Transtorming Growth Factor beta1 Induces Epithelial-to-Mesenchymal Transition of A549 Cells

Idiopathic pulmonary fibrosis (IPF) comprises an aggregate of mesenchymal cells. However, the cellular origin of these mesenchymal phenotypes remains unclear. Transforming growth factor beta1 (TGF-beta1) has been known as the main cytokine involved in the pathogenesis of IPF. We examined whether the potent fibrogenic cytokine TGF-beta1 could induce the epithelial-to-mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and determined whether snail expression is associated with the phenotypic changes observed in the A549 cells. EMT was investigated with cells morphology changes under phase-contrast microscopy, western blotting, and indirect immunofluorescence stains. E-cadherin and transcription factor, snail, were also evaluated by measuring mRNA levels using reverse transcriptase-polymerase chain rection (RT-PCR) analysis. The data showed that TGF-beta1 induced A549 cells with epithelial cell characteristics to undergo EMT in a concentration-dependent manner. Following TGF-beta1 treatment, A549 cells induced EMT characterized by cells morphological changes, loss of epithelial markers Ecaherin and cytokeratin, increased stress fiber reorganization by F-actin, and cytokeratin replacement by vimentin. Although IL-1beta failed to induce A549 cells to undergo EMT, the combination of TGF-beta1 and IL-1beta showed synergy effects in cells morphology changes and the expression of mesenchymal markers. The snail expression study using RT-PCR analysis provided that loss of E-cadherin expression was associated with snail expression. Stimulation of A54 cells with TGF-beta1 plus IL-1beta revealed a higher level of snail expression. Our data showed that EMT of A549 cells might be closely associated with snail expression.

Predictors on In-hospital Mortality Following In-hospital Diagnosis of Tuberculosis / 결핵및호흡기질환

STUDY OBJECTIVES: To determine the factors associated with mortality after an in-hospital diagnosis of tuberculosis in a region with low levels of HIV coinfection. METHODS: From January 2003 to December 2004, all subjects who were > 15 years of age and had received a diagnosis of tuberculosis were registered. The clinical, radiological and laboratory aspects of the patients who died (n=27) were compared with those of an age and gender matched control population(n=54). Logistic regression analyses were carried out, which included age, gender, hospital admission source, initial site of admission, dyspnea, general weakness and initial laboratory data. RESULTS: The mean age of the patients was 60 +/- 16 years and male patients outnumbered female patients. Univariate analysis identified hemoglobin, blood urea nitrogen, albumin, cholesterol, aspartate aminotransferase (AST), C-reactive protein and the risk factors for tuberculosis to be significantly associated with mortality. Among the characteristics of disease presentation and treatment, emergency department admission, intensive care unit, disease severity, general weakness and dyspnea at the time of admission were associated with mortality. Multiple regression analysis revealed the initial management in the intensive care unit and lower serum albumin to be independently associated with mortality. CONCLUSION: The markers of disease chronicity and severity appear to be associated with in-hospital mortality. Identifying potentially reversible factors such as malnutrition and respiratory failure suggests specific intervention that might lead to an improvement in the patients' outcomes.

A Case of Pulmonary Cryptococcosis by Capsule-deficient Cryptococcus neoformans

Pulmonary infection by capsule-deficient Cryptococcus neoformans (CDCN) is a very rare form of pneumonia and it is seldom seen in the immunocompetent host. The authors experienced a case of pulmonary cryptococcosis by CDCN in 25-year-old woman who was without any significant underlying disease. The diagnosis was made from the percutaneous lung biopsy and special tissue staining, including Fontana-Masson silver (FMS) staining. Fungal culture confirmed the diagnosis afterward. Her clinical and radiologic features improved under treatment with fluconazol. It's known that CDCN is not so readily confirmed because fungal culture does not always result in growth of the organism and the empirical fungal stain is not helpful for the differentiation between CDCN and the other infections that are caused by the nonencapsulated yeast-like organisms. In this report, we emphasize the diagnostic value of performing FMS staining for differentiating a CDCN infection from the other confusing nonencapsulated yeast-like organisms.

A 5-year review of clinical characteristics and mortality of burn patients with candidemia in a tertiary burn center / 대한내과학회지

