• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.69-84
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• 1997

Background : Although the overall prognosis of patients with lung cancer is poor, highly effective treatment exists for the small subset of patients with early lung cancer(carcinoma in situ/micro- invasive cancer). But very few patients have benefit from them because these lesions are difficult to detect and localize with conventional white-light bronchoscopy. To overcome this problem, a Lung Imaging Fluorescence Endoscopic device(LIFE) was developed to detect and clearly delineate the exact location and extent of premalignant and early lung cancer lesions using differences in tissue autofluorescence. Purpose : The purpose of this study was to determine the difference of sensitivity and specificity in detecting dysplasia and carcinoma between fluorescence imaging and conventional white light bronchoscopy. Material and Methods : 35 patients (16 with abnormal chest X-ray, 2 with positive sputum study, 2 with undiagnosed pleural effusion, 15 with respiratory symptom) have been examined by LIFE imaging system. After a white light bronchoscopy, the patients were submitted to fluorescence bronchoscopy and the findings of both examinations have been classified in 3 categories(class I, II, III). From of all class n and III sites, 79 biopsy specimens have been collected for histologic examination: a comparison between histologic results and white light or fluorescence bronchoscopy has been performed for assessing sensitivity and specificity of the two methods. Results : 1) Total 79 sires in 35 patients were examined. Histology demonstrated 8 normal mucosa, 21 hyperplasia, 23 dysplasia, and 27 microinvasive and invasive carcinoma. 2) The sensitivity of white light or fluorescence bronchoscopy in detecting dysplasia was 60.9% and 82.6%, respectively. 3) The results of this study showed 70.3 % sensitivity for microinvasive or invasive carcinoma with LIFE system, versus 100% sensitivity for white light in 27 cases of carcinoma. The false negative study of LIFE system was 8 cases(3 adenocarcinoma and 5 small cell carcinoma), which were infiltrated in submucosal area and had normal epithelium. Conclusion : To improve the ability 10 diagnose and stage more accurately, fluorescence imaging may become an important adjunct to conventional bronchoscopic examination because of its high detection rate of premalignant and malignant epithelial lesion. But. it has limitation to detect in submucosal infiltrating carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.853-860
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• 1997

Background : Chronic cough, defined as a cough persisting for three weeks or longer, is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, and gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. Method : 111 patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma, bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patients with wheeze, 22 patients with dyspnea, 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1s($PC_{20}FEV_1$) and 25% fall in maximal mid-inspiratory flow ($PC_{25}MIF_{50}$) were used as bronchial and extra thoracic hyperresponsiveness. Results : There were four response patterns to methacholine challenge study : BHR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in 8 patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BHR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze and/or dyspnea, BHR was more common than EAHR. Conclusion : These results show that among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.558-570
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• 1996

Background : The detection of Collapsible airways has important therapeutic implications in chronic airway disease and bronchial asthma. The distinction of a purely collapsible airways disease from that of asthma is important because the treatment of the dormer may include the use of pursed lip breathing or nasal positive pressure ventilation whereas in the latter, pharmacologic approaches are used. One form of irreversible airflow limitation is collapsible airways, which has been shown to be a Component of asthma or to emphysema, it can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmography. Method : To investigate whether volume difference between slow and forced vital Capacity(SVC-FVC) by spirometry may be used as a surrogate index of airway collapse, we examined pulmonary function parameters before and after bronchodilator agent inhalation by spirometry and body plethysmography in 20 cases of patients with evidence of airflow limitation(chronic obstructive pulmonary disease 12 cases, stable bronchial asthma 7 cases, combined chronic obstructive pulmonary disease with asthma 1 case) and 20 cases of normal subjects without evidence of airflow limitation referred to the Pusan National University Hospital pulmonary function laboratory from January 1995 to July 1995 prospectively. Results : 1) Average and standard deviation of age, height, weight of patients with airflow limitation was $58.3{\pm}7.24$(yr), $166{\pm}8.0$(cm), $59.0{\pm}9.9$(kg) and those of normal subjects was $56.3{\pm}12.47$(yr), $165.9{\pm}6.9$(cm), $64.4{\pm}10.4$(kg), respectively. The differences of physical characteristics of both group were not significant statistically and male to female ratio was 14:6 in both groups. 2) The difference between slow vital capacity and forced vital capacity was $395{\pm}317ml$ in patients group and $154{\pm}176ml$ in normal group and there was statistically significance between two groups(p<0.05). Sensitivity and specificity were most higher when the cut-off value was 208ml. 3) After bronchodilator inhalation, reversible airway obstructions were shown in 16 cases of patients group, 7 cases of control group(p<0.05) by spirometry or body plethysmography d the differences of slow vital capacity and forced vital capacity in bronchodilator response group and nonresponse group were $300.4{\pm}306ml$, $144.7{\pm}180ml$ and this difference was statistically significant. 4) The difference between slow vital capacity and forced vital capacity before bronchodilator inhalation was correlated with airway resistance before bronchodilator(r=0.307 p=0.05), and the difference between slow vital capacity and forced vital capacity after bronchodilator was correlated with difference between slow vital capacity and forced vital capacity(r=0.559 p=0.0002), thoracic gas volume(r=0.488 p=0.002) before bronchodilator and airway resistance(r=0.583 p=0.0001), thoracic gas volume(r=0.375 p=0.0170) after bronchodilator, respectively. 5) The difference between slow vital capacity and forced vital capacity in smokers and nonsmokers was $257.5{\pm}303ml$, $277.5{\pm}276ml$, respectively and this difference did not reach statistical significance(p>0.05). Conclusion : The difference between slow vital capacity and forced vital capacity by spirometry may be useful for the detection of collapsible airway and may help decision making of therapeutic plans.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.58-66
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• 1995

