• 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.

• 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.

• Journal of Environmental Health Sciences
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• v.46 no.6
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• pp.685-693
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• 2020

Objectives: Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. The aim of this study was to investigate relationships between indoor mold concentrations and pulmonary function parameters in asthmatic children with mold sensitization. Methods: Asthmatic subjects who had a positive result in skin-prick testing to more than one mold allergen, such as Alternaria, Aspergillus, or Penicillium, were enrolled. Their pulmonary function and methacholine challenge test results were collected. Measurements of blood eosinophil, serum IgE, and fractional exhaled nitric oxide (FeNO) were taken. Indoor levels of VOC, CO2, PM10 and PM2.5 in each subject's house were measured. We counted mold and bacteria colonies from the subjects' house air samples. Results: The mean levels of FEV1, FVC, FEV1/FVC, and FEF25-75 were 82.8±19.7, 87.3±17.9, 85.8±8.3, and 82.3±28.9%, respectively. The mean FeNO level was 19.8±11.2 ppb and the geometric mean (range of one SD) of methacholine PC20 was 3.99 mg/mL (0.67-23.74 mg/mL). The average indoor air pollutant levels were below the recommended levels set by the Ministry of Environment for multiplex buildings. Indoor mold levels showed a significant inverse correlation with methacholine PC20, but not with the baseline pulmonary function parameters. Conclusion: Indoor mold concentrations are a risk factor for increased bronchial hyperresponsiveness among asthmatic children with mold sensitization. Targeted environmental intervention should be considered for selected asthmatic children with mold sensitization for avoiding severe airway hyperresponsiveness.

• Tuberculosis and Respiratory Diseases
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• v.80 no.4
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• pp.344-350
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• 2017

Bronchial asthma is a disease characterized by the condition of airway hyper-responsiveness, which serves to produce narrowing of the airway secondary to airway inflammation and/or various spasm-inducing stimulus. Nonspecific bronchoprovocation testing is an important method implemented for the purpose of diagnosing asthma; this test measures the actual degree of airway hyper-responsiveness and utilizes direct and indirect bronchoprovocation testing. Direct bronchoprovocation testing using methacholine or histamine may have superior sensitivity as these substances directly stimulate the airway smooth muscle cells. On the other hand, this method also engenders the specific disadvantage of relatively low specificity. Indirect bronchoprovocation testing using mannitol, exercise, hypertonic saline, adenosine and hyperventilation serves to produce reactions in the airway smooth muscle cells by liberating mediators with stimulation of airway inflammatory cells. Therefore, this method has the advantage of high specificity and also demonstrates relatively low sensitivity. Direct and indirect testing both call for very precise descriptions of very specific measurement conditions. In addition, it has become evident that challenge testing utilizing each of the various bronchoconstrictor stimuli requires distinct and specific protocols. It is therefore important that the clinician understand the mechanism by which the most commonly used bronchoprovocation testing works. It is important that the clinician understand the mechanism of action in the testing, whether direct stimuli (methacholine) or indirect stimuli (mannitol, exercise) is implemented, when the testing is performed and the results interpreted.

• 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.45 no.6
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• pp.1188-1198
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• 1998

Background : The purpose of the present study was to determine the protective effect of antiasthmatic activity of inhaled heparin, cromolyn sodium, budesonide, furosemide in exercise-induced asthma(EIA). The other important considerable point of this study was the mechanism of bronchoconstriction on EIA. Methods : Eight subjects with a history of EIA were studied on 5 different experiment days. After obtaining baseline $FEV_1$ and FVC, subjects performed a standardized exercise challenge. EIA was assessed by measurement of $FEV_1$ before and after exercise. On experiment day 4, the exercise challenge was performed after the subjects inhaled either heparin (1,000 units/kg/day for 5 days), furosemide (1mg/kg for 5 days), cromolyn (4mg/day for 5 days), or budesonide ($400{\mu}g/day$ for 5 days). On experiment day 5, the methacholine bronchial provocation test was performed. On experiment day 3, activated partial thromboplastine time(aPTI) was checked. Results : Maximum decrements of $FEV_1$ (mean${\pm}$SE) among 0 to 120 minutes after exercise were as follows : heparin was $83.1{\pm}4.81%$ (p=0.010), furosemide was $80.5{\pm}6.87%$ (p=0.071), cromolyn was $86.8{\pm}6.53%$ (p=0.340), and budesonide was $79.4{\pm}7.31%$ (p=0.095). Above medications were compared to the control value ($72.5{\pm}18.2%$) by paired t-test. No medications had effect on $PD_{20}$ of methacholine bronchial provocation test The results were control $1.58{\pm}0.49{\mu}mol$), heparin ($4.17{\pm}1.96{\mu}mol$), furosemide ($1.85{\pm}0.86{\mu}mol$), cromolyn ($2.19{\pm}0.89{\mu}mol$), and budesonide ($3.38{\pm}1.77{\mu}mol$), respectively(p>0.05). The inhaled heparin had no effect of anticoagulation. Conclusion : These data demonstrate that inhaled heparin has a protective effect on EIA. The effect of inhaled cromolyn was statistically absent with manufacture's recommended dosage on EIA. So, the dosage of cromolyn should be carefully evaluated in future. Although inhalation of budesonide and furosemide have no statistical significance compared to control, these drugs also have some protective effects on EIA.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.842-847
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• 2008

