• Clinical and Experimental Pediatrics
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• v.45 no.12
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• pp.1577-1584
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• 2002

Purpose : Airway inflammation is considered to be a characteristic feature of asthma, and eosinophils are recognized as the most important inflammatory cells. This study aims to assess the importance of blood eosinophil count and serum eosinophil cationic protein(ECP) levels as a noninvasive marker of bronchial hyperresponsiveness(BHR) in children with suspected asthma. Methods : This study used data from 87 subjects with asthma-like symptoms(6-18 years old). The $FEV_1$ and provocative concentration producing a 20% fall in $FEV_1(PC_{20})$ on methacholin inhalation challenge test were measured. Four groups were classified based on $PC_{20}$[Group I : <2 mg/mL; Group II : 2-8 mg/mL; Group III : 8-18 mg/mL; Group IV : (18 mg/mL], and blood eosinophil count and serum ECP levels were analyzed. In addition, subjects were classified based on the cutoff value of $PC_{20}$(BHR positive group : <18 mg/mL; BHR negative group : (18 mg/mL). Then blood eosinophil count and serum ECP level were compared between these two groups. Results : Likelihood ratio test for trends revealed a significant association between the blood eosinophil count or serum ECP level, and the degree of BHR as measured by methacholine $PC_{20}$. Blood eosinophil count or serum ECP level was significantly higher in the BHR(+) group than in the BHR(-) group. Blood eosinophil count had a positive correlation with serum ECP level. Conclusion : Blood eosinophil count and serum ECP level may be a useful non-invasive clinical marker of BHR in subjects with suspected asthma. This supports the hypothesis that BHR in asthma is a consequence of airway eosinophilic inflammation.

• 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.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.184-191
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• 2003

Background : Nowadays asthma is considered to be an inflammatory disease characterized by airway hyperresponsiveness and pulmonary eosinophilia. Production of cytokines by bronchial epithelial cells may contribution to the local accumulation of inflammatory cells in patients with bronchial asthma. Chungsangboha-tang is the herbal treatment of choice in persistent asthma patients. It has been recognized that cessation of treatment with Chungsangboha-tang evokes a recurrence of symptoms in patients with controlled asthma. This study was designed to evaluate the long-term effect of Chungsangboha-tang. Materials and Methods : The subjects consisted of 24 patients with asthma who had been treated with Chungsangboha-tang for four weeks. Chungsangboha-tang is an herbal decoction which has been used as the traditional therapeutic agent for asthma. PFT, QLQAKA, blood eosinophils, serum IgE, Serum IL-4, IL-5, $IFN-{\gamma}$ were checked before treatment, before withdrawal and 3 months after cessation of treatment with Chungsangboha-tang. Results : Treatment with Chungsangboha-tang for four weeks resulted in significant increase in FEV1.0%, PEFR%, and QLQAKA. The patients were treated with Chungsangboha-tang for four weeks with no significant difference in the blood eosinophils, serum IgE, IL-4 and IL-5. The serum $IFN-{\gamma}$ in asthmatic patients decreased significantly after 4 weeks of treatment. Discontinuation of treatment with Chungsangboha-tang resulted in significant drops in QLQAKA. Others measures in asthmatic patients 3 months after discontinuation of treatment with Chungsangboha-tang showed no significant difference. Conclusion : This study demonstrates that asthma can be exacerbated by discontinuation of treatment with Chungsangboha-tang in patients with asthma. Obviously further research concerning this is still necessary.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.813-822
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• 1995

Background: Bronchial hyperresponsiveness and abnormal response such as a loss of distensibility are pathophysiologic characteristics if bronchial asthma. The only means of direct in vivo measurement of airway size had been a tantalium bronchography, until high-resolution computed tomography(HRCT) enabled to measure noninvasively two dimensional airway area more accurately and reliably. Method: To investigate airway area responses to bronchial provocation with methacholine and evaluate the major sites of bronchial constriction in patients with bronchial asthma. We examined HRCT scans in five patients with bronchial asthma who had significant bronchoconstriction(20% or more decrease in $FEV_1$) using CT scanner(5,000T CT, Shimadzu Co, Japan) before and in 3~5 min. after methacholine inhalation. Airways which were matched by parenchymal anatomic landmarks in each patient before and after methacholine inhalation were measured using film scanner(TZ-3X scanner; Truvel Co. Chatsworth CA, USA) and a semiautomated region growing method. Results: 1) We identified 9 to 12 airways in each patient which were matched by parenchymal anatomic landmarks before and after methacholine inhalation. 2) Airway responses to methacholine are quite different even in a patient. 3) The constriction of small airways(average diameter <2 mm; area < $3.14mm^2$) was 48.7%(8.3; SEM, n=43), being more prominant than that of large airways(average diameter >2 mm; area > $3.14mm^2$), 53.8% (4.4;SEM, n=10), but not significantly different(p>0.05). 4) There was no significant difference in the degree of constriction between upper(44.3% +5.8; mean + SEM, n=30) and lower lung regions(56.7% +4.5, n=23). Conclusions: Thus airway responses to methacholine bronchoprovocation is quite variable in a patient with bronchial asthma and has no typical pattern in patients with bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.341-350
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• 1998

