• Tuberculosis and Respiratory Diseases
• /
• v.39 no.4
• /
• pp.310-317
• /
• 1992

Background: Angiotensin converting enzyme is a glycoprotein peptidyldipeptide hydrolase which cleaves the c-terminal dipeptides of several oligopeptides. It is a menbrane-bound protein mainly synthesized by the endothelial cells. Since the lung has the largest capillary bed of any organ in the body, it is here that ACE acts on circulating substrates like angiotensin I and bradykinin. It is well known that ACE correlates with disease activity in sarcoidosis and also there are reports that changes in serum ACE activity are found in many acute and chronic lung diseases. So we planned this study to see if serum ACE activity can act as a prognostic factor in lung cancer. Methods: Forty-one newly diagnosed lung cancer patients were included in the study group. There were 19 patients with squamous cell lung cancer, 13 with adenocarcinoma, and 9 with small cell carcinoma. Patients were excluded from the study if they had high blood pressure, heart disease, liver disease, renal disease, or other lung disease. Serum ACE activity was analyzed according to cell type, staging, mode of treatment, and clinical response to treatment. Results: 1) There was no difference in serum ACE activity between lung cancer patients and the control group. Also no difference in serum ACE activity was found according to cancer cell type or staging. 2) In patients who underwent curative resection of lung cancer, serum ACE activity was decreased significantly after the operation. 3) In patients who were diagnosed as non-small cell lung cancer and were treated with 4 cycles of anti-cancer chemotherapy without clinical improvement, changes in serum ACE activity were not seen after the treatment. 4) In patients diagnosed as small cell lung cancer treated with 4 cycles of anti-cancer chemotherapy with clinical improvement, changes in serum ACE activity were also not observed. Conclusion: Serum ACE activity was decreased after lung resection but had no relation to cell type, staging, or clinical response to treatment in lung cancer patients. Therefore, serum ACE activity is not suitable in predicting clinical outcome of lung cancer patients.

• Tuberculosis and Respiratory Diseases
• /
• v.39 no.4
• /
• pp.304-309
• /
• 1992

Background: The alveolar macrophage may metabolize arachidonic acid through cyclooxygenase- and lipoxygenase- catalyzed pathways to produce a variety of metabolites of arachidonic acid. The production of these metabolites of arachidonic acid may enhance the defensive ability of the challenged lung. However, continued stimulation with the consequent production of proinflammtory metabolites of arachidonic acid, may ultimately enhance the disease process by contributing to chronic bronchoconstriction, fibrosis, and the persistent release of toxic oxygen species. Silicosis is an example of a disease process resulting from chronic exposure of the lung to foreign particles. This study was carried out to evaluate the changes of arachidonic acid metabolites from macrophages in experimental silicosis. Methods: We measured $PGE_2$, and $LTB_4$ in cultured macrophages taken from rats by radioimmunoassay at 24 and 48 hours after stimulation by silica dust, natural carbon dust, lipopolysaccharide, calcium ionophore (A23187) and medium (RPMI) as a control. For the experimental silicosis, 50 mg silica in 0.5 ml saline was administered intratracheally into the rat and grown to 20 weeks and measured $PGE_2$, and $LTB_4$ in the cultured macrophages lavaged from that rat. The used stimulants were the same as above. Results: 1) The amount of $PGE_2$ in the cultred macrophages from normal rat was significantly decreased in the group which was stimulated with silica dust for 48 hours compare with control non-stimulated group. 2) In the experimental silicosis group, $PGE_2$, release in cultured macrophages after 48 hours incubation with silica and natural carbon dust tended to be lower than those of non-stimulated group. 3) There were marked changes of $LTB_4$ in the groups of normal rats which were incubated with silica for 24, 48 hours and natural carbon for 48 hours compared with non-stimulated group. 4) In the experimental silicosis group, the release of $LTB_4$ was significantly increased macrophages cultured with silica and natural carbon dust after 24 and 48 hours incubation compared with non-stimulated group. Conclusion: The results of these studies suggest that the in vitro exposure of rat alveolar macrophge to silica and coal dust results in an alteration in alveolar macrophage metabolism of arachidonic acid that may promote an inflammatory reaction in lung tissue.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.1
• /
• pp.44-52
• /
• 1999

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and $PC_{20}$ for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, $901.6\pm220.4$ pg/ml, $810.9\pm290.8$ pg/ml for PBMC, $24.5\pm9.5$ pg/mL $30.5\pm13.5$ pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p<0.05). However there was no difference of IL-10 level according to $PC_{20}$ for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.3
• /
• pp.331-338
• /
• 2000

