• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1230-1234
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• 2003

Purpose : The aim of this study is to evaluate the value of lung biopsies for the management of children with lung disease. Methods : We retrospectively reviewed 19 lung biopsies done at Asan Medical Center, Seoul between 1993 and 2001. Data gathered included demographic information, underlying conditions, diagnosis before biopsy, final diagnosis, change in therapy, morbidity and mortality. Results : Nineteen patients underwent lung biopsy. Among them, 13 patients were male and six patients were female; the median age was 3.6 years(0.8 to 8.6 years). Twelve patients underwent open lung biopsies and seven patients had thoracoscopic biopsies. The overall diagnosis rate was 95 %. The most common diagnosis was interstitial lung disease(12 patients, 64%) and infection was detected in four patients(21%). The biopsy-proven bronchiolitis obliterance was confirmed in two of seven patients suspected by CT findings. Specific treatment was changed after biopsy in 16 patients (85%). The morbidity & overall mortality rates of the patients were 5%(one patient) and 21%(four patients) respectively. Only one complication was seen : empyema. The causes of death were acute respiratory distress syndrome(one patient), respiratory failure(two patients), and septicemia(one patient). Conclusion : The lung biopsy is a safe procedure and it contributes to more accurate diagnosis and proper management of pediatric lung diseases. We recommend lung biopsies should be considered more positively in the diagnosis of pediatric lung diseases.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.25-34
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• 1995

Background: Endobronchial tuberculosis is classified into 7 subtypes as fibrostenotic type, edematous-hyperemic type, actively caseating type, tumorous type, ulcerative type, granular type and nonspecific bronchitic type by bronchoscopic features, and we make a prospective study to follow up how bronchoscopic findings change during treatment-course in each subtype of active endobronchial tuberculosis. Methods: We planned to do follow-up bronchoscopic examination every month until there was no significant change in endobronchial lesion, then every 3 months and at the end of the treatment in each patient with biopsy proven endobronchial tuberculosis from May, 1990 to August, 1993. Results: 1) This study included 66 cases, but bronchoscopic follow-up was completed as scheduled in 47 cases. 2) In actively caseating and edematous-hyperemic type, bronchostenosis occurred within 2 or 3 months of treatment in about 2/3 of total cases. 3) In fibrostenotic type, bronchostenosis did not improve in spite of the treatment. 4) In tumorous type, the changes in bronchoscopic findings were unpredictable because new lesions occured on other sites even 4 or 6 months after treatment in 2 cases and the size of initial mass increased 6 months after treatment in 1 case (among 7 cases). 5) Granular and nonspecific bronchitic type improved without significant sequelae within 2 or 3 months of treatment. Conclusion: It may be necessary to follow up the patient with bronchoscopy repeatedly 2 or 3 months after starting treatment in active endobronchial tuberculosis, and it is better to perform bronchoscopic examination at 6 months of treatment, especially in patients with tumorous type because there is possibility that new endobronchial lesion occurs. Aggressive therapeutic modalities such as stent-insertion, laser therapy or electrocautery should be considered to prevent bronchostenosis in cases with granulation tissue, fibrostenotic and tumorous types of endobronchial tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.76-83
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• 1995

Background: Despite advances in chemotherapy, the treatment of inoperable non-small cell carcinoma of the lung remains poor. According to the recent reports, the response rates of mitomycin, vinblastine, and cisplatin(MVP) chemotherapy are higher than those of other cisplatin based polychemotherapy and MVP chemotherapy can be used as neoadjuvant chemotherapeutic regimen. But the overall response rates of MVP chemotherapy range from 17 to 53 percent, so we studied the effect of MVP chemotherapy in advanced non-small cell lung cancer. Method: We treated forty patients with stage III or IV non-small cell lung cancer with two courses of MVP chemotherapy($8mg/m^2$ of mitomycin on day 1, $6mg/m^2$ of vinblastine on day 2 & day 14, and $100mg/m^2$ of cisplastin on day 1) at 4 weeks interval. Then all patients were evaluated the response of chemotherapy 4 weeks later, and received further chemotherapy, palliative radiotherapy or supportive therapy according to the patient's condition. We also determined the median survival time and prognostic factors. Results: 1) Nine patients(23%) had a partial reponse, 23 patients(57%) had a stable disease, and disease progressed in 8 patients(20%). There were no patients with complete response. 2) The overall median survival time was 36 weeks(range, 9 to 119+ weeks). The median survival time of responder(partial response) and non-responder(stable and progressed) groups were 60 weeks(range, 36 to 82+ weeks) and 31 weeks(range, 9 to 119+ weeks) respectively(p=0.03). 3) The median survival time of the female group was 71 weeks and significantly prolonged in comparision with 35 weeks of the male group(p=0.01). But, the other prognostic factors didn't affect the survival time and response rate. 4) The median survival times of chemotherapy group and chemotherapy with palliative radiotherapy group were not significantly different. Conclusion: MVP combined chemotherapy is unsatisfactory in improving survival in advanced non-small cell lung cancer. Therefore, further studies are needed to find more active new agents and to estabilish the efficacy of the combined treatment with radiotherapy and/or surgery.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.185-194
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• 1999

