• Environmental Analysis Health and Toxicology
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• v.26
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• pp.11.1-11.6
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• 2011

Objects: The prevalence of asthma has increased in recent decades globally. The objective of the present study is to elucidate whether hospitalization for bronchiolitis in infancy and low socioeconomic status interact for bronchial hyperreactivity during teenage years. Method: We studied 522 children age 13-14 years attending schools in rural and urban areas to investigate the risk factors for bronchial hyperreactivity (BHR), defined as a provocation concentration of methacholine that causes a decrease of 20% ($PC_{20}$) in forced expiratory volume within 1 second. Clinical examination, skin prick test, spirometry, and methacholine challenge were performed on all study subjects, who provided written consent. We used multivariate logistic regression to investigate the risk factors for BHR, and analyze the interaction between hospitalization for bronchiolitis in infancy and low socioeconomic status. Results: Forty-six (10.3%) positive BHR cases were identified. In the multivariate logistic analysis, as independent predictors of BHR, adjusted odds ratio of bronchiolitis diagnosed before 2 years of age in low income families was 13.7 (95% confidence interval, 1.4 to 135.0), compared to reference group, controlling for age, gender, parental allergy history, skin prick test, and environmental tobacco smoke (ETS) exposure. Interaction was observed between bronchiolitis before 2 years old and low socioeconomic status on children's bronchial hyperreactivity (p-interaction=0.025). Conclusions: This study showed that bronchiolitis diagnosed before 2 years of age and low socioeconomic status interacted on children's bronchial hyperreactivity. Prevention of acute respiratory infection in early childhood in low socioeconomic status is important to prevent BHR as a precursor of asthma.

• Tuberculosis and Respiratory Diseases
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• v.38 no.2
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• pp.164-171
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• 1991

To evaluate the effect of damaged bronchial epithelium on epithelial permeability and physiologic changes of the airway in patients with bronchial asthma, we measured the concentration of protein and albumin in bronchoalveolar lavage fluid (BALF), the width of intercellular junction and bronchial hyperreactivity in 22 patients with bronchial asthma and 21 healthy subjects. The results were as follows: 1) The concentration of protein in BALF from patients with bronchial asthma was higher when compared with that of normal subjects ($237{\pm}182$ vs $113{\pm}78\;{\mu}g/mL$, p<0.05), and the concentration of albumin was also higher than that of normal subjects ($116{\pm}126$ vs $32{\pm}88\;{\mu}g/mL$, p<0.05). The ratio of the concentration of protein in BALF to that in serum was increased in patients with bronchial asthma when compared with that of normal subjects ($0.35{\pm}0.30$ vs $0.16{\pm}0.11%$, p<0.05). 2) The intercellular junction of bronchial epithelium was widened in 14 of 20 patients with bronchial asthma, in contrast, 5 of 14 normal subjects (p<0.05). The mean width of intercellular junction was greater when compared with that of normal subjects ($1.71{\pm}1.81$ vs $0.56{\pm}0.85\;{\mu}m$, p<0.05). The width was well correlated with the ratio of protein in BALF to that of serum (r=0.3226, p=0.047) when observed in 18 patients with bronchial asthma and 10 patients with normal subjects. 3) The bronchial hyperreactivity, expressed as $PC_{20}$, was inversely correlated with the concentration of protein in BALF (r=-0.3030, p=0.038) in when observed in 18 patients with bronchial asthma and 19 normal subjects. 4) The width of intercellular junction was well inversely correlated with $PC_{20}$ (r=-0.5006, p=0.002) when observed in 19 patients with bronchial asthma and 11 patients with normal subjects. In conclusion, increased permeability and the damage of bronchial epithelium may lead to change of bronchial hyperreactivity.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.270-276
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• 1994

Background: The measurement of nonspecific bronchial hyperreactivity is valuable for diagnosis and management of bronchial asthma. Methacholine or histamine is used for the pharmacologic provocation test. Usually a methacholine bronchial provocation test is performed by a dosing technique with counted number of breaths. A dosimeter is indispensable in the dosing technique. Recently a timed tidal breathing technique which dose not need an expensive dosimeter was introduced. We measured the degree of nonspecific bronchial hyperreactivity to histamine using a simple timed tidal breathing technique. Method: Forty two healthy volunteers, 12 patients with bronchial asthma(BA), 10 patients with rhinitis(RH) and 10 patients with upper respiratory infection(URI) participated in the study. The subject's nose was clipped and inhalation continued during tidal breathing for 2 minutes via a face mask. $FEV_1$ was measured at 30 seconds, 90 seconds after inhalation and inhalation of next solution was continued until there was a fall in $FEV_1$ of 20%. Histamine PC20 was defined as the concentration at 20% fall of $FEV_1$ and it was obtained from the log dose-response curve by linear interpolation. Results: Inhalation of serial dilution of histamine could be performed in all patients without significant side effects. The geometric mean${\pm}$standard deviation of histamine PC20 in healthy volunteers is $8.27{\pm}2.22mg/ml$, BA group $0.33{\pm}3.02mg/ml$, RH group $0.85{\pm}3.24mg/ml$, and URI group $1.47{\pm}1.98mg/ml$. Conclusion: Histamine bronchial provocation test using timed tidal breath method is a simple and suitable tool for management of patients with bronchial hyperreactivity.

