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2.  Involvement of Human Histamine N-Methyltransferase Gene Polymorphisms in Susceptibility to Atopic Dermatitis in Korean Children 
Histamine N-methyltransferase (HNMT) catalyzes one of two major histamine metabolic pathways. Histamine is a mediator of pruritus in atopic dermatitis (AD). The aim of this study was to evaluate the association between HNMT polymorphisms and AD in children.
We genotyped 763 Korean children for allelic determinants at four polymorphic sites in the HNMT gene: -465T>C, -413C>T, 314C>T, and 939A>G. Genotyping was performed using a TaqMan fluorogenic 5' nuclease assay. The functional effect of the 939A>G polymorphism was analyzed.
Of the 763 children, 520 had eczema and 542 had atopy. Distributions of the genotype and allele frequencies of the HNMT 314C>T polymorphism were significantly associated with non-atopic eczema (P=0.004), and those of HNMT 939A>G were significantly associated with eczema in the atopy groups (P=0.048). Frequency distributions of HNMT -465T>C and -413C>T were not associated with eczema. Subjects who were AA homozygous or AG heterozygous for 939A>G showed significantly higher immunoglobulin E levels than subjects who were GG homozygous (P=0.009). In U937 cells, the variant genotype reporter construct had significantly higher mRNA stability (P<0.001) and HNMT enzyme activity (P<0.001) than the common genotype.
Polymorphisms in HNMT appear to confer susceptibility to AD in Korean children.
PMCID: PMC3242058  PMID: 22211168
Atopic dermatitis; children; histamine, N-Methyltransferase; polymorphism
3.  Exhaled Nitric Oxide is Associated with Allergic Inflammation in Children 
Journal of Korean Medical Science  2011;26(10):1265-1269.
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.
PMCID: PMC3192335  PMID: 22022176
Exhaled Nitric Oxide; Asthma; Allergic Rhinitis; Allergy; Sensitization
4.  Association between Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations and Susceptibility for Childhood Asthma in Korea 
Yonsei Medical Journal  2010;51(6):912-917.
Classic cystic fibrosis is now known part of cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders. These include a wide spectrum, from multi-system disorders, such as cystic fibrosis, to mono-symptomatic conditions, such as chronic pancreatitis or congenital bilateral absence of the vas deferens. However, respiratory disease is considered typical for the multi system disorder, cystic fibrosis, and is the major cause of morbidity and mortality. The purpose of this study was to evaluate the potential effects of CFTR gene mutations in Korean children with asthma.
Materials and Methods
We selected 14 mutations identified in Korea and each of the 48 children with and without asthma were genotyped for the case-control study.
No significant differences were found in genotype and allele frequencies of the 9 polymorphisms observed between the non-asthma and asthma groups. In a haplotype determination based on a Bayesian algorithm, 8 haplotypes were assembled in the 98 individuals tested. However, we also did not find any significant differences in haplotype frequencies between the non-asthma and asthma groups.
We have concluded that this study did not show any evidence in support of providing that CFTR genetic variations significantly contribute to the susceptibility of asthma in Korean children.
PMCID: PMC2995957  PMID: 20879059
Cystic fibrosis transmembrane conductance regulator; asthma; children
5.  Relationship between mode of delivery in childbirth and prevalence of allergic diseases in Korean children 
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.
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.
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).
Delivery by cesarean section may not be associated with the subsequent development of asthma, allergic rhinitis, or atopic dermatitis in Korean children.
PMCID: PMC2831606  PMID: 20224675
Hypersensitivity; cesarean section; obstetric delivery, child
6.  Clinical Implications of Serum Retinol-Binding Protein 4 in Asthmatic Children 
Journal of Korean Medical Science  2009;24(6):1010-1014.
Recently the prevalence of both asthma and obesity have increased substantially in many countries. The aim of this study was to evaluate the role of retinol-binding protein (RBP) 4 in childhood asthma and its association with atopy markers, pulmonary function, and bronchial hyperresponsiveness in relation to obesity. We studied 160 children between the ages 6 to 10 yr, including 122 asthmatics and 38 controls. The body mass index, pulmonary function tests, and methacholine challenge tests were measured on the same day. Total eosinophil count, serum total IgE, serum eosinophil cationic protein, and serum RBP4 were measured in all subjects. There was no difference in serum RBP4 levels between the asthmatics and the control group. In all subjects or subgroups, serum RBP4 was not associated with total eosinophil count, serum total IgE, serum eosinophil cationic protein, or PC20. There was no relationship between serum RBP4 and pulmonary function in female asthmatics. Forced expiratory volume in 1 second/forced vital capacity (FVC) and forced expiratory flow between 25% and 75% of FVC contributed to serum RBP4 in male asthmatics. Our findings show an association between RBP4 and pulmonary function in prepubertal male asthmatics. This relationship may indirectly affect the high prevalence of childhood asthma in males.
