• Pediatric Infection and Vaccine
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• v.12 no.2
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• pp.166-177
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• 2005

Purpose : The purpose of this study was to examine the molecular epidemiology and genetic variability of adenovirus(Ad) serotypes Ad1, Ad2, and Ad5 over 14 years in Korea. Methods : A total of 382 adenoviral strains isolated from the nasopharyngeal aspirates of children with lower respiratory tract infections in Seoul, Korea from November 1990 to February 2003 were serotyped by neutralization assay with type-specific antisera. Viral DNAs were extracted from infected cell lysates by the modified Hirt procedure. Genome type(GT) was determined by DNA restriction analysis with 12 restriction enzymess(BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). To evaluate the genetic relatedness, pairwise comigrating restriction fragments(PCRF) analysis was performed. Results : Of 382 strains, 33 strains(9%) were Ad1, 45 strains(12%) were Ad2, and 24 strains(6%) were Ad5. Eighteen GTs(Ad1p1-Ad1p7, Ad1a, Ad1b, Ad1b1-Ad1b3, Ad1c, Ad1d, Ad1e, Ad1e1, Ad1e2, Ad1f) among Ad1, 24(Ad2p1-Ad2p11, Ad2a, Ad2a1-Ad2a6, Ad2b, Ad2c, Ad2d, Ad2e, Ad2e1-Ad2e3) among Ad2, and 10(Ad5p1, Ad5p2, Ad5a, Ad5a1-Ad5a7) among Ad5 strains were identified. One or two strains of the vast majority of GTs were isolated during the study period while a few GTs were identified sporadically with more than 2 strains. It is notable that some GTs such as Ad1p5 and Ad5a1 appeared in cluster during a short period. In analysis of genetic relatedness, the degree of PCRFs(pairwise comigrating restriction fragments) for Ad1 varied from 79 to 99%, for Ad2, 82 to 99%, and for Ad5, 85 to 99%. Conclusion : This study established the comprehensive nomenclature systems of Ad1, Ad2, and Ad5. Diverse GTs identified in this study have crucial implications in the genomic diversity and epidemiological characteristics of Ad1, Ad2, and Ad5.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.729-741
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• 1997

Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.500-518
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• 1996

Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patient. Many clinical characteristics(i.e. age, smoking history, prior history of malignancy) and radiological characteristics( i.e. size, calcification, growth rate, several findings of computed tomography) have been proposed to help to determine whether the SPN was benign or malignant. However, most of these diagnostic guidelines are based on the data collected before computed tomography(CT) has been introduced and lung cancer was not as common as these days. Moreover, it is not well established whether these guidelines from western populations could be applicable to Korean patients. Methods : We had a retrospective analysis of the case records and radiographic findings in 114 patients presenting with SPN from Jan. 1994 to Feb. 1995 in Seoul National University Hospital, a tertiary referral hospital. Results : We observed the following results ; (1) Out of 113 SPNs, the etiology was documented in 94 SP IS. There were 34 benign SP s and 60 malignant SPNs. Among which, 49 SPNs were primary lung cancers and the most common hi stologic type was adenocarcinoma. (2) The average age of patients with benign and malignant SPNs was $49.7{\pm}12.0$ and $58.1{\pm}10.0$ years, respectively( p=0.0004), and the malignant SPNs had a striking linear propensity to increase with age. (3) No significant difference in the hi story of smoking was noted between the patients with benign SPNs($13.0{\pm}17.6$ pack- year) and those with malignant SPNs($18.6{\pm}25.1$ pack-year) (p=0.2108). (4) 9 out of 10 patients with prior history of malignancy had malignant SPNs. 5 were new primary lung cancers with no relation to prior malignancy. (5) The average size of benign SPNs($3.01{\pm}1.20cm$) and malignant SPNs($2.98{\pm}0.97cm$) was not significantly different(p=0.8937). (6) The volume doubling time could be calculated in 22 SPNs. 9 SPNs had the volume doubling time longer than 400 days. Out of these, 6 were malignant SPNs. (7) The CT findings suggesting malignancy included the lobulated or spiculated border, air- bronchogram, pleural tail, and lymphadenopathy. In contrast, calcification, central low attenuation, cavity with even thickness, well-marginated border, and peri nodular micronodules were more suggestive for benign nodule. (8) The diagnostic yield of percutaneous needle aspiration and biopsy was 57.6%(19/33) of benign SPNs and 81.0%(47/58) of malignant SPNs. The diagnostic value of sputum analysis and bronchoscopic evaluations were relatively very low. (9) 42.3%(11/26) of SPNs of undetermined etiology preoperatively turned out to be malignant after surgical resection. Overall, 75.4%(46/61) of surgically resected SPNs were malignant. Conclusions : We conclude that the likelihood of malignant SPN correlates the age of patient, prior history of malignancy, some CT findings including lobulated or spiculated border, air-bronchogram, pleural tail and lymphadenopathy. However, the history of smoking, the size of the nodule, and the volume doubling time are not helpful to determent whether the SPN is benign or malignant, which have been regarded as valuable clinical parameters previously. We suggest that aggressive diagnostic approach including surgical resection is necessary in patient with SPNs.

• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.219-229
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• 2003

Background : The management of thoracic empyema and complicated parapneumonic effusion requires adequate antibiotics use and prompt drainage of infected pleural space. Tube thoracostomy for loculated empyema has low success rate and is also an invasive procedure with potential morbidity. Complications include hemothorax, perforation of intra-abdominal or intra-thoracic organs, diaphragmatic laceration, empyema, pulmonary edema, and Horner's syndrome. Given the potential morbidity of traditional chest tube insertion, use of the image-guided pigtail catheter drainage(PCD) of empyema has been employed. We retrospectively analyzed the medical records of patients with empyema or complicated parapneumonic effusion to determine the efficacy of percutaneous pigtail catheter drainage. Materials and Methods : 45 patients with complicated parapneumonic effusions or empyema were treated at Gil medical center from January 1998 to June, 1999. All were initially given PCD procedure and the following data were collected: clinical symptoms at the time of diagnosis, alcohol and smoking history, the characteristics of pleural effusion, radiologic findings (at the time of catheter insertion, removal and 1 month after catheter removal), the amount of effusion drained for initial 24 hours, the time from catheter insertion to removal and the use of surgical approach. Results : Male gender was more frequent (42 men vs. 3 women), the mean age of the study population was 52(range: 21~74) years. Empyema was found in 23 patients, complicated parapneumonic effusion in 22 patients. Four patients(three, parapneumonic effusion and one, with empyema) with PCD only treated, were cast off. Among the available patients, 36(80%) patients were treated with PCD only or PCD with urokinase. Among the 23 patients with empyema, surgical approach was required in five patients(27.1%, one required decortication, four open thoracostomy), one patient, treated with surgical procedure, died of sepsis. There was no significant difference of the duration of catheter insertion, the duration of hospital admission after catheter insertion and the mean amount of effusion drained for initial 24 hours between the patients with only PCD treated and the patients treated with PCD and urokinase. The duration of catheter insertion($9.4{\pm}5.25days$ vs. $19.2{\pm}9.42days$, p<0.05) and the duration of hospital admission after catheter insertion($15.9{\pm}10.45days$ vs. $38.6{\pm}11.46days$, p<0.01) of the patients with only PCD treated were more longer than those of the patients treated with surgical procedure after PCD. They were same between the patients treated with urokinase after PCD and the patients treated with surgical procedure after PCD($11.1{\pm}7.35days$ vs. $19.2{\pm}9.42days$, p<0.05, $17.5{\pm}9.17days$ vs. $38.6{\pm}11.46days$, p<0.01). In 16 patients(44.4%) with only PCD treated or PCD and urokinase treated, the amount of effusion at the time of catheter removal was decreased more than 75% and in 17 patients(47.2%) effusion decreased 50~75%. .In one patient effusion decreased 25~50%, in two patients effusion decreased less than 25%. One month after catheter removal, in 35 patients(97.2%, four patients were cast off), the amount of pleural effusion was successfully decreased more than 50%. There were no complications related to pigtail catheter insertion. Conclusion : In this study, PCD seemed to be an early efficacious procedure in treating the patients with complicated parapneumonic effusion or empyema without any serious procedure related complication.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.674-684
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• 1999

Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.303-314
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• 2001

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.69-87
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• 2003

