Circulating Cytokine Levels and Changes During the Treatment in Patients with Active Tuberculosis in Korea / 결핵

BACKGROUND: The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. METHOD: Serum interleukin-1 beta(IL-1 ), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-alpha), interferon-gamma(IFN-gamma) and transforming growth factor-beta(TGF-beta) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-alpha, IFN-gamma and TGF-beta levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. RESULTS: 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-1beta, IL-6(p<0.05), TNF-alpha, and IFN-gamma were elevated and TGF-beta was decreased comparing to control. IL-2, IL-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-alpha were elevated and TGF-beta was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-gamma level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 and TNF-alpha and between IL-12, IL-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-gamma was significantly decreased(p<0.05). CONCLUSION: These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

The Study of MHC class I Restricted CD8+ T Cell Mediated Immune Responses against Mycobacterium tuberculosis Infection: Evidence of M. tuberculosis Specific CD8+ T Cells in TB Patients and PPD+ Healthy Individuals

BACKGROUND: The protective immunity against tuberculosis (TB) involves both CD4+ T cells and CD8+ T cells. In our previous study, we defined four Mycobacterium tuberculosis derived peptide epitopes specific for HLA-A*0201 restricted CD8+ T cells (ThyA30-38, RpoB127-135, 85B15-23, PstA175-83). In this study, we investigated the immune responses induced by these peptide specific CD8+ T cells in latently and chronically infected people with TB. METHODS: We characterized these peptide specific CD8+ T cell population present in PBMC of both TB patients and PPD healthy people using IFN-gammaelispot assay, intracellular staining and HLA-A2 dimer staining. RESULTS: The frequency of peptide specific CD8+ T cell was in the range of 1 to 25 in 1.7x10(5) PBMC based on ex vivo IFN-gamma elispot assay, demonstrating that these peptide specific CD8+ T cell responses are induced in both TB patients and PPD people. Short term cell lines (STCL) specific for these peptides proliferated in vitro and secreted IFN-gamma upon antigenic stimulation in PPD+ donors. Lastly, HLA-A*0201 dimer assays indicated that PstA175-83 specific CD8+ T cell population in PPD+ healthy donors is heterogeneous since approximately 25~33% of PstA175-83 specific CD8+ T cell population in PPD+ healthy donors produced IFN-gamma upon peptide stimulation. CONCLUSION: Our results suggest that MHC class I restricted CD8+ T cell mediated immune responses to M. tuberculosis infection are induced in both TB patients and PPD+ people; however, the CD8+ T cell population is functionally heterogeneous.

Clinical Impact of Bronchial Reactivity and Its Relationship with Changes of Pulmonary Function After Asthmatic Attack Induced by Methacholine / 결핵

BACKGROUND: Bronchial reactivity is known to be a component of airway hyperresponsiveness, a cardinal feature of asthma, with bronchial sensitivity, and is increments in response to induced doses of bronchoconstric tors as manifested by the steepest slope of the dose-response curve. However, there is some controversy regarding methods of measuring bronchial reactivity and clinical impact of such measurements. The purpose of this study was to evaluate the clinical significance and assess the clinical use by analyzing the relationship of the bronchial sensitivity, the clinical severity and the changes in pulmonary function with bronchial reactivity. METHOD: A total of 116 subjects underwent a methacholine bronchial provocation test. They were divided into 3 groups : mild intermittent, mild persistent, moderate and cough asthma. Severe patients were excluded. Methacholine PC20 was determined from the log dose-response curve and PC40 was determined by one more dose inhalation after PC20. The steepest slope of log dose-response curve, connecting PC20 with PC40, was used to calculate the bronchial reactivity. Body plethysmography and a single breath for the DLCO were done in 43 subjects before and after methacholine test. RESULTS: The average bronchial reactivity was 38.0 in the mild intermittent group, 49.8 in the mild persistent group, 61.0 in the moderate group, and 41.1 in the cough asthma group. There was a weak negative correlation between PC20 and bronchial reactivity. A heightened bronchial reactivity tends to produce an increased clinical severity in patients with a similar bronchial sensitivity and basal spirometric pulmonary function. There were significant correlations between the bronchial reactivity and the initial pulmonary function before the methacholine test in the order of sGaw, Raw, FEV1/FVC, MMFR. There were no correlations between the bronchial sensitivity and the % change in the pulmonary function parameters after the methacholine test. However, there were significant correlations between the bronchial reactivity and the PEF, FEV1, DLCO. CONCLUSION: There was weak significant negative correlation between the bronchial reactivity and the bronchial sensitivity, and the bronchial reactivity closely reflected the severity of the asthma. Accordingly, measuring both the bronchial sensitivity and the bronchial reactivity can be of assistance in assessing of the ongoing disease severity and in monitoring the effect of therapy.

