• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.680-688
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• 2009

Purpose : Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. Methods : A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(＋927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. Results : Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC＋CC or TC＋CC) genotypes in asthmatics, atopic asthmatics, and EIA (＋) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. Conclusion : LTC4S A(-444)C and CysLTR1 T(＋927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

• Clinical and Experimental Pediatrics
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• v.46 no.4
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• pp.370-375
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• 2003

Purpose : It has been suggested that the exposure to aeroallergens during early infancy after birth is important in the subsequent development of sensitization and allergic diseases. In Korea, the level of house dust mites as one of the important aeroallergens is known to be the highest in autumn. The aim of this study was to test whether the distribution of month of birth bears a relationship to the presence of mite sensitization in children with respiratory allergy. Methods : Skin prick tests and methacholine provocation tests were performed on 1,327 patients with chronic respiratory symptoms who visited Seoul National University Children's Hospital from January 1995 to May 2002. An analysis of patients' month of birth distribution according to the presence of mite sensitization was performed. Results : Atopic subjects who had at least one positive skin test numbered 864(65.1%); and non-atopic subjects numbered 463(34.9%). Among atopic subjects, 787(59.3%) had positive skin tests to mites and 77(5.8%) had positive skin test only to minor allergens. A significantly greater than expected number of mite atopic subjects were born in the months between August and November(P=0.03), however, the birth month of non-atopic subjects didn't show a consistent seasonal preference. Asthma patients numbered 543(40.9%). Among these, atopic asthmatics numbered 421(77.5%) and non-atopic asthmatics, 122(22.5%). Dust-mite atopic asthmatics numbered 387(91.9%) out of 421 atopic asthmatics. Dust-mite atopic asthmatics were born significantly higher in the season lasting from August to November in comparison to non-atopic asthmatics(P=0.002). Conclusion : Month of birth seems to be related with sensitization to allergens. Our results show that August to November is the risk period for the development of mite sensitization in Korea.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.221-227
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• 2006

Background : Cough may be a consequence of bronchial hyperresponsiveness or inflammation. Empirical treatment is important in this context because it difficult to verify the obvious cause of cough using laboratory tests, Corticosteroid has a nonspecific anti-inflammatory effect, and can be used for cough management. However, its response rate has not yet been fully elucidated. This study investigated the short- term effects of inhaled corticosteroid on chronic cough Methods : Patients with chronic cough with a normal chest radiograph and a pulmonary function test were enrolled. Cases with a prior respiratory infection within 8 weeks, a history of bronchial asthma, objective wheezing on examination, subjective symptoms of gastroesophageal reflux or taking an ACE inhibitor were excluded. On the first visit, a methacholine bronchial provocation test, spontaneous sputum eosinophil count performed twice and a paranasal sinus radiograph were checked, and the patients were treated with budesonide turbuhaler $800{\mu}g/day$ for ten days. The primary outcome measure was a decrease in the cough score after treatment. Results : Sixty nine chronic coughers were finally analyzed. The final diagnoses by the routine tests were as follows: bronchial asthma 13.0%, eosinophilic bronchitis 18.8%, paranasal sinusitis 23.2% and non-diagnostic cases 53.6%. The following responses to the inhaled corticosteroid were observed: definite responders, 76.8%, possible responders, 2.9% and non-responders, 20.3%. The response rate was not affected by the final diagnosis even in the non-diagnostic cases. There were minimal adverse drug related effects during the empirical treatment. Conclusion : Routine objective tests such as methacholine provocation, sputum eosinophil count and simple radiographs were notare not suitable for diagnosing chronic cough Therefore, empirical treatment is important. Short term inhaled corticosteroid is effective and can guide a further treatment plan for chronic cough.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.535-542
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• 2004

Background : Despite the clinical clues of bronchial asthma, some chronic coughers fail to be diagnosed due to negative test results. This study was aimed at evaluating the diagnostic performance of routine objective tests and identifying a cost-effective approach for asthmatics with a chronic cough. Methods : Patients with a chronic cough of more than 3 weeks duration, and showing normal chest radiograph and spirometry were enrolled. On the first visit, objective tests, composed of serum total IgE, peripheral blood eosinophil count, spontaneous sputum eosinophil count, methacholine bronchial provocation test (MBPT) and paranasal sinus radiograph, were performed, with the simultaneous administration of oral prednisolone (0.5mg/kg) for one week. The final diagnoses were made on the basis of the test results, and the patients grouped according to their steroid responsiveness. The role of the etiologic diagnosis tests was evaluated, and the medical costs of the final management plan simulated with respect to three assumed models. Results : Sixty chronic coughers were finally analyzed. The final diagnoses were as follows: bronchial asthma 21.7%, eosinophilic bronchitis 6.7%, paranasal sinusitis 18.3%, presumptive allergy 8.3% and non-diagnostic case 45.0%. Ninety percent were steroid responder. With the bronchial asthma cases, the positive rate of MBPT was 38.5%, with sputum eosinophil count in 84.6%, serum total IgE in 38.5%, and a peripheral blood eosinophil count rate of 30.8%. When the test results and steroid responsiveness data were applied to the 3 models, the chest radiograph, spirometry, sputum eosinophil count and paranasal sinus radiograph test results, and simultaneous short term steroid treatment seemed to have acceptable diagnostic performances, which could be used as a further guide to cost-effective planning. Conclusion : Objective tests, composed of chest radiograph, spirometry, paranasal sinus radiograph and sputum eosinophil count, with simultaneous short term steroid treatment, are suggested as cost-effective approaches for asthmatics with a chronic cough.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.1013-1018
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• 2003

