• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.175-184
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• 1999

Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-$\gamma$, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-$\gamma$, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p<0.05). Degree of responses to tuberculin test were $12.0{\pm}9.6mm$ in patients with allergic asthma, $18.4{\pm}4.5mm$ in patients with intrinsic asthma and $10.9{\pm}8.8mm$ in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p<0.05). The serum levels of IL-5 in patients with allergic asthma were significantly higher than in patients with intrinsic asthma and normal controls (p<0.05), although it was insignificant. the serum levels of IL-4 and IL-10 in patients with allergic asthma were higher than that of intrinsic asthma and normal controls. The serum levels of IL-12 and IFN-$\gamma$ in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p<0.05). The serum levels of total immunoglobulin E (IgE) and peripheral blood eosinophile counts in patients with allergic asthma were significantly higher than those in normal controls. Peripheral blood esinophil counts had a significant correlation with the serum levels of total IgE, IL-5 and IL-10 in patients with allergic asthma (p<0.05). Conclusion: These results have showed that Th1 lymphocyte functions were lowered and Th2 lymphocyte functions were elevated in patients with allergic asthma than those in normal controls. Suppression of Th1 lymphocyte functions by activation of Th2 lymphocyte might be one of the important aspects of pathogenesis in allergic bronchial asthma.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.875-883
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• 2002

Purpose : Airways eosinophilia and increased IgE, characteristic features of asthma, result from a predominant Th2 response. In this study, we investigated the effect of CpG oligodeoxynucleotides (ODNs) on the inhibition of airways eosinophilia in mice with established airway inflammation. We also investigated the immunological mechanisms involved. Methods : Groups of BALB/c mice were sensitized intradermally with ovalbumin(OVA). At week 10, airway inflammation was induced by intranasal challenge of the mice with OVA. At week 14, the mice were challenged intranasally again with OVA in the presence and without the presence of CpG ODNs. Mice with saline administration served as negative controls. Bronchoalveolar lavage fluids(BALF) were obtained and eosinophils were counted. Th1 and Th2 cytokines in the spleen cell cultures were measured by ELISA. Serum OVA-specific IgE and IgG2a antibodies were also measured by ELISA. Results : BALF eosinophils were significantly inhibited in the CpG ODNs-treated mice(P<0.01). IgE and IgG2a levels increased significantly in both CpG ODNs-treated and untreated groups as compared to the negative control group; there was, however, no significant difference between the two groups four days after intranasal administration of CpG ODNs. Cytokine analysis revealed decreased production of IL-4, IL-5, and IL-13 and increased production of IL-12 in the CpG ODNs-treated group as compared to the untreated group. Interestingly, $IFN-{\gamma}$ levels were not upregulated in the CpG ODNs-treated group. Conclusion : CpG ODNs vaccination is a potentially useful approach for reversing airways eosinophilia in mice with established airways inflammation.

• 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.54 no.4
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• pp.386-394
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• 2003

Background : ATS(American Thoracic Society) defined new guidelines for COPD(chronic obstructive lung disease) in April 2001, following the results of the global initiative for chronic obstructive lung disease. The most important concept of COPD is an airflow limitation which is not fully reversible compared to bronchial asthma(BA). The criteria for COPD are postbronchodilator $FEV_1$ less than 80% of the predicted value and an $FEV_1$ per FVC ratio less than 70%. The global initiative for asthma(GINA) study defined asthma, which included immune-mediated chronic airway inflammatory airway disease, and found that airflow limitation was wide spread, variable and often completely reversible. Taken together COPD and BA may be combined in airflow limitation. This study was designed to evaluate the prevalence of BA in patients with COPD of moderate to severe airflow limitation. Methods : COPD was diagnosed by symptoms and spirometry according to ATS guidelines. Enrolled subjects were examined for peak flow meters(PFM), sputum eosinophils and eosinophil cationic protein(ECP) levels, serum total IgE with allergy skin prick test, and methacholine bronchial provocation test(MBPT). Results : About 27% of COPD patients with moderate to severe airflow limitation were combined with BA. There was significantly decreased response to PFM in severe COPD. However, there was no significant relationship between BA and COPD according to the degree of severity. The BA combined with COPD group showed significantly high eosinophil counts and ECP level in induced sputum. However, neutrophil counts in induced sputum showed significant elevation in the pure COPD group. Conclusion : Twenty-seven percent of COPD patients with moderate to severe ventilation disorder were combined with BA, but there were no significant differences according to the degree of severity.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.752-759
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• 1995

Background: Bronchial asthma is characterized by noctunal dyspnea, cough and wheezing because of airway hyperresponsiveness to nonspecific stimuli. These symptoms and signs are also observed in patients with congestive heart failure. Therefore, this is so called "cardiac asthma". There are lots of experimental and clinical datas to suggest that airway dysfunctions occur in acute and chronic congestive heart failure. However, it is still controversial whether bronchial hyperresponsiveness is present in patients with congestive heart failure. To assess whether bronchial hyperresponsiveness is present in patients with congestive heart failure and to demonstrate the relationship between bronchial responsiveness and vascular pressure, we performed methacholine provocation test in 11 patients with mitral valvular heart disease. Methods: All patients were in the New York Heart Association functional class II and treated continuously with digoxin and/or dichlozid and/or angiotensin converting enzyme inhibitor except one patient. All patients were undergone right and left side heart catheterization for hemodynamic measurements. A 20 percent fall of peak expiratory flow rate were considered as positive response to methacholine provocation test. Results: 1) Only one patient who has normal pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index was positive in methacholine provocation test. 2) Their mean pulmonary artery pressure, pulmonary capillary wedge pressure were $21.72{\pm}9.70mmHg$, $15.45{\pm}8.69mmHg$ respectively which were significantly higher. Conclusion: It is speculated that in stable congestive heart failure patients, bronchial responsiveness as assessed by methacholine provocation test may not be increased.

