• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.189-197
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• 2000

Background : Tissue inhibitor of metalloproteinase is a natural inhibitor that counteracts pro teolytic enzymes essential to the invasion of cancer cell. Whether or not TIMP-2 gene transfer via adenovirus could inhibit the invasion of lung cancer cell iη vitro was evaluated for the future purpose of gene therapy against lung cancer. Methods : Recombinant adenovirus-TIMP-2(Ad-TIMP-2) was generated by homologous recombination after pACCMV-TIMP-2 and pJM17 were cotransfected into 293 cell by standard calcium phosphate coprecipitate method. Calu-6, one of the most invasive lung cancer cells, was transduced with Ad-TIMP-2 or Ad-$\beta$gal. Anchorage-independent growth and invasiveness were assessed by soft agar clonogenicity assay and invasion assay using two-chamber, well divided by matrigel. Results : Ad-TIMP-2 transduced calu-6 cells produced biologically active TIMP-2 more than 50 times more than parental calu-6. TIMP-2 gene transfer did not suppress the in vitro tumorigenicity. However, two chamber well assay revealed that Ad-TIMP-2 transduction reduced the invasiveness of calu-6 efficiently (12% compared with parental cell) even at low 10moi. Conclusion : Even though TIMP-2 gene transfer did not inhibit in vitro tumorigenicity, it did inhibit invasion of lung cancer cell in vitro. The inhibition of invasion by Ad-TIMP-2 may be a useful strategy for the treatment of lung cancer.

• 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.43 no.6
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• pp.852-861
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• 1996

Background : Many clinicians have experienced the difficulty of decision on termination of antituberculosis chemotherapy after the 6th month due to relapse of disease. There is still controversy in the effect of 2S(K)HRZ/4HRZ 6-month short course chemotherapy including pyrazinamide for 6 months in patiems with pulmonary tuberculosis. And there is no long term follow-up study of 6-month short course chemotherapy for pulmonary tuberculosis in korea. So we had performed the study to find the result of 6-month antituberculosis chemotherapy for 4 years. Method : We studied prospectively the effect of 2S(K)HRZ/4HRZ in one hundred-fifty patients with pulmonary tuberculosis and followed up fifty-nine patients for more than 1 year to 4 years after the completion of 6-month short course therapy. Results : 1) Out of one hundred-fifty patients, seventy-two patients(48%) completed the prescribed 6-month chemotherapy. Sixty-eight patients(45.3%) have experienced premature discontinuation and the most common cause of premature discontinuation was drop-out against advice(thirty-six patients, 24%). Ten patients(6.7%) were treated beyond the 6 months mainly due to irregular treatment. 2) Fifty-nine patients(81.9%) among seventy-two patients with completed treatment have been followed up for more than 1 year and 32 patients(44.4%) for more than 4 years. There was three relapse patients of whom two patients have experienced relapse of pulmonary tuberculosis within 1 year after the termination of chemotherapy. 3) Among one hundred-thirty-four patients who have been assessible for more than two months of chemotherapy, including the patients who experienced within 2 months, there were eighty-two patients(61.2%) who have experienced adverse reactions and the treatment regimen was changed only in thirteen patients(9.7%). The most frequent cause of adverse reactions was arthralgia and/or hyperuricemia, which had occurred in 33 patients(24.6%). Conclusion : In a university hospital in Korea, 6-month shot course chemotherapy of 2S(K)HRZ/4HRZ had unnegligible relapses and premature discontinuation. Therefore, change of the regimen might be carefully considered by drug susceptibility results. Close monitoring of patients, retrial of sputum exam and radiologic evaluation during treatment might be required in the endemic area of drug resistant strains like in Korea. Further study about the effect of 6-month short course chemotherapy including pyrazinamide for 6-month might be needed.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.139-144
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• 2007