The Lymphocyte Dependent Bactericidal Assay of Human Monocyte and Alveolar Macrophage for Mycobacteria / 결핵

BACKGROUND: Though mononuclear phagocytes serve as the final effectors in killing intracellular Mycobacterium tuberculosis, the bacilli readily survive in the intracellular environment of resting cells. The mechanisms through which cellular activation results in the intracellular killing is unclear. In this study, we sought to explore an in vitro model of a low-level infection of human mononuclear phagocytes with MAC and H37Ra and determine the extent of the lymphocyte dependent cytotoxicity of human monocytes and alveolar macrophages. METHOD: The peripheral monocytes were prepared using the Ficoll gradient method from PPD positive healthy people and tuberculosis patients. The alveolar macrophages were prepared from PPD positive healthy people via a bronchoalveolar lavage. The human mononuclear phagocytes were infected at a low infection rate (bacilli:phagocyte 1:10) with MAC(Mycobacterium avium) and Mycobacterium tuberculosis H37Ra. Non-adherent cells(lymphocyte) were added at a 10:1 ratio. After 1,4, and 7 days culture in 37degrees C, 5% CO2 incubator, the cells were harvested and inoculated in a 7H10/OADC agar plate for the CFU assay. The bacilli were calculated with the CFU/1 X 10(6) of the cells and the cytotoxicity was expressed as the log killing ratio. RESULTS: The intracellular killing of MAC and H37Ra within the monocyte was greater in patients with tuberculosis compared to the PPD positive controls (p<0.05). Intracellular killing of MAC and H37Ra within the alveolar macrophage appeared to be greater than that within the monocytes of the PPD positive controls. There was significant lymphocyte dependent inhibition of intracellular growth of the mycobacteria within the monocytes in both the controls and tuberculosis patients and within the macrophages in the controls(p<0.05). There was no specific difference in the virulence between the MAC and the H37Ra. CONCLUSION: This study is an in vitro model of a low-level infection with MAC and H37Ra of human mononuclear phagocytes. The intracellular cytotoxicity of the mycobacteria within the phagocytic cells was significantly lymphocyte dependent. During the 7 days culture after the intracellular phagocytosis, the actual confinement of the mycobacteria was observed within the monocytes of tuberculosis patients and the alveolar macrophages of the controls as in the case of adding lymphocytes.

Measuring Intracellular Mycobacterial Killing Using a Human Whole Blood Assay / 결핵

BACKGROUND: The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. METHOD: The PPD positive subjects were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis H37Ra for 4 days by rotating the culture in a 37degrees C, 5% CO2 incubator. In some experiments, methylprednisolone- or pentoxifylline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The delta log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. RESULTS: 1. A trend was noted toward the improved killing of mycobacteria in PPD+subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifylline adversely affected the killing in the PPD+subjects, umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis H37Ra by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis H37Ra. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the delta logKR continuously decreased in a 3 and 4 days of whole blood culture. CONCLUSION: The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

Soluble IL-2R, IFN-gamma and Neopterin as Immunologic Markers in Patients with Tuberculosis / 결핵

BACKGROUND: The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-gamma with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-gamma and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. METHOD: The serum sIL-2R, IFN-gamma and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-gamma and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. RESULTS: 1) The serum sIL-2R and IFN-gamma levels were elevated in patients with tuberculosis when compared to those of healthy subjects (0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis(2967+/-2132.8 pg/ml) than in healthy controls(4949+/-1242.1 pg/ml)(p0.05), 41 52.8 pg/ml to 22+/-23.9 pg/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from 3158+/-2272.6 pg/ml to 3737+/-2307.5 pg/ml(0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. CONCLUSION: On the basis of this study, sIL-2R, IFN-gamma and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

