• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.504-511
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• 2008

Background: Particulate matter may be toxic to human tissue. Ambient air particulate matter ${\leq}10{\mu}m$ in aerodynamic size ($PM_{10}$), which changes under different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also spread unique particulate matter in affected areas. We evaluated production of ROS, $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$ by exposing normal epithelial cells to Asian dust particulate matter. Methods: Bronchial epithelial cells were exposed to 0, 50, ${\leq}100{\mu}g/ml$ of a suspension of $PM_{10}$ for 24 h. ROS were detected by measurement of DCF release from DCF-DA by FACScan. $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$ were detected by western blotting. Results: $PM_{10}$ exposure increased the expression of $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$. ROS production and $TGF-{\beta}$ levels were significantly higher with 50 or ${\leq}100{\mu}g/ml$ $PM_{10}$. Fibronectin and $NF{\kappa}B$ production were significantly higher after ${\leq}100{\mu}g/ml$ of $PM_{10}$. Conclusion: $PM_{10}$ from Asian dust particles might have fibrotic potential in bronchial epithelial cells via ROS induction after $PM_{10}$ exposure.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.775-785
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• 1999

Background : The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods : 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methlprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis oneway analysis. Results : Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methyprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion : These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.826-835
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• 1999

Background : The $\beta_2$ adrenergic receptor ($\beta_2$ AR) polymorphisms occurring at amino acid position 16 (Arg to Gly), 27 (Gln to Glu), 34 (Val to Met), and 164 (Thr to Ile) are known to be functionally relevant and also disease-modifying in subjects with asthma. However the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for allergic disease remains to be established. Methods : 109 patients with bronchial asthma and 42 healthy person were included. Serum total IgE, allergen specific IgE, and skin prick test were performed to all of the subjects. $\beta_2$ AR polymorphisms were checked by mutated allele specific amplification (MASA) method. Results : The results were as follows. The frequencies of $\beta_2$ AR polymorphisms in asthmatic patients and healthy person were not statistically different(p>0.05). There was no association between $\beta_2$ AR polymorphisms of amino acid position 16, 27, 34 and the existence of atopy among asthmatic patients(p>0.05). Between asthmatic patients with or without elevated IgE level and $\beta_2$ AR polymorphisms of amino acid position 16, 27, 34, there was no statistically significant association(p>0.05). Conclusion : There was no difference in frequency of the $\beta_2$ AR polymorphism between asthmatic patients and healthy person. In the bronchial asthma, association of $\beta_2$ AR polymorphism and atopy/serum total IgE was not found.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.290-297
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• 1997

Background : Despite remarkable progress of understanding the pathophysiology and therapy of bronchial asthma, asthma morbidity and mortality are on the rise. Also hospitalization and attending rates of emergency department for asthma have been increasing gradually. We analyzed clinical characteristics and prognosis of patients who visited emergency room due to asthma attack in order to define clinical characteristics of these group of patients. Method : We reviewed 105 adult asthmatic patients who attended emergency department of Korea University Hospital between August 1995 and July 1996, retrospectively. Results : 103 patients(56 female, 47 males, mean age : 48.6 years) attended-68 self referral, 18 practitioner referral and 17 OPD transfer- and 86 patients(83.5%) were admitted. Attending emergncy department was clearly more frequent in December(13.6%) and May(12.6%). Time lag between onset of asthmatic attack and arrival at the hospital was $14.2{\pm}15.5$ hour and initial peak expiratory flow rate was $166.7{\pm}68.3L/min$.(43.3% predicted) The commonest cause for visiting emergency room was aggravation of asthma due to upper respiratory tract infection in mild asthmatics. About half of them had history of previous ER visits. Their prognosis was not bad, but after discharge, about half of patients escaped from OPD follow-up. Conclusion : As a group they merit detailed attention and follow up arrangement. Clinician need to monitor and review the treatment plans, the medications, the patient's management technique, and the level of asthma control. For this group, plans for longer term treatment, including asthma education program and adjustment of overall treatment plan should be made.