BACKGROUND: Nosocomial candidemia is one of the most common blood-stream infection and associated with a high fatality rate in burn patients. To determine the clinical characteristics, strains of Candida species and to identify contributing factors to death, we analyzed severely burned patients with candidemia. METHODS: 60 cases with candidemia were reviewed retrospectively from January 1999 to December 2003 at a tertiary burn center in Korea. Candidemia was defined as at least one blood culture that grew Candida organisms. RESULTS: Burn size of all patients were 46+/-20.9% of total body surface area burn and overall mortality was 41.7%. 97 strains of Candida species from 60 cases were isolated. Candida albicans was the most frequently isolated species (53.6%), followed by C. tropicalis (20.6%), C. glabrata (15.5%) and C. parapsilosis (10.3%). Among various predisposing factors for candidemia, significant factors associated with death were endotracheal tube insertion or tracheostomy, mechanical ventilation, the use of vasoactive agents, arterial catheterization and nasogastric tube insertion in univariate analysis, but significant independent factors for mortality were mechanical ventilation (OR=26.63, 95% CI; 1.60, 444.18, p=0.022) and the use of vasoactive agents (OR=23.18, 95% CI; 2.80, 192.35, p=0.004) in multivariate analysis. Among 59 patients indwelling central venous catheters, only 24 patients (40.7%) received antifungal therapy with catheter removal while 19 patients (32.2%) had antifungal therapy without catheter removal. CONCLUSIONS: Clinical severity, such as mechanical ventilation or vasoactive agents dependencies, may contribute to high fatality in severely burned patients with candidemia.

A Case of Cavitary Lung Lesion as a Consequence of Smoke Inhalation Injury / 결핵및호흡기질환

Toxic gases and soot deposition as a consequence of smoke inhalation can cause direct injury to the upper and lower airways and even to the lung parenchyma. A delay in proper and prompt therapy can be detrimental to critically ill burn patients with an inhalation injury. Therefore, serial chest radiography is an important diagnostic tool for pulmonary complications during treatment. The radiographic findings of the chest include normal, consolidation, interstitial and alveolar infiltrates, peribronchial thickening, atelectasis, cardiogenic and non-cardiogenic pulmonary edema, and a pneumothorax as acute complications of smoke inhalation. In addition, bronchiectasis, bronchiolitis obliterans and pulmonary fibrosis can occur as late complications. We encountered a case of 44-year-old male who presented with acute lung injury after an inhalation injury. He required endotracheal intubation and mechanical ventilation due to respiratory failure. He was managed successfully with conservative treatment. Later, a cavitary lesion of the left upper lobe was observed on the chest radiography and computed tomography, which was complicated by massive hemoptysis during the follow-up. However, the cavitary lesion disappeared spontaneously without any clinical consequences.

The Role of Inhaled Corticosteroid in the Management of Chronic Cough / 결핵및호흡기질환

BACKGROUND: Cough may be a consequence of bronchial hyperresponsiveness or inflammation. Empirical treatment is important in this context because it difficult to verify the obvious cause of cough using laboratory tests, Corticosteroid has a nonspecific anti-inflammatory effect, and can be used for cough management. However, its response rate has not yet been fully elucidated. This study investigated the short-term effects of inhaled corticosteroid on chronic cough METHODS: Patients with chronic cough with a normal chest radiograph and a pulmonary function test were enrolled. Cases with a prior respiratory infection within 8 weeks, a history of bronchial asthma, objective wheezing on examination, subjective symptoms of gastroesophageal reflux or taking an ACE inhibitor were excluded. On the first visit, a methacholine bronchial provocation test, spontaneous sputum eosinophil count performed twice and a paranasal sinus radiograph were checked, and the patients were treated with budesonide turbuhaler 800 microgram/day for ten days. The primary outcome measure was a decrease in the cough score after treatment. RESULTS: Sixty nine chronic coughers were finally analyzed. The final diagnoses by the routine tests were as follows: bronchial asthma 13.0%, eosinophilic bronchitis 18.8%, paranasal sinusitis 23.2% and non-diagnostic cases 53.6%. The following responses to the inhaled corticosteroid were observed: definite responders, 76.8%, possible responders, 2.9% and non-responders, 20.3%. The response rate was not affected by the final diagnosis even in the non-diagnostic cases. There were minimal adverse drug related effects during the empirical treatment. CONCLUSION: Routine objective tests such as methacholine provocation, sputum eosinophil count and simple radiographs were notare not suitable for diagnosing chronic cough Therefore, empirical treatment is important. Short term inhaled corticosteroid is effective and can guide a further treatment plan for chronic cough.

Small Cell Carcinoma Manifesting as a Bulky Thoracic Mass in a Pregnant Woman: A Case Report

The classic presentation of small cell carcinoma is hilar or mediastinal lymph node metastases while the primary tumor remains an occult tumor. Grossly enlarged hilar and mediastinal lymph nodes can be frequently seen on the chest radiographs and CT scans. We report here on a case of small cell carcinoma that manifested as a unilateral bulky thoracic mass in a pregnant woman.

A case of septic embolism after fever, sore throat, and myalgia / 대한내과학회지

Lemierre syndrome or postanginal septicemia (necrobacillosis) is caused by an acute oropharygeal infection with secondary septic internal jugular vein thrombophlebitis and frequent metastatic infections. 17-aged girl visted emergency room with dyspnea. She had the symptoms of fever, sore throat and myalgia before 3 or 4 days. She had multiple septic emboli in both lung fields and septic thrombophlebitis of right internal jugular vein. Although Fusobacterium necrophorum is the most common pathogen isolated from the patients, The pathogen can not be confirmed. We experienced a case of Lemierre syndrome with septic embolism after fever, sore throat and myalgia. We present the case with the review of literature.

