• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.99-106
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• 1998

Purpose : We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Materials and Methods : Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and subrethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using $Sperman-H\"{a}rbor$ method and mathematical analysis of survival curves was done with linear-quadratic (LQ) , multitarget-single hit(MS) model and mean inactivation dose$(\v{D})$. Results : Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85 The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of $\alpha$ for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of $\beta$ were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79. MKN-45, HeLa and PC-14 were 1.59. 1.84. 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1 69 respectively. The $\v{D}s$ calculated by Gauss-Laguerre method were 1.62, 2.37, 2,01 and 3.95 respectively So the SF2 was significantly correlated with $\alpha$, Do and $\v{D}$. Their Pearson correlation coefficiencics were -0.953 and 0,993. 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, ${\alpha}$, ${\beta}$, Do, $\v{D}$. Conclusion : The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-l4 was the least sensitive. SF2 was well correlated with ${\alpha}$, Do, and $\v{D}$. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.736-745
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• 1996

Background : It is known that pulmonary rehabilitation improves dyspnea and exercise tolerance in patient with chronic lung disease, although it does not improve pulmonary function. But there is a controversy whether this improvement after pulmonary rehabilitation is due to increased aerobic exercise capacity. We performed this study to evaluate the effect of pulmonary rehabilitation for 6 weeks on the pulmonary function, gas exchange, exercise tolerance and aerobic exercise capacity in patients with chronic lung disease. Methods : Pulmonary rehabilitations including education, muscle strengthening exercise and symptom-Umited aerobic exercise for six weeks, were performed in fourteen patients with chronic lung disease (COPD 11, bronchiectasis 1, IPF 1, sarcoidosis 1 ; mean age $57{\pm}4$ years; male 12, female 2). Pre- and post-rehabilitaion pulmonary function and exercise capacity were compared. Results: 1) Before the rehabilitation, FVC, $FEV_1$ and $FEF_{25-75%}$ of the patients were $71.5{\pm}6.4%$. $40.6{\pm}3.4%$ and $19.3{\pm}3.8%$ of predicted value respectively. TLC, FRC and RV were $130.3{\pm}9.3%$, $157.3{\pm}13.2%$ and $211.1{\pm}23.9%$ predicted respectively. Diffusing capacity and MVV were $59.1{\pm}1.1%$ and $48.6{\pm}6.2%$. These pulmonary functions did not change after pulmonary rehabilitation. 2) In the incremental exercise test using bicycle ergometer, maximum work rale ($57.7{\pm}4.9$) watts vs. $64.8{\pm}6.0$ watts, P=0.036), maximum oxygen consumption ($0.81{\pm}0.07$ L/min vs. $0.96{\mu}0.08$ L/min, P=0.009) and anaerobic threshold ($0.60{\pm}0.06$ L/min vs. $0.76{\mu}0.06$ L/min, P=0.009) were significantly increased after pulmonary rehabilitation. There was no improvement in gas exchange after rehabilitation. 3) Exercise endurances of upper ($4.5{\pm}0.7$ joule vs. $14.8{\pm}2.4$ joule, P<0.001) and lower extremity ($25.4{\pm}5.7$ joule vs. $42.6{\pm}7.7$ joule, P<0.001), and 6 minute walking distance ($392{\pm}35$ meter vs. $459{\pm}33$ meter, P<0.001) were significantly increased after rehabilitation. Maximum inspiratory pressure was also increased after rehabilitation ($68.5{\pm}5.4$ $CmH_2O$ VS. $80.4{\pm}6.4$ $CmH_2O$, P<0.001). Conclusion: The pulmonary rehabilitation for 6 weeks can improve exercise performance in patients with chronic lung disease.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.389-396
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• 2005

Background : Central venous catheters(CVCs) area major source of nosocomial infection. Chlorhexidine-silver sulfadiazine coated catheters (CHSS) were developed to reduce the rate of CVC infection. However, the clinical effectiveness of CHSS in comparison wth non-coated catheter (NCC) remains to be evaluated. Methods : From January 2004 to December 2004 in medical intensive care unit (ICU) of Asan Medical Center, CVCs were inserted in 446 cases. We retrospectively analyzed characteristics of patients and catheterization,the catheter-related infection rate and colonization, microbiologic findings, and insertion sites (subclavian, jugular, femoral) according to the type of inserted CVCs (NCC: 187 cases, CHSS: 259 cases). Catheter related infection is defined as catheter related bacteremia and catheter related non-bacteremic sepsis. Results : 1) The mean age of the patients in each group was $62{\pm}16$ years, $63{\pm}15$ years (p=0.42), and sex ratio 94:50, 141:69 (p=0.9) in NCC and CHSS. Duration of ICU admission ($29{\pm}37$, $26{\pm}44$ p=0.42), duration of mechanical ventilation ($17{\pm}22$, $15{\pm}19$ p=0.17), and APACHE III score at the time of CVC insertion ($81{\pm}34$, $82{\pm}37$ p=0.61) were not different between both groups. 2) Mean duration of catheterization was 118 in NCC and 119 in CHSS (p=0.98). Number of catheter-days was 2176 days in NCC and 3035 days in CHSS. Catheter-related infection occurred in 9 (4.8%) cases receiving NCC and 4 cases (1.5%) receiving CHSS. Catheterrelated infection incidence per 1000 catheter-days was 4.1 and 1.3, respectively (p=0.04). CHSS was associated with a significant reduction of infection in jugular catheters regarding to insertion sites (p=0.01). 3) Microorganisms causing infection were Staphylococcus aureus (n=3), Candida (n=3), coagulase-negative Staphylococci (n=2), and Klebsiella (n=1) in NCC, and Candida species (n=2), coagulase-negative Staphylococci (n=2), Proteus (n=1) in CHSS. Conclusion : CHSS has significantly reduced the episodes of infection compared to NCC in jugular catheterization in medical ICU.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.522-529
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• 2005

Background : Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. Method : retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. Results : One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: ${\beta}$-lactam plus macrolide; ${\beta}$-lactam plus fluoroquinolone; anti-Pseudomonal ${\beta}$-lactam plus fluoroquinolone; Aminoglycoside combination regimen; ${\beta}$-lactam plus clindamycin; and ${\beta}$-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. Conclusion : S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.22-31
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• 2005

Purpose : To conduct a nationwide survey on the principals in radiotherapy for rectal cancer, and produce a database of Korean Patterns of Care Study. Materials and Methods : We developed web-based Patterns of Care Study system and a national survey was conducted using random sampling based on power allocation methods. Eligible patients were who had postoperative radiotherapy for rectal cancer without gross residual tumor after surgical resection and without previous history of other cancer and radiotherapy to pelvis. Data of patients were Inputted to the web based PCS system by each investigators in 19 institutions. Results : Informations on 309 patients with rectal cancer who received radiotherapy between 1998 and 1999 were collected. Male to female ratio was 59 : 41, and the most common location of tumor was lower rectum ($46\%$). Preoperative CEA was checked in $79\%$ of cases and its value was higher than 6 ng/ml in $32\%$. Pathologic stage were I in $1.5\%$, II in $32\%$, III in $53\%$, and IV in $1.6\%$. Low anterior resection was the most common type of surgery and complete resection was peformed in $95\%$ of cases. Distal resection margin was less than 2 cm in $30\%$, and number of lymph node dissected was less than 12 in $31\%$. Chemotherapy was peformed in $91\%$ and most common regimen was 5-FU and leucovorine ($59\%$). The most common type of field arrangement used for the initial pelvic field was the four field box (Posterior-Right-Left) technique ($65.0\%$), and there was no AP-PA parallel opposing field used. Patient position was prone in $81.2\%$, and the boost field was used in $61.8\%$. To displace bowel outward, pressure modulating devices or bladder filling was used in $40.1\%$. Radiation dose was prescribed to isocenter in $45.3\%$ and to isodose line in 123 cases ($39.8\%$). Percent delivered dose over $90\%$ was achieved in $92.9\%$. Conclusion : We could find the Patterns of Care for the radiotherapy in Korean rectal cancer patients was similar to that of US national survey. The type of surgery and the regimen of chemotherapy were variable according to institutions and the variations of radiation dose and field arrangement were within acceptable range.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.601-613
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• 2000

Background : Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrous disease of the lung of unknown etiology. Recently it has been classified into several distinct entities on the basis of pathologic and clinical characteristics, ie : usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), bronchiolitis obliterans with organizing pneumonia (BOOP), and nonspecific interstitial pneumonia (NSIP). IPF is now applied only for UIP, which has the worst prognosis. The previous reports of 3-5 year median survival appears to be overoptimistic because other types with better prognosis like NSIP or BOOP might have been included. Therefore, this study was performed to determine the clinical course and the prognostic factors of UIP as diagnosed by surgical lung biopsy. Methods : The subjects were 72 UIP patients (age $58.2{\pm}11.6$ years, M : F=45 : 27, median follow up period : 18.1 months (0.7-103.6) diagnosed by surgical lung biopsy at the Asan Medical Center (68 patients) and the Paik Hospital in Seoul (4 patients). Clinical scores (level of dyspnea : 1-20 points), radiologic score (honeycombing : HC score 0-5 points, ground glass : GG score 0-5 points), and physiologic scores (FVC : 1-12 points, $FEV_1$ : 0-3 points, TLC : 0-10 points, $D_{LCO)$ : 0-5 points, $AaDO_2$ : 0-10 points) were summed into a total CRP score. Results : 1) The one year survival rate was 78.3%, while the rate for three year survival was 58.1%, and the median survival period was 42.5months. 2) Short term (1 year) prognosis : The patients who died within one year of diagnosis (14 patients) had the higher initial total CRP score ($28.6{\pm}8.3$ vs. $16.6{\pm}9.7$) than those who lived longer than one year (46 patients). The difference in the total CRP score was attributed to the symptom score ($8.4{\pm}2.1$ vs. $5.7{\pm}3.9$) and the physiologic score ($15.7{\pm}7.1$ vs. $6.7{\pm}5.7$) including FVC, $D_{LCO)$ and $AaDO_2$. 3) Long-term (3year) prognosis : The total CRP score ($12.2{\pm}6.7$ vs. $28.7{\pm}7.9$ : including symptom score, FVC, $D_{LCO)$ and $AaDO_2$) at the time of diagnosis were also different for the long-term survivors and those who lived less than 3 years. 4) Cox regression analysis showed $D_{LCO)$ (${\geq}$60%) (Hazard ratio : 4.56, 95% CI : 2.30-16.04) was the independent prognostic factors of UIP (P<0.05). Conclusion : These results suggest that $D_{LCO)$ at the time of diagnosis seem to be a prognostic markers of biopsy-proven UIP.

• Tuberculosis and Respiratory Diseases
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• v.49 no.5
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• pp.624-632
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• 2000

Background : Home ventilation can decrease hospital-acquired infection, increase physical activity, improve nutritional status, enhance quality of life, and reduce medical costs. The number of patient using home ventilators has been increasing, particularly in Europe and United States. Although the number of patients with home ventilation has been increasing in Korea, the current status of these patients is not well known. This study was undertaken to obtain basic information upon these patients in addition to evaluating any problems related to patients' home care in our country. Methods : A register of 92 patients with home ventilators in Seoul and Kyunggi Province were obtained from commercial ventilator supply companies. The patients were contacted by phone and 29 of them accepted our visit. Information concerning education about home care before discharge, equipment cost, and problems related to home care were documented. The mode and preset variables of the home ventilator were checked; tidal volume (TV), peak airway pressure, and oxygen saturation were measured. Results : There were 26 males (90%) and their mean age was 48.0 (${\pm}20.1$) years. The underlying diseases were : 21 neuromuscular disorders, 2 spinal cord injuries, 6 chronic lung diseases. Among the caregivers, spouses (n=14) predominated. Education for home care before discharge was performed primarily by intensive care unit nurses and the education for ventilator management by commercial companies. Twenty-five of the 29 patients had tracheostomies. Volume targeted type (VTT ; n=20, 69%) was more frequently used than the pressure targeted type (PTT). Twenty-three of the 29 patients purchased a ventilator privately, which cost 7,450,000 (${\pm}$3,290,000) won for a PTT, and 14,280.000 (${\pm}$3,130,000) won for a VTT. Total cost for the equipment was 11,430,000 (${\pm}$634,000) won. The average cost required for home care per month was 1,120,000 (${\pm}$1,360, 000) won. Conclusion : The commonest underlying disease of the patients was neuromuscular disease. The VTT ventilator was primarily used with tracheostomy. Patients and their families considered the financial difficulties associated with purchasing and maintaining equipment for home care an urgent problem. Some patients were aided by a visiting nurse, however most patients were neglected and left without professional medical supervision.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.321-330
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• 1999

Background : Early diagnosis and proper antibiotic treatment are very important in the management of ventilator-associated pneumonia (VAP) because of its high mortality. Bronchoscopy with a protected specimen brush (PSB) has been considered the standard method to isolate the causative organisms of VAP. However, this method burdens consumer economically to purchase a PSB. Another useful method for the diagnosis of VAP is quantitative cultures of aspirated specimens through bronchoscopic bronchoalveolar lavage (BAL), for which the infusion of more than 120 m1 of saline has been recommended for adequate sampling of a pulmonary segment. However, occasionally it leads to deterioration of the patient's condition. We studied the diagnostic efficacy of minibronchoalveolar lavage (miniBAL), which retrieves only 25 ml of BAL fluid, in the isolation of causative organisms of VAP. Methods: We included 38 consecutive patients (41 cases) suspected of having VAP on the basis of clinical evidence, who had received antibiotics before the bronchoscopy. The two diagnostic techniques of PSB and miniBAL, which were performed one after another at the same pulmonary segment, 'were compared prospectively. The cut-off values for quantitative cultures to define causative bacteria of VAP were more than $10^3$ colony-forming units (cfu)/ml for PSB and more than $10^4$ cfu/ml for BAL. Results: The amount of instilled normal saline required to retrieve 25 ml of BAL fluid was $93{\pm}32 ml$ (mean${\pm}$SD). The detection rate of causative agents was 46.3% (19/41) with PSB and 43.9% (18/41) with miniBAL. The concordance rate of PSB and miniBAL in the bacterial culture was 85.4% (35/41). Although arterial blood oxygen saturation dropped significantly (p<0.05) during ($92{\pm}10%$) and 10 min after ($95{\pm}3%$) miniBAL compared with the baseline ($97{\pm}3%$), all except 3 cases were within normal ranges. The significantly elevated heart rate during ($l25{\pm}24$/min, p<0.05) miniBAL compared with the baseline ($1l1{\pm}22$/min) recovered again in 10 min after ($111{\pm}26$/min) miniBAL. Transient hypotension was developed during the procedure in two cases. The procedure was stopped in one case due to atrial flutter. Conclusion: MiniBAL is a safe and effective technique to detect the causative organisms of VAP.