PMCID: PMC2775845  PMID: 19949653
Asthma, Child; Pulmonary Function; Retinol-Binding Protein 4
7.  Acute Interstitial Pneumonia in Siblings: A Case Report 
Journal of Korean Medical Science  2008;23(3):529-532.
Acute interstitial pneumonia (AIP) is a rapidly progressive condition of unknown cause that occurs in a previously healthy individual and produces the histologic findings of diffuse alveolar damage. Since the term AIP was first introduced in 1986, there have been very few case reports of AIP in children. Here we present a case of AIP in a 3-yr-old girl whose other two siblings showed similar radiologic findings. The patient was confirmed to have AIP from autopsy showing histological findings of diffuse alveolar damage and proliferation of fibroblasts. Her 3-yr-old brother was also clinically and radiologically highly suspected as having AIP, and the other asymptomatic 8-yr-old sister was radiologically suspected as having AIP.
PMCID: PMC2526531  PMID: 18583894
Lung Diseases, Interstitial; Child; Siblings
8.  A Good Outcome for a Case of Chronic Pneumonitis of Infancy 
Yonsei Medical Journal  2007;48(5):865-867.
Chronic pneumonitis of infancy (CPI) is a very rare interstitial lung disease. Its pathological features differ from other types of interstitial pneumonia that occur in adults and children. The mortality rate of CPI is high, even with treatment. We report a case of a 3 month old girl diagnosed with CPI after an open lung biopsy who improved after proper treatment.
PMCID: PMC2628155  PMID: 17963346
Infants; interstitial lung disease; chronic pneumonitis of infancy
9.  House Dust Mite Induces Expression of Intercellular Adhesion Molecule-1 in EoL-1 Human Eosinophilic Leukemic Cells 
Journal of Korean Medical Science  2007;22(5):815-819.
The house dust mite (HDM) is considered to be the most common indoor allergen associated with bronchial asthma. In this study, we investigated whether crude extract of the HDM Dermatophagoides farinae could activate human eosinophilic leukemic cells (EoL-1) to induce upregulation of cell-surface adhesion molecules. When EoL-1 cells were incubated with D. farinae extract, expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased on the cell surfaces compared to cells incubated with medium alone. In contrast, surface expression of CD11b and CD49d in EoL-1 cells was not affected by D. farinae extract. In addition, pretreatment of cells with NF-κB inhibitor (MG-132) or JNK inhibitor (SP600125) significantly inhibited ICAM-1 expression promoted by HDM extract. However, neither p38 MAP kinase inhibitor nor MEK inhibitor prevented HDM-induced ICAM-1 expression in EoL-1 cells. These results suggest that crude extract of D. farinae induces ICAM-1 expression in EoL-1 cells through signaling pathways involving both NF-κB and JNK.
PMCID: PMC2693846  PMID: 17982228
Pyroglyphidae; EoL-1 Cells; Intercellular Adhesion Molecule-1; NF-KappaB
10.  Effect of Cosensitization with Buckwheat Flour Extract on the Production of House Dust Mite-specific IgE 
Journal of Korean Medical Science  2007;22(2):198-204.
There are studies reporting food sensitization in infancy increases the risk of sensitization to inhalants later in life. We performed a study to evaluate whether cosensitization with buckwheat (BW) has an effect on the production of house dust mite-IgE. C3H/HeJ mice (4 weeks, female) were sensitized with house dust mite (HDM)/Al (OH)3, intraperitoneally on day 0, followed by 4 intranasal sensitizations (on days 14, 15, 16, and 21). Group 1 was cosensitized intragastrically with BW/cholera toxin (CT) (on days 0, 1, 2, 7, and 18) during sensitization with HDM, group 2 was cosensitized intragastrically with CT only (on days 0, 1, 2, 7, and 18), and group 3 was used as controls. HDM- and BW-IgE and antigen-specific T-cell proliferation and cytokine production were evaluated. In Group 1, BW-IgE levels were highest at week 4, and the HDM-IgE at week 3 (98.45±64.37 ng/mL and 169.86±55.54 ng/mL, respectively). In Group 2, HDM-IgE levels reached a peak at week 3, remarkably higher (810.52±233.29 ng/mL) compared to those of Group 1 (169.86±55.54 ng/mL). The interleukin (IL)-4 and interferon (IFN)-γ in the HDM-stimulated culture supernatants of splenocytes were not significantly different among groups. We postulate that the cosensitization with BW may down-regulate the specific IgE response to HDM.
