• Tuberculosis and Respiratory Diseases
• /
• v.54 no.1
• /
• pp.45-56
• /
• 2003

Background : Mycobacterium abscessus is the most common respiratory pathogen in rapidly growing mycobacteria and is resistant to all of the first-line antituberculosis drugs. This report describes the clinical and radiographic characteristics in patients with pulmonary disease caused by M. abscessus. Materials and Methods : Twelve patients with pulmonary disease caused by M. abscessus who fulfilled the 1997 American Thoracic Society diagnostic criteria for a nontuberculous mycobacterial pulmonary infection were observed over a five-and-a-half year period. The clinical characteristics and chest radiographic findings were analyzed, retrospectively. Results : The patients were predominantly female(11/12, 92%) and nonsmokers(12/12, 100%). Coughing (10/12, 83%), sputum(10/12, 83%) and hemoptysis(10/12, 83%) were the common symptoms and they had prolonged periods from the onset of symptoms to the diagnosis of their disease(median 6.5 years). Eleven (92%) patients had a previous history of being treated for pulmonary tuberculosis. The sputum specimens were acid-fast bacilli smear-positive in all patients. All patients were administered antituberculosis drugs. Six (50%) patients were treated with second-line antituberculosis drugs on account of persistent smear-positive sputum specimens. The chest radiographs showed that reticulonodular opacities(11/12, 92%) were the most common pattern of abnormality, followed by cavitary lesions(5/12, 42%). The computed tomography findings suggested bronchiolitis from the centrilobular nodules with a tree-in-bud appearances(9/10, 90%) and bronchiectasis (9/10, 90%) were the most common, followed by well-defined nodules smaller than 10-mm in diameter(7/10, 70%). Conclusions : M. abscessus pulmonary disease should be recognized as a cause of chronic mycobacterial lung disease, and respiratory isolates should be assessed carefully.

• Tuberculosis and Respiratory Diseases
• /
• v.54 no.1
• /
• pp.80-90
• /
• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.4
• /
• pp.277-284
• /
• 2008

Background: In principle, cervical tuberculous lymphadenitis (CTBL) is a medical disease that may require surgical treatment, particularly in young women who complain of psychosocial and cosmetic problems. We encountered 13 cases of aggravated CTBL treated surgically despite the appropriate course of antituberculous chemotherapy. We report the clinical characteristis of these cases. Methods: The clinical data of 13 patients with aggravated CTBL requiring surgical treatment from January 2000 to December 2006 at the Department of Chest Medicine, Internal Medicine and Plastic Surgery, National Medical Center was reviewed retrospectively. Results: Twelve of the 13 cases (92%) were female. The most common age was 21~30 years (69%). Multiple nodes were palpated in 11 cases (85%). The supraclavicular lymph nodes were sites the most commonly involved (54%). The other involved sites in the order of decreasing frequency were the jugular chain, posterior cervical, submandibular and infraauricular lymph nodes. A palpable mass was the most commonsymptom. Neck pain was reported in 3 cases (23%). General symptoms such as weight loss, fatigue, anorexia and night sweats were noted in 5 cases (38%). Respiratory symptoms such as cough, sputum, hemoptysis, dyspnea and chest pain were observed in 4 cases (31%). Pulmonary tuberculosis was noted in 11 cases (85%). Other extrapulmonary tuberculosis coexisted in 4 cases (31%). This suggests that surgical CTBLs may be manifestations of a systemic disease and might be difficult to treat. Most cases (92%) were stages 2 and 3 at the initial diagnostic period but all cases fell into stage 4 and 5 when reassesed before surgery. The average duration of anti-TB chemotherapy before and after surgery was 10.2 and 15.2 months, respectively. The 13 patients were followed up until June. 2008. Among them, 2 cases had newly developed CTBL and the other 11cases showed no recurrence. Conclusion: In principle, CTBL is the medical disease. However, despite the appropriate course of anti-TB chemotherapy, CTBL can progress to a more advanced stages and grow rapidly to a large-sized or fistulous mass with a persistent abscess. Surgical treatment may be inevitable for patients with psychosocial and cosmetic problems caused by these masses, particularly in young women.

