• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.611-618
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• 2004

Background : Idiopathic pulmonary fibrosis(IPF), a subtype of IIP(idiopathic interstitial pneumonia), is a fatal disease with a 3-5 year median survival. Many attempts at treating this condition have failed to demonstrate a survival benefit in IPF. Recently Ziesche et $al^{12}$ reported the efficacy of IFN-${\gamma}$ for treating IPF but there is still some controversy. The aim of this study was to determine the efficacy of IFN-${\gamma}$ in patients with advanced IPF who had not been responsive to steroid and cytotoxic agents. Method : Nine patients with advanced IPF(age: $55.4{\pm}15.3$ years, Male: Female=8:1) were enrolled. One year treatment regime with 2 million IU of IFN-${\gamma}$ administered subcutaneously three times a week, and low dose prednisolone(10-30 mg/d) was also used. In the case of a definite aggravation and serious side effects, the IFN-${\gamma}$ was discontinued. During the IFN-${\gamma}$ trial, a pulmonary function test and chest radiography were checked every three month throughout the study. Result : 1) Among 9 patients, only 4 patients were able to complete the 12 month treatment with IFN-${\gamma}$, and 5 patients died during the treatment period. 2) No improvement either in the respiratory symptoms or pulmonary functions were observed any of the patients, even in those who completed the 12 months trial of IFN-${\gamma}$, 3) At the time of IFN-${\gamma}$ trial, the survivors who finished the IFN-${\gamma}$ treatment for 12 months had a higher oxygen level($81.3{\pm}2.8$ vs. $67.4{\pm}8.4$, P=0.024) and a better pulmonary function(FVC: $61.3{\pm}5.1$ % predicted vs. $45.7{\pm}12.3%$, P=0.048, and $D_Lco$: $45.0{\pm}5.0%$ predicted vs. $30.8{\pm}11.2%$, P=0.048) than the non-survivors. Conclusion : Our data suggested that IFN-${\gamma}$ therapy was not effective in the patients with advanced IPF refractory compared with other therapeutic agents. Furthermore, these results suggest that severe impairment of the pulmonary function and hypoxemia during the IFN-${\gamma}$ therapy requires special attention.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.345-350
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• 2004

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.159-166
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• 1992

Background:Sulfiting agents are widely used as preservatives and antioxidants in foods, beverages and drugs including bronchodilators. There have been reports of sulfite-related reactions such as anaphylaxis, urticaria, angioedema, abdominal discomfortness as well as bronchospasm. Several investigators reported that sulfite-sensitive asthmatic patients comprised from 3.9% to 8.2% of all asthmatic patients and its prevalence was higher in steroid-dependent group than in steroid-independent group. Subjects and Method:We performed oral provocation test with sodium bisulfite and aspirin in 17 asthmatic patients who have experienced aggravation of their symptoms after administration of drugs or foods. All of them were steroid dependent asthmatics. We observed clinical symptoms and steroid requirements from 1 to 18 months. Result:Ten of them showed severe bronchoconstriction after the ingestion of sodium bisulfite (50 to 200 mg) within 30 minutes. Concurrent aspirin intolerance was noted by oral provocation test in four cases (40%). Three of them showed positive responses on skin prick test with sulfite (10 or 100 mg/ml). Mean total eosinophil counts was $844/mm^3$ at asthmatic attack. And there was no significant responses on skin prick test and IgE-RAST to common inhalant allergens. After complete avoidance from sulfite containing foods and drugs as well as antiasthmatic medication for 1 to 18 months, nine of them (90%) could stop or reduce the steroid requirements. ConcIusion:It was suggested that severe steroid dependent and intrinsic type of asthmatic patients should be evaluated for sulfite-sensitivity.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1040-1050
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• 1997

