• Clinical and Experimental Pediatrics
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• v.45 no.9
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• pp.1090-1096
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• 2002

Purpose : We evaluated the clinical manifestations, bronchoscopic findings and therapeutic effects of flexible fiberoptic bronchoscopy in atelectasis of children. Methods : Sixty six children who received bronchoscopy due to persistent atelectasis, acute severe atelectasis and incidental atelectasis on plain chest radiography were studied retrospectively. Results : The most common causative underlying disease was pneumonia(60.4%). Other underlying conditions were pulmonary tuberculosis, chronic lung disease, postoperative state, bronchial asthma and chest trauma. The most common abnormal findings were inflammatory changes such as bronchial stenosis(n=15), mucosal edema and large amount of secretion(n=14), granulation tissue( n=3) and mucus plug(n=3) although 39.4% showed normal airways. Other findings were congenital airway anomalies, endobronchial tuberculosis, extrinsic compression and obstruction by blood clot. In 32 children with pneumonia-associated atelectasis, 43.7% revealed normal airways, and the most common abnormal findings were also inflammatory changes. Eighteen out of 39 patients who received therapeutic intervention such as suctioning of secretion, bronchial washing and intrabronchial administration of N-acetylcysteine($Mucomyst^{(R)}$) had complete or partial resolution of their atelectasis. In 32 patients with pneumonia-associated atelectasis, 56.5% showed improvement by therapeutic intervention. Conclusion : In this study, atelectasis was mainly associated with inflammatory airway diseases such as pneumonia. The most common abnormal bronchoscopic findings were inflammatory changes such as mucosal edema and large amounts of secretion and bronchial stenosis, although about 40% revealed normal airway. Flexible bronchoscopy is helpful for either diagnosis or treatment, especially in pneumonia-associated atelectasis.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.529-538
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• 2002

Background : Many clinicians are reluctant to prescribe systemic corticosteroids to manage an asthmatic attack because of many complications such as osteoporosis, cushing's syndrome, diabetes, hypertension and bleeding tendency. The use of nebulized budesonide may be of value in some infants, old men, and in particular adult asthmatic patients who complain of severe dyspnea. A clinical validation and steroid-sparing effect of nebulized budesonide in asthmatic adults and COPD were evaluated, and the short-term effects of budesonide use on the HPA axis were assessed. Materials and Methods : Study A was prospectively done with 41 patients diagnosed with pure asthma and 30 patients diagnosed with COPD (including asthmatic component) in Soonchunhyang Hospital, Chunan from June. 2000 to Sep. 2001. They were treated with nebulized budesonide including systemic steroids (Group 1), a budesonide tubuhaler including a systemic steroid (Group 2), or only the systemic steroid(Group 3). The peak flow rate, arterial blood gas in room air, pulmonary function test, symptom scoring, steroid amount and hospital stay were analyzed. Study B was conducted with 19 patients to evaluate the short-term effects on the HPA axis of treatment with nebulized budesonide 1mg twice daily and a budesonide turbuhaler 5 puffs twice daily. The adrenal function was assessed prior to budesonide inhalation and after 7 days of budesonide inhalation. Results : In the pure asthmatic patients, the mean value of the symptoms (dyspnea, wheezing, cough, night asthma) or the arterial BGAs, total amounts of steroid or hospital stay and the difference in the results of the pulmonary function tests or peak expiratory flow rate were similar in the three groups. In COPD with an asthmatic component, there were no significant differences among the three groups. Although nebulized budesonide suppressed HPA function,(p=0.006) the HPA responses from the nebulized budesonide and turbuhaler budesonide were similar (p=0.288) Conclusion : This result suggests that systemic steroid should only be made available for acute asthmatic patients irrespective of the inhaled budesonides. Nebulized budesonide at the therapeutic dose has similar effects on the HPA axis compared to that of turbuhaler budesonide.

• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.293-299
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• 2001

Background : Sustained-release theophylline, which is generally prescribed as a twice-daily equal-dose regimen, is one of the more common asthma treatments. The development of a sustained-release drug delivery technology that enables improved control of the theophylline blood levels represents a significant advancement in both the efficacy and safety of dosing. Method : A crossover study was conducted with 25 adult chronic asthmatic patients requiring daily bronchodilator therapy. The study group included thirteen males and twelve females with ages ranging from 19 to 71 years. The overall approach was to place the patients first on the twice-daily preparation($Etheophyl^{(R)}$) for 28 days at 8 AM and 8 PM, and measure the pulmonary function and theophylline level on the 28th day. The patients were subsequently switched to the once-daily preparation($Uniphyl^{(R)}$) in the same daily dose at 8 PM on the 29th day and the same parameters were measured on the 56th day. Results : The mean serum levels of theophylline were $8.18{\pm}1.66\;{\mu}g/ml$ in the $Etheophyl^{(R)}$-treated period and $8.00{\pm}1.75\;{\mu}g/ml$ in the $Uniphyl^{(R)}$-treated period. ln addition, the $FEV_1$ showed $71.40{\pm}7.48$ percent in the $Etheophyl^{(R)}$-treated and $69.18{\pm}9.00$ percent in the $Uniphyl^{(R)}$-treated period. Thus there were no significant differences between the once-daily and twice-daily preparation. Conclusion : The results indicated little clinical differences between the two medications. The two drugs are equally effective in controlling asthma over the four weeks of treatment.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.441-452
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• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.453-465
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• 2000

