• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1332-1342
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• 1997

Background : Acute pulmonary injury by paraquat are caused by multiple mechanisms including direct injury with oxygen free radicals and several mediators released from inflammatory cells. In order to clarify whether vitamin E could reduce tissue damages induced by intraperitoneal administration of paraquat and to investigate the pathogenetic mechanisms of paraquat-induced pulmonary injury, vitamin E as a free radical scavenger was administered. Method : Rats were divided into three groups (group 1 : control, group 2 : paraquat treated group, group 3 : paraquat and vitamin E treated group). Animals were sacrificed on day 1, day 2, day 3, and day 8 after the administration of saline, paraquat, or paraquat/vitamin E. Results : Treatment with vitamin E decreased the death rate of rats treated with paraquat. Comparing with control group ($1.37{\times}10^6/ml$), mean total cell counts recovered from the lavage fluid from animals treated with paraquat($1.65{\times}10^6/ml$) were increased(p=0.06). Magnitudes of increment of the total cell counts on the Day 8 in the vitamin E treated group were smaller than those of the animals treated with paraquat alone. The neutrophils began to appear in significant amounts in the lavage fluid on Day 8 after the administration of paraquat(37.0+12.7%). A significant decreasing neutrophil concentration at Day 8 was observed in the paraquat/vitamin E treated group(20.6+13.4%). Histologically the degree of pulmonary fibrosis was most prominent in the paraquat treated group while diffuse alveolar damage was continuously observed in the paraquat/vitamin E treated group and extensive interstitial lymphocytic infiltration was seen in the paraquat/vitamin E treated group. The paraquat/vitamin E treated group showed the less histologic changes. Conclusion : In this study vitamin E acting as a scavenger of neutrophil-derived free radicals and suppressant of lipid peroxidation, seemed to be the effective antioxidant in the inhibition of paraquat-induced pulmonary injury.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.731-736
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• 1995

Background: Surgical resection is the treatment of choice for localized, operable non-small cell carcinoma of the lung. Curative radiotherapy, however, is considered an alternative to surgery in patients with poor performance state, poor cardiopulmonary function, or who refuse surgery. However, the difference in prognosis after surgery and radiotherapy is not well established in the patients with stage I non-small cell lung cancer. Method: To evaluate the difference in progonsis between surgery and radiotherapy in stage I non-small cell lung cancer, a retrospective study was done with 15 patients treated with curative radiotherapy and 24 patients treated with curative surgery. Results: The overall response rate was 80%, with 33% complete response, after radiotherapy. The median survival time of the patients with radiotherapy was 14.9 months, with 2-year and 5-year survival rates of 22% and 0%, respectively. The median survival time of the patients with surgery was 37.7months, with 2-year and 5-year survival rates of 65% and 41%, respectively. Conclusion: These results suggest that surgery is better than the radiotherpy in view of survival rate and it is necessary to recommend, more strongly, curative surgery to patients with stage I non-small cell lung cancer if the patients are able to receive operation. To compare, more accurately, the difference in prognosis by the modality of therapy, large multicenter study is needed.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.547-558
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majorities of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to hoot. In previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF. Understanding the mechanisms of TNF-resistance in TNF-$\alpha$ gene transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of new protective protein synthesis in the acquired resistance to TNF of TNF-$\alpha$ gene transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164, a murine fibrosarcoma cell line, using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF gene transfected cells(WEHI164-TNF) and the changes of TNF sensitivities after treatments with actinomycin D(transcription inhibitor) and cycloheximide ( translation inhibitor). Results : WEHI164 which was sensitive to TNF became resistant to TNF after being transfected with TNF-$\alpha$ gene and the resistance to TNF was partially reversed after treatment with actinomycin D, but not with cycloheximide. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ gene transfection may be associated with synthesis of some protective proteins.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.629-638
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• 1997

Background : Surgical intervention is known as the principle management for hemoptysis of significant amount. But surgical procedure is applicable to only small number of patients because of increased mortality in emergency surgery and various functional and structural problems after lung resection. Bronchial artery embolization(BAE) has been used as an alternative interventional technique for immediate control of patients with increased risk for surgery due to recurrent or massive hemoptysis. BAE also has limitations such as recurrent bleeding after procedure and its role for the application to small amount of hemoptysis is still not established. Method : To evaluate immediate and long term effectiveness of BAE, we analysed 65 patients with hemoptysis according to therapeutic modalities they received ; BAE versus conservative management. Results : The success rate for immediate control of hemoptysis was significantly higher in BAE group with 43 cases(100%) among 43 cases compared with 17 cases(77%) among 22 cases in conservative group (p < 0.001). The disease control duration was $19.5{\pm}8.06$ months in BAE group and $18.8{\pm}6.06$ months in conservative group(p > 0.05). The therapeutic response in BAE group was 82%(36/43 cases) and 95%(21/22 cases) in conservative group (p > 0.05). According to the amount of hemoptysis, the therapeutic response were seen in 91%(29/32 cases) in less than 100ml and 85%(28/33 cases) in 100~400ml (p > 0.05). According to the manifestation of hemoptysis, the therapeutic response in groups of recurrent and nonrecurent were 87%(20/23 cases) and 88%(37/42 cases)(p > 0.05). Conclusion : The difference of therapeutic response between BAE and conservative group in patients with small amounts of hemoptysis was not found except for immediate control of hemoptysis.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.12-28
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• 2001

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.54-66
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• 2000