Outcomes in Relation to Time of Tracheostomy in Patients with Mechanical Ventilation / 결핵

BACKGROUND: Despite widespread use of tracheostomy in intensive care unit, it is still controversial to define the best timing from endotracheal intubation to tracheostomy under prolonged mechanical ventilation. Early tracheostomy has an advantage of easy airway maintenance and enhanced patient mobility whereas a disadvantage in view of nosocomial infection and tracheal stenosis. However, there is a controversy about the proper timing of tracheostomy. METHODS: We conducted a retrospective study of the 35 medical and 15 surgical ICU patients who had admitted to Ewha Womans University Mokdong Hospital from January 1996 to August 1998 with the observation of APACHE III score, occurrence of nosocomial infections, and clinical outcomes during 28 days from tracheostomy in terms of early (n=25) vs. late (n=25) tracheostomy. We defined the reference day of early and late tracheostomy as 7th day from intubation. RESULTS: 1. The number of patients were 25 each in early and late tracheostomy group. The mean age were 48 +/- 18 years in early tracheostomy group and 63 +/- 17 years in late tracheostomy group, showing younger in early tracheostomy group. The median duration of intubation prior to tracheostomy was 3 days and 13 days in early and late tracheostomy groups. Organs that caused primary problem were nervous system in 27 cases(54%), pulmonary 14(28%), cardiovascular 4(8%), gastrointestinal 4(8%) and genitourinary 1(2%) in the decreasing order. Prolonged ventilation was the most common reason for purpose of tracheostomy in both groups. 2. APACHE III scores at each time of intubation and tracheostomy were slightly higher in late tracheostomy group but not significant statistically. Day to day APACHE III scores were not different between two groups with observation upto 7th day after tracheostomy. 3. Occurrence of nosocomial infections, weaning from mechanical ventilation, and mortality showed no significant difference between two groups with observation of 28days from tracheostomy. 4. The mortality was increased as the APACHE III score up to 7 days after tracheostomy increased, but there were no increment for the mortality in terms of the time of tracheostomy and the days of ventilator use before tracheostomy. CONCLUSION: The early tracheostomy seems to have no benefit with respect to severity of illness, nosocomial infection, duration of ventilatory support, and mortality. It suggests that the time of tracheostomy is better to be decided on clinical judgement in each case. And in near future, prospective, randomized case-control study is required to confirm these results.

A case of thymic carcinoid tumour with multiple metastasis including bone marrow / 결핵

This report dscribes the thymic carcinoid tumor behaved in a highly aggressive fashion metastasis. Anti-cancer chemotherapy was not effective, the patient died of progressive disease after three months of diagnosis.

Relationship between Bronchial Sensitivity and Bronchial Reactivity in Asthma / 결핵

BACKGROUND: Airway hyperreponsiveness is a cardinal feature of asthma. It consists of both an increased sensitivity of the airways, as indicated by a smaller concentration of a constrictor agonist needed to initiate the brochoconstrictor response and an increased reactivity, increments in response induced subsequent doses of constrictor, as manifested by slopes of the dose-response curve. The purpose of this study is to observe the relationship between bronchial sensitivity and reactivity in asthmatic subjects. METHOD: Inhalation dose-response curves using methacholine were plotted in 56 asthmatic subjects. They were divided into three groups(mild, moderate and severe) according to clinical severity of bronchial asthma. PC20 were determined from the dose-response curve as the provocative concentration of the agonist causing a 20% fall in FEV1. PC40 were presumed or determined from the dose response curve, using the PC20 and the one more dose after PC20. Reactivity was calculated from the dose-response curve regression line, connecting PC20 with PC40. RESULTS: PC20 were 1.83mg/ml in mild group, 0.96mg/ml in moderate, and 0.34mg/ml in severe. PC4O were 7.17mg/ml in mild group, 2.34mg/ml in moderate, and 0.75mg/mI in severe. Reactivity were 24.7+/-17.06 in mild group, 46.1+/-22.10 in moderate, and 59.0+/-5.82 in severe. There was significant negative correlation between PC2O and reactivity (r=-0.70, P<0.01). CONCLUSION: Accordingly, there was significant negative correlation between bronchial sensitivity and brochial reactivity in asthmatic subjects. However, in some cases, there were wide variations in terms of the reactivity among the subjects who have similar sensitivity. So both should be assessed when the bronchial response tor bronchoconstrictor agonists is measured.

