• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1178-1187
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• 1998

Background : Recently the incidence of tuberculosis is increasing in many countries and control of the disease is further threatened by the emergence of multi-drug resistant tuberculosis. So rapid detection of drug resistance is very important. Pyrazinamide (PZA) is a first-line chemotherapeutic agent for tuberculosis. Now in Korea, we perform PZase activity test instead of actual pyrazinamide susceptibility test for the detection of PZA resistant M. tuberculosis. Recently the pncA gene, encoding the PZase of M. tuberculosis, was completely sequenced. And it was reported that the mutation of pncA gene would be associated with PZA resistance of M. tuberculosis. Therefore we performed this study to evaluate the possibility for the rapid detection of PZA resistant M. tuberculosis using PCR-SSCP of pncA gene. Method : 44 cultured clinical isolates of M. tuberculosis, BCG Tokyo strain. BCG French strain, and one M. bovis isolate were studied. We used H37Rv as the reference strain, The PZase activity test was done at the reference laboratory of Korean Tuberculosis Institute. DNA was extracted by bead-beater method and 561 bp fragment including pncA gene was amplified by PCR. The PCR product were digested by BstB I enzyme. SSCP was done using MDE gel. Of the 44 strains of M. tuberculosis, 22 strains were PZase-positive and other 22 strains were PZase negative. Results : Of the 22 PZase positive strains, 18 strains(82%) showed the same mobility compared with that of H37Rv and 4(18%) showed different mobility. Of the 22 PZase-negative strains, 19(86%) strains showed the same mobility pattern compared with that of H37Rv and 3(14%) showed different mobility. Naturally PZA-resistant BeG-French strain, BCG-Tokyo strain, and one M. bovis isolate showed the same band pattern each other, but their mobility were different from that of H37Rv. The results of PZase activity test and PCR-SSCP of pncA of M. tuberculosis were statistically significantly correlated each other (p<0.01). Conclusion : The PCR-SSCP after BstB I restriction of pncA gene of M. tuberculosis may be a useful method for the rapid detection of PZA-resistant M. tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.329-337
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• 1997

Background : Since endotracheal tube is the most important factor involved in the imposed work of breathing during mechanical ventilation, extubation of endotracheal tube is supposed to reduce respiratory work of patient. However, some patients show labored breathing after extubation despite acceptable blood gases. We investigated the changes of work of breathing before and after extubation and the factors involved in the change of WOB after extubation. Methods : The subjects were 34 patients(M : F = 20 : 14, mean age = $61{\pm}17yre$) who recovered from respiratory failure after ventilatory support and were considered to be ready for extubation. The patients with clinical or radiologic evidences of upper airway obstruction before endotracheal intubation for mechanical ventilation were excluded. Vital sign, physical examination, chest X-ray, work of breathing and other respiratory mechanic indices were measured prior to, immediately, 6, 24 and 48 hours after extubation serially. Definition of weaning failure after extubation was resumption of ventilatory support or reintubation of endotracheal tube within 48 hour after extubation because of respiratory failure. The patients were classified into group 1(decreased work of breathing), group 2(unchanged work of breathing) and group 3(increased work of breathing) depending on the statistical difference in the change of work of breathing before and after extubation. Results : Work of breathing decreased in 33%(11/34, group 1), unchanged in 41%(14/34, group 2) and increased in 26%(9/34, group 3) of patients after extubation compared with before extubation. Weaning failure occurred 9%(1/11) of group, 1, 28.6%(4/14) of group 2 and 44%(4/9) of group 3 after extubation(p = 0.07). The change of work of breathing after extubation was positively correlated with change of mean airway resistance(mRaw). (r = 0.794, p > 0.01). In three cases of group 3 whose respiratory indices could be measured until 48 hr after extubation, the change in work of breathing paralleled with the sequential change of mRaw. The work of breathing was peaked at 6 hr after extubation, which showed a tendency to decrease thereafter. Conclusions : Reversible increase of work of breathing after extubation may occur in the patients who underwent extubation, and the increase in mRaw could be responsible for the increase in work of breathing. In addition, the risk of weaning failure after extubation may increase in the patients who have increased WOB immediately after extubation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.116-127
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• 1998

