• 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.47 no.4
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• pp.442-450
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• 1999

Background : Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. Methods : Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB 800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonrenal clearance(CLnr), and renal clearance(CLr) were calculated. Results : 1) Pharmacokinetic parameters of INH were as follows: Cmax; $7.63{\pm}3.20{\mu}g/ml$, Tmax; $0.73{\pm}0.22hr$, half-life; $2.12{\pm}0.84hrs$, Ke; $0.83{\pm}0.15hrs^{-1}$, CLtot; $17.54{\pm}8.89L/hr$, CLnr; $14.74{\pm}8.35L/hr$, CLr; $2.79{\pm}1.31L/hr$. 2) Pharmacokinetic parameters of RFP were as follows: Cmax; $8.93{\pm}3.98{\mu}g/ml$, Tmax; $1.76{\pm}1.13hrs$, half-life; $2.27{\pm}0.54hrs$, Ke; $0.32{\pm}0.08hrs^{-1}$, CLtot; $14.63{\pm}6.60L/hr$, CLr; $1.04{\pm}0.55L/hr$, CLnr; $13.59{\pm}6.21L/hr$. 3) While the correlation between body weight and Cmax of INH was not statistically significant (r=-0.514, p value>0.05), Cmax of RFP was significantly affected by body weight of the patients(r=-0.662, p value<0.01). Conclusion : In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.149-161
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• 2000

Background : Residual pleural thickening (RPT) develops in about 50% of tuberculous pleurisy ($PL_{TB}$). Some reports have suggested that elevated TNF-$\alpha$ and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-$\beta$ has been known to promote fibrogenesis and is increased in tuberculous pleural fluid (PF). $PL_{TB}$ and malignant pleurisy ($PL_{MAL}$) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-$\alpha$ TGF-$\beta$, and fibrinolytic parameters between $PL_{TB}$ and $PL_{MAL}$, and to find the predictors of RPT in $PL_{TB}$. Methods : Thirty-five $PL_{TB}$ and 14 $PL_{MAL}$ patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All $PL_{TB}$ patients were prescribed a primary, short-course, anti-tuberculosis regimen. INF-$\alpha$ tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, $\alpha$2-antiplasmin, and D-dimer were measured in both PF and PB. TGF-$\beta$was measured only in PF. Clinical characteristics, TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. Results : The levels of TNF-$\alpha$ tPA, PAI-1, plasminogen, $\alpha$2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in $PL_{TB}$, whereas only plasminogen, $\alpha$2-antiplasmin, and D-dimer were higher in PF than in PB in $PL_{MAL}$. Pleural fluid TNF-$\alpha$ TGF-$\beta$, PAI-1, plasminogen, $\alpha$2-antiplasmin were increased in $PL_{TB}$ compared with $PL_{MAL}$, but these factors did not show any further advantages over ADA in differentiation between $PL_{TB}$ and $PL_{MAL}$. TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. Conclusion : Our data suggest that TNF-$\alpha$, TGF-$\beta$ and fibrinolytic parameters may play some role for the development of RPT in $PL_{TB}$, but they failed to predict the occurrence of RPT in $PL_{TB}$. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.813-822
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• 1998

Background: Extubation is recommended to be performed at minimum pressure support (PSmin) during the pressure support ventilation (PSV). In field, physicians sometimes perform additional 1 hr T-piece trial to the patient at PSmin to reduce re-intubation risk. Although it provides confirmation of patient's breathing reserve, weaning could be delayed due to increased airway resistance by endotracheal tube. Methods: To investigate the effect of additional 1 hr T-piece trial on weaning outcome, a prospective study was done in consecutive 44 patients who had received mechanical ventilation more than 3 days. Respiratory mechanics, hemodymic, and gas exchange measurements were done and the level of PSmin was calculated using the equation (PSmin=peak inspiratory flow rate $\times$ total ventilatory system resistance) at the 15cm $H_2O$ of pressure support. At PSmin, the patients were randomized into intervention (additional 1 hr T-piece trial) and control (extubation at PSmin). The measurements were repeated at PSmm, during weaning process (in cases of intervention), and after extubation. The weaning success was defined as spontaneous breathing more than 48hr after extubation. In intervention group, failure to continue weaning process was also considered as weaning failure. Results: Thirty-six patients with 42 times weaning trial were satisfied to the protocol. Mean PSmin level was 7.6 (${\pm}1.9$)cm $H_2O$. There were no differences in total ventilation times (TVT), APACHE III score, nutritional indices, and respiratory mechanics at PSmin between 2 groups. The weaning success rate and re-intubation rate were not different between intervention group (55% and 18% in each) and control group (70% and 20% in each) at first weaning trial. Work of breathing, pressure time product, and tidal volume were aggravated during 1 hr T-piece trial compared to those of PSmin in intervention group ($10.4{\pm}1.25$ and $1.66{\pm}1.08$ J/L in work of breathing) ($191{\pm}232$ and $287{\pm}217$cm $H_2O$ s/m in pressure time product) ($0.33{\pm}0.09$ and $0.29{\pm}0.09$ L in tidal volume) (P<0.05 in each). As in whole, TVT, and tidal volume at PSmin were significantly different between the patients with weaning success ($246{\pm}195$ hr, $0.43{\pm}0.11$ L) and the those with weaning failure ($407{\pm}248$ hr, $0.35{\pm}0.10$L) (P<0.05 in each). Conclusion : There were no advantage to weaning outcome by addition of 1 hr T-piece trial compared to prompt extubation to the patient at PS min.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1199-1213
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• 1998