Clinical Investigation of 11 Cases of Chronic Eosinophilic Pneumonia Reported in Korea / 결핵

BACKGROUND: Chronic eosinophilic pneumonia(CEP) presents with profound systemic symptoms, including fever, malaise, night sweats, weight loss, and anorexia together with localized pulmonary manifestations such as cough, wheeze, and sputum. It is an illness occurring predominantly in women. The chest radiogragh shows fluffy opacities that often have a characteristic peripheral configuration. The hallmark of CEP is the peripheral blood eosinophilia and a prompt response to oral corticosteroid therapy. We investigated characteristics of eleven patients of chronic eosinophilic pneumonia, reported in Korea. METHOD: There were eleven reports of CEP from 1980 to 1996, including three cases experienced in our hospital. The journals were analysed in respects of clinical history, laboratory, and radiographic findings. RESULTS: 1) Male vs. female ratio is 3 : 8. The peak incidence occurred in forty and fifty decades. The atopic diseases were present in 6 cases. Asthma was the commonest manifestation. 2) The presenting symptoms were as follows: cough, dyspnea, sputum, weight loss, fever, general weakness, night sweats, urticaria with the descending incidence. 3) Peripheral blood eosinophilia was present in all patients(mean; 38.4%) and serum Ig E level was elevated in nine patients(mean; 880IU/ml). CONCLUSION: The diagnosis of chronic eosinophilic pneumonia is based on classic symptoms, including fever, night sweats, weight loss with a typical roentgenogram of peripheral pulmonary infiltrates and peripheral blood eosinophilia, and that is confimed by lung biopsy and/or bronchoalveolar lavage. Chronic eosinophilic pneumonia is responsive to corticosteroid promptly and recommended at least 6 months of therapy to prevent relapse.

The Change of SaO2, PFT and ABGA During the Bronchofiberscopy / 결핵

BACKGROUND: Bronchofiberscopy is a procedure with a chance of airway irritation and it may cause pathophysiologic changes of respiratory system. So we tried to evaluate the influence of bronchofibercopy on O2 saturation, ABGA and PET by patient's basal status and procedure type. METHOD: O2 saturation was measured every 1 minute from the left index finger tip with percutaneous oximetry. ABGA was done before and right after the bronchofiberscopy and PFT was done before and within 10 minutes after the bronchofiberscopy. RESULTS: The mean time for bronehofiberscopy procedure was 14.5mim and SaO2 maximally fall to 89.0 below 8% of the baseline after mean time of 8.4mm, which was recorvered at the end of the procedure. SaO2 change amount was 8.4% on Non-O2 supply group, which was lower compared to 6.4% of the O2-supply group without statistically significance. Biopsy Group and BAL group showed more SaO2 fall than washing only group. The level of PaO2 and FEV1 of the patient didn's influence significantly on SaO2 fall during the procedure. ABGA taken before and after the bronchofiberscopy showed mild fall of Pa02 and mild rise of PaCO2. Whereas PET showed decrease of FEV1(P<0.05) and increase of RV without changes in airway resistance and pulmonary diffusion capacity. Comparing before and after the bronchofiberscopy, the washing group showed no significant changes on PET, while the biopsy group and the BAL group showed increase of RV & decrease of FEV1 after the bronchofiberscopy. BAL group showed more changing tendency rather than biopsy group although not statistically significant. CONCLUSION: Bronchofiberscopy is considered as a relatively safe procedure, but it would be better to be done with O2 supply especially in the patient with low PaO2 and in the case of biopsy and BAL

Comparative Analysis of Risk Factors and Severity of Illness Scores for Predicting Mortality in Sepsis Patients Treated in Medical Intensive Care Unit / 대한내과학회지