Purpose : Measurement of forced expiratory volume in 1 second ($FEV_1$) is usually difficult to obtain in children under six years of age because it requires active cooperation. This study evaluates the sensitivity of impulse oscillometry system (IOS) parameters for detecting airway obstruction in comparison with $FEV_1$. Methods : We studied 174 children who performed the lung function and methacholine challenge tests to diagnose asthma by IOS and spirometry. Children were divided into two subgroups according to their $PC_{20}$, which is a parameter for bronchial sensitivity. We compared IOS parameters with $FEV_1$ at the baseline, post-methacholine challenge, and evaluated their correlation. Results : At the baseline, reactance at 5 Hz (X5) and resistance at 5 Hz (R5) significantly differed between the $PC_{20}$ positive ($PC_{20}{\leq}16mg/mL$) group and $PC_{20}$ negative ($PC_{20}$ >16 mg/mL) group; however, $FEV_1$, $FEV_1$ % predicted, $FEV_1_-Zs$ (Z score) did not differ. $FEV_1$ is correlated with X5 (r=0.45, P<0.01) and R5 (r=-0.69, P<0.01). $FEV_1_-Zs$ is also correlated with X5_Zs (r=-0.26, P<0.01) and R5_Zs (r=-0.31, P<0.01). After the methacholine challenge test, dose-response slopes in $FEV_1$ and X5 significantly differed between the two subgroups (P<0.05). Conclusion : IOS parameters were more discriminative than $FEV_1$ for detecting decreased baseline lung function between two subgroups and have a good correlation with $FEV_1$.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.490-501
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• 1992

Background: Isocyanate is the most significant cause of occupational asthma in this country. The mechanism of isocyanate induced bronchoconstriction is unclear. Subjects and Method: To observe its immunologic and clinical findings, we performed methacholine bronchial challenge test (MBCT), toluene diisocyanate (TDI)-bronchoprovocation test (BPT) and RAST to TDI-, diphenylmethane diisocyanate (MDI)-, and hexamethylene diisocyanate (HDI)-human serum albumin (HSA) conjugate in 22 isocyanate-sensitive asthmatic workers. Results: BPT revealed early (11), dual (5), and late only (6) asthmatic responses. Their latent period ranged from 3 to 120 months (mean:45.9 months). Three cases (13.6%)showed a negative response on initial MBCT, but following MBeT performed 24 hours after TDI-BPT revealed the development of airway hyperresponsivenss. Twelve (54.5%) workers had increased specific IgE to TDI-HSA, seven (31.8%) had to MDI-HSA, and nine (40.9%) had to HDI-HSA conjugate. The prevalence of specific IgE was not associated with latent period, type of asthmatic responses, smoking, and atopic status. After 3 months' avoidance from workplace, airway hyperresponsiveness was improved in 10 (38.3%), among 12 followed cases. Conclusion: It is suggested that isocyanate can induce IgE-mediated bronchoconstriction in 59.1% of isocyanate-sensitive asthmatic workers. Isocyanate-induced asthma can occur even though MBeT showed a negative result, and measurement of the changes of airway hyperresponsivenss after isocyanate-BPT could be helpful to diagnose isocyanate-sensitive asthma.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.433-439
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• 2006

Background: Although airway hyper-responsiveness is one of the characteristics of asthma. bronchial hyper-responsiveness has also been observed to some degree in patients with chronic obstructive pulmonary disease (COPD). Moreover, several reports have demonstrated that a number of patients have both COPD and asthma. The methacholine bronchial challenge test (MCT) is a widely used method for the detecting and quantifying the airway hyper- responsiveness, and is one of the diagnostic tools in asthma. However, the significance of MCT in differentiating asthma or COPD combined with asthma from pure COPD has not been defined. The aim of this study was to determine the role of MCT in differentiating asthma from pure COPD. Method: This study was performed prospectively and was composed of one hundred eleven patients who had undergone MCT at Chonbuk National University Hospital. Sixty-five asthma patients and 23 COPD patients were enrolled and their MCT data were analyzed and compared with the results of a control group. Result: The positive rates of MCT were 65%, 30%, and 9% in the asthma, COPD, and control groups, respectively. The mean $PC_{20}$ values of the asthma, COPD, and control groups were $8.1{\pm}1.16mg/mL$, $16.9{\pm}2.21mg/mL$, and $22.0{\pm}1.47mg/mL$, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MCT for diagnosing asthma were 65%, 84%, 81%, and 69%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MCT (ed note: please check this as I believe that these values correspond to the one $PC_{20}$ value. Please check my changes.) at the new cut-off points of$PC_{20}{\leq}16mg/ml$, were 80%, 75%, 78%, and 78%, respectively. Conclusion: MCT using the new cut-off point can be used as a more precise and useful diagnostic tool for distinguishing asthma from pure COPD.

• 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.