Background: Bronchial anthracofibrosis, which is defined as bronchial narrowing with black pigmentation of the overlying bronchial mucosa, is frequently associated with tuberculosis. The aim of this study was to examine the relationship between bronchial anthrocofibrosis and to identify the clinical and radiological characteristics of non-tuberculous bronchial anthracofibrosis. Methods: All patients who showed bronchial anthracofibrosis in more than one segment on a bronchoscopic examination from January 2003 to July 2006 at Kangnam St. Mary's hospital were enrolled in this study. The underlying diseases, baseline clinical characteristics, characteristic findings on a computed tomogram (CT) of the chest, pathologic findings of the bronchial mucosa, and the clinical response to steroid therapy were analyzed retrospectively. Results: A total 54 patients (19 males, 35 females) were enrolled with a mean age of 75 years. The most common presenting symptoms were cough, sputum and dyspnea. The predominant X-ray findings were peribronchial soft tissue attenuation with or without calcification, mediastinal lymphadenopathy with or without calcification and atelectasis. Fourteen non-tuberculous anthracofibrosis patients were treated with steroid. Nine patients were improved clinically, and 6 patients were improved radiologically. Conclusion: Bronchial anthracofibrosis is frequently associated with various pulmonary diseases not only tuberculosis but also COPD pneumonia etc.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.158-164
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• 1993

Background: Recently, lung abscess tends to be increased in patients with underlying disease, most of whom are unsuitable for surgery when medical treatment fails. The patients with giant lung abscesses do not frequently respond to antibiotics and often have life-threatening complications. Therefore, more intensive cares are required in these patients. We studied the results and effects of percutaneous catheter drainage in these patients. Method: We performed fluoroscopy-guided percutaneous pigtail catheter (8.3 F) drainage by Seldinger technique in 9 cases of lung abscess (in 7 cases, intractable to medical treatment for an average of 8.4 days and in 2 cases, catheter drainage immediately performed due to a large cavity that was initially 10 cm in diameter). We compared 10 cases of lung abscess as control group which had receieved conventional medical treatment alone. Results: Seven of the 9 patients in study group of percutaneous drainage and 7 of the 10 patients in control group of medical treatment alone clinically improved in the average of 1.8 and 8.7 days, respectively. The mean duration of drainage was 13.2 days. There were 3 cases of death from massive hemoptysis, asphyxia of pus, and sepsis in control group, as compared with 2 cases of death from hepatic encephalopathy and sepsis in study group. The malfunctions of catheter occurred in these 2 cases, obstruction and dislodgement. But there were no significant pleuropulmonary complications of percutaneous drainage. Conclusion: Percutaneous drainage is effective and relatively safe in the management of lung abscesses refractory to medical therapy or giant lung abscesses.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.128-137
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• 1996

Background : We can diagnose pulmonary tuberculosis with sputum AFB smear and culture, but sputum AFB smear has low sensitivity and culture needs long period, and they are not available in the patients who can not expectorate effectively. Recently developed, PCR is a fast diagnostic tool in tuberculosis, but false positive and false negative are important problems. So, we studied the diagnostic value of bronchoalveolar lavage fluid AFB smear, culture, PCR through the bronchoscopy. Methods : The 67 pulmonary tuberculosis patients and 43 non-pulmonary tuberculosis patients were analyzed with their sputum specimen AFB smear and culture. Also, bronchoscopy and bronchoalveolar lavage were done, and bronchoalveolar lavage fluid AFB smear, culture and PCR were done. Results: 1) In the cases of pulmonary tuberculosis, the sensitivity of sputum AFB smear and culture were 32.8% and 57.4%, respectively. And the sensitivity of bronchoalveolar lavage fluid AFB smear and culture were 47.8% and 80.6%. respectively. 2) In the cases of pulmonary tuberculosis, the sensitivity and the positive predictive value(for predicting a positive culture) of PCR were 80.6% and 81.5%, respectively. 3) In the cases of sputum AFB smear-negative and culture-negative pulmonary tuberculosis, the sensitivity of bronchoalveolar lavage fluid AFB smear, culture, PCR, and the positive predictive value(for predicting a positive culture) of PCR were 23.1%, 100%, 88.5%, and 82.4%, respectively. 4) The specificity of bronchoalveolar lavage fluid PCR was 77.0%. 5) The median number of days between obtaining a specimen and starting therapy was 5 days for sputum AFB smear, 9 days for bronchoalveolar lavage fluid AFB smear, 26 days for bronchoalveolar lavage fluid PCR, 32 days for sputum culture, 56 days for bronchoalveolar lavage fluid culture. Conclusion : The sensitivity of bronchoalveolar lavage fluid AFB smear and culture are higher than sputum AFB smear and culture. So, the bronchoscopy must be considered for evaluating suspected cases of pulmonary tuberculosis in patients from whom smears of expectorated sputum do not reveal mycobacteria or from whom no sputum can be obtained. Especially, combined with PCR, it is expected that pulmonary tuberculosis can be diagnosed more rapidly and more accurately, so bronchoalveolar lavage fluid APB smear and PCR can be helpful in the early treatment of pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.493-504
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• 1997