PMCID: PMC2693581  PMID: 17449923
Buckwheat; House Dust Mite; Immunoglobulin E; Bystander Effect; Animal Models
11.  Comparison of Allergic Indices in Monosensitized and Polysensitized Patients with Childhood Asthma 
Journal of Korean Medical Science  2006;21(6):1012-1016.
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.
PMCID: PMC2721920  PMID: 17179678
Asthma; Child; Immunotherapy; Immunoglobulin E
12.  Atopy and House Dust Mite Sensitization as Risk Factors for Asthma in Children 
Yonsei Medical Journal  2005;46(5):629-634.
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.
PMCID: PMC2810567  PMID: 16259059
Asthma; atopy; house dust mite
13.  Production of Egg Yolk Antibodies Specific to House Dust Mite Proteins 
Yonsei Medical Journal  2014;55(4):999-1004.
House dust mites (HDMs) are an important source of indoor allergens associated with asthma, rhinitis and atopic dermatitis. Chicken immunoglobulin (Ig) Y is known to be a good alternative to mice and rabbit antibody production. In this study, we produced IgYs specific to HDMs and investigated their IgE immunoreactivities.
Materials and Methods
Total IgYs were isolated from the yolks of White Leghorn hens immunized with either Dermatophagoides pteronyssinus or D. farinae protein extract. Control antibodies were separated from the yolks of immunized hens with phosphate buffered saline. IgYs specific to HDMs were analyzed using enzyme-linked immunosorbent assay and Western blotting analysis.
The concentration of egg IgY specific to D. farinae in an immunized hen increased and the highest achieved was 661.3 ug/mg (per an egg) on day 47, compared with 760 ug/mg IgY specific to D. pteronyssinus on day 16. The D. pteronyssinus or D. farinae-specific IgY was detected by binding of each mite proteins, and their immunoreactivities were elevated dependent of the specific IgY concentration.
IgY specific to HDMs may be a promising antibody for immunological diagnosis as well as identification of possible resistance relating to HDM allergy.
PMCID: PMC4075406  PMID: 24954330
House dust mite; immunoglobulin Y; D. pteronyssinus; D. farinae
14.  A Case of Eosinophilic Fasciitis Presenting as Pitting Edema of the Lower Extremities 
Eosinophilic fasciitis is a rare disease characterized by diffuse fasciitis with peripheral eosinophilia and progressive induration and thickening of the skin and soft tissues. We report a 19-year-old female who presented with pitting edema in both lower extremities. She had a history of excessive physical activity before her symptoms developed. Physical examination revealed 2+ pitting edema in both lower legs. She complained of mild pain in both knee joints and feet, with no tenderness or heating sensations. Laboratory results were unremarkable except for severe eosinophilia. Parasite infection, venous thrombosis, and cardiac and renal problems were excluded. A magnetic resonance imaging study of both lower extremities revealed increased signal intensity in the subcutaneous lesions, consistent with superficial inflammation of the fascia. Mixed perivenular lymphoplasmacytic and eosinophilic infiltration in the subcutaneous lesion were observed on biopsy. The patient was treated with corticosteroids, resulting in remarkable improvement in both edema and eosinophilia.
PMCID: PMC3936049  PMID: 24587957
Eosinophilia; eosinophilic fasciitis; pitting edema
15.  Fractional Exhaled Nitric Oxide and Impulse Oscillometry in Children With Allergic Rhinitis 
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).
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.
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.
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.
PMCID: PMC3881396  PMID: 24404390
Asthma; allergic rhinitis; bronchial hyper-responsiveness; bronchodilator effect; child; nitric oxide
16.  Effect of Cholesterol Depletion on Interleukin-8 Production in Human Respiratory Epithelial Cells 
The lipid entities of cell membranes are components of the immune system and important mediators of inflammation. Despite increasing interest in the function of epithelial cells in inflammation, the role of cholesterol in this process has not been described. Here, we investigated the effect of cholesterol depletion on the inflammatory process in airway epithelial cells via the expression of interleukin (IL)-8 as a marker of inflammation.
A 549 cells were treated with 0.5% methyl-β-cyclodextrin as a selective cholesterol extractor. The IL-8 level was assessed by enzyme-linked immunosorbent assay and reassessed after cholesterol repletion. Mitogen-activated protein kinase (MAPK) inhibitors were used to determine the upstream signaling pathway for IL-8 production in cholesterol-depleted cells.