• Radiation Oncology Journal
• /
• v.25 no.3
• /
• pp.160-169
• /
• 2007

Purpose: This study reports the results of the use of preoperative concurrent radiochemotherapy (CRCT) for the treatment of locoregionally advanced esophageal cancer. Materials and Methods: From 1998 through 2005, 61 patients with intrathoracic esophageal cancer at stages II-IVB (without distant organ metastasis and presumed to be respectable) received preoperative CRCT. CRCT consisted of radiotherapy (45 Gy /25 fractions /5 weeks) and FP chemotherapy (5-FU 1 g/$m^{2}$/day, days 1-4 and 29-32, Cisplatin 60 mg/$m^{2}$/day, days 1 and 29). An esophagectomy was planned in $4{\sim}6$ weeks after the completion of CRCT. Results: There were two treatment-related deaths. Among the 61 patients, 53 patients underwent surgery and 17 patients achieved a pathological complete response (pCR). The overall survival (OS) rates of all 61 patients at 2 and 5 years were 59.0% and 38.0%, respectively. The rates of OS and disease-free survival (DFS) of the surgically resected patients at 2 and 5 years were 61.6%, 40.1 % and 53.3%, 41.8%, respectively. By univariate analysis, achieviement of pCR and a clinically uninvolved distant lymph node (cMO) were favorable prognostic factors for OS and DFS. There were 27 patients that experienced a relapse-a locoregional relapse occurred in 5 patients, a distant metastasis occurred in 12 patients and combined failure occurred in 10 patients. Conclusion: The results of the current study are favorable. pCR and an uninvolved distant lymph node were found to be favorable prognostic factors.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.217-224
• /
• 2000

Background : It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-$\alpha$ and IL-1$\beta$. However, there is an alteration in the macrophages' responsiveness when they are challenged with repeated bouts of endotoxin, termed "endotoxin tolerance" which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. Methods : Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE II score. Peripheral blood monocytes were isolated from the patients and diluted to $1{\times}10^5$ well. After stimulation with endotoxin (LPS of E. coli O114 : B4, 100 ng/ml), they were incubated at $37^{\circ}C$ in 5% $CO_2$ incubator for 24 hours. Supernatant was collected for the measurement of TNF-$\alpha$ and IL-1$\beta$ with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. Results : The APACHE II score (mean$\pm$SD) of the patients at the time of blood sampling was 12.2$\pm$5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods (10 cases), gram positive cocci (6 cases) with two cases of mixed infection. Serum TNF-$\alpha$ could be measured in 4 cases with 29.9$\pm$27.7 pg/ml. Serum IL-1$\beta$was measurable in only one patient. The TNF-$\alpha$ level of supernatant of cultured peripheral blood monocytes was 2,703$\pm$2,066 pg/ml in patients and 2,102$\pm$1914 pg/ml in controls. The IL-1$\beta$level of supernatant was 884$\pm$1,050 pg/ml in patients and 575$\pm$558 pg/ml in controls. There was no difference of TNF-$\alpha$ and IL-1$\beta$ level between patients and controls. Conclusion : We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.697-704
• /
• 1998

Background: Asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils in the bronchial mucosa. Asthmatic bronchial mucosa produces many factors described as being chemotactic for inflammatory cells. IL-5, RANTES, and MCP-1 alpha are the chemotactic factors for eosinophils, but their roles are controversial. Recently eotaxin that is a potent eosinophil chemoattractant cytokine was detected in a guinea-pig model of allergic airway inflammation, and human eotaxin was cloned. Eotaxin is a specific chemoattractant for eosinophils, but its role in asthma is not confirmed. We examined the in vivo expression of eotaxin in bronchi of asthmatic patients. Methods : 11 asthmatics and 2 normal controls were enrolled. All subjects were underwent bronchoscopy with bronchial biopsies in 2nd or 3rd carina. RNA extraction from biopsy samples was done by acid-guanidium method. Semi-quantitaive RT-PCR was done for evaluation of eotaxin mRNA expression The extent of eosinophil infiltration was evaluated by counting the eosinophils in submucosa in HPF of microscope. Results : Eotaxin mRNA expressed in symptomatic, uncontrolled asthma. Steroid inhibited expression of eotaxin mRNA in asthma. Expression of eotaxin mRNA correlated with eosinophil infiltration in bronchial tissues. Conclusion: Expression of eotaxin mRNA increases in uncontrolled asthma and eotaxin is involved in the recruitment of eosinophils.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1188-1198
• /
• 1998