• 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.51 no.6
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• pp.530-539
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• 2001

Background : Bronchial asthma is an inflammatory disease of the airways that is associated with airway remodeling. The vascular endothelial growth factor (VEGF) is a potent, multifunctional cytokine that contributes to angiogenesis and inflammation. Matrix metalloproteinase-9 (MMP-9) is a major proteolytic enzyme that in duces bronchial remodeling in asthma. However, there is no data available on the possible role of the VEGF or on the potential relationship between the VEGF and MMP-9 in acute asthma. Therefore, the VEGF was studied to determine whether or not it participates in airway inflammation during acute asthma. An additional aim of this study was to determine whether or not the VEGF levels correlated with the MMP-9 levels in the sputum of acute asthma patients. Methods: Both the VEGF and MMP-9 levels were measured by an enzyme immunoassay and zymographic analysis in the sputum of patients with either stable asthma or with acute asthma. The VEGF and MMP-9 levels were also evaluated during a spontaneous asthma attack. Results : The VEGF levels were significantly higher in the sputum of acute asthmatic patients than in either the stable patients the control subjects. The VEGF levels in the sputum during asthma exacerbation were significantly higher than those on the remission days, and those levels decreased after asthma therapy. In acute asthmatic patients, the VEGF levels in the sputum correlated with the number of neutrophils and eosinophils. In addition, a significant correlation was established between the VEGF and MMP-9 levels in the sputum. Conclusion : These results suggest that VEGF overproduction is associated with airway inflammation during acute asthma and is related to the MMP-9 function.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.747-756
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• 1999

Background: Acid-fast stain and cultures for diagnosis of pulmonary tuberculosis are primary and essential method, but have their limitation : low sensitivity and time consuming. The objective of this study is comparison of amplified Mycobacterium tuberculosis direct test(MTD) by the conventional AFB smears and cultures in the detection of Mycobacterium tuberculosis in respiratory specimens. Methods: During the period between November, 1997 and May, 1998 a total of 267 respiratory specimens (sputum 173, bronchial washing 94) from 187 patients suspected pulmonary tuberculosis were subjected to AFB smears, cultures and MID test. MID is based on nucleic acid amplification. We compared the MID with 3% Ogawa culture method. In positive AFB smear and negative MID specimen, positive culture identification between nontuberculous mycobacterium and M.tuberculosis was assesed by using Accuprobe M.tuberculosis complex probe. In negative AFB smear and negative AFB culture, MTD results are assessed by clinical follow-up. Results : 1) Compared with culture in sputum and bronchial fluid specimens, sensitivity and specificity of MTD in positive AFB smear is 79.7% and 20.0%, sensitivity and specificity of MTD in negative AFB smear specimens is 75.0% and 79.7%. 2) Discrepant analysis is assessed by clinical follow-up and other specimen results beyond study. Culture negative but MTD positive specimens were proved to be true positive and gave MTD sensitivity 79.2%, specificity of 84.4%, positive predictive value 80.5% and negative predictive value 83.2%. 3) 14 out of 31 specimens in negative AFB smear, negative AFB culture and positive MTD showed pulmonary tuberculosis diagnosed on clinical follow-up and sensitivity is 45.2%. 4) 2 out of 13 specimens in positive AFB smear, positive AFB culture and negative MID diagnosed as non tuberculous mycobacterium by Accuprobe culture. Conclusion: This study suggested that MID in respiratory specimens is simple and rapid diagnostic method, but considered adjuvant method rather than replace the conventional AFB smear and culture.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.585-593
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• 2000

Background : International consensus guidelines have recently been developed to improve the assessment and management of asthma. One of the major recommendation of these guidelines is that asthma severity should be assessed through the recognition of key symptoms, such as nocturnal waking, medication requirements, and objective measurements of lung function. Differential classification of asthma severity would lead to major differences in both long term pharmacological management and the treatment of severe exacerbation. Methods : This study examined the relationship between the symptom score and measurements of $FEV_1$ and PEF when expressed as a percentage of predicted values in asthmatics (n=107). Results : The correlation of $FEV_1$ % with PEFR% was highly significant (r=0.83, p<0.01). However, there was agreement in terms of the classification of asthma severity in 76.6% of the paired measurements of $FEV_1$ % and PEFR%. Agreement in the classification of asthma severity was also found in 57.1% of the paired analysis of $FEV_1$ % and symptom score. 39% of the patients classified as having moderate asthma on the basis of $FEV_1$ % recording would be considered to have severe asthma if symptom score alone were used. Low baseline $FEV_1$ and high bronchial responsiveness were associated with a low degree of perception of airway obstruction. Conclusion : The relationships between the symptom score, PEFR and $FEV_1$ were generally poor. When assessing asthma severity, age, duration, $PC_{20}$, and baseline $FEV_1$ should be considered.