Background: Acute interstitial pneumonia is a relatively rare form of interstitial pneumonia, since the vast majority of interstitial pneumonia have a more chronic course. It corresponds to the lesion described by Hamman and Rich, as Hamman-Rich disease in 1944. Another name in the clinical literature is accelerated interstitial pneumonia, idiopathic acute respiratory distress syndrome (idiopathic ARDS), and the organizing stage of diffuse alveolar damage. Acute interstitial pneumonia differs from chronic interstitial pneumonia by clinical and pathologic features. Clinically, this disease is characterized by a sudden onset and a rapid course, and reversible disease. Method and Purpose: Five cases of pathologically proven acute interstitial pneumonia were retrospectively studied to define the clinical, radiologic, and pathologic features. Results: 1) The five cases ranged in age from 31 to 77 years old. The onset of illness was acute in all patients, it began with viral-like prodrome 6~40 days prior to shortness of breath, and respiratory failure eventually developed in all patients. In 2 cases, generalized skin rash was accompanied with flu-like symptoms. Etiologic agent could not be identified in any case. 2) All patients had leukocytosis and severe hypoxemia. Pulmonary function test of 3 available cases shows restrictive ventilatory defect, and one survived patient(case 5) has a complete improvement of pulmonary function after dismissal. 3) Diffuse bilateral chest infiltrates were present radiologically. Theses were the ground-glass, consolidation, and reticular densities without honeycomb fibrosis in all patients. The pathologic abnormalities were the presence of increased numbers of macrophages and the formation of hyaline membranes within alveolar spaces. There was also interstitial thickening with edema, proliferation of immature fibroblast, and hyperplasia of type II pneumocyte. In the survived patient(case5), pathologic findings were relatively early stage of acute interstitial pneumonia, such as hyaline membrane with mild interstitial fibrosis. 4) Of the 5 patients, four patients died of respiratory failure 14~90 days after onset of first symptom, and one survived and recovered in symptoms, chest X ray, and pulmonary function test Conclusion: These results emphasize that acute interstitial pneumonia is clinically, radiologically, and pathologically distinct form of interstitial pneumonia and should be separated from the group of chronic interstitial pneumonia. Further studies will be needed to evaluate the pathogenesis and the treatment of acute interstitial pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.6-15
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• 1993