Background : The purpose of the present study was to determine the protective effect of antiasthmatic activity of inhaled heparin, cromolyn sodium, budesonide, furosemide in exercise-induced asthma(EIA). The other important considerable point of this study was the mechanism of bronchoconstriction on EIA. Methods : Eight subjects with a history of EIA were studied on 5 different experiment days. After obtaining baseline $FEV_1$ and FVC, subjects performed a standardized exercise challenge. EIA was assessed by measurement of $FEV_1$ before and after exercise. On experiment day 4, the exercise challenge was performed after the subjects inhaled either heparin (1,000 units/kg/day for 5 days), furosemide (1mg/kg for 5 days), cromolyn (4mg/day for 5 days), or budesonide ($400{\mu}g/day$ for 5 days). On experiment day 5, the methacholine bronchial provocation test was performed. On experiment day 3, activated partial thromboplastine time(aPTI) was checked. Results : Maximum decrements of $FEV_1$ (mean${\pm}$SE) among 0 to 120 minutes after exercise were as follows : heparin was $83.1{\pm}4.81%$ (p=0.010), furosemide was $80.5{\pm}6.87%$ (p=0.071), cromolyn was $86.8{\pm}6.53%$ (p=0.340), and budesonide was $79.4{\pm}7.31%$ (p=0.095). Above medications were compared to the control value ($72.5{\pm}18.2%$) by paired t-test. No medications had effect on $PD_{20}$ of methacholine bronchial provocation test The results were control $1.58{\pm}0.49{\mu}mol$), heparin ($4.17{\pm}1.96{\mu}mol$), furosemide ($1.85{\pm}0.86{\mu}mol$), cromolyn ($2.19{\pm}0.89{\mu}mol$), and budesonide ($3.38{\pm}1.77{\mu}mol$), respectively(p>0.05). The inhaled heparin had no effect of anticoagulation. Conclusion : These data demonstrate that inhaled heparin has a protective effect on EIA. The effect of inhaled cromolyn was statistically absent with manufacture's recommended dosage on EIA. So, the dosage of cromolyn should be carefully evaluated in future. Although inhalation of budesonide and furosemide have no statistical significance compared to control, these drugs also have some protective effects on EIA.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1167-1177
• /
• 1998

Background : Pulmonary tuberculosis is one of the diseases characterized granuloma formation which was controlled by cellular immune reactions. In the process of granulomatous changes, activated alveolar macrophages and T lymphocytes secrete many cytokines including interleukin-1 (IL-1), tumor necrosis factor-alpha(TNF-$\alpha$), interferon-gamma(IFN-$\gamma$) which mediate inflammatory reactions. Intercelluar adhesion molecule-1(ICAM-1) also known to major role player in inflammatory processes, and increased cellular expressions when endothelial cell was stimulated by IL-1, TNF and IFN. Method : To evaluate relationships among cellular immune reactions and clinical stages, pulmonary tuberculosis patients were classified into three groups according to their clinical stages including minimal, moderate and far advanced tuberculosis. TNF-$\alpha$ IFN-$\gamma$, sICAM-1 (soluble form of ICAM-1) were measured at the time of diagnosis and after 6-months anti-tuberculosis medications by radioimmuno assay or enzyme linked immunosolvent assay. Result : TNF-$\alpha$, IFN-$\gamma$, sICAM-1 were significantly increased in moderate and far advanced pulmonary tuberculosis patients but no meaningful changes in minimal staged patients. 6-months anti-tuberculosis medications reduced serum sICAM-1 levels significantly, related to clinical improvement but no significant changes were found in the serum levels of TNF-$\alpha$ and IFN-$\gamma$. In the point of correlations. positive ones revealed between TNF-$\alpha$ and sICAM-1, also between IFN-$\gamma$ and sICAM-1 but no correlation between TNF-$\alpha$ and IFN-$\gamma$. Conclusion : Measurement of serum sICAM-1 could be useful parameter to evaluate the severity of pulmonary tuberculosis and to monitor disease activities during anti-tuberculosis medications.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.2
• /
• pp.329-337
• /
• 1997