Background: Pneumoconiosis, like other chronic respiratory diseases, is essentially incurable and, for many, progressive. While improved survival time is an important aim of treatment, there is growing recognition that for some people, improving the quality of life is more important than extending the length of life. Currently the measurement of the quality of life is used to assess the efficacy of therapeutic agents. Methods: Sixty-three pnemoconiotics who were admitted to St. Mary's Hospital between April and August 1999 were interviewed using COOP charts, Chronic Respiratory Questionnaire(CRQ) and Pneumoconiotic Respiratory Questionnaire(PRQ), a newly developed questionnaire concerning clinical and socioeconomic features of pneumoconiotics. Also, ILO classification of the chest film, pulmonary function test, and arterial blood gas analysis of the patients were evaluated. The scores between Industrial Accident Compensation Insurance(IACI) covered and uncovered patients and between clinically stable and unstable patients were compared. Results: Domains of CRQ and PRQ showed a high internal consistency reliability($\alpha$=0.86-0.89, 0.77-0.81) except the dyspnea domain($\alpha$=0.63) of CRQ. The scores on the CRQ and PRQ showed statistically significant correlations with the results of COOP charts, pulmonary function test and arterial blood gas analysis. The dyspnea domain and social activity domain of the PRQ showed significant difference between IACI covered and uncovered patients and between clinically stable and unstable patients. Conclusion : Korean translation of the Chronic Respiratory Questionnaire and the newly developed Pneumoconiotic Respiratory Questionnaire are reliable and valid methods and are likely to be useful in measuring the quality of life in patients with the chronic respiratory disease including pneumoconiosis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.703-714
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• 2000

Background : Surfactant protein A (SP-A) is important in the regulation of surfactant secretion, synthesis and recycling. SP-A has important roles in regulating surfactant metabolism as well as in determining surfactant's physical properties. Since systemic sepsis is one of the common causes of acute respiratory distress syndrome (ARDS) and abnormalities in surfactant function have been described in ARDS, the authors investigated the effects of endotoxemia on the accumulation of mRNA encoding SP-A and SP-A protein content. Methods : Adult rats were given various doses of intraperitoneal endotoxin from Salmonella enteritidis and sacrificed at different times. SP-A mRNA was measured by filter hybridization method. Lung SP-A protein content was determined by double sandwich ELISA assay using a polyclonal antiserum raised in rabbits against purified rat SP-A. Results : 1) The accumulation of SP-A mRNA in the endotoxin treated group 24 hours after 2mg/kg and 5mg/kg endotoxin treatments was significantly increased 50.9% and 27.3%, respectively, compared to the control group (P<0.001, P<0.025). 2) The accumulation of SP-A mRNA 24 hours in the 5mg/kg endotoxin treated group was significantly increased by 26.5% compared to the control group (P<0.01). 3) Total amount of lung SP-A was not altered at 24 hours by various doses of treatment. Total lung SP-A content 144 hours after endotoxin administration was significantly decreased by 51.4% compared to the control group (P<0.01). Conclusions : The specific regulation of SP-A by various time course in vivo is evident. The late decline in SP-A protein content was unexpected and suggests that SP-A may be differentially regulated during lung inflammation. The functional significance of these alterations remains to be clarified.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.715-723
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• 2000

Background : Obstructive sleep apnea syndrome (OSAS) affects systemic blood pressure and cardiac function. The development of cardiovascular dysfunction including the changes of systemic blood pressure and cardiac rhythm, suggests that recurrent hypoxia and arousals from sleep may increase a sympathetic nervous system activity. Continuous positive airway pressure (CPAP) therapy has been found to be an effective treatment of OSAS. However, only a few studies have investigated the cardiovascular and sympathetic effects of CPAP therapy. We evaluated influences of nasal CPAP therapy on the cardiovascular system and the sympathetic activity in patients with OSAS. Methods : Thirteen patients with OSAS underwent CPAP therapy and were monitored using polysomnography, blood pressure, heart rate, presence of arrhythmia and the concentration of plasma catecholamines, before and with CPAP therapy. Results: The apnea-hypopnea index (AHI) was significant1y decreased (p<0.01) and the lowest arterial oxygen saturation level was elevated significantly after applying CPAP (p<0.01). Systolic blood pressure tended to decrease after CPAP but without statistical significance. Heart rates during sleep were not significantly different after CPAP. However, the frequency and number of types of arrhythmia decreased and sinus bradytachyarrhythmia disappeared after CPAP. Although there was no significant difference in the level of plasma epinephrine concentration, plasma norepinephrine concentration significantly decreased after CPAP (p<0.05). Conclusion : CPAP therapy decreased the apnea-hypopnea index, hypoxic episodes and plasma norepinephrine concentration. In addition, it decreased the incidence of arrhythmia and tended to decrease the systemic blood pressure. These results indicate that CPAP may play an important role in the prevention of cardiovascular complications in patients with OSAS.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.495-509
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• 2003

Background : Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor-${\kappa}B$ transcription factor, we hypothesized that nuclear factor-${\kappa}B$ might be related to the reduced neutrophil apoptosis observed in sepsis. Methods : Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches : by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-${\kappa}B$ was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. Results : We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after cycloheximide treatment, suggesting that decreased spontaneous neutrophil apoptosis is dependent on de novo protein synthesis. In patients with sepsis, basal neutrophil nuclear factor-${\kappa}B$ was activated compared to the level in healthy controls. Moreover, a blockade of nuclear factor-${\kappa}B$ activity reversed the decreased spontaneous neutrophil apoptosis in sepsis patients. Meanwhile, X-linked inhibition of apoptosis expression, which is regulated by nuclear factor-${\kappa}B$, decreased 24 hours after incubation in healthy persons, but persisted for 24 hours in patients with sepsis. Conclusion : These observations suggest that the reduced spontaneous neutrophil apoptosis observed in patients with sepsis may be related to the induction of survival protein by nuclear factor-${\kappa}B$.

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