Background : Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH). Methods : We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53. Results : In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location of microsatellite, D3S1285 as a marker of FH1T was observed in 5 cases out of 26 specimens; D9S171 as a marker of p16 in 5 out of 17; and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally. Conclusion : Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.298-309
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• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.121-128
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• 2006

Background: The "health-related quality of life" (HRQL) for patients with chronic respiratory disease has been emphasized, because chronic respiratory disease (CRD) is chronic and progressive, and it finally causes disability. HRQL instruments may be useful for monitoring patients' progress or for determining the most appropriate choice of treatment. We describe the adapting St George's Respiratory Questionnaire (SGRQ), which is a self-administered questionnaire developed by Jones et al. (1991), into the Korean version for covering three domains of health for the patients suffering with airways disease. Method: We obtained the original SGRQ from the author after gaining permission. For adaptation, we created an expert panel and translated the original questionnaire into Korean language. The translated questionnaire was then back-translated by bilingual experts and we compared it with the original questionnaire. After correction and feasibility testing, 74 patients with chronic respiratory disease (COPD, asthma, destroyed lung) completed the Korean version of the SGRQ. The clinical status of each patients was evaluated concurrently with measurement of their health status. Result: The Korean version of the SGRQ was acceptable and easy to understand. Cronbach's alpha reliability coefficient was 0.92 for the overall scale and 0.63 for the "Symptoms", subscale, 0.87 for the "Activity", subscale, and 0.89 for the "Impacts" subscales. The correlation coefficients between the overall score and the Borg scale score, oxygen saturation, and forced expiratory volume in one second ($FEV_1$) were 0.52, -0.32 and -0.26, respectively. These results support that the Korean SGRQ was correlated with other measurements. Conclusion: The Korean SGRQ was reliable and valid for patients with chronic respiratory disease, such as COPD, asthma, and destroyed lung. The SGRQ score was well correlated with other respiratory measurements as well. Although further studies should complete the adaptation work, our results suggest that the SGRQ may be used in Korea and also for international studies involving Korean CRD patients.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.98-103
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• 2009

Background: Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by a proliferation of Langerhans cells and this results in granulomas that involve multiple organs of the body. Because the incidence of PLCH is very low in Korea and worldwide, collecting the clinical data of patients with PLCH nationwide is needed to determine the clinical features of Korean patients with PLCH. Methods: The patients with PLCH confirmed by biopsy at any body site were included and the patients should have lung lesions present. A questionnaire that had items on the symptoms, lung function tests, the roentgenographic findings and the treatment was collected retrospectively at a Korean ILD Research Meeting. Results: A total of 56 cases were collected. The number of males and females was 48 and 8, respectively, and their median age was 43 years (range: 18-67 years). The patients were current or ex-smokers in 79% of the cases. The most frequent symptom was coughing (39%), followed in decreasing order by dyspnea (38%), sputum (20%) and chest pain (20%). Pneumothorax was observed in 16 (29%) patients. Lung function tests showed a normal, restrictive, mixed or obstructive pattern in 26 (61%), 7 (16%), 7 (16%) and 3 patients (7%), respectively. Nodular-cystic lesion was most frequently observed in 59% of the patients on HRCT. The lung lesions were located in the middle and upper lobes in almost the cases. The median follow-up period was 90 months (range: 1-180 months) and only two patients died during this period. Conclusion: This study provides a national survey of the patients with PLCH during a long follow-up period.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.93-97
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• 2009

Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.178-185
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• 2009

Background: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1$\alpha$ and VEGF in A549 cell line. Methods: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a $CO_2-N_2$ gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 ${\mu}mol/L$), and then examined by real-time-PCR analysis of HIF-1$\alpha$, VEGF, and $\beta$-actin mRNA. Results: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1$\alpha$ transcription in A549 cells in a dose-dependent manner. Compared to HIF-1$\alpha$, VEGF was not inhibited by EGCG. Conclusion: HIF-1$\alpha$ can be inhibited by EGCG. This suggests that targeting HIF-1$\alpha$ with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.