients with childhood asthma. Measurements included symptom scores, eosinophil counts, skin prick tests, serum total and specific IgE levels, and IL-10 levels, and were used to compare allergic indices between the two groups. Patients were followed for 18 months following immunotherapy to examine the effectiveness of the treatment. Symptom scores and total IgE levels were significantly higher in the polysensitized group than those in the monosensitized group (p<0.05). The levels of skin test response decreased significantly in both groups following immunotherapy. In the monosensitized group, symptom scores and specific IgE levels were significantly reduced after immunotherapy (p<0.05). In the polysensitized group, symptom scores were reduced after immunotherapy (p<0.05), but the degree of reduction was less than that of the monosensitized group (p<0.05). Moreover, in the polysensitized group, specific IgE levels after immunotherapy did not differ from that before immunotherapy. Serum IL-10 levels were not significantly increased after immunotherapy in either group. In conclusion, polysensitized patients tend to show higher allergic indices and immunotherapy might be less effective for these patients.
Asthma is commonly described as an atopic disease in childhood, but some cases of this disorder do not fit this description. The aim of this study was to evaluate the frequency of atopy, asthma, and sensitization to house dust mites in children with allergic symptoms. This study was performed at the Severance Hospital of Yonsei University with patients who visited the allergy clinic for evaluation of nonspecific upper respiratory symptoms, typical symptoms of asthma, or a general health workup. The patients were divided into three age groups: 0-3 years (group 1), 4-7 years (group 2), and 8-12 years (group 3). Of the 1,244 children examined, 844 (67.8%) were atopic and 400 (32.2%) were non-atopic. The frequency of atopy and asthma increased with age. Asthma was diagnosed in the same proportion (64%) of atopic and non-atopic children. As risk factors for asthma symptoms, the positive values of house dust mite (HDM) sensitivity were significantly increased in groups 1, 2, and 3 to 53.5%, 68.9%, and 80.2%, respectively. A significant difference between the percentage of asthmatics sensitized to HDM and that of asthmatics not sensitized to HDM was found only in group 3. In conclusion, asthma is related to atopy with increasing age, and house dust mite sensitization seems to be an important determinant of asthma in older children in Korea.
Sensitization to aeroallergens is associated with diminished lung function in adults. Little has been studied on the relationship between the inhalant allergen-specific IgE and pulmonary function in asthmatic children. This study was focused on four major inhalant allergens found in Korea, including Dermatophagoides pteronyssinus (Der p.), Dermatophagoides farinae (Der f.), and Alternaria- and German cockroach-specific IgEs, with evaluation of pulmonary function in relation to the amount of allergens. The parents or legal guardians of participants enrolled in this study gave informed consent. Fifty-five asthmatic patients and 48 nonasthmatic children were included. The amounts of specific IgE for the four specified inhalant allergens were determined by employing the CAP system FEIA. Forced expiratory volume in 1 sec (FEV(1))/forced vital capacity (FVC), FEV(1), and forced expiratory flow between 25% and 75% of FVC (FEF(25-75)) of subjects were evaluated through pulmonary function tests. In the asthmatic group, FEV(1), FEV(1)/FVC, and FEF(25-75) were significantly reduced (P < 0.05): reduction in FEV(1) (r = -0.44) and FEF(25-75) (r = -0.33) in association with the Der f.-specific allergen, and reduction in FEV(1) (r = -0.37) and FEF(25-75) (r = -0.34) in association with the Der p.-specific allergen, were observed. However, there was no significant correlation with German cockroach and Alternaria allergen. In the control group, no significant correlation was detectable between the allergen-specific IgE titers and the results of pulmonary function tests. In asthmatic patients, Der p.- and Der f.-specific IgEs, and not German cockroach and Alternaria, seem to play a considerable role in reduced pulmonary function among asthmatic children.
OBJECTIVE: The hygiene hypothesis postulates that infections early in life might influence the development of asthma later in childhood. However, this hypothesis is controversial. The objective of this study was to determine whether there is a relationship between infection-related risk factors during infancy and development of asthma later in childhood. METHODS: Data were obtained by a nationwide, population-based, cross-sectional study of 26,400 children, 7 to 12 years of age. Parents completed a questionnaire on symptoms of and risk factors for asthma, including the number of fever episodes, acute gastroenteritis, use of antibiotics, and immunization during infancy. The presence of asthma was defined by parental report of "wheeze in the last 12 months" or "asthma ever." Data were analyzed by logistic regression analysis. RESULTS: The occurrence of fever during infancy was weakly associated with the development of asthma (P < 0.05). A higher frequency of episodes of fever was associated with a higher risk of development of asthma. The relationship between antibiotic use during infancy and development of asthma was also significant (P < 0.0001). The adjusted odds ratios of childhood asthma increased in proportion to the number of antibiotic courses during infancy. A history of acute gastroenteritis during infancy increased the risk of developing asthma in later life (P < 0.001). In contrast, immunization in infancy was not related to development of asthma in childhood (P > 0.05). CONCLUSIONS: These data suggest that the development of childhood asthma is associated with episodes of fever, antibiotic use, and acute gastroenteritis during infancy.