We found a relationship between the amount of cholesterol in A 549 cells and inflammation of the airway. IL-8 production was increased in cholesterol-depleted A 549 cells and restored by cholesterol repletion. IL-8 production was decreased by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor U0126 but not with JNK inhibitor II or the p38 MAPK inhibitor SB202190.
Our findings suggest that inflammatory responses are increased in cholesterol-depleted epithelial cells via the MAPK signaling system, predominantly by the ERK pathway. We conclude that the lipid components of airwayepithelial cells may play a role in the inflammatory process.
PMCID: PMC3810548  PMID: 24179688
Cholesterol; epithelial cell; inflammation; interleukin-8; MAP kinase signaling system
17.  Avoidable Causes of Delayed Enteral Nutrition in Critically Ill Children 
Journal of Korean Medical Science  2013;28(7):1055-1059.
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.
PMCID: PMC3708077  PMID: 23853489
Enteral Nutrition; Parenteral Nutrition; Critical Illness; Child
18.  Prognostic Usefulness of Eosinopenia in the Pediatric Intensive Care Unit 
Journal of Korean Medical Science  2013;28(1):114-119.
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.
PMCID: PMC3546089  PMID: 23341721
Biomarkers; Child; Eosinophils; Infection; Intensive Care Units; Prognosis
19.  The Cockroach and Allergic Diseases 
The cockroach represents one of the most common sources of indoor allergens worldwide, and 40%-60% of patients with asthma in urban and inner-city areas possess IgE antibodies to cockroach allergens. In Korean homes, four cockroach species have been found, of which the most commonly encountered is the German cockroach. The pathogenic mechanism underlying the association between cockroach allergens and allergic diseases has not been fully elucidated. Allergenicity is associated with the cockroach allergens themselves, enzymatic protease activity, and ligands for pattern recognition receptors. Although allergen-specific adaptive immune responses orchestrate the cockroach allergic response, recent data suggest that the innate immune system is also a critical contributor to pathogenesis. We review the current evidence for the demographics of cockroach exposure and sensitization, characteristics of cockroach allergens, and inflammatory responses to cockroach allergens initiated through protease-dependent pathways.
PMCID: PMC3423599  PMID: 22950031
Allergy; allergen; asthma; cockroach; protease-activated receptor 2
20.  520 Involvement of Il-10 Gene Promoter Polymorphisms in the Susceptibility for Childhood Asthma 
Asthma and atopy have a complex background which may result from the interaction of genes and environments. 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 non-atopic asthma, and 248 normal controls. We performed a genetic association study of 3 genetic polymorphisms (IL-10–1082A>G, IL-10 –819T>C, –592A>C) of the IL-10 promoter.
There was no difference between atopic asthma, non-atopic asthma and normal controls in 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 hyperresponsiveness (AHR) and the –819T>C, –592A>C, and ATA and ACC haplotypes were also shown to be related with serum eosinophil cationic protein (ECP).
Our results suggest that the polymorphisms within the IL-10 promoter may have a disease-modifying effect in asthmatic airway.
PMCID: PMC3512647
21.  534 Clinical Characteristics of Eosinophilic Asthma Compared to Noneosinophilic Asthma in Children 
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 and NEA manifest different clinical characteristics.
A total of 158 children with EA and 89 children with NEA were enrolled in this study. We performed pulmonary function and methacholine challenge tests, and measured blood eosinophil count, total serum immunoglobulin E (IgE), serum eosinophil cationic protein (ECP), and sputum cell counts.
There were no significant differences in age, sex, and body mass index between the EA and NEA groups. The blood eosinophil count and serum ECP were higher in EA than in NEA, whereas the total serum IgE was similar in both groups. Pulmonary function, as measured by forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25 to 75% of forced vital capacity (FEF25–75%), and postbronchodilator (postBD) FEV1 were significantly decreased in children with EA compared to those with NEA. In EA, FEV1, FEF25–75%, and postBD FEV1 correlated negatively with sputum eosinophils. In NEA, FEV1/forced vital capacity (FVC) and FEF25–75% correlated negatively with sputum neutrophils. Sputum eosinophils (in EA) and sputum neutrophils (in NEA) increased with increase in asthma severity.
The pulmonary function of children with EA is significantly lower than that of children with NEA. In addition, pulmonary function and asthma severity are associated with eosinophilic inflammation in EA and with neutrophilic inflammation in NEA.
PMCID: PMC3512864
22.  522 Association between Eosinophilic Airway Inflammation and Persistent Airflow Limitation in Asthmatic Children 
The World Allergy Organization Journal  2012;5(Suppl 2):S182-S183.