Background: NF-$\kappa$B is a characteristic transcriptional factor whose functional activity is determined by post-translational modification of protein and subsequent change of subcellular localization. The involvement of the NF-$\kappa$B family of the transcription factors in the control of such vital cellular functions as immune response, acute phase reaction, replication of certain viruses and development and differentiation of cells has been clearly documented in many previous studies. Several recent observations have suggested that the NF-$\kappa$B might also be involved in the carcinogenesis of some hematological and solid tumors. Investigating the possibility that members of the NF-$\kappa$B family participate in the molecular control of malignant cell transformation could provide invaluable information on both molecular pathogenesis and cancer-related gene therapy. Method: To determine the expression patterns and functional roles of NF-$\kappa$B family transcription factors in human lung cancer cell lines NCI-H792, NCI-H709, NCI-H226 and NCI-H157 were analysed by western blot, using their respective antibodies. The nuclear and the cytoplasmic fraction of protein extract of these cell lines were subsequently obtained and NF-$\kappa$B expression in each fraction was again determined by western blot analysis. The type of NF-$\kappa$B complex present in the cells was determined by immunoprecipitation. To detect the binding ability of cell-line nuclear extracts to the KB consensus oligonucleotide, electrophoretic mobility shift assay(EMSA) was performed. Results: In the cultured human lung cancer cell lines tested, transcription factors of the NF-$\kappa$B family, namely the p50 and p65 subunit were expressed and localized in the nuclear fraction of the cellular extract by western blot analysis and immunocytochemistry. Immunoprecipitation assay showed that in the cell, the p50 and p65 subunits made NF-$\kappa$B complex. Finally it was shown by Electrophoretic Mobility Shift Assay(EMSA) that nuclear extracts of lung cancer cell lines are able to bind to NF-$\kappa$B consensus DNA sequences. Conclusion: These data suggest that in human lung cancer cell lines the NF-$\kappa$B p50/p65 complex might be activated. and strengthen the hypothesis that NF-$\kappa$B family transcription factors might be involved in the carcinogenesis of human lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.740-747
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• 2000

Background : To compare the efficacies and side effects of etoposide, cisplatin/cyclophosphamide, adriamycin, vincristine(VPP/CAV) with those of carboplatin etoposide(CE) in extensive stage small cell lung cancer patients. Method : Patients with extensive stage small lung cancer who has measurable disease were eligible. VPP/CAV group(n=22) was treated with cisplatin(60mg/$m^2$ iv. D1) etoposide(100mg/$m^2$ iv. D1-3), and 3 weeks later cyclophosphamide(1000mg/$m^2$ iv. D1), adriamycin( 40mg/$m^2$ iv. D1), and vincristine(1.4mg/$m^2$ iv. D1), were administered alternatively. CE group(n=22) was treated with carboplatin(325mg/$m^2$ iv. D1) and etoposide (100mg/$m^2$ iv. D1-3) ; repeated treatment was performed every 3 weeks. Result : Forty four patients were eligible for the study. The overall response rate was 61.4% (complete remission rate 0%, partial response rate 61.4%, stable disease rate 25%, progressive disease rate 13.6%), and median survival was 10.8 months. In VPP/CAV group, response rate was 54.5% (complete remission rate 0%, partial response rate 54.4%, stable disease rate 27.3%, progressive disease rate 18.2%), and, in carboplatin/etoposide group, the response rate was 68.2%(complete remission rate 0%, partial response rate 68.2%, stable disease rate 22.7%, progressive disease rate 9.1%). The median survival time was 9.5 months in the VPP/CAV group and 11 months in CE group. The toxicity of both group was moderate, and anemia was more frequent in the CE group. Conclusion : VPP/CAV regimen and CE regimen produced similar response rates and survival times in extensive stage small cell lung cancer patients. CE regimen may be effective as part of the initial therapy for extensive stage small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.636-644
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• 1999

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. The mechanisms of TNF cytotoxicity are not clearly understood and some has reported that reactive oxygen species(ROS) might be associated with them, but there is controversy about antioxidant effect on TNF cytotoxicity. This study was designed to compare the TNF cytotoxicity after antioxidant pretreatment with that of control to evaluate the role of ROS in the mechanism of TNF cytotoxicity. Method : We compared the TNF cytotoxicies to WEHI164(murine fibrosarcoma cell line) and ME180(human cervix cancer cell line) after antioxidant pretreatment with those of control by MIT(dimethylthiazolyl-diphenyltetrazolium bromide) assay. Results : In the control group, the TNF cytotoxicities were $92.2{\pm}2.8%$(WEHI164) and $59.9{\pm}7.0%$(MEl80). In the TMTU(tetramethyl thiourea) pretreatment group, those were $91.4{\pm}3.7%$ and $74.6{\pm}7.0%$. In the PMZ(promethazine) pretreatment group, those were $90.2{\pm}2.5%$ and $62.5{\pm}5.7%$. In the BHT(butylated hydroxytoluene) pretreatment group, those were $93.2{\pm}1.3%$ and $66.3{\pm}6.1%$. So there was no reduction in TNF cytotoxicity after antioxidants pretreatment. Conclusion : The ROS may not have major role in the mechanisms of TNF cytotoxicity.