Background: Positive end, expiratory pressure (PEEP) has become one of the standard therapies for adult respiratory distress syndrome (ARDS). Total static compliance has been proposed as a guide to determine the size of PEEP ('best PEEP') which is of unproven clinical benefit and remains controversial. Besides increasing functional residual capacity and thus improving oxygenation, PEEP stimulate prostacyclin secretion and was proposed for the treatment of acute pulmonary embolism. But little is known about the effect of PEEP on hemodynamic and gas exchange disturbances in acute pulmonary embolism. Methods: To study the validity of total static compliance as a predictor of 'best PEEP' in ARDS and acute pulmonary embolism, experimental ARDS was induced in mongrel dog with oleic acid and acute pulmonary embolism with autologous blood clot. Then hemodynamic and gas exchange parameters were measured with serial increment of PEEP. Results:In ARDS group, total static compliance and oxygen transport were maximal at 5 cm$H_2O$, and decreased thereafter (p<0.05). With increment of PEEP, arterial oxygen tension ($PaO_2$) and arterial carbon dioxide tension ($PaCO_2$) increased and cardiac output and physiological shunt decreased. In pulmonary embolism group, total static compliance, oxygen transport, physiological shunt and cardiac output decreased and $PaO_2$ and $PaCO_2$ increased with increment of PEEP (p<0.05). Comparing the change induced by increment of PEEP by 1 cm$H_2O$ in ARDS group with that in pulmonary embolism group, there was no significant difference between two groups except cardiac output which decreased more in pulmonary embolism group (p<0.05). In ARDS group, oxygen transport and total static compliance increased after PEEP application, and total static compliance was maximal at the PEEP level where oxygen transport was maximal. However in pulmonary embolism group, oxygen transport and total static compliance decreased after application of PEEP. There was significant correlation between change of total static compliance and change of oxygen transport in both groups. Conclusion: In both ARDS and acute pulmonary embolism, it can be concluded that total static compliance is useful as a predictor of 'best PEEP'.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.409-419
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• 2002

Background : The therapeutic effects of surfactant on acute lung injury derive not only from its recruiting action on collapsed alveoli but also from its anti-inflammatory effects. Pro-apoptotic action on alveolar neutrophils represents one of the important anti-inflammatory mechanisms of surfactant. In the present study, we evaluated the effects of sufactant on the apoptosis of human peripheral and rat alveolar neutrophils. Methods : In the (Ed- the article is not definitely needed but it helps to separate the two prepositions 'in') in vitro study, human neutrophils were collected from healthy volunteers. An equal number of neutrophils ($1{\times}10^6$) (Ed-confirm) was treated with LPS (10, 100, 1000ng/ml), surfactant (10, 100, $1000{\mu}g/ml$), or a combination of LPS (1000ng/ml) and surfactant (10, 100, $1000{\mu}g/ml$). After incubation for 24 hours, the apoptosis of neutrophils was evaluated by Annexin V method. In the in vivo study, induction of acute lung injury in SD rats by intra-tracheal instillation of LPS (5mg/kg) was followed by intra-tracheal administration of either surfactant (30mg/kg) or normal saline (5ml/kg). Tenty-four hours after LPS instillation, alveolar neutrophils were collected and the apoptotic rate was evaluated by Annexin V method. In addition, changes of the respiratory mechanics of rats (respiratory rate, tidal volume, and airway resistance) were evaluated with one chamber body plethysmography before, and 23 hours after, LPS instillation. Results : in the in vitro study, LPS treatment decreased the apoptosis of human peripheral blood neutrophils (control: $47.4{\pm}5.0%$, LPS 10ng/ml; $30.6{\pm}10.8%$, LPS 100ng/ml; $27.5{\pm}9.5%$, LPS 1000ng/ml; $24.4{\pm}7.7%$). The combination of low to moderate doses of surfactant with LPS promoted apoptosis (LPS 1000ng/ml + Surf $10{\mu}g/ml$; $36.6{\pm}11.3%$, LPS 1000ng/ml +Surf $100{\mu}g/ml$; $41.3{\pm}11.2%$). The high dose of surfactant ($1000{\mu}g/ml$) decreased apoptosis ($24.4{\pm}7.7%$) and augmented the anti-apoptotic effect of LPS (LPS 1000ng/ml + Surf $1000P{\mu}g/ml$; $19.8{\pm}5.4%$). In the in vivo study, the apoptotic rate of alveolar neutrophils of surfactant-treated rats was higher than that of normal saline-treated rats ($6.03{\pm}3.36%$ vs. $2.95{\pm}0.58%$). The airway resistance (represented by Penh) of surfactant-treated rats was lower than that of normal saline-treated rats at 23 hours after LPS injury ($2.64{\pm}0.69$ vs. $4.51{\pm}2.24$, p<0.05). Conclusion : Surfactant promotes the apoptosis of human peripheral blood and rat alveolar neutrophils. Pro-apoptotic action on neutrophils represents one of the important anti-inflammatory mechanisms of surfactant.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.323-331
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• 2000