Background : The number of immunocompromised hosts has been increasing steadily and a new pulmonary infiltrate in these patients is a potentially lethal condition which needs rapid diagnosis and treatment. In this study we sought to examine the clinical manifestations, radiologic findings, and therapeutic outcomes of pulmonary mycoses presenting as a new pulmonary infiltrate in immunocompromised hosts. Method : All cases presenting as a new pulmonary infiltrate in immunocompromised hosts and confirmed to be pulmonary mycoses by pathologic examination or by positive culture from a sterile site between October of 1996 and April of 1998 were included in the study and their chart and radiologic findings were retrospectively reviewed. Results : In all, 14 cases of pulmonary mycoses from 13 patients(male : female ratio = 8 : 5, median age 47 yr) were found. Twelve cases were diagnosed as aspergillosis while two were diagnosed as mucormycosis. Major risk factors for fungal infections were chemotherapy for hematologic malignancy(10 cases) and organ transplant recipients(4 cases). Three cases were receiving empirical amphotericin B at the time of appearance of new lung infiltrates. Cases in the hematologic malignancy group had more prominent symptoms : fever(9/10), cough(6/10), sputum(5/10), dyspnea(4/10), chest pain(5/10). Patients in the organ transplant group had minimal symptoms(p<0.05). On simple chest films, all of the cases presented as single or multiple nodules(6/14) or consolidations(8/14). High resolution computed tomograph showed peri-lesional ground glass opacities(14/14), pleural effusions(5/14), and cavitary changes(7/14). Definitive diagnostic methods were as follows : 10 cases underwent minithoracotomy, 2 underwent video-assisted thoracoscopic surgery, 1 underwent percutaneous needle aspiration and 1 case was diagnosed by culture of abscess fluid. All cases received treatment with amphotericin B with 1 case each being treated with liposomal amphotericin B and itraconazole due to renal toxicity. Lung lesion improved in 12 of 14 patient but 4 patients died before completing therapy. Conclusion : When a new lung infiltrate develops presenting either as a nodule or consolidation in a neutropenic patient with hematologic malignancy or in a transplant recipient, you should always consider pulmonary mycoses as one of the differential diagnosis. By performing aggressive work up and early treatment, we may improve prognosis of these patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.57-67
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• 1998

Purpose : This study was undertaken to determine the preoperative predictors of mortality and morbidity after lung cancer resection. Method: During the period from October 1, 1995 to August 31, 1996, a prospective study was conducted in 92 lung resection candidates diagnosed as lung cancer. For preoperative predictors of nonpulmonary factors, we considered age, sex, weight loss, hematocrit, serum albumin, EKG and concomitant illness, and for those of pulmonary factors, smoking history, presence of pneumonia, dyspnea scale(1 to 4), arterial blood gas analysis with room air breathing, routine pulmonary function test. And predicted postoperative(ppo) pulmonary factors such as PPO-$FEV_1$, ppo-diffusing capacity(DLco), predicted postoperative product(PPP) of ppo-$FEV_1%{\times}ppo$-DLco% and ppo-maximal $O_2$ uptake($VO_2$max) were also considered. Results: There were 78 men and 14 women with a median age of 62 years(range 42 to 82) and a mean $FEV_1$ of $2.37\pm0.06L$. Twenty nine patients had a decreased $FEV_1$ less than 2.0L. Pneumonectomy was performed in 26 patients, bilobectomy in 12, lobectomy in 54. Pulmonary complications developed in 10 patients, cardiac complications in 9, other complications(empyema, air leak, bleeding) in 11, and 16 patients were managed in intensive care unit for more than 48hours. Three patients died within 30 days after operation. The ppo-$VO_2$max was less than 10ml/kg/min in these three patients, but its statistical significance could not be determined due to small number of patients. In multivariate analysis, the predictor related to postoperative death was weight loss(p<0.05), and as for pulmonary complications, weight loss, dyspnea scale, ppo-DLco and extent of resection(p<0.05). Conclusions: Based on this study, preoperative nonpulmonary factors such as weight loss and dyspnea scale are more important than the pulmonary factors in the prediction of postoperative mortality and/or morbodity in lung resection candidates, but exercise pulmonary fuction test may be useful Our study suggests that ppo-$VO_2$max value less than 10ml/kg/min is associated with death after lung cancer resection but further studies are needed to validate this result.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.128-139
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• 1998

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.954-964
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• 1996

Background : The type of the infiltrating cells in al veolitis may be determined by the chemokines in the lesion. MIP-1 ${\alpha}$, a C-C type chemokine, stimulates proliferation and cytokine secretion from macrophages and induces early neutrophilic and later monocytic inflammation in vi vo. IL-8, a C-X-C type chemokine is known to attract neutrophils and T-lymphocytes. This study is performed to find out the relative role of two different chemokines in diffuse interstitial lung disease. Subject and Method : We measured the secretion of MIP- 1 ${\alpha}$ and IL-8 from alveolar macrophages(AM), and their level in BAL fluid of 26 patients with DILD (10 IPF, 4 collagen disease, 10 sarcoidosis, and 2 hypersensitivity pneumonitis) and 7 normal control. Result: IL-8 secretion was significantly increased in patients with DILD ($8.15{\pm}4.58$ ng/ml) than in normal ($1.10{\pm}0.93$ ng/ml, p=0.0003). Significant correlation was found between IL-8 secretion and total cell number in BAL fluid (r=0.484, p=0.0068), %(r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte, and % of AM (r=-0.505, 0.0032). MIP- 1 ${\alpha}$ secretion was also increased in DILD ($2.41{\pm}1.45$ ng/ml) compared to control ($0.63{\pm}0.30$ ng/ml, p=0.0031), and showed a tendency of correlation with total cell number (r=0.368, p=0.0456) and No. of alveolar macrophages (r=0.356, p=0.0579) in BAL fluid. The concentration of IL-8 in BAL fluid was significantly increased in the patients with DILD ($40.4{\pm}34.5$ pg/ml) compared to control ($3.90{\pm}2.47$ pg/ml, p=0.0094) and it showed a significant correlation with the total cell number (r=0.484, p=0.0068), %(r=-0.505, p=0.0032) of AM, and % (r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte in BAL fluid. But there was a no significant difference in MIP- 1 ${\alpha}$ concentration in BAL fluid between normal control group and the patients with DILD. Conclusion : From the above results, we concluded that AM of DILD releases increased amount of both IL-8 and MIP- 1 ${\alpha}$ but IL-8 has better correlation with the type of alveolitis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.882-893
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• 1996

Background : Over one-third of solitary pulmonary nodules are malignant, but most malignant SPNs are in the early stages at diagnosis and can be cured by surgical removal. Therefore, early diagnosis of malignant SPN is essential for the lifesaving of the patient. The incidence of pulmonary tuberculosis in Korea is somewhat higher than those of other countries and a large number of SPNs are found to be tuberculoma. Most primary physicians tend to regard newly detected solitary pulmonary nodule as tuberculoma with only noninvasive imaging such as CT and they prefer clinical observation if the findings suggest benignancy without further invasive procedures. Many kinds of noninvasive procedures for confirmatory diagnosis have been introduced to differentiate malignant SPNs from benign ones, but none of them has been satisfactory. FOG-PET is a unique tool for imaging and quantifying the status of glucose metabolism. On the basis that glucose metabolism is increased in the malignant transfomled cells compared with normal cells, FDG-PET is considered to be the satisfactory noninvasive procedure which can differentiate malignant SPNs from benign SPNs. So we performed FOG-PET in patients with solitary pulmonary nodule and evaluated the diagnostic accuracy in the diagnosis of malignant SPNs. Method : 34 patients with a solitary pulmonary nodule less than 6 cm of irs diameter who visited Samsung Medical Center from Semptember, 1994 to Semptember, 1995 were evaluated prospectively. Simple chest roentgenography, chest computer tomography, FOG-PET scan were performed for all patients. The results of FOG-PET were evaluated comparing with the results of final diagnosis confirmed by sputum study, PCNA, fiberoptic bronchoscopy, or thoracotomy. Results : (I) There was no significant difference in nodule size between malignant (3.1 1.5cm) and benign nodule(2.81.0cm)(p>0.05). (2) Peal SUV(standardized uptake value) of malignant nodules (6.93.7) was significantly higher than peak SUV of benign nodules(2.71.7) and time-activity curves showed continuous increase in malignant nodules. (3) Three false negative cases were found among eighteen malignant nodule by the FDG-PET imaging study and all three cases were nonmucinous bronchioloalveolar carcinoma less than 2 em diameter. (4) FOG-PET imaging resulted in 83% sensitivity, 100% specificity, 100% positive predictive value and 84% negative predictive value. Conclusion: FOG-PET imaging is a new noninvasive diagnostic method of solitary pulmonary nodule thai has a high accuracy of differential diagnosis between malignant and benign nodule. FDG-PET imaging could be used for the differential diagnosis of SPN which is not properly diagnosed with conventional methods before thoracotomy. Considering the high accuracy of FDG-PET imaging, this procedure may play an important role in making the dicision to perform thoracotomy in diffcult cases.