OBJECTIVES: Despite the advances in medical practice and technology, a steady increase in the incidence of sepsis has been reported and the mortality has been persistently high ranging from 20 to 50%, especially in medical intensive care unit. Therefore, objective assessment of severity of illness based on risk estimates derived from severity of illness score has been important. Thus this study was designed for identification of risk factors and comparison of severity of illness scores: Acute physiology and chronic health evaluation II(APACHE II), Acute physiology and chronic health evaluation III (APACHE III), Multiorgan failure scoring system(MOF), Simplified acute physiology score(SAPS), Septic severity score(SSS). METHODS: A retrospective clinical study was done on 97 patients with sepsis treated in medical intensive care unit, who had been admitted to Ewha Womans University Mokdong Hospital from September 1994 to May 1997. Multiple factors which may influence mortality and severity of illness score were evaluated by univariate and logistic regression analysis. RESULTS: 1) Of the 97 patients, 52 were male and 45 were female. The mean age was 62 years and the overall mortality was 59.8%. 2) On severity of illness, sepsis was 21cases, severe sepsis 36 and septic shock 40. On primary source of infection, pulmonary origin was 39cases, gastrointestinal origin 23 and urinary tract origin 13. The infection caused by documented organism was 53cases. 3) Based on the univariate analysis, age, sex, respiratory rate, number of organ failure, admission source, ventilatory support, hematocrit, WBC, prothrombin time, Na and K, pH, PaO2/FiO2, D(A-a)O2 and the following severity of illness scores :APACHE II, APACHE III, MOF, SAPS, and SSS for predicting mortality risk were all significant factors discriminating between survivors and nonsurvivors. 4) In distribution curve of APACHE II, APACHE III, MOF, SAPS, and SSS, the cut-off values in predictive risk of 50% were 21, 88, 4, 15, and 29. By logistic regression analysis after substituting their cut off value, APACHE II and APACHE III were significant independent predictors influencing survival with odd ratio 3.82 in APACHE II and 4.62 in APACHE III. In predictive risk of 50%, sensitivity was 55%, specificity 85%, accuracy 85% and relative risk 6.77 in APACHE II. And sensitivity was 47%, specificity 97%, accuracy 88% and relative risk 7.62 in APACHE III. CONCLUSION: APACHE II and APACHE III were significant predictor influencing mortality in sepsis patients treated in medical intensive care unit and APACHE III was superior to that of its predecessor. In near future, prospective and multicentral studies are required to confirm these results.

Spontaneous and cStimulated Release of the TNF-alpha, IL-1beta, IL-6 and IL-8 of Alveolar Macrophages in the Patients with Pulmonary Tuberculosis / 결핵

The aim of this study was to evaluate spontaneous and LPS stimulated proinflammatory cytokines and chemokine release of alveolar macrophages in the patients with pulmonary tuberculosis and healthy individuals, as a control. Alveolar macrophages recovered from bronchoalveolar lavage fluids were cultured with or without LPS 0.1, 1, or 10 micrograms/ml for 24 and 48 hours in 37C, 5% CO2. TNF-alpha, IL-1beta IL-6 and IL-8 amount were evaluated using ELISA kit from the supernatants. There were a significant increase in the spontaneous 24 hours release of TNF-alpha and IL-6 from the involved segments of tuberculosis patients compared with uninvolved segments and normal control. There were also increasing trends of release of them after LPS stimulation in involved segments, but not significant. IL-1beta IL-6 and IL-8 were not evaluated from the involved segments of tuberculosis and there were not significant differences of them between uninvolved segments of tuberculosis and normal control. It is concluded that cytokine release of alveolar macrophages in the pulmonary tuberculosis was markedly increased, and it was localized to the alveolar macrophages from the involved segments.

A Case of Sarcoidosis with Cavitary Nolule of the Lung / 결핵

Sarcoidosis is a chronic multisystemic disorder of unknown cause characterized by presence of noncaseating epithelioid granuloma in affected organ It is relatively common In western countries, but it is uncommon in East Asia including Korea. The lung is the most frequently affected organ. Usual radiologic manifestation of thoracic sarcoidosis art readily recognized, but there are extremely diverse manifestation Sarcoidosis rarely causes large pulmonary nodules, and cavitation in such lesion is very rare. We experienced one case of Sarcoidosis with Cavitary nodule of the lung and report it with brief review of the literature.

