• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.530-542
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• 2000

Background : Nonspecific interstitial pneumonia (NSIP) has been reported recently to have shown much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating it from UIP have not been clearly defined. Method : Among 120 patients with biopsy-proven diffuse interstitial lung diseases admitted to the Samsung Medical Center between July 1996 and March 2000, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. Results : 1) At diagnosis, 17 patients were female and the average age was $55.2{\pm}8.4$ years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was $9.9{\pm}17.1$ months. Increase in bronchoalveolar lavage fluid lymphocytes ($23.0{\pm}13.1%$) was noted. On HRCT, ground glass and irregular linear opacity were observed, but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients, but the medication was stopped in 3 patients due to severe side effects. Further medical therapy was not possible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascular necrosis of the hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of the 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuing with the medication. 3) After medical treatment, 14 of 17 patients improved, and 3 patients remained stable (mean follow-up ; $24.1{\pm}11.2$ months). FVC increased by $20.2{\pm}11.2%$ of predicted value and the extent of ground glass opacity on HRCT decreased significantly ($15.7{\pm}14.7%$). 4) Of the 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 became aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. Conclusion : Since idiopathic NSIP has unique clinical profiles and shows good prognosis, diagnosis different from UIP, and aggressive medical treatment are needed.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.803-810
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• 1999

Background : The patient's work of breathing(WOBp) during assisted ventilation may vary according to many factors including ventilatory demand of the patients and applied ventilatory setting by the physician. Pressure-controlled ventilation(PCV) which delivers gas with decelerating flow may better meet patients' demand to improve patient-ventilator synchrony compared with volume-controlled ventilation(VCV) with constant flow. This study was conducted to compare the difference in WOBp in two assisted modes of ventilation, PCV and VCV with constant flow. Methods : Ten patients with respiratory failure were included in this study. Initially, the patients were placed on VCV with constant flow at low tidal volume($V_{T,\;LOW}$)(6-8 ml/kg) or high tidal volume($V_{T,\;HIGH}$)(10-12 ml/kg). After a 15 minute stabilization period, VCV with constant flow was switched to PCV and pressure was adjusted to maintain the same tidal volume($V_T$) received on VCV. Other ventilator settings were kept constant. Before changing the ventilatory mode, WOBp, $V_T$, minute ventilation($V_E$), respiratory rate(RR), peak airway pressure (Ppeak), peak inspiratory flow rate(PIFR) and pressure-time product(PTP) were measured. Results : The mean $V_E$ and RR were not different between PCV and VCV during the study period. The Ppeak was significantly lower in PCV than in VCV during $V_{T,\;HIGH}$. HIGH ventilation(p<0.05). PIFR was significantly higher in PCV than in VCV at both $V_T$ (p<0.05). During $V_{T,\;LOW}$ ventilation, WOBp and PTP in PCV($0.80{\pm}0.37\;J/min$, $164.5{\pm}74.4\;cmH_2O.S$) were significantly lower than in VCV($1.06{\pm}0.39J/mm$, $256.4{\pm}107.5\;cmH_2O.S$)(p<0.05). During $V_{T,\;HIGH}$ ventilation, WOBp and PTP in PCV($0.33{\pm}0.14\;J/min$, $65.7{\pm}26.3\;cmH_2O.S$) were also significantly lower than in VCV($0.40{\pm}0.14\;J/min$, $83.4{\pm}35.1\;cmH_2O.S$)(p<0.05). Conclusion : During assisted ventilation, PCV with decelerating flow was more effective in reducing WOBp than VCV with constant flow. But since individual variability was shown, further studies are needed to confirm these results.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.817-825
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• 1999

Background : Forceps biopsy, bronchial brushing, and bronchial washing are used in conjunction with bronchoscopy to provide specimens for histologic and cytologic analysis in patients with suspected lung cancer. This study was performed to evaluate how many times brushing should be done and how much fluid should be used during bronchial washing for increasing diagnostic yield, and to evaluate which combination of these procedures gives the highest diagnostic yield. Methods : Forty patients, with suspected lung cancer, who had bronchoscopically visible lesions were enrolled in this prospective study. During one bronchoscopic examination four forceps biopsies, four bronchial brushings, and bronchial washing were done in all patients. The patients were divided into four groups by the amount of normal saline used for bronchial washing; group I, 10 ml ; group II, 20ml ; group III 30ml, and group IV, 40ml. We analyzed the results in 36 patients confirmed as lung cancer. Results : The diagnostic sensitivity of bronchial washing before and after forceps biopsy and bronchial brushing were 36% and 28%, respectively. The cumulative diagnostic sensitivity of bronchial washing was 47% and significantly higher than that of bronchial washing before or after forceps biopsy and bronchial brushing (p<0.05). The diagnostic sensitivity of bronchial washing with saline of 30ml was significantly higher than that of bronchial washing with saline of 10ml or 20ml (p<0.05). The diagnostic sensitivity of the first brushing was 75%, the second brushing 78%, the third brushing 83%, and the fourth brushing 67%. With repeated brushing up to three times, the diagnostic sensitivity increased to 92% (p<0.05). However, inclusion of the fourth brushing did not give a further increase of the diagnostic sensitivity. The diagnostic sensitivity of forceps biopsy was 86%. The diagnostic sensitivities of forceps biopsy by the type of bronchial lesion were as follows: tumor, 88%; infiltration, 67%; infiltration with nodularity, 80%; and collapse, 100%. The combination of forceps biopsy and bronchial washing gave a diagnostic sensitivity of 89%. The diagnostic sensitivity of combining forceps biopsy with bronchial brushing was 97%. Addition of bronchial washing did not increase the diagnostic yield over forceps biopsy and bronchial brushing. Conclusion : In patients with central lung cancer, forceps biopsies and repeated brushings up to three times should be done for maximal diagnostic yield.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.426-436
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• 2001

Background : Chronic obstructive pulmonary disease(COPD) is one of the major contributors to morbidity and mortality among the adult population. Cigarette smoking(CS) is undoubtedly the single most important factor in the pathogenesis of COPD. However, its mechanism is unclear. The current hypothesis regarding the pathogenesis of COPD postulates that an imbalance between proteases and antiproteases leads to the destructive changes in the lung parenchyma. This study had two aims. First, to evaluate the effect of CS exposure on histologic changes of the lung parenchyme, and second, to evaluate the effect of CS exposure on the expression of the gelatinolytic enzymes in BAL fluid cells in guinea pigs. Methods : Two groups of five guinea pigs were exposed to the whole smoke of 20 commercial cigarettes per day, 5 hours/day, 5 days/week, for 6weeks, and 12 weeks, respectively, using a smoking apparatus. Five age-matched guinea pigs exposed to room air were used as controls. Five or more sections were microscopically extamined(${\times}400$) and the number of cellular infiltration of the alveolar wall was measured in order to evaluate the effect of CS exposure on the histologic changes of lung parenchyme. The statistical significance was analyzed by a linear regression method. To evaluate the expression of the gelatinolytic enzymes in intraalveolar cells, BAL fluid was obtained and the intraalveolar cells were separated by centrifugation (500 g for 10 min at $4^{\circ}C$). Two sets of culture plates were loaded with $1{\times}10^6$ intraalveolar cells. One plate, contained O.1mM EDTA, a inhibitor of matrix metalloproteases(MMPs), and the other plate had no EDTA. Both plates were incubated for 48 hours at $37^{\circ}C$. After incubation, gelatinolytic protease expression in the supernatants was analyzed by gelatin zymography. Results : At the end of CS exposure, the level of blood carboxy Hb had increased significantly(4.1g/dl in control group, 24g/dl immediately after CS exposure, 18g/dl 30 min after CS exposure, 15g/dl 1 hour after CS exposure). Alveolar inflammatory cells were identified in the CS exposed guinea pigs. The number of alveolar cellular cells observed in a microscopic field ($400{\times}$) was $121.4{\pm}7.2$, $158.0{\pm}20.2$, $196.8{\pm}32.8$, in the control, the 6 weeks, and the 12 weeks group, respectively. The increased extent of inflammatory cellular infiltration of the lung parenchema showed a statistically significant linear relationship with the duration of CS exposure(p=0.001, $r^2=0.675$). Several types of gelatinolytic enzymes in the intraalveolar cells of CS exposed guinea pigs were expressed, of which some were inhibited by EDT A. However, the gelatinolytic enzymes were not expressed in the control groups. Conclusion : CS exposure increases inflammatory cellular infiltration of the alveolar wall and the expression of gelatinolytic proteases in guinea pigs. EDTA inhibits some of the gelatinolytic proteases. These findings suggest a possibility that CS exposure may increase MMP expression in the lungs of guinea pigs.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.450-461
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• 2001

Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.416-425
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• 2001

Background : The incidence of drug-resistant tuberculosis has recently decreased in Korea. However, it is still one of the major obstacles in treating pulmonary tuberculosis. This study was performed to determine the prevalence and clinical characteristics associated with drug-resistance in pulmonary tuberculosis at the tertiary referral hospital in Pusan, Korea. Methods : The medical records of 138 patients, who had been diagnosed as active pulmonary tuberculosis were retrospectively reviewed, and results of drug susceptibility from May 1997 to June 2000. The relationships among those with a history of previous tuberculosis treatment, the extent of lung involvement, the presence of cavities on the initial chest X-ray films and patterns of drug resistance were analyzed. Results : The total number of patients who had drug resistance to at least one drug was 55(39.9%). Among them 34(24.6%) had resistance to isoniazid(INH) and rifampin(RFP). There was drug resistance in 20(22%) of 91 patients without previous tuberculosis therapy, and among them 9(9.9%) were multi-drug resistant. Thirty-two(74.5%) out of 47 patients with previous therapy were drug-resistant and 25(53.2%) were multidrug resistant. For all 138 patients, resistance to INH was the most common(34.1%), followed by RFP(26.1%) and ethambutol(EMB)(14.5%). Drug resistance to INH, RFP, PZA and streptomycin(SM) were independently associated with a history of previous treatment(odds ratio; 9.43, 9.09, 8.93 and 21.6 respectively, p<0.01). The extent of lung involvement on the chest films was significantly associated with the drug resistance to INH and RFP(odds ratio; 2.12 and 2.40 respectively, p<0.01). The prevalence of drug resistance to RFP, INH and RFP was significantly more common in patients with a cavitary lesion on the chest films by multivariate analysis(odds ratio; 4.17 and 4.81 respectively, p<0.05). Conclusion : This study revealed that patients with a prior treatment history for pulmonary tuberculosis, and the presence of a cavitary lesion on chest films had a higher prevalence of anti-tuberculosis drug resistance. A very careful clinical and microbiological examination is needed for patients with such characteristics.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.428-437
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• 2000

Background : Five year survival rate of postoperative stage I non-small cell lung cancer(NSCLC) reaches to 66%. In the remaining one third of patients, however, cancer recurs and the overall survival of NSCLC remains dismal. To evaluate clinical and pathologic characteristics of recurred NSCLC, the patterns and factors for postoperative recurrence in patients with staged I and II NSCLC were studied. Method : A retrospective analysis was performed in 234 patients who underwent radical resection for pathologic stage I and II NSCLC. All patients who were followed up for at least one year were included in this study. Results : 1) There were 177 men and 57 women The median age was 63. The median duration of the follow up period was 732 days (range 365~1,695 days). The overall recurrence rate was 26.5%, and the recurrence occurred $358.8{\pm}239.8$ days after operation. 2) The ages of recurred NSCLC patients were higher ($63.2{\pm}8.8$ years) than those of non-recurred patients ($60.3{\pm}9.8$ years)(p=0.043). The recurrence rate was higher in stage II (46.9%) than in stage I (18.8%) NSCLC p<0.001. The size of primary lung mass was larger in recurred ($5.45{\pm}3.22\;cm$) than that of non-recurred NSCLC ($3.74{\pm}1.75\;cm$, p<0.001). Interestingly, there were no recurrent cases when the resected primary tumor was less than 2cm. 3) Distant recurrence was more frequent than locoregional recurrence (66.1% vs. 33.9%). Distant recurrence rate was higher in females and in cases of adenocarcinoma. Brain metastasis was more frequent in patients with adenocarcinoma than in those with squamous cell carcinoma (p=0.024). Conclusion: The tumor size and stage were two important factors for determining the possibility of a recurrence. Because distant brain metastasis was more frequent in patients with adenocarinoma, a prospective study should be conducted to evaluate the effectiveness of preoperative brain imaging.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.448-463
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• 2000

Background : Pulmonary infiltrate is a frequent cause of morbidity and mortality in patients with leukemia. It is often hard to obtain a reliable diagnosis by clinical and radiologic findings alone. The aim of this study was to evaluate diagnostic and therapeutic benefits of invasive procedures for new lung infiltrates in leukemia. Methods : Patients with leukemia who developed new lung infiltrates from December 1994 to March 1999 were included in this study. These patients were classified into the empirical group who received empirical therapy only and into the invasive group who underwent bronchoscopy or surgical lung biopsy for the diagnostic purpose of new lung infiltrates. A retrospective chart review was done to find the etiologies of new lung infiltrates, the yield of invasive procedures, outcome as well as predicting factors for survival. Results : 1) One hundred-two episodes of new lung infiltrates developed in 90 patients with leukemia. Invasive procedures were performed in 44 episodes while 58 episodes were treated with empirical therapy only. 2) Invasive procedures yielded a specific diagnosis in 72.7%(32/44), of which 78.1% had infectious etiology. Therapeutic plan was changed in 52.3%(23/44) of patients after invasive procedures. None of them showed procedure-related mortality. 3) The overall survival rate was 62.7%(64/102). Survival rate in the invasive group (79.5%) was significantly better than that in the empirical group (50.0%) (p=0.002). 4) Upon multivariate analysis, the performance of invasive procedures, no need for mechanical ventilation and achievement of complete remission of leukemia after induction chemotherapy were the independent predicting factors for survival in patients with leukemia and new lung infiltrates. Conclusion : Bronchoscopy and surgical lung biopsy are useful in the diagnosis of new lung infiltrates in patients with leukemia. However, survival benefits of invasive procedures should be considered together with disease status of leukemia and severity of respiratory compromise.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.53-64
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• 1999

Background : Massive and untreated hemoptysis is associated with a mortality of greater than 50 percent. Since the bleeding is from a bronchial arterial source in the vast majority of patients, embolization of the bronchial arteries(BAE) has become an accepted treatment in the management of massive hemoptysis because it achieves immediate control of bleeding in 75 to 90 percent of the patients. Methods: Between 1990 and 1996, we treated 146 patients with hemoptysis by bronchial artery embolization. Catheters(4, 5, or 7F) and gelfoam, ivalon, and/or microcoil were used for embolization. Results: Pulmonary tuberculosis and related disorders were the most common underlying disease of hemoptysis(72.6%). Immediate success rate to control bleeding within 24hours was 95%, and recurrence rate was 24.7%. The recurrence rate occured within 6 months after embolization was 63.9%. Initial angiographic findings such as bilaterality, systemic-pulmonary artery shunt, neovascularity, aneurysm were not statistically correlated with rebleeding tendency(P>0.05). Among Initial radiographic findings, only pleural lesions were significantly correlated with rebleeding tendency(P<0.05). At additional bronchial artery angiograpy done due to rebleeding, recanalization of previous embolized arteries were 63.9%, and the presence of new feeding arteries were 16.7%, and 19.4% of patients with rebleeding showed both The complications such as fever, chest pain, headache, nausea and vomiting, arrhythmia, paralylytic ileus, transient sensory loss (lower extremities), hypotension, urination difficulty were noticed at 40 patients(27.4%). Conclusion: We conclude that bronchial artery embolization is relatively safe method achieving immediate control of massive hemoptysis. At initial angiographic findings, we could not find any predictive factors for subsequent rebleeding. It may warrant further study whether patients with pleural disease have definetely increased rebleeding tendency.