Background : While the incidence of lung cancer is gradually leveling off in developed countries, it is continuing to rise in Korea. With the rapid increase in the prevalence of smoking among women and the young, the incidence of lung cancer is also expected to increase within the next three and four decades. The aims of the present study are to analyze the smoking habits in patients with lung cancer and to evaluate of the relative risk of lung cancer according to patients' smoking habits. Method : This investigation was a hospital-based, case control study, which included data of 93 case subjects with lung cancer and 1132 controls with disease unrelated to smoking, obtained through a smoking history questionnaire by a direct personal interview. Result : Compared with non-smokers, those who smoked for more than 50 years had an odds ratio for lung cancer of 8.8(1.8-20.7). The odds ratios was 8.5(3.5-20.7) for those who smoke more than a total of 40 cigarettes per day and 5.5(2.3-13.3) for men who started habitual smoking under the age of 20. The risk increased for men with more than of cigarette smoking(OR : 5.5, 95% CIa : 2.6-11.9). Odds ratios associated with cigarette smoking were 2.5(1.1-5.8) and 5.1(2.6-10.4) for ex-smokers and current smokers, respectively and 2.2(0.0-4.6) for non-filter smokers of more than 16 years. Conclusion : There was a clear dose-response relationship between the risk of lung cancer and smoking. It can be concluded that dose is an important risk factor for lung cancer, as well as smoking habits.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.522-529
• /
• 2000

Backgrounds : Assessment of the presence and degree of reversibility of airflow obstruction is clinically important in patients with asthma or chronic obstructive pulmonary disease. The measurement of peak expiratory flow(PEF) is a simple, fast, and cheap method to assess the severity of obstruction and its degree of reversibility. Assessing the reversibility of airflow obstruction by peak expiratory flow(PEF) measurements is practicable in general practice, but its usefulness has not been well investigated. We compared PEF and $FEV_1$ in assessing reversibility of airflow obstruction in patients with chronic obstructive pulmonary disease or asthma and developed a practical criterion for assessing the presence of reversibility in general practice. Methods : PEF measurements were performed (Spirometry) in 80 patients(aged 24-78) with a history of asthma or chronic obstructive lung disease before and after the inhalation of 200 g salbutamol. The change in PEF was compared with the change in forced expiratory volume in one second($FEV_1$). Reversible airflow obstruction was analyzed according to American Thoracic Society(ATS) criteria. Results : A 12% increase above the prebronchodilator value and a 200ml increase in either FVC or $FEV_1$ reversibility were observed in 45%(36) of the patients. Relative operating characteristic(ROC) analysis showed that an absolute improvement in PEF of 30 l/min gave optimal discrimination between patients with reversible and irreversible airflow obstruction(the sensitivity and specificity of an increase of 30 l/min in detecting a 12% increase above the prebronchodilator value and a 200ml increase in either FVC or $FEV_1$ were 72.2% and 72.7% respectively, with a positive predictive value of 68.4%). Conclusions : Absolute changes in PEF can be used to diagnose reversible airflow obstruction.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.3
• /
• pp.357-364
• /
• 2000

Background : Complicated exudative pleural fluid collections have traditionally been treated by either closed tube thoracostomy drainage or by open surgical drainage. Complete drainage is important in order to control pleural sepsis, restore pulmonary function, and entrapment. Recently intracavitary fibrinolytic therapy has been advocated as a method to facillitate drainage of complicated exudative pleural effusion and to allow enzymatic debridemant of the restrictive fibrinous sheets covering the pleural surface. The purpose of this study is to prospectively evaluate the effects of image-guided catheter drainage with high dose urokinase(UK) instillation in the treatment of complicated pleural effusions. Patients : Twenty complicated pleural effusion patients that poorly respond to image-guided drainage were allocated to receive UK. There were 8 pneumonia and 12 tuberculosis. Methods : Drugs were diluted in 250 mL normal saline and were infused intrapleurally through the chest tube or pig-tail catheter in a daily dose of 250,000 IU of UK. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasound and/or computed tomography. Results : The mean UK instillation time was $1.63{\pm}0.10$. The mean volume drained UK instillation was $381.3{\pm}314.4\;mL$, and post-UK was $321.6{\pm}489.5\;mL$. The follow up duration after UK therapy was mean $212.9{\pm}194.5$ days. We had successful results in 19 cases (95.0%). There were 12 pleural thickenings (60.0%), 2 markedly decreased effusions (10.0%) and 5 cases of no thickening or effusion. There was recurrence after treatment in only one patient(5%) with complicated pleural effusiondue to tuberculosis. Conclusions : Image-guided drainage with high dose UK instillation (250,000 U/day) in complicated pleural effusion is a safe and more effective method than closed thoracostomy drainage. And this management, in turn, can obviate surgery in most cases.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.420-427
• /
• 2000

