• Tuberculosis and Respiratory Diseases
• /
• v.60 no.6
• /
• pp.645-652
• /
• 2006

Objective: Patients with lung cancer have a relative high risk of developing secondary primary lung cancers. This study examined the additional value of autofluorescence bronchoscopy (AFB) for diagnosing synchronous lung cancers and premalignant lesions. Methods: Patients diagnosed with lung cancer from January 2005 to December 2005 were enrolled in this study. The patients underwent a lung cancer evaluation, which included white light bronchoscopy (WLB), followed by AFB. In addition to the primary lesions, any abnormal or suspicious lesions detected during WLB and AFB were biopsied. Results: Seventy-six patients had non-small cell lung cancer (NSCLC) and 23 had small cell lung cancer (SCLC). In addition to the primary lesions, 84 endobronchial biopsies were performed in 46 patients. Five definite synchronous cancerous lesions were detected in three patients with initial unresectable NSCLC and in one with SCLC. The secondary malignant lesions found in two patients were considered metastatic because of the presence of mediastinal nodes or systemic involvement. One patient with an unresectable NSCLC, two with a resectable NSCLC, and one with SCLC had severe dysplasia. The detection rate for cancerous lesions by the clinician was 6.0% (6/99) including AFB compared with 3.0% (3/99) with WLB alone. The prevalence of definite synchronized cancer was 4.0% (4/99) after using AFB compared with 2.0% (2/99) before, and the staging-up effect was 1.0% (1/99) after AFB. Since the majority of patients were diagnosed with advanced disease, the subjects with newly detected cancerous lesions did not have their treatment plans altered, except for one patient with a stage-up IV NSCLC who did not undergo radiotherapy. Conclusions: Additional AFB is effective in detecting early secondary cancerous lesions and is a more precise tool in the staging workup of patients with primary lung cancer than with WLB alone.

• Journal of Yeungnam Medical Science
• /
• v.12 no.2
• /
• pp.366-385
• /
• 1995

Epidemiological studies are important in both the prevention and treatment of mycobacterial infections. This study was initiated to establish the pulsed-field gel electrophoresis (PFGE) method, which are not yet extensively studied. The most apprpriate restriction endonucleases included DraI, AsnI, and XbaI. The optimal PFGE condition was different according to the enzymes used. Two stage PFGE was performed, in case of DraI first stage was performed with 10 seconds of initial pulse and 15 seconds of final pulse, while the second stage was performed with 60 seconds of initial pulse and 70 seconds of final pulse. The electrophoresis time for DraI-PFGE was 14 hours for each stage. Electrophoresis was performed for 22 hours, in case of XbaI, with 3 seconds of initial pulse and 12 seconds of final pulse. Electrophoresis was performed for 22 hours, in case of AsnI, with 5 seconds of initial pulse and 25 seconds of final pulse. In all cases the voltage of the electrophoresis was maintained constantly at 200 voltage. Standard mycobacterial strains, which included Mycobacterium bovis BCG, M. tuberculosis, and M. fortuitum, could not be differentiated by PFGE analysis. PFGE analysis was performed to differentiate 9 clinically isolated M. fortuitum strains using AsnI. All M. fortuitum strains showed different genotypes except 2 strains. Cluster analysis divided M. fortuitum strains into 2 large groups. PFGE analysis was performed to further differentiate M. fortuitum isolates using XbaI. The undifferentiated 2 M. fortuitum strains showed different PFGE patterns with Xba I. Cluster analysis of the XbaI-PFGE patterns showed more complex grouping than AsnI-PFGE patterns, which showed that XbaI-PFGE analysis was better than AsnI-PFGE in M. fortuitum genotyping. The top dissimilarity values of AsnI-PFGE and XbaI-PFGE were 0.74 and 0.75, respectively. This value was higher than that of arbitrarily primed polymerase chain reaction (AP-PCR) analysis and lower than that of restriction fragment length polymorphism (RFLP) analysis. This suggested that PFGE can be used as a supportive or alternative genotyping method to RFLP analysis.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.479-492
• /
• 1997

Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.2
• /
• pp.241-250
• /
• 1999

Background: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined ; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. Methods: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood and agarose gel electrophoresis. Results: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M : F=24.3% : 75.7%) compared to the non-cough group (M : F=49.7% : 50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D=16.2% : 18.9% : 64.9% in the cough group and 18.9% : 18.2% : 62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7% : 74.3% and 28.0% : 72.0% in the cough and non-cough group respectively and the difference was not significant(p = 0.676). Conclusion: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induced cough. ACE inhibitor-induced dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.5
• /
• pp.763-773
• /
• 1996

Background : Behçet's syndrome is a chronic multisystemic disease affecting many organs such as skin, mucosa, eye, joint, central nervous system and blood vessels. Lung involvement occurs in 5% of Behçet's syndrome and is thought to be due to the pulmonary vasculitis leading to thromboembolism, aneurysm and arteriobronchial fistula. Pulmonary vasculitis in Behçet's syndrome is a unique clinical feature, differing from other vasculitis affecting the lung and is one of the major causes of death. Therefore, we examined the incidence, the clinical features, the radioloic findings and the clinical courses of the lung involvement in Behçet's syndrome. Methods: We retrospectively reviewed the medical records and radiologic studies of 10 cases of the lung involvement in Behçet's syndrome diagnosed at Yongdong Severance Hospital and Severance Hospital from 1986 to 1995. We analysed the clinical features, the radiological findings, the treatment modalities and the clinical courses. Results: 1) The incidence of the lung involvement in Behçet's syndrome was 2%(10/487). The male to female ratio was 8 : 2 and the mean age was 34 years. The presenting symptom was hemoptysis in 5 of 10 cases, and massive hemoptysis was noted in 2 cases. Other pulmonary symptoms were cough(6/10), dyspnea(4/10), and chest pain(2/10). Other manifestations were oral ulcers(10/10), genital ulcers(9/10), skin lesions(7/10), and eye lesions(6/10). 2) The laboratory findings were nonspecific. The posteroanterior views of chest radiographies showed multiple infiltrates(6/10), nodular or mass-like opacities(4/10), or normal findings(2/10). The chest CT scans showed multifocal consolidations(6/8), and aneurysms of the pulmonary aneries(4/8). The pulmonary angiographies were performed in 3 cases, and showed pulmonary artery aneurysms in 2 cases. The ventilation-perfusion scans in 2 cases of normal chest x-ray showed multiple mismatched findings. 3) The patients were treated with combination therapy consisting of corticosteroids, cyclophosphamide, and colchicine or anticoagulant agents. Surgical resection was performed in one case with a huge aneurysm. 4) We have followed up nine of ten cases. Three cases are well-being with medical therapy, two cases are severely disabled now and four cases died due to massive hemoptysis, massive pulmonary embolism, or sepsis. Conclusion : Pulmonary vasculitis is a main feature of the lung involvement of Behçet's syndrome, causing hemorrhage, aneurysmal formation, and/or thromboemboism. The lung involvement of Behçet's syndrome is uncommon but is one of the most serious prognostic factors of the disease. Therefore, an aggressive diagnostic work-up for early detection and proper treatment are recommended to improve the clinical course and the survival.

• Tuberculosis and Respiratory Diseases
• /
• v.54 no.4
• /
• pp.449-458
• /
• 2003

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

• Tuberculosis and Respiratory Diseases
• /
• v.54 no.1
• /
• pp.57-70
• /
• 2003

Background : Small cell lung cancer represents approximately 20% of all carcinomas of the lung, and is recognized as having a poor long term outcome compared to non-small cell lung cancer. Therefore, this study investigated the prognostic factors in small cell lung cancer patients in order to improved the survival rate by using the proper therapeutic methods. Material and method : The clinical data from 394 patients who diagnosed with small cell lung cancer and treated from 1993 to 2001 at the Kosin University Gospel Hospital, were analyzed. Result : There were 314 male patients (79.7%), and 80 female patients (20.3%). The number of those with limited disease was 177 (44.9%), and the number of those with extensive disease was 217 (55.1%). Overall, 366 out of 394 enrolled patients had died. The median survival time was 215 days (95% CI : 192-237days). The disease stage, Karnofsky performance state, 5% body weight loss for the recent 3 months, chemotherapy regimens, and the additive chest radiotherapy were identified as being statistically significant factors for the survival time. The median survival times of the supportive care group, one anticancer therapy, and two or more treatment groups were 17 days, 211 days, and 419 day, respectively (p<0.001). These data emphasize the importance of anticancer treatment to improve survival time for patients. The group of concurrent chemoradiotherapy (30 patients) showed significantly longer survival time than the group given sequential chemoradiotherapy (55 patients) (528 days versus 373 days, p=0.0237). The favorable prognostic factors of laboratory study were groups of leukocyte =8,000/mm3, ALP=200 U/L, LDH=450 IU/L, NSE=15 ng/mL, s-GOT=40 IU/L. In extensive disease, there was no difference according to the number of metastatic site. However, the median survival time of patients with ipsilateral pleural effusion had longer than patients having other metastatic sites. According to the survey periods, three groups were divided into 1993-1995, 1996-1998, and 1999-2001. The median survival time was significantly prolonged after 1999 in comparison to previous groups (177 days, 194 days, 289 days, p=0.001, 0.002, respectively). Conclusion: Disease stage and 5% body weight loss for recent 3 months at diagnostic state were significant prognostic factors. In addition, the performance status, serum ALP, LDH, NSE, CEA levels also appear to be prognostic factors. The survival time of those patients with small cell lung cancer has been prologned in recent years. It was suggested that the used of the EP (etoposied and cisplatin) chemotherapy method and concurrent chemoradiotherapy for patients with a limited stage contributed to the improved survival time.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.3
• /
• pp.372-385
• /
• 1999

Background: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. Method: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. Results: The experimental group was divided into two subgroups-those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 $cells/mm^3$ while control group's mean was 0.4 $cells/mm^2$(p=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 $cells/mm^2$ with 28.4 $cells/mm^2$ of control group(P=0.026). In addition, the mean thickness of the basement membrane of experimental group was $14.20{\pm}5.20{\mu}m$ in contrast of control group whose mean was $3.50{\pm}1.37{\mu}m$(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough variant asthma ; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive (21.4%) with the skin prick test In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). Conclusion: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.6
• /
• pp.922-931
• /
• 2000

Background : It has been well known that bronchia1 asthma is a chronic airway inflammatory disorder. Recently, sputum induced with hypertonic saline was introduced as a simple and useful nonivasive medium to investigate airway inflammation and symptom severity in patients with asthma. We examined the eosinophil, eosinophil cationic protein (ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating facta (GM-CSF), and nitric oxide (NO) derivatives in induced sputum from patients with bronchia1 asthma in order to determine the role of NO and various inflammatory cytokines as a useful markers of airway inflammation or changes in pulmonary function tests and symptoms. Methods : A total 30 patients with bronchia1 asthma received oral prednisolone 30 mg daily for 2 weeks. Forced expiratory volume in one second ($FEV_1$), total blood eosinophil count and induced sputum eosinophil count, ECP, IL-3, IL-5, GM-CSF, and NO derivatives were determined before and after the administration of prednisolone. Results : Of the 30 patients, 13 (43.3%) were male and 17 (56.7%) were female. The mean age of patients was 41.8 years (range 19-64 years). Two patients could not produce sputum at the second study and 3 could not be followed up after their first visit. Two weeks after the prednisolone administration, there was a significant increase in $FEV_1$ (% of predicted value) from 78.1$\pm$20.6 % to 90.3$\pm$ 18.3 % (P<0.001). The eosinophil percentages in induced sputum were significantly decreased after treatment with prednisolone, with values of 56.1$\pm$27.2 % versus 29.6$\pm$21.3 % (P<0.001), and ECP were $134.5\pm68.1\;{\mu}g/L$ versus $41.5\pm42.4\;{\mu}g/L$ (P<0.001) respectively. After the prednisolone treatments, the eotaxin concentration also showed a decreasing tendency from 26.7$\pm$12.8 pg/ml to 21.7$\pm$8.7 pg/ml. There was a decreasing tendency but no significant differences in total blood eosinophil count (425.7$\pm$265.9 vs 287.7$\pm$294.7) and in the concentration of NO derivatives ($70.4\pm44.6{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) after the prednisolone treatments. IL-3, IL-5, GM-CSF were undetectable in the sputum of most subjects either before the prednisolone treatments or after the treatments. Before the prednisolone treatments, a significant inverse correlation was observed between FEV1 and sputum ECP (r=-D.364, P<0.05) and there was a significant correlation between sputum eosinophils and eotaxin (r=0.369, P<0.05) Conclusion : The eotaxin and ECP concentration in induced sputum may be used as markers of airway inflammation after treatments in bronchia1 asthma. In addition, the measurement of sputum eosinophil percent ages is believed to be a simple method displaying the degree of airway inflammation and airway obstruction before and after the prednisolone treatment in bronchia1 asthma. However, unlike exhaled NO, the examination of NO derivatives with Griess reaction in induced sputum is considered an ineffective marker of changing airway inflammation and obstructing symptoms.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.6
• /
• pp.740-751
• /
• 2000

Background : Moxifloxacin is a newly developed drug which is more potent and safe compared to previous fluoroquinolones. This drug effectively eradicates organisms such as beta-lactamase-producing or other resistant bacteria. Moxifloxacin is known to be effective in treating respiratory infections such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniaeme, Legionella spp. and Mycoplasma pneumoniae. Methods : In a multicenter, randomized, open, comparative study, the efficacy and safety of oral moxifloxacin taken 400 mg once a day and clarithromycin taken 500 mg twice daily for 7 days were compared for the treatment of Korean patients with acute exacerbations of chronic bronchitis. Results : A total of 170 patients were enrolled, and they were divided into two groups: 87 in the moxifloxacin group and 83 in the clarithromycin group. Of those enrolled, 76 (35 for bacteriologic efficacy) in the moxifloxacin group and 77 (31 for bacteriologic efficacy) in the clarithromycin group were included in the efficacy analysis. All were included in the safety analysis. Clinical success was noted in 70 (92.1%) of 76 moxifloxacin-treated patients and 71 (92.2%) of 77 clarithromycin-treated patients. Bacteriologic success rate seemed to be higher in moxifloxacin group (73.5%) than in clarithromycin group (54.8%), but statistically insignificant (p=0.098). Drug susceptibility among organisms initially isolated was higher in moxifloxacin group on Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae (p<0.001). Adverse events were reported by 12.8% of 86 patients receiving moxifloxacin and 21.7% of 83 patients receiving clarithromycin. Headache (4.7% vs 4.8%, moxifloxacin group vs clarithromycin group, respectively) and indigestion (2.3% vs 6.0%, moxifloxacin group vs clarithromycin group, respectively) were the most frequent side effects in the two groups. Conclusion : This study demonstrated that for the treatment of acute exacerbations of chronic bronchitis a 7-day course of moxifloxacin 400 mg od was clinically equivalent and microbiologically superior to clarithromycin 500 mg bid.