Purpose: Brain metastases are present in approximately 10-16% of small cell lung cancer patients at diagnosis. Brain metastasis is an important clinical problem associated with increasing the survival rate, with a cumulative incidence of up to 80% in patients surviving 2 years. Prophylactic cranial irradiation(PCI) reduces the incidence of brain matastasis and may prolong survival in patients with limited small-cell lung cancer who achieved complete remission. This study was performed to analyze the incidence of brain metastasis, survival and clinical aspects after PCI in patients with limited small-cell lung cancer who achieved complete remission. Methods : Between 1989 and 1999, forty-two patients with limited small-cell lung cancer who achived achieved complete remission after therapy were enrolled into this study retrospectively. All patients received etoposide and cisplatin(VPP) alternating with cytoxan, adriamycin, and vincristine(CAV) every 3 weeks for at least 6 cycles initially. All patients received thoracic radiotherapy: concurrent(38.1%) and sequential(61.9%). All patients received late PCI. Results : Most patients(88.1%) were men, and the median age was 58 years. The median follow-up duration was 18.1 months. During the follow-up period, 57.1% of the patients developed relapse. The most frequent site of relapse was chest(35.7%), followed by brain(14.3%), liver(11.9%), adrenal gland(44%), and bone(2.2%). With the Kaplan-Meier method, the average disease-free interval was 1,090 days(median 305 days). The average time to development of brain relapse after PCI and other sites relapse(except brain) were 2,548 days and 1,395 days(median 460 days), respectively. The average overall survival was 1,233 days(median 634 days, 21.1 months), and 2-year survival rates was 41.7%. The average overall survival in the relapse group was 642 days(median 489 days) and in the no relapse group was 2,622 days(p<0.001). The average overall survival in the brain relapse group was 928 days(median 822 days) and in the no brain relapse group was 1,308 days(median 634 days)(p=0.772). In most patients(85.7%), relapse(except brain) or systemic disease was the usual cause of death. Brain matastasis was the cause of death in 14.3% of the cases. Conclusions : We may conclude that PCI reduces and delays brain metastasis in patients with limited small cell lung cancer who achieved complete remission. We found decreased survival in relapse group but, no significant survival difference was noted according to brain matastasis. And relapse(except brain) or systemic disease was the usual cause of death. In order to increase survival, new treatment strategies for control methods for relapse and systemic disease are required.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.795-802
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• 1999

Objective : Cardiopulmonary exercise test is a useful tool to evaluate the operative risk and to plan exercise treatment for the patients with chronic obstructive pulmonary disease(COPD). In cardiopulmonary exercise test, most of the measured parameters are recorded at the time of peak exercise, which are hard to attain in COPD patients. So we evaluated the usefulness of the parameter, breathing reserve index(BRI=minute ventilation [$V_E$]/maximal voluntary ventilation[MVV]) at the time of anaerobic threshold($BRI_{AT}$) for the differentiation of COPD patients with normal controls. Methods : Thirty-six COPD patients and forty-two healthy subjects underwent progressive, incremental exercise test with bicycle ergometer upto possible maximal exercise. All the parameters was measured by breath by breath method. Results : The maximal oxygen uptake in COPD patients (mean$\pm$SE) was $1061.2{\pm}65.6ml/min$ which was significantly lower than $2137.6{\pm}91.4ml/min$ of normal subjects(p<0.01). Percent predicted maximal oxygen uptake was 54.3% in COPD patients and 86.0% in normal subjects(p<0.01). Maximal exercise(respiratory quotient; $VCO_2/VO_2{\geq}1.09$) was accomplished in 7 of 36 COPD patients(19.4%) and in 18 of 42 normal subjects(42.9%). The $BRI_{AT}$ of COPD patients was higher($0.50{\pm}0.03$) than that of control subject($028{\pm}0.02$, p<0.01), reflecting early hyperventilation in COPD patient during exercise. The correlation between $BRI_{AT}$ and BRI at maximal exercise in COPD patients was good(r=0.9687, p<0.01). Conclusion : The $BRI_{AT}$ could be a useful parameter for the differentiation of COPD patients with normal controls in the submaximal cardiopulmonary exercise test.