Purpose : Bronchial hyperresponsiveness(BHR) in asthma is thought to be a consequence of underlying airway inflammation. But the mechanism responsible for persistent BHR in adolescents with long-term asthma remission is poorly understood. The aim of this study was to examine whether BHR in adolescents with asthma remission is associated with peripheral blood eosinophilia and/or increased serum levels of eosinophil cationic protein(ECP). Methods : We studied 35 adolescents with long-term asthma remission(neither symptoms nor medication during the previous two years) who have persistent BHR(remission group) and 35 adolescents with symptomatic asthma(symptomatic group) who were matched for methacholine provocative concentration producing a 20% fall in $FEV_1(PC_{20})$ with subjects in the remission group. The peripheral blood eosinophil counts and serum ECP concentrations were compared between these two groups. Correlations between $PC_{20}$ and peripheral blood eosinophil counts or serum ECP concentrations were assessed in these two groups. Results : Peripheral blood eosinophil counts and serum ECP concentrations were significantly lower in the remission group than in the symptomatic group($273{\pm}108$ vs. $365{\pm}178/{\mu}L$; $16.3{\pm}9.4$ vs. $26.5{\pm}15.1{\mu}g/L$, both, P<0.05). $PC_{20}$ was correlated with peripheral blood eosinophil counts and serum ECP concentrations in the symptomatic group(r=-0.385, P=0.022; r=-0.439, P=0.008), but not in the remission group(r=-0.292, P=0.089; r=-0.243, P=0.159). Conclusion : BHR in adolescents with long-term asthma remission is not associated with peripheral blood eosinophilia or an increase in serum ECP concentration, which suggests that BHR in this clinical setting may not be attributed to airway eosinophilic inflammation. Further studies including direct assessment of airway inflammation are needed to confirm this conclusion.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.481-487
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• 2010

Purpose: Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS) and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR) in mouse model of asthma. Methods: Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA), LPS or $1.0{\mu}g$ LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL) fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; $P$ values for significance were set to 0.05. Results: Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL)-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion: These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic responses to OVA in this mouse model of astham. Our data show that early life exposure with OVA and/or LPS may have a protective role in the development of allergic airway inflammation and development of allergen-induced airway responses in mouse model of asthma.

• Journal of Life Science
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• v.20 no.1
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• pp.147-152
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• 2010

Exercise-induced anaphylaxis (EIA) is a physical allergy, sometimes severe, triggered by exertion following specific food intake. It was defined for the first time in 1980. EIA is associated with different kinds of exercise. The clinical manifestations progress from itching, erythema and urticaria to some combination of cutaneous angioedema and vascular collapse. Mast cell participation in the pathogenesis of this syndrome has been proved by the findings of an elevated serum histamine level during exhaustive exercise. As predisposing factors of EIA, a specific or even nonspecific sensitivity to food has been reported. Food-dependent exercise-induced anaphylaxis (FDEIA) is a distinct form of food allergy induced by physical exercise. It is typified by the onset of anaphylaxis during exercise which was preceded by the ingestion of the causal food allergens. The diagnosis of FDEIA is heavily dependent on clinical history. Allergy tests may need to be performed using a broad panel of food and food additives. As with food allergies, FDEIA diagnosis is based on interview, biological test and skin test. Prophylaxis aims to prevent a recurrence; the patient should be given an emergency kit to deal with any recurrent episodes. After the food allergen has been identified, it should be avoided for at least 4 to 5 hours before any exercise. Two cases of EIA are presented (EIA to circumstances; FDEIA) in this paper, The diagnosis, pathophysiology and therapy of FDEIA are also reviewed.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.44-52
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• 1999

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and $PC_{20}$ for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, $901.6\pm220.4$ pg/ml, $810.9\pm290.8$ pg/ml for PBMC, $24.5\pm9.5$ pg/mL $30.5\pm13.5$ pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p<0.05). However there was no difference of IL-10 level according to $PC_{20}$ for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.196-204
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• 2001

Background : Bronchial asthma is characterized by a reversible airway obstruction, airway hyperresponsiveness, and eosinophilic airway inflammation. The bronchodilator response(BDR) after short acting beta agonist inhalation and PC20 with methacholine inhalation are frequently used for diagnosing bronchial asthma. However, the relationship between the presence of a bronchodilator response and the degree of airway hyperresponsiveness is uncertain. Therefore, the availability of a eosinophil cationic protein (ECP) and a correlation ECP with a bronchodilator response and airway hyperresponsiveness was investigated. Method : A total 71 patients with a moderate to severe degree of bronchial asthma were enrolled and divided into two groups. 31 patients with a positive bronchodilator response and 38 patients with a negative bronchodilator response were evaluated. In both groups, the serum ECP, peripheral blood eosinophil counts, and total IgE level were measured and the methacholine bronchial provocation test was examined. Results : There were no differences observed in age, sex, atopy, and baseline spirometry in both groups. The peripheral eosinophil counts showed no difference in both groups, but the ECP level in group 1 (bronchodilator responder group) was higher than in group 2(non-bronchodilator responder group) ($22.4{\pm}20.7$ vs $14.2{\pm}10.4$, mean$\pm$SD). The PC20 in group 1 was significantly lower than in group 2 ($1.14{\pm}1.68$ vs $66{\pm}2.98$). There was a significant positive correlation between the BDR and ECP, and a negative correlation between the bronchial hyperresponsiveness and ECP. Conclusion : The bronchodilator response significantly correlated with the bronchial hyperresponsiveness and serum ECP in the moderate to severe asthma patients. Hence, the positive bronchodilator response is probably related with active bronchial inflammation and may be used as a valuable index in treatment, course and prognosis of bronchial asthma.