Pulmonary rehabilitation has been known to improve dyspnea and exercise tolerance in patients with chronic lung disease, although it does not improve pulmonary function. The mechanism of this improvement is not clearly explained till now; however some authors suggested that the improvement in the skeletal muscle metabolism after the rehabilitation could be a possible mechanism. The metabolc changes in skeletal muscle in patients with COPD are characterized by impaired oxidative phosphorylation which causes early activation of anaerobic glycolysis and excess lactate production with exercise. In order to evaluate the change in the skeletal muscle metabolism as a possible cause of the improvement in the exercise tolerance after the rehabilitation, noninvasive $^{31}P$ magnetic resonance spectroscopy(MRS) of the forearm flexor muscle was performed before and after the exercise training in nine patients with chronic lung disease who have undertaken intensive pulmonary rehabilitation for 6 weeks. 31p MRS was studied during the sustained isometric contraction of the dominant forearm flexor muscles up to the exhaustion state and the recovery period. Maximal voluntary contraction(MVC) force of the muscle was measured before the isometric exercise, and then 30% of MVC force was constantly loaded to each patient during the isometric exercise. After the exercise training, exercise endurance of upper and lower extremities and 6 minute walking distance were significantly increased(p<0.05). There were no differences of baseline intracellular pH (pHi) and inorganic phosphate/phosphocreatine(Pi/PCr). After rehabilitation pHi at the exercise and the exhaustion state showed a significant increase($6.91{\pm}0.1$ to $6.99{\pm}0.1$ and $6.76{\pm}0.2$ to $6.84{\pm}0.2$ respectively, p<0.05). Pi/PCr at the exercise and the recovery rate of pHi and Pi/PCr did not show significant differences. These results suggest that the delayed intracellular acidosis of skeletal muscle may contribute to the improvement of exercise endurance after pulmonary rehabilitation.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1063-1071
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• 1997

Backgroung : The efficacy of oral corticosteroids in the treatment of chronic asthma is undisputed, but their long-term use is associated with adverse side-effects, including supression of the hypothalamic-pituitary adrenal axis function, osteoporosis, weight gain, hypertension and impaired glucose tolerance. The introduction of inhaled corticosteroids in the early 1970's represented a significant therapeutic advance in the management of asthma, since these compounds combined high topical potency with low systemic activity. Fluticasone propionate is a new topically active synthetic glucocorticosteroid that combinds a high degree of efficacy with negligible systemic bioavailability. This study was perfomed to determine the effect of inhaled fluticasone propionate on the adreocortical supression in patients with bronchial asthma or chronic obstructive pulmonary disease. Method : The adrenocortical function was assessed by measurement of plasma cortisol concentration at 8 o'clock in morning and free cortisol in 24 hour urine collection at interval. Absolutely, no steroid was taken during pretreatment period of 10days. There after each subject inhaled fluticasone aerosol, in daily doses of 500 or 1000micrograms for 12days. The dose was delivered by metered dose inhaler(MDI). Results : The serum cortisol and 24hour urinary free cortisol were not decreased during the treatment period in patients with inhaled fluticasone propionate in daily doses of 500 micrograms. In contrast, serum cortisol was significantly decreased on 9th and 12th day(p less than 0.05). And, 24hour urinary free cortisol was also significantly decreased on 3rd and 12th day of treatement period(p less than 0.05) in patients with inhaled fluticasone in daily doses of 1000 micrograms. Conclusion : These results suggested that endogenous cortisol secretion was not supressed after short-term inhalation of fluticasone in daily dose of 500 micrograms, but in daily dose of 1000 micrograms, the endogenous cortisol secretion was supressed.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.236-245
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• 2000

Background: Transbronchial lung biopsy(TBLB) has known to yield useful information for pulmonary infiltrates of uncertain etiology, However, its safety and usefulness have not been conclusive in the critically ill patients with respiratory failure. Moreover, TBLB has not been recommended for patients with mechanical ventilation. This study was conducted to investigate the diagnostic values and risks of Will performed on critically ill patients at bedside to obtain information on the pulmonary infiltrate of unknown etiology. Methods: Twenty patients(21 admissions with 23 cases) with diffuse pulmonary infiltrates who were treated in a medical intensive care unit of a tertiary referral hospital from January 1994 to May 1998, were enrolled for the study. Their medical records were retrospectively reviewed. TBLB was opted when a noninvasive diagnostic work-up failed to reveal the cause for the pulmonary infiltrate. The procedure was performed at patients' bedside without assistance of fluoroscopy. Bronchial washing or bronchoalveolar lavage was performed on the same pulmonary segment before performing TBLB. Results: Adequate specimens were obtained in 18 cases(78%). TBLB provided a specific diagnosis in two cases. The results of TBLB suggested the underlying etiology in 9 cases; bacterial pneumonitis(4), hypersensitivity pneumonitis(1), polymyositis(1), radiation fibrosis(1), idiopathic pulmonary fibrosis(1), and BOOP(1). Therapeutic decisions were altered in 11 cases(47.8%) based on the TBLB results. Pneumocystis carinii was found in the BAL fluid of another case. Ten patients with a therapeutic change and ten patients without a management change had mortality rates of 40% and 80%, respectively. The APACHE III scores were significantly higher in patients with complications($72.8{\pm}21.8$) compared with those without complications ($48.3{\pm}18.9$)(p<0.05). The complication rates were higher in those with mechanical ventilation(50%) than in those without Mechanical ventilation(33%), but the difference was not statistically significant(p=0.3). Conclusions: TBLB may be a useful diagnostic option for critically ill patients with unknown cause of pulmonary infiltrates. However, it should be cautious be used with care for patients with mechanical ventilation or for severely ill patients.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.547-557
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• 1996

Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.613-622
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• 1996

Constrictive bronchiolitis, one of small airway diseases, is very rare and occupies one of the two arms of bronchiolitis obliterans together with proliferative bronchiolitis. Proliferative bronchiolitis, presenting the prototype with bronchiolitis obliterans with organizing pneumonia(BOOP), can be easily taken into diagnostic consideration in terms of relatively rapid clinical course and radiologic presentation as if atypical pneumonia with interstitial and alveolar infiltrations. Meanwhile constrictive bronchiolitis is not only very Tare but also easily overlooked as chronic obstructive pulmonary diseases such as emphysema, because it usually shows normal chest radiographic finding and obstructive pattern in pulmonary function test. In the aspects of the response to treatment, proliferative bronchiolitis showed dramatic response to the corticosteroid while constrictive bronchiolitis is intractable, which is easily explained on the basis of the pathologic characteristics of cicartrical replacement of bronchiolar walls. The bronchiolitis, both proliferative and constrictive, can be associated with diverse conditions such as inhalational injury, postinfectious process, drug of chemical induced reactions, connective tissue diseases, and organ trasplantation. And there is idiopathic type which has no associated condition. There is one explanation that both types of bronchiolitis lie on the same disease spectrum because the different disease pattern can be evoked from the same etiology. In contrast, another explanation is suggested that both types of bronchiolitis are one of nonspecific tissue reaction rather than a disease specific histologic finding because the various types of causes can provoke the same histologic findings. These dilemma remains for further investigation. With literature investigation, the authors report a case of constrictive bronchiolitis proven by open lung biopsy in 47 year old female who was diagnosed as non-Hodgkin's lymphoma and simultaneously had relatively rapid progression of airflow obstruction and showed negative radiographic finding without the rise factors for the development of chronic obstructive lung disease. We consider it as idiopathic because we could not find any relationship between constrictive bronchiolitis and non-Hodgkin's lymphoma on the literature search and it requires further investigation.

• Tuberculosis and Respiratory Diseases
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• v.39 no.5
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• pp.400-406
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• 1992

Background: It has been known that see antigen was used in diagnosis of uterine cervical cancer and also known to be higher in squamous cell lung cancer. There has been no report about see antigen in squamous cell lung cancer in Korea. This study was designed to evaluate the usefulness of see antigen as a diagnostic tool and index for follow up after treatment. Method: The serum level of see antigen was measured in 12 cases with squamous cell lung carcinoma, 9 patients with other types of lung cancer, 7 patients with benign lung disease and 7 normal subjects by radioimmunoassay with Abott see Riabeap radioimmunoassay kit. We also measured see antigen after treatment in 6 patients who had received chemotherapy or sugery. Result: 1) The level of see antigen ($mean{\pm}1$ SD) was $2.27{\pm}1.53$, $0.67{\pm}0.38$, $0.62{\pm}0.53$, $0.53{\pm}0.36\;ng/ml$ respectively. 2) The see antigen activity in squamous cell lung carcinoma according to stage were as gollows. I; $2.07{\pm}1.56$, $III_a$; $5.04{\pm}0.53$ $III_b$; $1.94{\pm}0.7$ IV; $1.07{\pm}0.64$ (ng/ml). 3) In squamous cell lung cancer, 5 of 12 (42%) cases was shown more than 2.0 ng/ml see antigen. (sensitivity; 42%), but there was no case in any other type of lung cancer, benign lung disease, and in control groups (specificity; 100%). 4) The serum sec antigen level after treatment was significantly decreased in patients with partial or complete remission (p<0.01). Conclusion; It was suggested that see antigen might be used as a useful tumor marker for the response of treatment and assessment of prognosis in squamous cell lung cancer, but further study should be performed for the clinical use of see antigen.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.42-54
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• 1992

Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.