Background: Airway hyperreponsiveness is a cardinal feature of asthma. It consists of both an increased sensitivity of the airways, as indicated by a smaller concentration of a constrictor agonist needed to initiate the brochoconstrictor response and an increased reactivity, increments in response induced subsequent doses of constrictor, as manifested by slopes of the dose-response curve. The purpose of this study is to observe the relationship between bronchial sensitivity and reactivity in asthmatic subjects. Method: Inhalation dose-response curves using methacholine were plotted in 56 asthmatic subjects. They were divided into three groups(mild, moderate and severe) according to clinical severity of bronchial asthma. PC20 were determined from the dose-response curve as the provocative concentration of the agonist causing a 20% fall in FEVl. PC40 were presumed or determined from the dose response curve, using the PC20 and the one more dose after PC20. Reactivity was calculated from the dose-response curve regression line, connecting PC20 with PC40. Results: PC20 were 1.83mg/ml in mild group, 0.96mg/ml in moderate, and 0.34mg/ml in severe. PC40 were 7.l7mg/ml in mild group, 2.34mg/ml in moderate, and 0.75mg/ml in severe. Reactivity were $24.7{\pm}17.06$ in mild group, $46.1{\pm}22.l0$ in moderate, and $59.0{\pm}5.82$ in severe. There was significant negative correlation between PC20 and reactivity (r= -0.70, P<0.01). Conclusion: Accordingly, there was significant negative correlation between bronchial sensitivity and brochial reactivity in asthmatic subjects. However, in some cases, there were wide variations in terms of the reactivity among the subjects who have similar sensitivity. So both should be assessed when the bronchial response tor bronchoconstrictor agonists is measured.

• 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.

• Clinical and Experimental Pediatrics
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• v.48 no.10
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• pp.1126-1131
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• 2005

Purpose : Bronchial hyperresponsiveness(BHR) is considered a hallmark of asthma. Increased levels of eosinophil cationic protein(ECP) have been identified in serum of asthma patients. Several studies have examined the relationship between serum ECP and bronchial responsiveness, expressed as methacholine $PC_{20}$ in asthmatic patients, with conflicting results. The aims of this study were to examine the relationship between serum ECP and ${\Delta}FVC$, another index of bronchial responsiveness, which reflects increased maximal airway response. Methods : Six to 8-year-old children with asthma(n=109) underwent methacholine bronchoprovocation testing. The $PC_{20}$ dose of methacholine and ${\Delta}FVC$ were calculated for each individual from the methacholine dose response curves. Serum ECP levels and blood total eosinophil counts were also measured. Results : Serum ECP correlated with ${\Delta}FVC$(r=0.217, P=0.023), as well as $PC_{20}$(r=-0.208, P=0.030). However, blood eosinophil counts failed to show any correlations with ${\Delta}FVC$(r=0.085, P=0.378) or $PC_{20}$(r=-0.148, P=0.125). ${\Delta}FVC$ did not correlate with $PC_{20}$(r=-0.079, P=0.417). Conclusion : Blood eosinophil activation is associated with both components of BHR including increased sensitivity and increased maximal response in 6-8 year old children with asthma.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.12-28
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• 2001

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.581-588
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• 2006

Asthma is a chronic inflammation of the airway associated with increased bronchial hyperresponsiveness that leads to recurrent episodes of cough, wheezing, breathless, chest tightness. According the recent studies, repeated airway inflammation leads to structural changes so called 'airway remodeling' and associated with decreased pulmonary function. Airway remodeling begins form the early stage of asthma and the early diagnosis and management is very important to prevent airway remodeling. Medication for asthma can be classified into acute symptom reliever and chronic controller. Short acting beta2 agonist is a well-known reliever that reduced asthma symptoms within minutes. Controllers should be taken daily as a long-term basis to control airway inflammation. Inhaled corticosteroid(ICS) is the most effective controller in current use. However, in some patients ICS monotherapy is not sufficient to control asthma. In those cases, other medications such as long acting beta2 agonist, leukotriene modifier or sustained-release theophylline should be added to ICS, which called Add-on-Therapy. Combination inhaler devices are easy to use. Oral leukotriene modifier has a good compliance especially in children. Finally, as asthma is a chronic disease, the development of on-going partnership among health care professionals, the patients, and the patients' family is necessary for the effective management of asthma.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.251-261
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• 2019

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.