• Tuberculosis and Respiratory Diseases
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• v.51 no.1
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• pp.35-43
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• 2001

Background : The eosinophil chemotactic and activating effects of eotaxin and the known association of eosinophils with asthma suggest that eotaxin expression is increased during an asthma attack. This study was aimed to determine whether the plasma eotaxin levels are higher in patients during an asthma attack and to correlate the eotaxin levels with the disease activity, severity and response to therapy. Method : A case-control study of the plasma eotaxin levels was performed in 100 patients with exacerbated asthma and 48 age- and sex-matched subjects with stable asthma. Results : The plasma eotaxin levels were significantly higher in the 100 patients with exacerbated asthma($233{\pm}175\;pg/mL$) than in the 48 subjects with stable asthma($169{\pm}74\;pg/mL$). A trend toward higher eotaxin levels was observed in asthmatic subjects who were taking oral steroids ($332{\pm}225\;pg/mL$) than in those who were not ($214{\pm}159\;pg/mL$) and higher levels were found in those admitted to the hospital ($275{\pm}212\;pg/mL$) than in those discharged after receiving only emergency treatment ($190{\pm}115\;pg/mL$). The eotaxin levels inversely correlated with the $FEV_$ (r=-0.25, p<0.01). The eotaxin levels were higher in moderate persistent ($323{\pm}256\;pg/mL$) and severe persistent asthmatics ($276{\pm}170\;pg/mL$) than in mild intermittent asthmatics ($l60{\pm}60\;pg/mL$). Conclusion : Eotaxin expression is directly associated with asthma exacerbation, impaired pulmonary function and the disease severity.

• Tuberculosis and Respiratory Diseases
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• v.54 no.3
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• pp.295-303
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• 2003

Backgroung : The incidence of penicillin-resistant streptococcus pneumoniae(PRSP) accounts for almost 70% of all pneumococcal pneumonia cases in Korea. It is still unclear as to whether the efficacy of penicillin or equally active beta-lactam agents is compromised in PRSP pneumonia. This study investigated the prevalence of PRSP in community-acquired pneumonia and its clinical course. Methods : A total of 42 patients with community-acquired pneumococcal pneumonia were evaluated from July 1999 to May 2001. The cultured strains of Streptococcus pneumoniae were divided into susceptible, intermediately resistant, and resistant strains by an E-test, and the effect of the clinical course was investigated. Results : From a total of 42 patients, 22 (52.4%) patients had an intermediate resistance (MIC $0.1-1{\mu}g/m{\ell}$) and six (14.3%) showed a high resistance ($MIC{\geq}2.0{\mu}g/m{\ell}$) with current penicillin susceptibility categories. However, according to the classification of the DRSPTWG (Drug Resistant Streptococcus pneumoniae Therapeutic Working Group), there were 11 cases (26.2%) of intermediate resistance and no case of high resistance. Under empirical antimicrobial treatment, there was no difference in the clinical outcome between the penicillin susceptible and resistant group. Conclusion : The clinical outcome of PRSP pneumonia with empirical therapy was acceptable. These results suggest that the current MIC breakpoint for penicillin resistance in Streptococcus pneumoniae has been set at a very low level and penicillin resistance according to the NCCLS classification does not significantly influence the outcome of the empirical treatment for pneumococcal pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.314-320
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• 2006

Background : The overall response (20-30%) to chemotherapy in non-small cell lung cancer (NSCLC) is quite poor. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation. There is increasing evidence suggesting that the induction of HO-1 might have an important protective effect against oxidative stress including cisplatin containing chemotherapy. This study retrospectively investigated the relationship between HO-1 expression and the response to chemotherapy containing cisplatinin advanced NSCLC patients. Material and Methods : The medical records including the responses to chemotherapy of fifty nine cases were evaluated retrospectively, and the tissue samples of these patients were immunohistochemically stained for HO-1. Results : Forty three of the fifty nine patients(72.8%) showed positive staining for HO-1 in their cancer tissues. There was no significant difference according to the cell type, stage and tumor size. In addition, there was no correlation between HO-1 expression and the responses to chemotherapy. Conclusion : HO-1 expression in tumor tissue dose not predict the response to cisplatin containing chemotherapy in advanced NSCLC. Further prospective studies with a larger number of patients will be needed to confirm these results.