• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.8-12
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• 2013

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

• Clinical and Experimental Pediatrics
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• v.46 no.3
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• pp.230-235
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• 2003

Purpose : Lower respiratory tract infections in infant and young children are often due to a virus, especially the Respiratory syncytial(RS) virus. Chest X-ray findings in bronchiolitis and bronchopneumonia are different. The radiographic hallmark of bronchiolitis is pulmonary hyperinflation and similar to that of bronchial asthma. Bronchiolitis is predisposed to later development of bronchial asthma. To evaluate the difference of immuno-pathophysiology between bronchiolitis and bronchopneumonia, we measured $IFN-{\gamma}$(Th1 cytokine), IL-5(Th2 cytokine) and ECP. We also investigated whether X-ray findings in infants with viral infected respiratory disease are useful in predicting the development of asthma. Methods : We measured IL-5, ECP, $IFN-{\gamma}$ levels in serum from 21 infants with bronchiolitis and 21 infants with bronchopneumonia and 16 infants without pulmonary viral diseases. Results : IL-5 levels of bronchiolitis and bronchopneumonia were significantly higher than those of the control(P=0.02, P=0.042). IL-5 levels of bronchiolitis were higher than those of bronchopneumonia but there was no significant difference. $IFN-{\gamma}$ levels of bronchopneumonia were higher than those of bronchiolitis but there was no significant difference. ECP levels of bronchiolitis and bronchopneumonia were higher than those of the control but only those of bronchiolitis were significantly higher than those of the control(P=0.045). IL-5 and ECP levels did not show any significant correlation in bronchiolitis, bronchopneumonia and control groups. Conclusion : We cannot prove the distinct differences in serum Th1/Th2 cytokine profiles between bronchiolitis and bronchopneumonia in infants. These results suggest that the different findings on chest X-ray between bronchiolitis and bronchopneumonia could not be a predictor of later development of asthma.

• Clinical and Experimental Pediatrics
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• v.45 no.10
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• pp.1227-1233
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• 2002

Purpose : Several studies have shown that increases of eosinophil markers are common findings of asthma and Mycoplasma pneumoniae infection, and eosinophil markers reflect the clinical stage of asthma. The purpose of this study was to investigate the change of eosinophil markers according to the clinical stage of Mycoplasma pneumonia. Methods : The patient group consisted of 33 outpatient children with Mycoplasma pneumonia. Peripheral blood total eosinophil count(TEC) and serum eosinophilic cationic protein(ECP) level were measured at both acute and recovery stages and were compared between both stages. The patient group was subdivided into the wheezing(n=16) and the nonwheezing group(n=17), and the TECs and the ECPs of one group were compared with those of the other group. The correlation between Mycoplasma antibody titer and the eosinophil markers of acute stage were analyzed. Results : In the whole patient group, the TECs and the ECPs of the acute stage were significantly higher than those of the recovery stage(P=0.018, P=0.005), but there were no differences in the TEC and the ECP between the wheezing and the nonwheezing group. In the wheezing group, there were no significant differences in the TEC and the ECP between acute and recovery stages. There were no correlations between acute stage Mycoplasma antibody titer and the eosinophil markers. Conclusion : Eosinophil markers reflect the clinical stage of Mycoplasma pneumonia and eosinophilic inflammations may continue even after the acute stage in wheezing patients with Mycoplasma pneumonia.

• Clinical and Experimental Pediatrics
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• v.49 no.11
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• pp.1216-1222
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• 2006