A Case of Pulomonary Lymphomatold Granulomatosis / 대한내과학회지

Lymphomatoid granulomatosis was described by Liebow as a peculiar angiocentric and angiodestructive lymphoreticular proliferative granulomatous disease. Although the lung is most frequently involved, lymphomatoid granulomatosis is also commonly found in the upper respiratory tract, skin, kidneys and central nervous system. Pulmonary infiltrates are histologically polymorphous and show variable degree of cytologic atypic in the lymphoid cells. Infrequent involvement of the bone marrow, spleen and peripheral lymph nodes initially supported the distinction of lymphomatoid granulomatasis from lymphoma. We experienced a rare case of 26-year-old female diagnosed as lymphomatoid granulomatosis by per cutaneous needle aspiration biopsy and transbronchial lung biopsy with symptoms of fever, cough, sputum and right chest pain. After 4th chemotherapy it showed partial remission and chemotherapy is going on.

A Case of Lobal-type Chronic Eosinophilic Pneumonia / 대한내과학회지

Chronic eosinophilic pneumonia is characterized by multiple and dense areas of consolidation on chest radiographs and computed tomographic scans, persistent symptoms, a requirement for steroid therapy and possible relapses. The finding of increased BAL eosinophils is most helpful in diagnosis of patients presenting with chronic eosinophilic pneumonia. Therefore, although biopsy remains the gold standard for diagnosis of chronic eosinophilic pneumonia, it is usually not required if the clinical findings are characteristic and if the response to a trial of corticosteroids is rapid and complete. The male patient, aged 40years, presented with cough, chest pain, weight loss and peripheral infiltration of right middle lobe on the chest radiograph and chest computed tomographic scans. We confirmed chronic eosinophilic pneumonia with bronchoalveolar lavage analysis and transbronchial lung biopsy. We herein report a lobal type of chronic eosinophilic pneumonia with a brief review of literature.

A study of Tumor Angiogenesis in Human Lung Cancerby Immunohistochemical Stain / 결핵

Background: Tumor angiogenesis is the growth of new vessels toward and within tumor. It has been demonstrated that the growth of tumor beyond a certain size requires angiogenesis and it is closely involved in tumor progression and metastasis. The finding that intensity of neovascularization correlates independently with metastasis may lead to identification of patients in whom radical surgery should be supplemented by systemic treatment. Method: We have collected paraffin blocks of bronchoscopic biopsy of patients with non-small cell lung cancer. We highlighted the vessel by staining endothelial cell with JC70 monoclonal antibody(to CD31) immunohistochemically and counted microvessels under 200 X field using light microscopy. Results: 1) The mean microvessel count was 32.7+/-20.8 (9-96) in total 29 cases. 2) There were no correlations between microvessel counts and pathologic cell type, T staging, node metastasis(N) and hematogenous metastasis(M) (p>0.05). 3) The median follow-up duration was 15 months(2-46) and there was no correlation between the microvessel counts and survival rate of lung cancer patients (p>0.05). Conclusion: Tumor angiogenesis seems to be an important prognostic factor suggesting the probability of metastasis. But the microvessel count in the bronchoscopic biopsy specimen was inadequate and very limited. There has been no data about angiogenesis of lung cancer in korea yet. So the study of tumor angiogenesis using resected lung tumor specimen would be demanded.

A Study of Effect on Pulmonary Function of Pleural Effusion in Tuberculous pleurisy patients / 결핵

BACKGROUND: Pleural effusion is a common disease in clinical practice but its effect on pulmonary function and altered pulmonary mechanics after removal of effusion are not still largely understood. Previous studies have shown that there is little or a relatively small improvement in pulmonary function and arterial blood oxygenation after therapeutic thoracentesis. The present study was designed to assess the effect on pulmonary function of pleural effusion and to test whether there was a significant improvement in pulmonary function and arterial oxygenation after thoracentesis and to observe long term effect after thoracentesis. METHOD: We examined flow-volume curve, body box and arterial blood gas analysis according to severity of effusion, present symptom, and symptom duration. Then, we measured changes of pulmonary function after thoracentesis and observed longterm effect after thoracentesis. RESULT: 1) Pleural effusion cause restrictive pulmonary insufficiency. Not only functional impairment of small airway but also large airway is provoked. 2) MMFR, FEV1, Raw, PO2 are earlier improved than FVC and TLC after thoracentesis and patients without complication have mild restrictive pulmonary insufficiency after longterm observation 3) FVC, FEV1, & TLC are similarly restricted as severity of pleural effusion and PO2 is relatively decreased. 4) Cases with symptom duration 1 week or less and cases with dyspnea have more severe pulmonary insufficiency than others. 5) The flow volume curves show a relatively greater improvement in flow rates at large lung volumes than small airway. 6) Significant relationship is shown between first thoracentesis amount and changes of FEV1, FVC, TLC. CONCUSION: Pleural effusion cause restrictive pulmonary insufficiency and not only functional impairment of small airway impairment but also large airway is provoked. Then, Pulmonary function is progressively improved after thoracentesis and remained mild restrictive pulmonary insufficiency after recovery