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is a surface molecule of activated T cells with sequence homologous to CD28, and may act as a negative regulator of T-cell activation. In murine animal models, cross-linkage of CTLA-4 molecules on the cell surface results in decreased T-cell proliferation, accompanied by increased interleukin (IL)-2 production and apoptosis. To clarify the activation of peripheral blood T cells, we studied the CTLA-4 expression in 32 patients with atopic dermatitis who visited our institution, and 19 normal children who visited for pre-operative laboratory examination were used as normal controls. Whole blood was obtained from all subjects and stained with anti-CD3, anti-CD4, anti-CD8 monoclonal antibodies (mAb). After erythrocyte lysis with lysing solution, the cells were stained with anti-CTLA-4 mAb, and stained cells were analysed by fluorescence-activated cell sorter (FACScan) flow cytometer. Intracellular expression of CTLA-4 was significantly upregulated in peripheral blood CD3+ T cells (36.8%), CD4+ T cells (21.7%) and CD8+ T cells (18.7%) of patients with atopic dermatitis, compared with normal control (18.3%, 9.7%, 9.8%; respectively). Furthermore, CTLA-4-positive CD3+ T cells in patients with severe atopic dermatitis were significantly higher compared with milder group (42.8% vs. 32.2%). However, no significant difference was obtained in CD4+ and CD8+ T cells. Mean percentage of T cells expressing CTLA-4 in patients with atopic dermatitis was higher than the control group. These observations suggest the possibility that the disease activity can be correlated with the CTLA-4 level.
The storage mite, Tyrophagus putrescentiae, is one of the important causes of allergic disorders. Fifteen allergenic components were demonstrated in storage mite by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting, but only the group 2 allergen Tyr p 2 has been cloned and characterized. In this study, we attempted to identify and characterize new allergens from T. putrescentiae, which is a dominant species of storage mite in Korea. Expressed sequence tags were analyzed to identify possible storage mite allergens, and the cDNA sequence encoding a protein homologous to fatty acid binding protein, a mite group 13 allergen, was identified and named Tyr p 13. Its deduced amino acid sequence showed 61.1 to 85.3% identity with other mite group 13 allergens. The recombinant protein was expressed in Escherichia coli using a pET 28b vector system, and its allergenicity was investigated by enzyme-linked immunosorbent assay (ELISA). The recombinant allergen was detected in 5 of 78 (6.4%) T. putrescentiae-positive sera tested, and it inhibited 61.9% of immunoglobulin E binding to crude extract at an inhibitor concentration of 10 mug/ml by inhibition ELISA using serum from the patient who showed the strongest reaction by ELISA. In this study, a novel allergen was identified in T. putrescentiae. This allergen could be helpful for more-detailed characterizations of storage mite allergy.
STUDY OBJECTIVES: Mycoplasma pneumoniae is a common cause of lower respiratory disease. Several studies have suggested that respiratory infection by M pneumoniae is associated with reactive airway disease and asthma. Interleukin (IL)-8 has been suggested to have a role in the pathogenesis of the allergic inflammation of bronchial asthma, and is well known to be expressed in bronchial epithelial cells. MEASUREMENTS: An examination was carried out into the effect of M pneumoniae lysate (MPL) and the role of mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinase (ERK) on IL-8 expression in human lung epithelial cells. A549 cells were seeded at a density of 5 x 10(4) cells per well and incubated in basal medium for a further 24 h. IL-8 levels were determined by an enzyme-linked immunosorbent assay. MAPK phosphorylation was assessed by Western blotting. RESULTS: In A549 cells, MPL induced IL-8 release in a time- and dose-dependent manner. Pretreatment with PD 98059, which blocks the activation of MAPK/ERK kinase 1, inhibited MPL-induced IL-8 production by 64.4% at 25 micromol/L. Stimulation of A549 cells by MPL also caused an increase in the activity of ERK, compared with the nonstimulated cells. The MPL stimulation had no effect on the activities of p38. CONCLUSION: These observations suggest that activation of ERK by MPL may be one of the mechanisms that result in an increase of the production of IL-8.