Purpose : Though atopic and nonatopic asthma have different clinical manifestations, bronchial hyperresponsiveness (BHR) and airway inflammations are common characteristics of them. We investigated BHR to both methacholine and adenosine 5'-monophosphate (AMP), and their relationships with blood eosinophil markers in nonatopic asthma as well as atopic asthma. Methods : We studied 116 children (82 atopics; 34 nonatopics) with mild to moderate asthma. Methacholine and AMP challenge tests were performed and bronchial responsiveness was expressed as $PC_{20}$ (provocative concentration causing a 20 percent fall in $FEV_1$); blood eosinopil counts (ETCs) and serum eosinophil cationic protein (ECP) levels were gauged. Results : In atopics, 95.1 percent and 90.2 percent showed hyperreactivity to methacholine ($PC_{20}$<16 mg/mL) and AMP ($PC_{20}$<200 mg/mL), respectively. Meanwhile, in nonatopics, 94.1 percent and 52.9 percent displayed hyperreactivity to methacholine and AMP, respectively. The geometric mean of AMP $PC_{20}$ was lower in atopics (31.6 mg/mL) than in nonatopics (125.9 mg/mL); that of methacholine $PC_{20}$ was similar in the two groups. AMP $PC_{20}$ correlated with blood ETCs in both atopics(r=-0.30, P<0.01) and nonatopics (r=-0.57, P<0.01), and correlated with serum ECP levels (r=-0.23, P<0.01) in atopics, but not in nonatopics. Apart from AMP, methacholine $PC_{20}$ was not associated with blood eosinophil markers in either group. Conclusion : Atopics more frequently displayed BHR to AMP than nonatopics. Furthermore, BHR to AMP was associated with not only blood ETCs, but serum ECP levels in atopics but was correlated with only blood ETCs in nonatopics. Those results suggest that BHR to AMP reflects airway inflammation in asthma and is more related to atopy.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.1
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• pp.83-89
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• 2008

Eighty-four Holstein cows were used to evaluate effects of feeding two diets that differed in dietary cation-anion difference (cationic; +28 or anionic; -138 mEq/kg DM) on prepartum and postpartum dry matter intake (DMI), body weight (BW), body condition score (BCS), serum Ca concentrations and on subsequent milk production and composition. Treatments were in a $2{\times}3{\times}2$ factorial arrangement that included prepartum diet, dry period length (30 d dry, 30 d dry+estradiol cypionate (ECP), and 60 d dry), and prepartum and postpartum bST ($POSILAC^{(R)}$ 10.2 mg/d). No interaction of prepartum diet with dry period length or bST supplementation was detected for any measure evaluated either prepartum or postpartum. No significant effects of prepartum diet on prepartum DMI, BW or BCS were observed. Mean DMI during the first 28 d postpartum were similar for cows fed the cationic or anionic diets prepartum (25.5 vs. 26.1 kg/d). During postpartum wk 1 to 14, no differences in mean BW or BCS were detected due to prepartum diet fed but decreases for both groups were observed during the first 6 wk postpartum. No differences due to prepartum diet were observed for mean milk or 3.5% FCM yields or for milk composition during the first 10 wk of lactation. Similarly, mean milk yield of cows during the first 21 wk did not differ significantly due to prepartum diet fed (38.5 vs. 38.6 kg/d). Overall, cows fed the prepartum cationic or anionic diets had similar mean postpartum serum concentrations of Ca (9.34 vs. 9.35 mg/dl). Subsequent milk production, milk composition and concentrations of Ca did not differ. Importantly, the two prepartum diets were equally satisfactory in minimizing incidence of milk fever and in supporting initiation of lactation, irrespective of dry period length and supplemental ECP and bST.

• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.487-491
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• 2008