• Clinical and Experimental Pediatrics
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• v.58 no.5
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• pp.190-193
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• 2015

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease due to bronchial colonization of Aspergillus fumigatus that occurs in susceptible patients with asthma or cystic fibrosis. A 10-year-old girl was referred to the Department of Pediatric Pulmonology for persistent consolidations on chest radiography. Pulmonary consolidations were observed in the right upper and left lower lobes and were not resolved with a 4-week prescription of broad-spectrum antibiotics. The patient had a history of atopic dermatitis and allergic rhinitis but no history of asthma. She had no fever but produced thick and greenish sputum. Her breathing sounds were clear. On laboratory testing, her total blood eosinophil count was $1,412/mm^3$ and total serum IgE level was 2,200 kU/L. Aspergillus was isolated in the sputum culture. The A. fumigatus-specific IgE level was 15.4 kU/L, and the Aspergillus antibody test was also positive. A chest computed tomography scan demonstrated bronchial wall thickening and consolidation without bronchiectasis. An antifungal agent was added but resulted in no improvement of pulmonary consolidations after 3 weeks. Pulmonary function test was normal. Methacholine provocation test was performed, revealing bronchial hyperreactivity ($PC_{20}=5.31mg/mL$). Although the patient had no history of asthma or bronchiectasis, ABPA-seropositivity was suspected. Oral prednisolone (1 mg/kg/day) combined with antifungal therapy was started. Pulmonary consolidations began decreasing after 1 week of treatment and completely resolved after 1 month. This is the first observed and treated case of seropositive ABPA in Korean children without previously documented asthma.

• 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.51 no.3
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• pp.323-328
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• 2008

Purpose : Asthma is defined as chronic inflammation of the lower small airways, and bronchial hyperreactivity (BHR) is a pathophysiologic feature of asthma. It has been proposed that although there is no direct variable capable of assessing the small airways, a forced expiratory flow of between 25 and 75 percent ($FEF_{25-75}$) might be considered a more sensitive early marker of small airway obstruction than the forced expiratory volume in 1 second ($FEV_1$). Thus, we proposed that the presence and degree of positive responses to bronchial methacholine testing were related to the difference (DFF) and ratio (RFF) between $FEV_1$ and $FEF_{25-75}$ in asthmatic children. Methods : The subjects were 583 symptomatic children, including 324 children with BHR and 259 controls. Pulmonary function tests, methacholine challenge tests, and skin prick tests were performed, and the total eosinophil count, total serum IgE, and serum eosinophil cationic protein level were measured in all subjects. From a concentration-response curve, the methacholine concentration required to produce a decrease of 20% from post-saline $FEV_1$ was calculated ($PC_{20}$). Results : The median DFF and RFF values decreased in controls compared to subjects with bronchial hyperresponsiveness, and this trend was found in groups ranked by its severity. $PC_{20}$ had a negative correlation with DFF and RFF. Cutoff values of 0.5 for DFF and 1.042 for RFF were identified, and sensitivity and specificity were calculated. Conclusion : This study revealed that DFF and RFF might be predictive of bronchial hyperresponsiveness in the context of normal $FEV_1$ in children.

• Tuberculosis and Respiratory Diseases
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• v.38 no.3
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• pp.270-279
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• 1991

It has been well known that the integrity of airway epithelium is important in developing of bronchial hyperreactivity or bronchial asthma. But the mechanisms underlying this nonspecific airway hyperresponsiveness are not yet determined. To evaluate the ability of guinea pig trachea to release an epithelium derived relaxing factor (EpDRF) which relax rat vascular smooth muscle, we performed the coaxial bioassay using guinea pig trachea and rat aorta. And to evaluate the nature of EpDRF we investigate the influence of methylene blue and indomethacin on the coaxial bioassay. Results were as follows. 1) Vascular smooth muscle mounted into the epithelium intact trachea which was precontracted with phenylephrine was relaxed by addition of histamine or acetylcholine. But vascular smooth muscle mounted into epithelium denuded trachea failed to be relaxed. 2) Epithelium dependent relaxation of vascular smooth muscle was not affected by pretreatment of methylene blue or indomethacin. These results strongly suggests that guinea pig tracheal epithelium releases EpDRF which is able to relax rat vascular smooth muscle. And EpDRF released by airway epithelium is not related to endothelium derived relaxing factor (EDRF) or cyclooxygenase products.