Food allergies affect about 4% of the Korean population, and buckwheat allergy is one of the most severe food allergies in Korea. The purpose of the present study was to develop a murine model of IgE-mediated buckwheat hypersensitivity induced by intragastric sensitization. Young female C3H/HeJ mice were sensitized and challenged intragastricly with fresh buckwheat flour (1, 5, 25 mg/dose of proteins) mixed in cholera toxin, followed by intragastric challenge. Anaphylactic reactions, antigen-specific antibodies, splenocytes proliferation assays and cytokine productions were evaluated. Oral buckwheat challenges of sensitized mice provoked anaphylactic reactions such as severe scratch, perioral/periorbital swellings, or decreased activity. Reactions were associated with elevated levels of buckwheatspecific IgE antibodies. Splenocytes from buckwheat allergic mice exhibited significantly greater proliferative responses to buckwheat than non-allergic mice. Buckwheat-stimulated IL-4, IL-5, and INF-gamma productions were associated with elevated levels of buckwheat-specific IgE in sensitized mice. In this model, 1 mg and 5 mg dose of sensitization produced almost the same degree of Th2-directed immune response, however, a 25 mg dose showed blunted antibody responses. In conclusion, we developed IgE-mediated buckwheat allergy by intragastric sensitization and challenge, and this model could provide a good tool for future studies.
In vitro determination of specific IgE antibodies in serum is the most frequently used method, besides the skin test, for diagnosing allergies. Standardized and reproducible assays of specific IgE antibodies contribute to the quality of diagnosis and treatment of allergic disease. This study compared the results and performance characteristics of the Pharmacia CAP system and a new specific IgE method using the VIDAS Stallertest (manufactured by bioMériux). To evaluate their clinical efficiency, the results of the CAP and VIDAS Stallertest assays were compared with skin prick test (SPT) results. After allergic patients completed SPTs, serum samples were collected and CAP and VIDAS Stallertest assays were performed to determine specific IgEs for Dermatophagoides farinae, D. pteronyssinus, cockroach, and alternaria. For egg and milk, we measured only the correlation between the 2 in vitro assays. When SPT was used as a reference standard, the sensitivity and specificity of the CAP assay was a little higher in respect to all inhalant allergens. There were significant correlations between the results of VIDAS Stallertest and CAP assays for IgE antibodies to inhalant and food allergens. This study indicates that the VIDAS Stallertest and Pharmacia CAP assays are feasible and replicable for measuring allergen-specific IgE.
BACKGROUND: The German cockroach has been reported to act as an allergen that might be associated with a protease reaction in asthma. However, the molecular identities of the antigens in German cockroach extract (GCE) with protease activity and the protease-activated receptors (PARs) that are activated by GCE in human airway epithelial cells have not been characterized. OBJECTIVE: We investigated the direct effect of GCE on Ca(2+) signaling in human airway epithelial cells and the type of PARs activated by GCE. METHODS: The Ca(2+)-sensitive dye Fura2 was used to determine intracellular Ca(2+) concentration ([Ca(2+)](i)) by means of spectrofluorometry. RESULTS: GCE induced a baseline type of [Ca(2+)](i) oscillations in a dose-dependent manner. The oscillations persisted for long periods of time in the absence of Ca(2+) entry across the plasma membrane, suggesting that the observed [Ca(2+)](i) increases were due to Ca(2+) release from intracellular stores. Accordingly, after depleting endoplasmic reticulum Ca(2+) with thapsigargin, an endoplasmic reticulum Ca(2+) ATPase inhibitor, the GCE-mediated [Ca(2+)](i) signals were abolished. Whereas desensitization of PAR-1, PAR-3, and PAR-4 had no effect on GCE-mediated Ca(2+) mobilization, no GCE-mediated [Ca(2+)](i) increase was observed after desensitization of PAR-2. CONCLUSIONS: These results indicate that GCE has a direct effect on human airway epithelial cells, in particular generating [Ca(2+)](i) oscillations through Ca(2+) release from thapsigargin-sensitive Ca(2+) stores through activation of PAR-2.