Background : Isolated leukopenia is rare, but it has important clinical implications during antituberculosis treatment. Inadvertent discontinuation of short-course regimen drugs for fear of leukopenia inevitably will extend the duration of treatment, and the completion of treatment will be delayed. However no guidelines concerning proper management for leukopenia during antituberculosis treatment have been presented. Therefore, this study was performed to evaluate the possibility of continuing the same short-course regimen if a mild-to-moderate degree of isolated leukopenia was to develop during antituberculosis treatment. Method : Thirty-six patients who had been prescribed a short-course antituberculosis regimen between January 1997 and August 1999, had newly developed, mild-to-moderate degree, isolated leukopenia during medication, and had continued the same drug regimen despite leukopenia were enrolled. One patient was not available for the follow-up, so the remaining thirty-five (twenty-five prospectively and ten retrospectively) patients were analyzed. Patients who had other known causes of leukopenia were excluded. A mild-to-moderate degree of isolated leukopenia was arbitrarily defined as having a peripheral blood leukocyte count between 2,000 and $3,499/mm^3$ and no evidence of coexisting hematologic abnormalities. Results : 1) All thirty-five patients were able to complete short-course anti-tuberculosis treatment without complication or further decrease of leukocytes count to less than $2,000/mm^3$ despite continuous treatment with the same regimen. 2) The mean duration from start of antitituberculosis medication to detection of leukopenia was $64{\pm}65$ days. 3) The mean leukocyte count was $5,035{\pm}1,583/mm^3$ before treatment, and the its lowest count was $2,908{\pm}390/mm^3$ during treatment. Leukopenia recovered after completion of treatment ($4,283{\pm}1,269/mm^3$). 4) The main component of leukopenia was the decrease in neutrophil count ($3,361{\pm}1,732$ vs. $1,512{\pm}423/mm^3$, p<0.05). Conclusion : For mild-to-moderate degree of isolated leukopenia ($2,000/mm^3{\leq}$ WBC < $3,500/mm^3$), developing during short-course antituberculosis treatment, the short-course antituberculosis regimen may be continued without complications.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.471-477
• /
• 2000

Background : Coughing is the most common complaint for which patients seek medical service. When caughing continues over 3 weeks in non-smokers who do not take cough-provoking drugs, they are classified as patients with chronic cough. Three well known main causes of chronic caugh are postnasal drip syndrome, bronchial asthma and gastroesophaseal reflux disease. Among them, postnasal drip syndrome is reported to be the most common cause of all in chronic cough diseases, and allergic inflammation plays an important role in the pathogenesis of postnasal drip syndrome. CD23 and CD25 which are low affinity receptor for IgE and IL-2 receptor alpha, respectively, are closely related to allergic inflammation and their roles were evaluated in chronic cough patients. Methods : We evaluated 105 patients with chronic cough and selected 56 patients for measurement of serum CD23 & CD25 levels. We selected 10 normal, medical students for comparison of serum CD23 & CD25 levels. Result : The postnasal drip syndrome was found to be the most common cause of chronic cough. Serum CD23 and CD25 did not increase in chronic cough patient compared to normal controls. However in bronchial asthma patient, serum CD23 level was increased relative to normal control (p<0.05). Conclusion : In bronchial asthma presented as chronic cough, lymphocyte mediated allergic inflammation may related with the pathogenesis of the disease.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.4
• /
• pp.487-499
• /
• 2000

Background : Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. Methods : Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. Results : Intratracheal endotoxin instillation increased the respiration rate decreased the tidal volume and int creased the Penh in all group of rats. Intratracheal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation at both times of administration (30 minute and 5 hour after endotoxin instillation). Conclusion : Intratracheal instillation of surfactant can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated for treatment of human acute lung injury.

• Tuberculosis and Respiratory Diseases
• /
• v.53 no.2
• /
• pp.136-147
• /
• 2002

Background : Interstitial lung disease has various manifestations that are differentiated by their pathology, progress and treatment. However, all manifestations eventually progresses to pulmonary fibrosis. Recent studies have shown that apoptosis of pulmonary epithelial cells might be related to pulmonary fibrosis. The correlation of the apoptotic index with the clinical manifestations, pathological findings, HRCT findings and the response to treatment were examined. Materials and Methods : Twenty subjects (14 men, 16 women), who had been diagnosed with interstitial lung disease through an open lung biopsy, were enrolled in this study. The subtypes were one AIP, two NIP, eight BOOP, and seven UIP cases. The apoptotic index was scaled from 0-2 depending on the fraction of positive staining cells by TUNEL method. The clinical severity was assessed by a modification of a previously developed CRP scoring system. The pathologic scores were based on 4 components: fibrosis, cellularity, desquamation, and granulation. In the HRCT study, each lobe was scored by the radiologists on a scale for both fibrosis and ground-glass attenuation. The treatment response was assessed by an increase in more than 10% of the CRP score, and comparing the results 3 months before and after treatment. Results : The apoptotic index showed no correlation with the CRP and HRCT scoring system. The apoptotic index correlated with the pathologic elements including fibrosis, cellularity and the desquamation score (p<0.05). Of the 16 patients who received corticosteroid therapy, 9 patients (56.3%) responded to therapy. There was no correlation between the response to corticosteroid and the apoptotic index. In the case of patients with acute and subacute ILD, the apoptotic index showed a correlation with the cellularity, desquamation, and the total histological score (p<0.05). In the case of patients with chronic ILD, the apoptotic index correlated with the fibrosis and cellularity score (p<0.05). Conclusion : Apoptosis of the pulmonary epithelial cells is implicated in the pathogenesis of interstitial lung disease particularly on a pathological basis.