Purpose : Although Mycoplasma pneumoniae (M. pneumoniae) infection can cause wheezing in non-asthmatic children, the mechanisms of this symptom remain unclear. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and vascular permeability, and is also known to be elevated in cases of chronic pulmonary disease such as asthma. We hypothesized that VEGF may increase in children with acute M. pneumoniae pneumonia and wheezing. Methods : Nine patients with clinical and laboratory evidence of acute M. pneumoniae pneumonia were enlisted from children admitted to Korea University Hospital. They had had more than one episode of wheezing during the illness, which was confirmed by a physician; they comprised the wheezer group. The individuals with M. pneumoniae pneumonia without wheezing were 63 in number, and they comprised the non-wheezer group. Patients with a history of asthma or who had received asthma medications were excluded. Serum concentrations of VEGF, total IgE, eosinophil cationic protein (ECP), and peripheral blood eosinophil counts were measured. Results : The serum VEGF concentrations were higher in the wheezer group ($mean{\pm}SD$; $650.2{\pm}417.9pg/mL$) than in the non-wheezer group ($376.5{\pm}356.2pg/mL$, P=0.049). M. pneumoniae antibody (1:1,380 vs. 1:596, P=0.048) and serum total IgE (591.8 IU/mL vs. 162.2 IU/mL, P=0.032) were higher in the wheezer group than in the non-wheezer group. There were no differences between the two groups in terms of serum ECP concentration or blood eosinophil count. Conclusion : In the presence of wheezing, serum VEGF concentrations were higher in the children with M. pneumoniae pneumonia. This finding suggests that VEGF may associate with wheeze-related symptoms in children with acute M. pneumoniae pneumonia.

• Clinical and Experimental Pediatrics
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• v.50 no.3
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• pp.284-291
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• 2007

Purpose : Theophylline has recently been reported to have concurrent anti-inflammatory effects at low therapeutic plasma concentrations which are below the doses at which significants, clinically useful bronchodilatation is evident. Sustained-release formulation in capsule and dry syrup forms were developed to reduce its adverse effects and improve its clinical effects. We compared the therapeutic effects of theophylline dry syrup and capsules in children with mild asthma. Methods : Ninety children with mild asthma were randomized to receive either theophylline dry syrup (n=44) or theophylline capsules (n=46); 4 mg per kilogram of body weight, twice a day, for 12 weeks. Baseline and serial measurements of daytime and nighttime asthma symptom score were performed. Compliance scores, drug swallowing scores, and drug usability scores were measured every 4 weeks. Each scoring was rated on a scale of 0-4. Serum theophylline concentration were measured at 4 and at 12 weeks. To examine the anti-inflammatory effect of theophylline on asthma, Serum eosinophilic cationic protein as a marker of airway inflammation caused by eosinophil was measured 12 weeks pre- and post-administration. Results : The daytime and nighttime asthma symptom scores of the two groups after 4 weeks significantly improved over the baseline score. Daytime and nighttime asthma symptom scores in the dry syrup group were statistically lower at all time points except for the nighttime symptom scores at 4 weeks. Compliance scores, drug swallowing scores, and drug usability scores in the dry syrup group were significantly higher at the end time point. Only in the dry syrup group was the serum ECP at the end time point statistically lower than baseline. Conclusion : Low-dose sustained-release theophylline may be safe and effective in bronchial asthma and this effect may be mediated by its anti-inflammatory action mechanisms. Especially, when used in children with asthma, dry syrup formulation is recommended because of its higher compliance than capsule formulation.

• Journal of Microbiology and Biotechnology
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• v.16 no.11
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• pp.1699-1705
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• 2006

Recent studies have suggested that oral bacteriotherapy with probiotics might be useful for preventing and managing childhood atopic dermatitis (AD). The purpose of this investigation was to evaluate the efficacy and safety of oral treatment with probiotics for adolescent and adult AD patients as well as for childhood AD patients. Sixty-four patients with mild to moderate AD were recruited for treatment with a mixture of four probiotic strains (Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus casei, and Biftdobacterium lactis) twice daily for 8 weeks. The degree of pruritus was determined by a 10-point visual analog scale every other week, and the patients' global assessments of their clinical responses (i.e., better, unchanged, or worse) was done at the end of intervention. The clinical severity of the eczema was evaluated by eczema area and severity index (EASI) score every other week. As laboratory markers, total immunoglobulin E (IgE), eosinophil cationic protein (ECP) in the serum, and cytokine production [interleukin-4 (IL-4), interleukin-10 (IL-10), and $interferon-{\gamma}\;(IFN-{\gamma})$ by the peripheral blood mononuclear cells (PBMCs) were measured at the beginning and at the end of intervention. Of the 64 enrolled AD patients, only 50 patients finally completed the 8-week study. After 8-week treatment with probiotics, the EASI score was significantly improved (p<0.0001), 50% of the patients experienced improvement of their eczema, and significant improvement of the pruritus was also observed (p=0.0002). The effect was more pronounced for the patients with very high IgE levels (>1,000 ku/l) or for the patients with moderate disease severity. There was no significant difference in the therapeutic effects between the childhood AD and adolescent and adult AD patients. There were no significant changes of cytokines, as well as the total IgE and ECP levels, in the patients' serum. Treatment with the mixture of four probiotic strains was generally well tolerated. Our results suggest that the treatment with the mixture of four probiotic strains is beneficial for the management of the adolescent and adult AD patients, as well as for the childhood AD patients.