Background : LB20304(gemifloxacin) is a new fluoroquinolone antibacterial agent with excellent activity against both Gram-negative and Gram-positive organisms. In vitro studies using clinical isolates have shown gemifloxacin to be highly active against penicillin-resistant strains of S. pneumoniae and in contrast to other reference quinolones, gemifloxacin retained good activity against clinical isolates of S. pneumoniae that were resistant to other members of the quinolone class. Therefore, gemifloxacin is thought to be effective in treating acute bacterial exacerbation of chronic bronchitis(AECB). The objective of this study was to evaluate the efficacy and safety of oral gemifloxacin at doses of 160mg or 320mg once daily for 7 days for the treatment of AECB in Korean adult population. Methods : This was a randomized, multicenter, double-blind, parallel group Phase II study to assess the clinical and antibacterial efficacy and safety of oral gemifloxacin for the treatment of AECB. Treatment Group A (67 patients) took oral gemifloxacin 160mg once daily for seven days and treatment Group B (70 patients) took oral gemifloxacin 320mg once daily for seven days. Results : The demographic profiles of the two treatment groups were similar. The clinical response at follow-up was 84.2% in the gemifloxacin 160-mg group, and 88.7% in the gemifloxacin-320 mg group, showing no statistically significant difference between two treatment groups(p=0.49). The clinical response at the end of therapy was 96.5% in the 160-mg group, and 96.4% in the 320-mg group. The bacteriological response at the end of therapy and follow-up were 81.8% and 78.9%, respectively, in the 160-mg group, and 86.4% and 84.2%, respectively, in the 320-mg group, showing no statistically significant difference between two treatment groups(p=0.68 and 0.68, respectively). S. pneumoniae(12 isolates) and H. influenzae(10 isolates) were the most prevalent pathogens. The MICs were lower for gemifloxacin than other quinolones against these key pathogens, and for S. pneumoniae, the MICs for gemifloxacin were considerably lower(${\leq}0.03$ ug/mL) than those for other quinolones, beta-lactams and macrolides. In the period on-therapy plus 30 days post-therapy, a total of 18 patients(26.9%) in the gemifloxacin 160mg group and 22 patients(31.4%) in the 320mg group reported at least one adverse event(AE). The most frequently reported AE was abdominal pain(3/67 patients, 4.5%) in the gemifloxacin 160mg group and increased level of hepatic enzyme(5/70 patients, 7.1%) in the 320mg group. The overall AE profiles for the two treatment groups were similar. Two out of 67 patients(3.0%) in the gemifloxacin 160mg group and 1/70 patients(1.4%) in the 320mg group reported at least one serious AE, however, none of which was considered by the investigator to be of suspected or probable relationship to study medication. Conclusion : The results of this study showed that gemifloxacin at doses of 160mg or 320mg once daily for 7 days in the treatment of acute exacerbations of chronic bronchitis(AECB) in adult Koreans was a very effective and safe treatment both clinically and bacteriologically.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.498-506
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• 2005

Background : This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules ($18{\mu}g$ once daily) with a ipratropium metered dose inhaler (2 puffs of $20{\mu}g$ q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). Method : After the initial screening assessment and a two-week run-in period, patients received either tiotropium $18{\mu}g$ once daily or ipratropium $40{\mu}g$ four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second ($FEV_1$) and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. Result : In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted $FEV_1$ of 42 (12)% were analyzed. The trough $FEV_1$ response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. Conclusion : This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.

• Tuberculosis and Respiratory Diseases
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• v.41 no.1
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• pp.1-10
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• 1994

Background: Patients with mitral stenosis(MS) have been demonstrated to have a variable degree of pulmonary dysfunction and exercise impairment. The hemodynamic changes of MS can be reversed after percutaneous mitral balloon valvuloplasty(PMV), but the extent and time course of the imporvement in pulmonary function and exercise capacity are not defined. Methods: In order to investigate the early(3 weeks or less)and late(3 months or more) effects of PMV on pulmonary function and determine if the pulmonary dysfunction is reversible even in patients with moderate to severe pulmonary hypertension, we performed the spirometry, measurements of diffusing capacity and lung volumes, and incremental exercise tests in patients with MS before and after PMV. Results: In 46 patients with MS(age: $40{\pm}12$years, male to female ratio: 1:2, mitral valve area: $0.8{\pm}0.2cm^2$) there was a significant increase in FVC(P<0.0025), $FEV_1$(P<0.001), $FEF_{25-75%}$(P<0.001, $FEF_{50%}$(P<0.001), PEF(P<0.0005), MVV(P<0.005), $\dot{V}O_2$max (P<0.0001), and AT(P<0.0001) after average 10 days of PMV. Also there was a significant decrease in DLco(P<0.0001) and DL/VA(P<0.0001). At later($5{\pm}2$months) follow-up in 11 patients, there was no further improvement in any parameters of pulmonary function and exercise test. Twenty nine patients with sinus rhythm were divided into 16 patients with pulmonary arterial pressure(PAP) more than 35mmHg and/or tricuspid regurgitation grade n or more(group A) and 13 patients with PAP less than 35mmHg(group B). Group A Patients had significantly lower FVC(P<0.001), $FEV_1$(P<0.001), DLco(P<0.05), $\dot{V}O_2$ max(P<0.025) and mitral valve area(P<0.025) than group B patients. Group A patients after PMV, showed significant increase in FVC(P<0.001), maximum $O_2$ pulse(P<0.00001) and $\dot{V}O_2$ max(P<0.00025). Both group showed an increase in AT(P<0.0001, P<0.005), but group A showed greater decrease in $\dot{V}E/\dot{V}O_2$ and $\dot{V}E/\dot{V}CO_2$ both at AT(P<0.001, P<0.001) and $\dot{V}O_2$ max(P<0.0001, P<0.0001) after PMV compared with group B. Conclusion: These data suggest that patients with MS can show increased pulmonary function and exercise performance within 1 month after PMV. Patients with moderate to severe pulmonary hypertension had a significant increase in exercise performance compared with those with mild to no pulmonary hypertension and it is thought to be related to a significat decrease of ventilation for a given oxygen consumption at maximum exercise.