The role of the pulmonary function test and the exercise test for assessing impairment/disability in patients with chronic airflow obstruction / 결핵

BACKGROUND: In 1980, WHO made a definition in which the term "impairment" as applied to the respiratory system is used to describe loss of lung function, "disability" the resulting diminution in exercise capacity. The measurement of pulmonary function during exercise would give us information about overall functional capacity and respiratory performance that would be lacking in tests performed at rest. We conducted this study to investigate the role of resting pulmonary function test and exercise test for assessing impairment/disability in patients with chronic airflow obstruction(CAO). METHOD: We studied 19 patients with CAO. The spirometry and body plethysmograph were performed in stable condition. And then patients performed a progressive incremental exercise test to a symptom-limited maximum using cycle ergometer. Patients were divided in two groups, severe and non-severe impairment, according to the resting PFTs and compaired each other. A patient was considered to be severely impaired if FVC < 50%, FEV1 < 40% or FEV1/FVC < 40%. RESULTS: 1) The airway obstruction and hypoxemia of severe impairment group were more severe and exercise performance was markedly reduced compairing to non-severe impairment group. 2) The severe impairment group showed ventilatory limitation during exercise test and the limiting symptomes ware dyspnea in 9/10 patients. 3) The impairment and disability of the patients with tuberculous destructed lung were most marked in patients with CAO. 4) The FEV1 was the most prevalent criterion for the determination of severe impairment based on resting PFTs and was the varuable best correlated to VO2max(r=0.8l, p < 0.001). 5) The sensitivity of exercise limits for predicting severe disability according to resting PFTs was 80% and specificity 89%. CONCLUSION: In patients with severe CAO, FEV1 is a good predictive of exercise performance and impairment measured by resting PFTs can predict a disability by exercise test.

Walking test for assessing lung function and exercise performance in patients with cardiopulmonary disease / 결핵

BACKGROUND: Dyspnea is common among patients with cardiopulmonary disease, and "daily disability" is defined as a functional impairment resulting from exercise intolerance. The maximal oxygen uptake(VO2max) during exhausting work is not only the best single physical indicator of the capacity of a man for sustaining hard muscular work, but also the most objective method by which one can determine the physical fitness of an individual as reflected by his cardiovascular system. However, the expense, time and personnel requirements make this procedure prohibitive for testing large group. The walking test is well-known type of exercise and it cost nothing to perform and have good reproducibility. Thus we performed the walking test and investigated correlations with spirometry, ABG and exercise test. METHOD: We observed the walking test and exercise test by cycle ergometer in 37 patients who visited our hospital because of dyspnea. Arterial blood gas analysis and spiromety, dyspnea index were performed, too. RESULT: (1) The VO2max was significantly lower in patients with COPD and cardiovascular disease than asthma and dyspnea on exertion group(p<0.05). The walking test distance was also lower in former. (2) The 12 minute walking test was significantly correlated with VO2max, PaCO2, FVC(%), FEV1(%) in all patients(p<0.05), and the walking test was only correlated with VO2max in patients with COPD(p<0.05). (3) In COPD patients, the VO2max was best correlated with FEV1(%) and FVC(%) and significantly correlated with walking test. But there was no correlation between walking test and FEV1(%) & FVC(%). (4) The 6 minute walking test was well correlated with 12 minute walking test(r=0.92, p<0.01). CONCLUSION: The walking test is the simple method for assessing exercise performance in patient with cardiopulmonary disease and a reliable indicator for VO2max. And the walking test is practical method for assessing on everyday disability rather than maximal exercise capacity. The 6 minute walking test is highly correlated with 12 minute walking test and a less exhausting for the patients and a time-saving for the investigator.