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.298-304
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• 2006

Purpose : We compared the asthma predictive index(API) and the modified asthma predictive index (mAPI) of the Tuscon Children's Respiratory Study Group in Korean children with recurrent wheezing. We investigated the atopic profiles and presence of allergen sensitization of each risk group, and ascertained the significant clinical risk factors. Methods : Two hundred and sixty two children, who visited for recurrent wheezing from 1998 to 2005, were enrolled and divided into groups by API and mAPI. We investigated the history of the patients and their families, atopic profiles, and sensitization to aeroallergen and food allergens. Twenty nine children were followed up to 6 years of age and we evaluated the sensitivity, specificity and positive and negative predictive value of both indices. Results : The high risk group of API were of older age, were more likely to be sensitized to aeroallergen(P=0.001) and food allergen(P=0.034) and had higher levels of total eosinophil count, eosinophil percent, serum ECP, total IgE, and D.p-, D.f-specific IgE. High risk group of mAPI showed higher levels of atopic markers such as egg-, milk-, D.p- and D.f-specific IgE. Even though API did not include allergen sensitization, the high risk group was more significantly sensitized to common allergens than the low risk group. Twenty nine children were followed up until 6 years of age; therefore 15 children were diagnosed as asthma, clinically. The sensitivity, specificity, positive and negative predictive values of mAPI were higher than API. Conclusion : Both high risk groups of API and mAPI had higher levels of atopic markers and were more sensitized to common allergens. These findings suggest that sensitization to aeroallergens and food allergens are more objective markers as asthma predictive indices. In addition, mAPI is a more reliable index in predicting asthma in Korean children with recurrent wheezing than is API. But only 29 patients were followed until the age of 6, so we need to include more children with long term follow up for future study.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.386-394
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• 2003

Background : ATS(American Thoracic Society) defined new guidelines for COPD(chronic obstructive lung disease) in April 2001, following the results of the global initiative for chronic obstructive lung disease. The most important concept of COPD is an airflow limitation which is not fully reversible compared to bronchial asthma(BA). The criteria for COPD are postbronchodilator $FEV_1$ less than 80% of the predicted value and an $FEV_1$ per FVC ratio less than 70%. The global initiative for asthma(GINA) study defined asthma, which included immune-mediated chronic airway inflammatory airway disease, and found that airflow limitation was wide spread, variable and often completely reversible. Taken together COPD and BA may be combined in airflow limitation. This study was designed to evaluate the prevalence of BA in patients with COPD of moderate to severe airflow limitation. Methods : COPD was diagnosed by symptoms and spirometry according to ATS guidelines. Enrolled subjects were examined for peak flow meters(PFM), sputum eosinophils and eosinophil cationic protein(ECP) levels, serum total IgE with allergy skin prick test, and methacholine bronchial provocation test(MBPT). Results : About 27% of COPD patients with moderate to severe airflow limitation were combined with BA. There was significantly decreased response to PFM in severe COPD. However, there was no significant relationship between BA and COPD according to the degree of severity. The BA combined with COPD group showed significantly high eosinophil counts and ECP level in induced sputum. However, neutrophil counts in induced sputum showed significant elevation in the pure COPD group. Conclusion : Twenty-seven percent of COPD patients with moderate to severe ventilation disorder were combined with BA, but there were no significant differences according to the degree of severity.