Background : Since endotracheal tube is the most important factor involved in the imposed work of breathing during mechanical ventilation, extubation of endotracheal tube is supposed to reduce respiratory work of patient. However, some patients show labored breathing after extubation despite acceptable blood gases. We investigated the changes of work of breathing before and after extubation and the factors involved in the change of WOB after extubation. Methods : The subjects were 34 patients(M : F = 20 : 14, mean age = $61{\pm}17yre$) who recovered from respiratory failure after ventilatory support and were considered to be ready for extubation. The patients with clinical or radiologic evidences of upper airway obstruction before endotracheal intubation for mechanical ventilation were excluded. Vital sign, physical examination, chest X-ray, work of breathing and other respiratory mechanic indices were measured prior to, immediately, 6, 24 and 48 hours after extubation serially. Definition of weaning failure after extubation was resumption of ventilatory support or reintubation of endotracheal tube within 48 hour after extubation because of respiratory failure. The patients were classified into group 1(decreased work of breathing), group 2(unchanged work of breathing) and group 3(increased work of breathing) depending on the statistical difference in the change of work of breathing before and after extubation. Results : Work of breathing decreased in 33%(11/34, group 1), unchanged in 41%(14/34, group 2) and increased in 26%(9/34, group 3) of patients after extubation compared with before extubation. Weaning failure occurred 9%(1/11) of group, 1, 28.6%(4/14) of group 2 and 44%(4/9) of group 3 after extubation(p = 0.07). The change of work of breathing after extubation was positively correlated with change of mean airway resistance(mRaw). (r = 0.794, p > 0.01). In three cases of group 3 whose respiratory indices could be measured until 48 hr after extubation, the change in work of breathing paralleled with the sequential change of mRaw. The work of breathing was peaked at 6 hr after extubation, which showed a tendency to decrease thereafter. Conclusions : Reversible increase of work of breathing after extubation may occur in the patients who underwent extubation, and the increase in mRaw could be responsible for the increase in work of breathing. In addition, the risk of weaning failure after extubation may increase in the patients who have increased WOB immediately after extubation.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.3
• /
• pp.348-358
• /
• 1996

Background : Interleukin-5 (IL-5) is responsible for eosinophilia in allergic diseases. In allergic bronchial asthma, there is a correlation between the extent of eosinophil infiltration in bronchial mucosa and IL-5 concentrations. In addition, IL-2 concentration is elevated in the airways and associated with eosinophilia in symptomatic patients with bronchial asthma. In animal studies, IL-2 can induce eosinophilia by increasing the synthesis of IL-5, however, it is still unknown how IL-2 can induce eosinophila in human being. The aim of this study is to evaluation the effect and mechanism of IL-2 on prolongation of eosinophil survival. Methods : After purifiing the eosinophils from the venous blood of allergic patients with eosinophilia, we measured the survival rates of eosinophils using trypan blue dye exclusion test, and the number of eosinophils with Randolp's solution. We compared the survival rates of eosinophils in the presence of IL-2 or IL-5. Neutralizing antibody for IL-5 was added in IL-2 treated eosinophils to reveal whether IL-2 induced prolongation of eosinophil survival was mediated by IL-5. We checked IL-5 m-RNA expression of lymphocytes in the presence of IL-2 by using Reverse transcription-Polymerase chain reaction (RT-PCR) method to revealed the effect of IL-2 on IL-5 m-RNA expression on lymphocyte. $\alpha$ and $\beta$ IL-2 receptors were measured on eosinophils and lymphocytes with flow-cytometer after stimulated with IL-2. Results : 1) Eosinophil survival rates increased dose dependently on IL-5 and IL-2. 2) The eosinophil survival rates increased by IL-2 were not inhibited by the pretreatment with neutralizing antibody for IL-5. 3) IL-5 m-RNA was not expressed on lymphocytes by the treatment with IL-2 up to 96 hours. 4) IL-2 upregulate the expression of IL-$2R{\alpha}$ on eosinophils, instead of no effect on the expression of IL-$2R{\beta}$. Conclusion: Interleukin-2 had the enhancing effect on the survival rates of eosinophils. The mechanism behind IL-2 induced eosinophilia might be the increment of IL-2 receptors on eosinophils rather than IL-5 synthesis by lymphocytes.