• Journal of Preventive Medicine and Public Health
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• v.27 no.2 s.46
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• pp.274-285
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• 1994

The effects of resin on the respiratory health have been investigated in 309 workers from four iron and steel foundries and the results compared with those from 122 workers who were not significantly exposed to resin gas and silica dust at the same industries. Phenol-formaldehyde resin was used in the core making and molding processes and workers were exposed to their decomposition products as well as to silica dust containing particulates. The subjects were grouped according to formaldehyde, dust and other gas exposures, and smoking habits were considered also in thi analysis. Standardized respiratory symptom questionnaire was administered by trained interviewers. Chest radiograph, pulmonary funtion tests, and methacholine challenge tests were done. Environmental measurements at the breathing zone were carried out to determine levels of formaldehyde, respiable dust and total dust. Foundry workers had a higher prevalence of symptoms of chronic bronchitis with chronic phlegm and chronic cough when exposed to dust. Exposure to gas was significantly associated with lowered $FEV_1$ and obstructive pulmonary function changes. Exposure to formaldehyde and phenol gas was associated with wheezing symptom among workers, but $FEV_1$ changes after methacholine challenge were not significantly different among different exposure groups. When asthma was defined as the presence of bronchial hyperreactivity with more than 20% decrease in $FEV_1$ after methacholine challenge, 17 workers out of 222 tested had asthma. Fewer asthmatic welters were found among groups exposed to formaldehyde, gas and dust, which indicates a healthy worker effects ill a cross-sectional study. The concentration of formaldehyde gas ranged from 0.24 to 0.43 ppm among studied foundries. The authors conclude that formaldehyde and phenol gas from combusted resin is probably the cause of asthmatic symptoms and also a selection force of those with higher bronchial reactivity away from exposures.

• Tuberculosis and Respiratory Diseases
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• v.38 no.1
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• pp.8-15
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• 1991

It has been well known that the integrity of airway epithelium is important in development of bronchial hyperreactivity and bronchial asthma. But the mechanisms involved are still unclear. To evaluate that airway epithelium is able to modulate the contraction of guinea pig tracheal smooth muscle, we investigated the responsiveness of intact and epithelium-denuded tracheal strips to histamine and acetylcholine. And to evaluate whether cyclooxgenase products play a role in this modulatory mechanism, we also investigated the effect of indomethacin pretreatment on the tracheal responsiveness to histamine. Results were as follows: 1) In guinea pig tracheal smooth muscle the presence of airway epithelium significantly reduced the response to histamine. 2) In the presence of indomethacin dose-response curves and $EC_{50}$ values were similar between intact and epithelium-denuded tracheal strips, that is, indomethacin abolished the influence of epithelium on the contracion of tracheal smooth muscle. 3) The response of tracheal smooth muscle to acetylcholine was similar both in the presence and absence of epithelium. These results suggest that airway epithelium of guinea pig may generate an inhibitory signal to decrease the response of tracheal smooth muscle to histamine and cyclooxygenase products may contrbute to the modulation of airway epithelium on the contracion of tracheal smooth muscle.

• Tuberculosis and Respiratory Diseases
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• v.39 no.3
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• pp.219-227
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• 1992

Background: Acute and chronic airway inflammation are important in the pathogenesis of bronchial asthma. Corticosteroids have proved to be very effective in the management of asthma. Although the mechanism by which they produce this effect is still debated, suppression of the inflammatory response is thought to be the most likely. Although inhaled steroids are known to be safe and have less side effects than oral steroids, the extent which inhaled steroids have beneficial and the detrimental effects in the treatment of asthma has remained open to question. Budesonide is a recently developed corticosteroid for inhalation treatment with a strong local effect combined with rapid inactivation in the systemic circulation. We set out to look in more detail at the time course of change in bronchial reactivity, clinical symptoms and the effects on the adrenal function during 6 weeks of treatment with budesonide (800 ug per day). Methods: Clinical symptoms, pulmonary function test, histamine $PC_{20}$, serum ACTH and cortisol (8 AM and 4 PM) were measured in 23 allergic asthmatic patients before and after 6 weeks of treatment with budesonide. Results: 1) Pulmonary function test; PEFR, FEV1 and FVC after 6 weeks of treatment with budesonide were higher than those before treatment. 2) Clinical symptoms; Clinical symptoms were significantly improved after 3 weeks and 6 weeks of treatment with budesonide. 3) Histamine provocation; Histamine $PC_{20}$ after 6 weeks of treatment with budesonide was significantly higher than that before treatment. 4) Adrenal function; 6 weeks of budesonide therapy did not significantly affect the level of serum ACTH and cortisol. Conclusion: From these results, it is concluded that budesonide therapy improved the clinical symptoms, pulmonary function and bronchial hyperreactivity after 3 weeks of treatment and the improvement after 6 weeks of treatment was higher than that after 3 weeks of treatment. During 6 weeks of treatment with budesonide, the inhibitory effect on the adrenal function was not obvious.