Background: The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. So the assessment of disease activity is important but no single parameter was generally accepted as a good marker. Recently several studies suggested that adhesion molecules, especially ICAM-1 can be a marker, but there are some controversies. And only few data are available about the relationship of ICAM-1 with clinical follow-up course. Methods: We measured the expression of adhesion molecules on BAL cells by flow cytometry and the level of soluble ICAM-1(sICAM-1) in serum and BALF at the time of diagnosis in 12 patients with active disease and 7 inactive sarcoidosis(5 male, 14 female, mean age: $39.4{\pm}10.7$ years, mean follow-up : $20{\pm}15$ months). Follow-up clinical course were compared with the changes in serum sICAMA-1 level and the adhesion molecule on BAL cells. Results: In the patients with active disease, the ICAM-1 on AM(RMFI: $3.68{\pm}1.71$) and sICAM-1 level in serum($582{\pm}193$ng/ml) and BAL fluid($47.8{\pm}16.5$ng/ml) were all higher than those of 7 inactive disease(RMFI: $1.89{\pm}0.75$, p=0.0298, serum: $294{\pm}117$ ng/ml, p=0.0049, BALF: $20.9{\pm}8.3$ ng/ml). In the active sarcoidosis, ICAM-1 on AM(RMFI : $1.51{\pm}0.84$) and serum sICAM-1 were decreased after the therapy($250{\pm}147$ ng/ml) but no significant change was noted in inactive disease. Also we found the initial ICAM-1 on AM and serum sICAM-1 had a significant correlation with the degree of improvement in PFT after the therapy. During the follow-up, the disease relapsed in 4 patients after the discontinuation of steroid and the serum sICAM-1 level went-up again at the time of relapse. Conclusion: Our data suggest that the serum sICAM-1 level and the ICAM-1 expression on AM can be a good marker of disease activity and also a predictor of outcome in sarcoidosis.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.540-548
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• 2001

Backgrounds : Because ventilator-induced lung injury is partly dependent on the intensity of vascular flow, we hypothesized that hypothermia may attenuate the degree of such an injury through a reduced cardiac output. Methods : Twenty-seven male Sprague-Dawley rats were randomly assigned to normothermia ($37{\pm}1^{\circ}C$)-injurious ventilation (NT-V) group (n=10), hypothermia ($27{\pm}1^{\circ}C$)-injurious ventilation (HT-V) group (n=10), or nonventilated control group (n=7). The two thermal groups were subjected to injurious mechanical ventilation for 20 min with peak airway pressure 30 cm $H_2O$ at zero positive end-expiratory pressure, which was translated to tidal volume $54{\pm}6\;ml$ in the NT-V group and $53{\pm}4\;ml$ in the HT-V group (p>0.05). Results : Pressure-volume (P-V) curve after the injurious ventilation was almost identical to the baseline P-V curve in the HT-V group, whereas it was shifted rightward in the NT-V group. On gross inspection, the lungs of the HT-V group appeared smaller in size, and showed less hemorrhage especially at the dependent regions, than the lungs of the NT-V group. [Wet lung weight (g)/body weight (kg)] ($1.6{\pm}0.1$ vs $2.4{\pm}1.2$ ; p=0.014) and [wet lung weight/dry lung weight] ($5.0{\pm}0.1$ vs $6.1{\pm}0.8$ ; p=0.046) of the HT-V group were both lower than those of the NT-V group, while not different from those of the control group($1.4{\pm}0.4$, $4.8{\pm}0.4$, respectively). Protein concentration of the BAL fluid of the HT-V group was lower than that of the NT-V group($1,374{\pm}726\;ug/ml$ vs $3,471{\pm}1,985\;ug/ml$;p=0.003). Lactic dehydrogenase level of the BAL fluid of the HT-V group was lower than that of the NT-V group ($0.18{\pm}0.10\;unit/ml$ vs $0.43{\pm}0.22\;unit/ml$;p=0.046). Conclusions : Hypothermia attenuated pulmonary hemorrhage, permeability pulmonary edema, and alveolar cellular injuries associated with injurious mechanical ventilation, and preserved normal P-V characteristics of the lung in rats.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.853-869
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• 2000

Background : Following several decades of decline, the incidence of tuberculosis has recent1y begun to increase in many countries of this the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutations of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB. Methods : Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients who visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the results were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB. Results : Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526. Conclusion : The frequency and pattern of mutations of the rpoB gene of Korean MDR-TB isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.169-178
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• 2000

Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.207-216
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• 2000

Background : The occurrence of lung complications after allogenic bone marrow transplantation(BMT) has been reported as 40-60 percent. The risk factors for lung complications are whole body irradiation, high dose chemotherapy, graft versus host disease, old age and CMV infection. The prevalence of graft versus host disease is less in Korea than in Western countries, but frequency of CMV infection is higher. Therefore, the pattern of lung complications may be different in Korea from those in Western countries. Methods : A retrospective cohort study was performed on one hundred consecutive adult patients who underwent allogenic bone marrow transplantation from December, 1993 to May, 1999 at Asan Medical Center. Lung complications were divided into two groups by the time of development, within 30days (pre-engraftment) and beyond 30 days (post-engraftment), and then subdivided into infectious and non-infectious complication. Infectious complications were defined as having the organism in blood, BAL fluid, pleural fluid or sputum, or compatible clinical findings in patients, which improved with antibiotics or an anti-fungal therapy. Result: 1) Eighty three episodes of lung complications had occurred in 54 patients. 2) Within thirty days after BMT, non-infectious complications were more common than infections, but this pattern was reversed after 30 days. After one year post-BMT, there was no infectious complication except in cases of recurrence of underlying disease or development of chronic GVHD. 3) Among the non-infectious complications, pleural effusion (27 episodes) was most common, followed by pulmonary edema (8 episodes), bronchiolitis obliterans(2 episodes), diffuse alveolar hemorrhage (1 episode) and bronchiloitis obliterans with organizing pneumonia (1 episode). 4) The infectious complications were pneumonia (bacterial: 9 episodes, viral: 4 episodes, fungal : 5 episodes, pneumocystis carinii : 1 episode), pulmonary tuberculosis(3 episodes) and tuberculous pleurisy (3 episodes). 5) Lung complications were more frequent in CMV positive patients and in patients with delayed recovery of neutrophil count. 6) The mortality was higher in the patients with lung complications. Conclusion : Lung complications developed in 54% after allogenic BMT and were associated with higher mortality.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.169-175
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• 1998

Background: Heliox is known to decrease $PaCO_2$ in patients with increased airway resistance by increasing minute ventilation and reducing work of breathing(WOB). Besides these effect, heliox is expected to decrease functional anatomic dead space owing to improvement of peak expiratory flow rate(PEFR) and enhancement of gas distribution. We investigated whether heliox can decrease $PaCO_2$ even at the same minute ventilation (VE) and WOB with $N_2-O_2$ to speculate the effect of the heliox on the anatomic dead space. Material and Method: The subjects were 8 mechanically ventilated patients with asthma or upper airway obstruction(M : F=5 : 3, $68{\pm}10$years) who were under neuromuscular paralysis. The study was consisted of three 15-minutes phases: basal $N_2-O_2$ heliox and washout Heliox was administered via the low pressure inlet of servo 900C, and respiratory parameters were measured by pulmonary monitor(CP-100 pulmonary monitor, Bicore, Irvine, CA, USA). To obtain the same tidal volume(Vt) in heliox phase, the Vt on monitor was adjusted by the factor of relative flow rate of heliox to $N_2-O_2$. Dead space was calculated by Bohr equation. Results: 1) Vt, VE, peak inspiratory pressure(PIP) and peak inspiratory flow rate(PIFR) were not different between $N_2-O_2$ and heliox. 2) PEFR was higher on heliox($0.52{\pm}0.19$L/sec) than $N_2-O_2$($0.44{\pm}0.13$L/sec)(p=0.024). 3) $PaCO_2$(mmHg) were decreased with heliox($56.1{\pm}14.1$) compared to $N_2-O_2$($60.5{\pm}15.9$)(p=0.027). 4) Dead space ventilation(%) were decreased with heliox($73{\pm}9$ with $N_2-O_2$ and $71{\pm}10$ with heliox)(p=0.026). Conclusion: Heliox decreased $PaCO_2$ even at the same VE and WOB with $N_2-O_2$, and the effect was considered to be related with the reduction of anatomic dead space.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.98-104
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• 2007

Background: Although there is an increasing incidence of Mycobacterium abscessus pulmonary disease in Korea, the optimal therapeutic regimen has not yet been established and there are no reports of the long-term treatment outcomes. This study examined the long-term treatment outcomes of M. abscessus pulmonary disease. Methods: Twenty-nine patients diagnosed with M. abscessus pulmonary according to the American Thoracic Society criteria and treated from January 1996 to December 2003 were enrolled in ghis study. The clinical characteristics, radiological findings, treatment outcome, and follow up data were analyzed retrospectively. Results: The mean age of the 29 patients was 56.1 (${\pm}13.6$) years and there was a female (22/29) dominance. The chest radiography revealed the nodular bronchiectatic type to be dominant (69%, 20/29). Twenty-seven (93.1%) were prescribed clarithromycin-containing regimens, and injectable drugs, mainly aminoglycosides, were included in the regimen of nineteen patients. The most predominant regimen (48.3%) consisted of clarithromycin and amikacin. The treatment success, failure, and default were achieved in 19(65.5%), 9(31.0%), and 1(3.4%), respectively. The median duration to culture conversion was 42 days (range 15-362) and the median duration of treatment in the success group was 543 days (range 176-1,160). An adjunctive surgical resection was performed in five patients, which resulted in treatment success in two patients. After the completion of treatment, nineteen patients were followed up for a median duration of 931 days (range 230-2,294). Only one (5.3%) patient relapsed 45 days after completing treatment. Conclusion: Treatment with clarithromycin-containing regimens resulted in a successful treatment in approximately two thirds of patients with M. abscessus pulmonary disease. The long-term relapse rate was also quite low.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.113-118
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• 2007

Background: Paraquat is known to induce oxidant injury that results in multiorgan failure and lung fibrosis. Iron has been considered to play a key role in paraquat-induced oxidant lung injury. This study examined the effect of deferoxamine, an iron-chelating agent, in the treatment of paraquat poisoning. Methods: From September, 2001 to April, 2005, 28 patients with paraquat poisoning who were admitted at a medical intensive care unit of a University-affiliated hospital, were enrolled in this study. Sixteen patients were treated according to the paraquat poisoning treatment guidelines and 12 received an intravenous infusion of deferoxamine in addition to the treatment guidelines. Results: There were no differences between the two groups in terms of age, gender, severity of paraquat poisoning, and the time elapsed from ingestion to presentation at hospital. There was no difference in overall mortality between the two groups but the incidence of respiratory failure in the deferoxamine group was higher than in the conventional group(4/7 versus 0/9, p=0.019). Conclusion: Deferoxamine seems to have no clinical benefit compared with the conventional treatment.