Background : Non-small cell lung cancer is one of the most frequent cause of death due to cancer in men, and its incidence among women is rapidly increasing. Although there has been a recent surge of interest in combined modality therapy for stageIII non-small cell lung cancer(NSCLC), the optimal treatment is still not well established. Thoracic irradiation has long been the gold standard for locally advanced unresectable NSCLC. However, although conventional radiotherapy(XRT) can palliate symptom and improve local control of disease, it has at most only a modest effect on survival. Recently, cisplatin(cis-diamminedichloroplatinum) has been reported to enhance the cell-killing effect of radiation For patients with unresectable NSCLC, cisplatin-based concurrent chemoradiotherapy(CCRT) had the advantage of therapeutic response over XRT alone and therapeutic side effect more commonly occurred in CCRT group in EORTC(European Organization for Research and Treatment of Cancer) and other trials. Objectives : We compared therapeutic response, compliance, and side effects between CCRT and XRT in patients with advanced NSCLC. Patients and Method : Thirty patients with biopsy-proven inoperable NSCLC were randomized to one of two treatment arms. Arm A consisted of XRT, radiotherapy for 4~6 weeks(1.8 Gy given 20~33 times, in five fractions a week), and arm B consisted of CCRT, radiotherapy for 2 weeks(3 Gy given to times, in five fractions a week), followed by 3 week rest period and then radiotherapy 2 more weeks(2.5 Gy given 10 times, in five fractions a week), combined with 6mg cisplatin per square meter, given daily before radiotherapy. We evaluate therapeutic response, compliance, change of performance status, side effects, and radiation pneumonitis by using the author's made scoring system. Results : There was no significant difference in therapeutic response and compliance. But there was a significantly lower laboratory complication and radiation pneumonitis in CCRT group (p < 0.05). There's significant negative correlation between stage and therapeutic response score in both groups(R=0.353, p < 0.05) In both groups, patients with squamous cell carcinoma had a tendency to higher therapeutic response score than those with adenocarcinoma. Conclusion : There was no difference between CCRT and XRT in respect to therapeutic response and compliance. But CCRT had a advantage of decreased side effects.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.29-41
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• 2001

Background : The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. Methods : In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. Results : Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. Conlcusion : An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drugsusceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.289-296
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• 2004

Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.40-50
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• 2004

Background : Radiation pneumonitis(RP) is the major serious complication of thoracic irradiation treatment. In this study, we attempted to retrospectively evaluate the long-term prognosis of patients who experienced acute RP and to identify factor that might allow prediction of RP. Methods : Of the 114 lung cancer patients who underwent thoracic radiotherapy between December 2000 and December 2002, We performed analysis using a database of 90 patients who were capable of being evaluated. Results : Of the 44 patients(48.9%) who experienced clinical RP in this study, the RP was mild in 33(36.6%) and severe in 11(12.3%). All of severe RP were treated with corticosteroids. The median starting corticosteroids dose was 34 mg(30~40) and median treatment duration was 68 days(8~97). The median survival time of the 11 patients who experienced severe RP was significantly poorer than the mild RP group. (p=0.046) The higher total radiation dose(${\geq}60Gy$) was significantly associated with developing in RP.(p=0.001) The incidence of RP did not correlate with any of the ECOG performance, pulmonary function test, age, cell type, history of smoking, radiotherapy combined with chemotherapy, once-daily radiotherapy dose fraction. Also, serum albumin level, uric acid level at onset of RP did not influence the risk of severe RP in our study. Conclusion : Only the higher total radiation dose(${\geq}60Gy$) was a significant risk factor predictive of RP. Also severe RP was an adverse prognostic factor.