Kyu Earn Kim

Identification and characterization of the major allergens of buckwheat

Background: Buckwheat (BW) has been recognized as a common food allergen in Korea, Japan, and other countries. Until now, serologic findings of BW food‐allergic patients and its major allergenic components have not been clarified. In this study, we analyzed the serologic findings of BW food allergy and characterized its major allergenic components.

Changes in the Prevalence of Childhood Asthma in Seoul from 1995 to 2008 and Its Risk Factors

Purpose To investigate the prevalence of asthma and determine its risk factors in elementary school students in Seoul. Methods A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 4,731 elementary school students from five areas in Seoul between April and October, 2008. Results In elementary school children, the lifetime and recent 12-month prevalence of wheezing were 11.7% and 5.6%, respectively. The lifetime prevalence of asthma diagnosis was 7.9%, and the recent 12-month prevalence of asthma treatment was 2.7%. Male sex (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.36-2.66), history of atopic dermatitis (AD) (aOR, 2.76; 95% CI, 1.98-3.84), history of allergic rhinitis (AR) (aOR, 3.71; 95% CI, 2.61-5.26), history of bronchiolitis before 2 years of age (aOR, 2.06; 95% CI, 1.39-3.07), use of antibiotics during infancy for >3 days (aOR, 1.88; 95% CI, 1.35-2.62), parental history of asthma (aOR, 2.83; 95% CI, 1.52-5.27), exposure to household molds during infancy (aOR, 1.84; 95% CI, 1.18-2.89), and the development or aggravation of asthma symptoms within 6 months after moving to a new house (aOR, 11.76; 95% CI, 5.35-25.86) were the independent risk factors for wheezing within 12 months. Conclusions The prevalence of wheezing and asthma in elementary school students in 2008 was similar to that in the past decade. Male sex, history of AD, history of AR, history of bronchiolitis before 2 years of age, parental asthma, use of antibiotics during infancy, exposure to molds in the house during infancy, and development or aggravation of asthma symptoms within 6 months after moving to a new house, could be risk factors for wheezing within 12 months.

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.

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 Multicenter Retrospective Case Study of Anaphylaxis Triggers by Age in Korean Children

Purpose Although anaphylaxis is recognized as an important, life-threatening condition, data are limited regarding its triggers in different age groups. We aimed to identify anaphylaxis triggers by age in Korean children. Methods We performed a retrospective review of medical records for children diagnosed with anaphylaxis between 2009 and 2013 in 23 secondary or tertiary hospitals in South Korea. Results A total of 991 cases (mean age=5.89±5.24) were reported, with 63.9% involving patients younger than 6 years of age and 66% involving male children. Food was the most common anaphylaxis trigger (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic factors (9.2%), and exercise (3.6%). The most common food allergen was milk (28.4%), followed by egg white (13.6%), walnut (8.0%), wheat (7.2%), buckwheat (6.5%), and peanut (6.2%). Milk and seafood were the most common anaphylaxis triggers in young and older children, respectively. Drug-triggered anaphylaxis was observed more frequently with increasing age, with antibiotics (34.9%) and nonsteroidal anti-inflammatory drugs (17.9%) being the most common causes. Conclusions The most common anaphylaxis trigger in Korean children was food. Data on these triggers show that their relative frequency may vary by age.

Relationship between mode of delivery in childbirth and prevalence of allergic diseases in Korean children.

Purpose We tested the hypothesis that cesarean section might increase the risk for allergic diseases compared to vaginal delivery, by depriving the newborn of exposure to maternal microflora. Methods We evaluated the prevalence of allergic diseases, allergic inflammation, and allergic sensitization according to mode of delivery for 279 Korean children aged ≤16 years. Data were extracted from medical records and a questionnaire filled out by parents. Logistic regression was used to determine the association between cesarean section and the outcomes of interest. Results Of the 279 children, 179 (62.6%) were delivered vaginally and 100 (37.4%) by cesarean section. There were no differences in the prevalence of allergic diseases, allergic inflammation, or allergic sensitization according to mode of delivery. Children born by cesarean section had no higher risk of allergic disease than those delivered vaginally, regardless of a parental history for allergic disease. Adjusted odds ratios (95% confidence intervals) for cesarean section compared to vaginal delivery were not statistically significant for any outcome considered: asthma, 0.76 (0.37-1.57), allergic rhinitis, 1.14 (0.61-2.10), atopic dermatitis, 1.01 (0.59-1.71). Conclusions Delivery by cesarean section may not be associated with the subsequent development of asthma, allergic rhinitis, or atopic dermatitis in Korean children.

Atopy and House Dust Mite Sensitization as Risk Factors for Asthma in Children

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.

Fractional exhaled nitric oxide and impulse oscillometry in children with allergic rhinitis.

Purpose Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response (BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a risk factor for asthma development, we evaluated these 3 characteristics in AR using measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test (MCT), and impulse oscillometry (IOS). Methods This study included 112 children with asthma (asthma group), 196 children with AR (AR group), and 32 control subjects (control group). We compared pulmonary function parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2 categories: the AR group with BHR and the AR group without, and again pulmonary function and FeNO levels were compared between the 2 subgroups. Results FeNO levels were more increased in the AR and asthma groups than in the control group; within the AR group, FeNO was higher in the AR group with BHR than in the AR group without. The BDR was more increased in the AR group than in the control group when percent changes in reactance at 5 Hz (Δ X5) and reactance area (Δ AX) were compared. In the AR group, however, there was no difference in Δ X5 and Δ AX between the AR group with BHR and the AR group without. Conclusions Reversible airway obstruction on IOS and elevated FeNO levels were observed in children with AR. Because elevated FeNO levels can indicate airway inflammation and because chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS can be a useful tool for detecting lower airway involvement of AR independent of BHR assessed in the MCT.

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.

Exhaled nitric oxide is associated with allergic inflammation in children.

Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 ± 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 ± 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 ± 31.92 ppb) and in those with allergic rhinitis (43.59 ± 29.84 ppb) than in healthy controls (27.01 ± 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization.