• Tuberculosis and Respiratory Diseases
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• v.67 no.4
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• pp.311-317
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• 2009

Background: The methacholine bronchial provocation test is a useful tool for evaluating asthma in patients with normal or near normal baseline lung function. However, the sensitivity of this test is 82~92% at most. The purpose of this study is to evaluate the clinical usefulness of $FEF_{25-75%}$ in identification of airway hyperresponsiveness in patients with suspected asthmatic symptoms. Methods: One hundred twenty-five patients who experienced cough and wheezing within one week prior to their visiting the clinic were enrolled. Results: Sixty-four subjects showed no significant reduction of $FEV_{1}$ or $FEF_{25-75%}$ on the methacholine bronchial provocation test (Group I). In 24 patients, $FEF_{25-75%}$ fell more than 20% from baseline without a 20% fall of $FEV_{1}$ during methacholine challenge (Group II). All patients who had more than 20% fall of $FEV_{1}$ (n=37) also showed more than 20% of reduction in $FEF_{25-75%}$ (Group III). Baseline $FEV_{1}$/FVC (%) and $FEF_{25-75%}$ (L) were higher in group II than group III (81.51${\pm}$1.56% vs. 75.02${\pm}$1.60%, p<0.001, 3.25${\pm}$0.21 L vs. 2.45${\pm}$0.21 L, p=0.013, respectively). Group II had greater reductions of both $FEV_{1}$ and $FEF_{25-75%}$ than group I at 25 mg/mL of methacholine (p<0.001). The provocative concentration of methacholine causing a 20% fall in $FEF_{25-75%}$ in group II was about three-fold higher than that in group III. Conclusion: A 20% fall of $FEF_{25-75%}$ by methacholine provocation can be more sensitive indicator for detecting a milder form of airway hyperresponsiveness than $FEV_{1}$ criteria.

• Clinical and Experimental Pediatrics
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• v.46 no.5
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• pp.495-499
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• 2003

Purpose : Eosinophil is one of the important inflammatory cell involved in the airway inflammation in childhood asthma. It has been demonstrated that markers of eosinophil activation, including eosinophil cationic protein or eosinophil protein X(EPX), are increased in childhood asthma. Furthermore, they are related to disease activity and are assumed to be helpful in monitoring the treatment effect as urinary EPX(U-EPX) can be obtained easily and in a noninvasive way in children of all ages. Methods : Twenty-five children(22 male and three female) aged $11.87{\pm}3.82$ years with stable asthma were challenged with methacholine and urine was collected from each child during the following periods; before methacholine challenge test(MCT); 0-3 hr after the end of MCT; 4-7 hr after the end of MCT; and 8-24 hr after the end of MCT. Bronchial reactivity was determined by using Dosimeter( Jeager, Germany) with serially diluted methacholine from 0.05 to 25.0 mg. The $FEV_1$ less than 80% of baseline value were classified into positive MCT. U-EPX was measured with a sensitive and specific radioimmunoassay(Pharmacia & Upjohn AB, Uppsala, Sweden). Results were expressed as ${\mu}gEPX/mmol$ creatinine. Results : An early airway response after MCT was associated with an increase of U-EPX excretion for 0-3 hr after methacholine inhalation in comparison with beseline values. Most subjects showed a small increase in U-EPX excretion during late asthmatic response for 4-7 hr, which then decreased to normal level in 8-24 hr. Also, a tendency for a higher increase of U-EPX was associated with a lower threshold of methacholine challenge and a longer duration of asthma. Conclusion : Measurement of EPX in urine is a noninvasive and easy method to assess the severity of airway inflammation in asthmatic children. It may be a helpful index of the events underlying the airway inflammatory responses during nonspecific bronchial challenge, and in monitoring asthma management.

• Korean Journal of Radiology
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• v.1 no.3
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• pp.127-134
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• 2000

Objective: To determine the extent to which thin-section and volumetric three-dimensional CT can depict airway reactivity to bronchostimulator, and to assess the effect of different airway sizes on the degree of reactivity. Materials and Methods: In eight dogs, thin-section CT scans were obtained before and after the administration of methacholine and ventolin. Cross-sectional areas of bronchi at multiple levels, as shown by axial CT, proximal airway volume as revealed by three-dimensional imaging, and peak airway pressure were measured. The significance of airway change induced by methacholine and ventolin, expressed by percentage changes in cross-sectional area, proximal airway volume, and peak airway pressure was statistically evaluated, as was correlation between the degree of airway reactivity and the area of airways. Results: Cross-sectional areas of the bronchi decreased significantly after the administration of methacholine, and scans obtained after a delay of 5 minutes showed that normalization was insufficient. Ventolin induced a significant increase in cross-sectional areas and an increase in proximal airway volume, while the effect of methacholine on the latter was the opposite. Peak airway pressure increased after the administration of methacholine, and after a 5-minute delay its level was near that of the control state. Ventolin, however, induced no significant decrease. The degree of airway reactivity did not correlate with airway size. Conclusion: Thin-section and volumetric spiral CT with three-dimensional reconstruction can demonstrate airway reactivity to bronchostimulator. The degree of reactivity did not correlate with airway size.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.723-735
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• 1998

Background : Vitamin C has been reported to have a role in the decrease of airway hyperresponsiveness in animal models. This data is based on some metabolic actions of vitamin C, such as promotion of histamine degradation, producing more $PGE_2$ than $PGF_{2\alpha}$ in cyclooxygenase pathway, decrease of smooth muscle contraction, and acting as reducing agent of oxidant. It has been also known that heavy smokers have lower blood levels of vitamin C than nonsmokers and this deficiency in heavy smokers have been explained by several mechanisms, such as increased oxidation by oxidants and free radicals, increased biosynthesis of catecholamine and serotonin released by nicotine, and inadequate dietary intake. In this study, We attempted to assess effect of vitamin C on bronchial hyperresponsiveness in heavy smokers who have bronchial hyperresponsiveness and role of vitamin C on bronchial hyperresponsiveness. Method: To assess acute effect of vitamin C on airway hyperresponsiveness, blood sample for vitamin C level and spirometry, methacholine challenge test were done in 17 smokers and 8 nonsmokers, and one hour after oral administration of vitamin C 3 g, blood sample for vitamin C level and spirometry, methacholine challenge test were repeated. To assess chronic effect of vitamin C on airway hyperresponsiveness, after daily administration of vitamin C 1 g for one week in 17 smokers, blood sample for vitamin C level and spirometry, methacholine challenge test were done. To assess role of vitamin C, after oral administration of vitamin C 3 g plus indomethacin 100 mg in 12 of 15 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were done and after oral intake of indomethacin 100 mg in 12 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were repeated. Result: There were no significant differences in whole blood vitamin C levels between smokers($1.17{\pm}0.22$ mg/dL) and nonsmcikers($1.14{\pm}0.19$ mg/dL) (p>0.05). Fifteen of the 17 smokers(88.2%) were reactive to methacholine challenge test and 10 of the 15 smokers who were reactive to methacholine challenge test were less than 8 mg/dL in $PC_{20}FEV-2$, and 7 of the 8 nonsmokers(87.5%) were nonreactive to methacholine challenge test There were significant decrease in bronchial responsiveness after oral administration of vitamin C 3 g in 13 of the 15 smokers who were reactive to methacholine challenge test This significant decrease persisted with maintenance daily administration of 1 g for one week. $PC_{20}FEV-2$ were not correlated to vitamin C levels in smokers. After oral administration of indomethacin 100 mg, significant reduction of bronchial responsiveness that occured after oral administration of vitamin C 3 g in smokers were attenuated. Conclusion: Although there were no significant differences in whole blood vitamin C levels between smokers and nonsmokers. heavy smokers have significant increase in bronchial responsiveness than nonsmokers. This bronchial hyperresponsiveness of heavy smokers can be attenuated by vitamin C supplement. Disappearance of vitamin C effect by indomethacin supplement may suggest that vitamin C exert its effect via alteration of arachidonic acid metabolism.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.165-174
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• 1995

Background: Exercise is one of the most common precipitants of acute asthma encountered in clinical practice. The development of airflow limitation that occurs several minutes after vigorous exercise, i. g. exercise-induced bronchoconstriction(EIB), has been shown to be closely correlated with the nonspecific bronchial hyperresponsiveness, which is the hallmark of bronchial asthma. All previous reports that assessed the correlation of EIB to nonspecific bronchial hyperresponsiveness have focused on airway sensitivity($PC_{20}$) to inhaled bronchoconstrictor such as methacholine or histamine. However, maximal airway narrowing(MAN), reflecting the extent to which the airways can narrow, when being exposed to high dose of inhaled stimuli, has not been studied in relation to the degree of EIB. Methods: Fifty-six children with mild asthma(41 boys and 15 girls), aged 6 to 15 years(mean${\pm}$SD, $9.9{\pm}2.5$ years) completed this study. Subjects attended the laboratory on two consecutive days. Each subject performed the high-dose methacholine inhalation test at 4 p.m. on the first day. The dose-response curves were characterized by their position($PC_{20}$) and MAN, which was defined as maximal response plateau(MRP: when two or three data points of the highest concentrations fell within a 5% response range) or the last of the data points(when a plateau could not be measured). On the next day, exercise challenge, free running outdoors for ten minutes, was performed at 9 a.m.. $FEV_1$ was measured at graduated intervals, 3 to 10 minutes apart, until 60 minutes after exercise. Response(the maximal ${\triangle}FEV_1$ from the pre-exercise value) was classified arbitrarily into three groups; no response((-) EIB: ${\triangle}FEV_1$<10%), equivocal response ($({\pm})$EIB:10%<${\triangle}FEV_1$<20%) and definite response($({\pm})$EIB:${\triangle}FEV_1$>20%). Results: 1) When geometric mean $PC_{20}$ of the three groups were compared, $PC_{20}$ of (+) EIB group was significantly lower than that of (-)EIB group. 2) There was a close correlation between $PC_{20}$ and the severity of EIB in the whole group(r=-0.568, p<0.01). 3) Of the total 56 subjects, MRP could be measured in 36 subjects, and the MRP of these subjects correlated fairly with the severity of EIB(r=0.355, p<0.05) 4) The MAN of (+) EIB group was significantly higher than that of (-)EIB group(p<0.01). 5) The MAN correlated well with the severity of EIB in the whole group(r=0.546, p<0.01). Conclusion: The degree of MAN as well as bronchial sensitivity($PC_{20}$) to methacholine is correlated well with the severity of EIB. The results suggest that the two main components of airway hyperresponsiveness may be equally important determinants of exercise reactivity, although the mechanism may be different from each other. The present study also provides further evidence that EIB is a manifestation of the increased airway reactivity characteristic of bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.99-106
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• 1998

Background: Bronchial asthma is a complex disease, which is characterized by spontaneous exacerbations of airway obstruction and persistent bronchial hyperresponsiveness. Animal models have fallen short of reproducing the human disease, particularly in mimicking the spontaneous and persistent airflow obstruction that characterized in asthma. In animals, airflow obstruction is usually assessed by measuring airflow resistance during tidal breathing under such invasive technique as tracheostomy and anesthesia. A noninvasive technique for measuring pulmonary function in small animals is needed to evaluate long-term changes in lung function during the course of experimentally produced disease without sacrificing the animal. Purpose: The purpose of this study was to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness (AR) to inhaled methacholine in nonanethetized, unrestrained guinea pigs. Method: Guinea pig model of asthma was sensitized by subcutaneous injection with ovalbumin and challenged by inhalation of aerosolized ovalbumin(1% wt/vol ovlabumin). Airflow obstruction of conscious guinea pig was measured as specific airway resistance (airway resistance $\times$ thoracic gas volume). Airway resistance and thoracic gas volume of conscious guinea pig were assessed by body plethysmography before challenge and at regular intervals for as long as 30 minutes after challenge. AR to aerosolized methacholine of asthma group was compared with that of control group in body plethysmography. Result: Asthma model<> developed in 13 (65%) among 20 guinea pigs, in which early responses occurred in the airways after the exposure to inhalation with ovalbumin. Airway challenge with ovalbumin caused increase in specific airway resistance, which peaked at 6 minutes and amounted to a $231.5{\pm}30.4%$ increase from baseline. AR to aerosolized methacholine of asthma model increased significantly compared with control group. Conclusion: These results have showed a useful animal model to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness in nonanethetized, unrestrained guinea pigs.

• Tuberculosis and Respiratory Diseases
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• v.39 no.5
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• pp.392-399
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• 1992

Background: Despite dyspnea is a predominant complaint of patients with respiratory disease, the mechanisms contributing to the sensation of breathlessness are poorly understood. Traditionally, physicians have measured objective pulmonary function to assess severity of dyspnea. But it will be also useful to measure subjective dyspnea index because dyspnea probably depends on a complex interplay of mechanical, experimental, emotional and other factors. Method: We measured breathlessness at rest, after Methacholine challenge and then bronchodilator inhalation using a Visual Analogue Scale (VAS) and Borg Scale Dyspnea Index (BSDI) in stable asthmatic patients. Spirometry was performed concomittently. Results: There was no correlation between dyspnea index and FEV1. There was also no correlation between the change in dyspnea index and change in FEV1. The change in dyspnea index after methacholine and bronchodilator was greater in clinically mild asthmatic patients than clinically severe symptomatic group. Conclusion: In asthmatic patients, there was a wide variation in sensory response for any given FEV1, and the change in perception of dyspnea was greater in those with clinically mild symptoms. The measurement of dyspnea index may yield information complementary to that obtained by spirometry.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.853-860
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• 1997

Background : Chronic cough, defined as a cough persisting for three weeks or longer, is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, and gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. Method : 111 patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma, bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patients with wheeze, 22 patients with dyspnea, 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1s($PC_{20}FEV_1$) and 25% fall in maximal mid-inspiratory flow ($PC_{25}MIF_{50}$) were used as bronchial and extra thoracic hyperresponsiveness. Results : There were four response patterns to methacholine challenge study : BHR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in 8 patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BHR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze and/or dyspnea, BHR was more common than EAHR. Conclusion : These results show that among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.

• Clinical and Experimental Pediatrics
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• v.64 no.5
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• pp.229-238
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• 2021

Background: Bronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma. Purpose: We aimed to investigate the factors associated with BHR in adolescents with childhood asthma. Methods: Two hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (<25 mg/mL of provocation concentration causing a 20% fall in forced expiratory volume in 1 second [FEV₁] [PC₂₀], n=113) or non-BHR group (≥25 mg/mL of PC₂₀, n=102). We examined longitudinal changes in BHR and the risk factors for its persistence in the 108 adolescents for whom baseline data, including methacholine PC₂₀ at age 6 years, were available. Multivariate logistic regression analyses were performed to assess the factors associated with BHR in adolescents. Results: Mold sensitization (adjusted odds ratio [aOR], 5.569; P=0.005) and increased blood eosinophil count (aOR, 1.002; P=0.026) were independently associated with BHR in boys but not girls. The odds of BHR decreased by 32% with each 1-year increase in age in boys (aOR, 0.683; P=0.010) but not girls. A reduced FEV₁/forced vital capacity ratio (<90%) was independently related with BHR in female patients only (aOR, 7.500; P=0.007). BHR decreased with age throughout childhood. A low methacholine PC₂₀ at age 6 years was independently associated with persistent BHR throughout childhood in male and female patients, whereas early mold sensitization was a risk factor for persistent BHR in male patients only (aOR, 7.718; P=0.028). Conclusion: Our study revealed sex-specific differences in the factors associated with BHR in adolescents with childhood asthma. Our findings suggest the risk factors that might affect asthma transition from childhood to adolescence and adulthood.