To validate the prevalence rate of symptoms of asthma produced by the phase I ISAAC (International Study of Asthma and Allergies in Childhood) study, hypertonic saline challenge test was carried out during the phase II study at a year after the phase I study. For the phase II study, six middle schools from three cities in the phase I study were selected. Finally, 499 children who responded to both studies were analyzed. All subjects were asked to complete the written questionnaire (WQ) first, followed by a video questionnaire (AVQ 3.0) during the phase I study. Of the 499 children, only 19 (3.8%) were positive to the hypertonic saline bronchial challenge test. The degree of agreement between responses to the two corresponding questions "wheezing at rest" and "nocturnal wheeze" in the AVQ 3.0 and WQ were moderate and weak with a Kappa indices of 0.45 and 0.23, respectively. The question on "severe wheeze" in the AVQ 3.0 had the highest Youden's index among the five questions related to asthma symptoms in the previous 12 months, but its specificity was low whereas its sensitivity was 1.0. There was no consistency of priority between the two questionnaires in predicting bronchial hyperreactivity in a group of Korean schoolchildren. Therefore we need to develop more appropriate WQ or AVQ to compare the prevalences of asthma to other countries.
Pulmonary function testing plays a key role in the diagnosis and management of asthma in children. However, the literature does not clearly show whether children with clinically stable asthma have significantly reduced lung function when compared with normal children. We compared the lung function of 242 clinically stable asthmatic children who were initially diagnosed with mild intermittent or mild persistent asthma with the lung function of 100 nonasthmatic controls. The lung function was assessed using FEV1, FEV1/FVC, FEF25-75 and PEF. In addition, we measured bronchial hyperresponsiveness (BHR) using the provocation concentration of methacholine needed to produce a 20% fall in FEV1. All measures of pulmonary function were significantly decreased in the children with asthma. Pulmonary function was not influenced by atopy, serum IgE, or total eosinophil count (TEC). However, the likelihood ratio for trends revealed a significant association between our pulmonary parameters and the degree of BHR. Children with mild-to-severe BHR had greatly decreased lung function compared with those with normal BHR, the control group. In addition, a direct correlation was found between PC20 and our pulmonary parameters in asthmatic children. However, only atopic children with asthma had a significant correlation between PC20 and TEC. We found children with clinically stable asthma to have pulmonary obstruction, which associated strongly with their degree of BHR.
Rice is a cereal that is mainly produced and widely consumed in Asian countries including Korea. Several reports have suggested a role of IgE-mediated hypersensitivity in asthma and eczema associated with ingestion or inhalation of rice. In Japan, hypoallergenic rices are used for a substitute of common rice in some atopic patients. We performed this study to identify major allergens of rice and changed allergenicity in cooked and hypoallergenic rice. We purified crude extracts from a variety of rice and analyzed their protein distributions by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Based on UniCAP test and skin-prick test, we selected sera with high sensitivity and analyzed specific IgE binding to rice by immunoblotting. In addition, the inhibition rate among some rice was determined by enzyme linked immunosorbent assay and CAP test. As the result of this study, rice with various origins and polishing levels had no difference in protein band pattern. After cooking, it was difficult to detect protein bands distributed in raw rice; and, even through IgE immunoblot analysis, it was impossible to differentiate between wild and hypoallergenic rice. In addition, both wild and hypoallergenic rice still had IgE binding activity on their remaining protein bands. In conclusion, almost all proteins of rice were excluded or weakened in the process of boiling and IgE binding activity still remained even in hypoallergenic rice.
Exotoxins secreted by Staphylococcus aureus have been identified as a possible trigger factor in atopic dermatitis (AD). We investigated the production and role of circulating antibodies, with specificity to staphylococcal enterotoxin B (SEB), in children with AD compared with those of healthy controls. The children with AD had significantly higher levels of serum SEB-specific immunoglobulin G (IgG; p = 0.0193), IgM (p = 0.011), and IgE (p = 0.0001) than the nonatopic children. The proportions of IgG, IgM, and IgE seropositivity in children with AD were 52.5% (21/40), 62.5% (25/40), and 67.5% (27/40), respectively. The levels of SEB-specific IgE and the severity of AD (p = 0.0004) were compared, but no correlation was seen for IgG or IgM. SEB may be involved in exacerbation of AD. SEB-specific IgE may be an important index of the clinical severity of AD. The SEB-specific IgG or IgM was produced during the exposure to the SEB antigen but may not be protective against SEB in AD.
Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by reduced interferon (IFN) gamma production with concurrent up-regulation of interleukin (IL)-4. Recently, it was reported that IL-18, formerly called IFN gamma-inducing factor, induces the production of T helper (Th)2-related cytokines without help from IL-12. This study was performed to evaluate the contribution of IL-18 in the pathogenesis of AD. Significantly higher serum IL-18 concentrations were found in patients with severe AD than in healthy subjects. Under staphylococcal enterotoxin B stimulation, IL-18 secretion was increased in peripheral blood mononuclear cells from patients with AD. There were significant differences in the concentrations of IL-10, IL-12, and soluble Fas ligand between AD patients and normal controls. In conclusion, increased serum IL-18 concentrations may be involved in the pathogenesis of AD.