• 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.52 no.1
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• pp.24-36
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• 2002

Background: Bronchial reactivity is known to be a component of airway hyperresponsiveness, a cardinal feature of asthma, with bronchial sensitivity, and is increments in response to induced doses of bronchoconstrictors as manifested by the steepest slope of the dose-response curve. However, there is some controversy regarding methods of measuring bronchial reactivity and clinical impact of such measurements. The purpose of this study was to evaluate the clinical significance and assess the clinical use by analyzing the relationship of the bronchial sensitivity, the clinical severity and the changes in pulmonary function with bronchial reactivity. Method: A total of 116 subjects underwent a methacholine bronchial provocation test. They were divided into 3 groups : mild intermittent, mild persistent, moderate and cough asthma. Severe patients were excluded. Methacholine PC20 was determined from the log dose-response curve and PC40 was determined by one more dose inhalation after PC20. The steepest slope of log dose-response curve, connecting PC20 with PC40, was used to calculate the bronchial reactivity. Body plethysmography and a single breath for the DLCO were done in 43 subjects before and after methacholine test. Results: The average bronchial reactivity was 38.0 in the mild intermittent group, 49.8 in the mild persistent group, 61.0 in the moderate group, and 41.1 in the cough asthma group. There was a weak negative correlation between PC20 and bronchial reactivity. A heightened bronchial reactivity tends to produce an increased clinical severity in patients with a similar bronchial sensitivity and basal spirometric pulmonary function. There were significant correlations between the bronchial reactivity and the initial pulmonary function before the methacholine test in the order of sGaw, Raw, $FEV_1$/FVC, MMFR. There were no correlations between the bronchial sensitivity and the % change in the pulmonary function parameters after the methacholine test. However, there were significant correlations between the bronchial reactivity and the PEF, $FEV_1$, DLCO. Conclusion: There was weak significant negative correlation between the bronchial reactivity and the bronchial sensitivity, and the bronchial reactivity closely reflected the severity of the asthma. Accordingly, measuring both the bronchial sensitivity and the bronchial reactivity can be of assistance in assessing of the ongoing disease severity and in monitoring the effect of therapy.

• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.105-112
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• 2017

Spirometry is a physiological test for assessing the functional aspect of the lungs using an objective indicator to measure the maximum amount of air that a patient can inhale and exhale. Acceptable spirometry testing needs to be conducted three times by an acceptable and reproducible method for determining forced vital capacity (FVC). Until the results of three tests meet the criteria of reproducibility, the test should be repeated up to eight times. Interpretation of spirometry should be clear, concise, and informative. Additionally, spirometry should guarantee optimal quality prior to the interpreting spirometry results. Our guideline adopts a fixed normal predictive value instead of the lower limit of normal as the reference value because fixed value is more convenient and also accepts FVC instead of vital capacity (VC) because measurement of VC using a spirometer is impossible. The bronchodilator test is a method for measuring the changes in lung capacity after inhaling a short-acting ${\beta}-agonist$ that dilates the airway. When an obstructive ventilatory defect is observed, this test helps to diagnose and evaluate asthma and chronic obstructive pulmonary disease by measuring reversibility with the use of an inhaled bronchodilator. A positive response to a bronchodilator is generally defined as an increase of ${\geq}12%$ and ${\geq}200mL$ as an absolute value compared with a baseline in either forced expiratory volume at 1 second or FVC.

• Clinical and Experimental Pediatrics
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• v.63 no.3
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• pp.104-109
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• 2020

Background: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children. Purpose: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children. Methods: We performed a population-based cross-sectional study in 916 preschool children aged 4-6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma. Results: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed. Conclusion: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

• Tuberculosis and Respiratory Diseases
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• v.62 no.3
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• pp.197-202
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• 2007

Background: Cigarette smoking is an important risk factor for chronic bronchitis and COPD. Airway epithelial cells exposed to cigarette smoke components such as nicotine, cotinine and benzopyrene can generate reactive oxygen species (ROS) and be subject to oxidative stress. This oxidative stress can induce the inflammatory response in the lung by the oxidant itself or by the release of proinflammatory cytokines. It has been reported that nicotine stimulates ROS, which are associated with NF-${\kappa}B$. Methods: Beas2B cells were treated with nicotine, cotinine and benzopyrene. RT PCR was used to measure the expression of several antioxidant factors using the total RNA from the Beas2B cells. The level of superoxide dismutase(CuZnSOD), thioredoxin, glutathione reductase expression was examined. Results: 0.5 to 4 hours after the benzopyrene, nicotine and cotinine theatments, the level of thioredoxin and glutathione reductase expression decreased. Longer exposure to these compounds for 24 to 72 hours inhibited the expression of most of these antioxidant factors. Conclusion: During exposure to smoke compounds, thioredoxin and glutathione reductase are the key antioxidant factors induced sensitively between 0.5 and 4 hours but the levels these antioxidants decrease between 24 hour and 72hours.