Eosinophilic airway inflammation contributes to persistent airflow limitation in adults with severe asthma. We aimed to evaluate the association between eosinophilic inflammation in induced sputum and pulmonary function, and persistent airflow limitation in children.
A total of 92 asthmatic children and 72 control children were enrolled in this study. Eosinophil count (%) and eosinophil cationic protein (ECP) levels were measured in induced sputum. We performed spirometry and methacholine challenge test while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects. Subjects with persistent airflow limitation were defined as the patients with postBD FEV1/FVC below the lower limit of controls, which is subtraction of 2 standard deviation from the mean ratio.
Asthmatic children had significantly higher levels of sputum eosinophils (18.1 ± 21.5 vs 0.5 ± 1.3%, P < 0.001) and sputum ECP (2.3 ± 0.7 vs 1.6 ± 0.6 log ug/L, P < 0.001) compared to controls. No differences in sputum eosinophils and ECP among 4 asthmatic groups divided by the degree of persistent airflow limitation. Sputum ECP level had statistically significant inverse correlation with postbronchodilator (postBD) FEV1 (r = –0.307, P = 0.001) and postBD FEV1/FVC (r = –0.286, P = 0.002), whereas sputum eosinophils didn't show any correlation with postBD FEV1 and postBD FEV1/FVC.
Our findings suggest that sputum eosinophilic inflammation, especially ECP, is associated with pulmonary function and persistent airflow limitation, which is manifested by low postBD FEV1 and postBD FEV1/FVC.
PMCID: PMC3513043
23.  Association Between Body Mass Index and Asthma Symptoms Among Korean Children: A Nation-Wide Study 
Journal of Korean Medical Science  2011;26(12):1541-1547.
The purpose of this study was to investigate the association between body mass index (BMI) and the prevalence of wheeze using nation-wide cross-sectional study in Korean children. Total 50,200 children from 427 elementary schools were randomly selected according to residential areas (metropolitan, provincial, rural, and industrial areas) by the cluster sampling method. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires were used to measure the prevalence of wheeze. Among 31,026 respondents, 25,322 were analyzed. BMI was classified into quartiles based on BMI-for-age percentile. In all residential areas, pets at home and visible mold or moisture were associated with an increased prevalence of wheeze in both genders. However, other living environment factors were not consistently associated among residential areas and gender. Among girls, lowest BMI was negatively associated with prevalence of wheeze and highest BMI was positively associated in all residential areas. In multilevel logistic regression analysis, environmental tobacco smoking exposure, pets at home, visible mold or moisture, and being in the lowest and highest BMI quartile were significantly associated with the prevalence of wheeze in both genders. BMI has become an important risk factor for asthma symptoms among Korean children.
PMCID: PMC3230012  PMID: 22147989
Asthma; Body Mass Index; Child; Residence Characteristics
24.  The Chitinase-like Proteins Breast Regression Protein-39 and YKL-40 Regulate Hyperoxia-induced Acute Lung Injury 
Rationale: Prolonged exposure to 100% O2 causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)–39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed.
Objectives: We hypothesized that BRP-39 and YKL-40 (also called chitinase-3–like 1) play important roles in the pathogenesis of HALI.
Methods: We characterized the regulation of BRP-39 during HALI and the responses induced by hyperoxia in wild-type mice, BRP-39–null (−/−) mice, and BRP-39−/− mice in which YKL-40 was overexpressed in respiratory epithelium. We also compared the levels of tracheal aspirate YKL-40 in premature newborns with respiratory failure.
Measurements and Main Results: These studies demonstrate that hyperoxia inhibits BRP-39 in vivo in the murine lung and in vitro in epithelial cells. They also demonstrate that BRP-39−/− mice have exaggerated permeability, protein leak, oxidation, inflammatory, chemokine, and epithelial apoptosis responses, and experience premature death in 100% O2. Lastly, they demonstrate that YKL-40 ameliorates HALI, prolongs survival in 100% O2, and rescues the exaggerated injury response in BRP-39−/− animals. In accord with these findings, the levels of tracheal aspirate YKL-40 were lower in premature infants treated with hyperoxia for respiratory failure who subsequently experienced bronchopulmonary dysplasia or death compared with those that did not experience these complications.
Conclusions: These studies demonstrate that hyperoxia inhibits BRP-39/YKL-40, and that BRP-39 and YKL-40 are critical regulators of oxidant injury, inflammation, and epithelial apoptosis in the murine and human lung.
PMCID: PMC2970863  PMID: 20558631
BRP-39; YKL-40; hyperoxygen; BPD; HALI

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