Combined Large Cell Neuroendocrine Carcinoma with Component of Adenocarcinoma: A case report / 대한흉부외과학회지

Combined large cell neuroendocrine carcinoma is an uncommon lung cancer that include large cell neuroendocrine carcinoma with components of adenocarcinoma, squamous cell carcinoma, giant cell carcinoma and/or spindle cell carcinoma histologically. We report a case that pathologically diagnosed as combined large cell neuroendocrine carcinoma with component of adenocarcinoma after right pneumonectomy and mediastinal lymph node dissection. A 44-year-old man with intermittent chest pain was referred to our hospital for lung mass on the right mid lung field.

A Case of Bronchial Varices in a Patient with Severe Mitral Stenosis / 결핵및호흡기질환

The bronchial varices in mitral stenosis are uncommon and incidentally discovered during bronchoscopy. Although bronchial varices are primarily associated with bronchial or pulmonary disease, the bronchial vein can be dilated with increased pulmonary venous pressure secondary to mitral stenosis. The bronchial varices may present massive hemoptysis. The hemoptysis can be controlled by mitral commissurotomy or mitral valve replacement in case of mitral stenosis. We report a case of bronchial varies in a patient with severe mitral stenosis. The bronchial varices were found incidentally during bronchoscopy and they were nearly disappeared by mitral valve replacement.

A Case of Interstitial Pneumonitis Caused by Leflunomide / 결핵및호흡기질환

Leflunomide is a new disease modifying anti rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis. Its mechanism of action differs from other DMARDs in that it inhibits the de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase and therefore prevents the proliferation of activated lymphocytes. As it has been prescribed worldwide, there is a great deal of much concerns regarding its potential adverse effects. Because leflunomide has an active metabolite with a long elimination half life of approximately 2 weeks, serious adverse reactions may occur even after the leflunomide treatment has been stopped. The profile of serious reactions includes liver dysfunction, hematological disorders, severe skin reactions and respiratory dysfunction. Respiratory dysfunctions with leflunomide therapy are very rare and its incidence is lower than that of methotrexate therapy. However, there are reports in Japan showing that 5 patients died of interstitial pneumonitis and another 11 patients developed serious lung complications associated with leflunomide. This suggests the possibility of fatal respiratory toxicity of leflunomide. There are no reports of interstitial pneumonitis associated with leflunomide in Korea. We report a case of a 62-year old woman who developed interstitial pneumonitis, which might have been induced by leflunomide during the treatment of rheumatoid arthritis.

The Role of Respiratory Viral Infections in Exacerbation of Asthma and Chronic Obstructive Pulmonary Disease (COPD) / 결핵및호흡기질환

BACKGROUNDS: The exacerbations of asthma and chronic obstructive pulmonary disease (COPD) have been suggested to be associated with respiratory tract viral infections (RTVIs). However, the rates of virus detection in previous studies have been quite variable, with lower rates for the exacerbation of COPD. Therefore, the virus detection of patients with exacerbation of asthma and COPD were investigated. METHODS: 20 and 24 patients with exacerbation of asthma and COPD, respectively, were enrolled. Nasal and sputum samples were taken, and polymerase chain reaction (PCR) for rhinovirus and coronavirus and virus culture for influenza A, B, RSV and parainfluenza virus performed. RESULTS: The mean FEV1/FVC in the exacerbation of asthma and COPD patients were 1.9/2.9 L (65.5%) and 1.1/2.6 L (42.3%), respectively. Respiratory virus was detected in 13 (65%) patients with exacerbation of asthma and rhinovirus was detected in 9. Coronavirus, influenza A, RSV and parainfluenza virus were detected in 2, 2, 1 and 1 patients with asthma. Among patients with exacerbation of COPD, a virus was detected in 14 (58.3%) patients, with rhinovirus, coronavirus and influenza A detected in 10, 3 and 4, respectively. CONCLUSIONS: This study suggested that RTVIs may have a role in the exacerbation of COPD as well as asthma.

A Case of Intrapulmonary Solitary Fibrous Tumor: A case report / 대한흉부외과학회지

Solitary fibrous tumor is an uncommon submesothelial mesenchymal neoplasm that arises primarily from the pleura. Extrapleural solitary fibrous tumors are rare. Solitary Fibrous tumors are often asymptomatic and discovered incidentally but may become symptomatic when vital structures are involved or they grow large. In general, solitary fibrous tumor is diagnosed on the basis of radiologic findings and its histologic features, with immunohistochemistry serving to support the diagnosis. Most solitary fibrous tumors pursue a benign course, and the single most important predictor of clinical outcome is the ability to excise the entire lesion. We experienced a case of intrapulmonary solitary tumor arising from the right lower lobe which was treated with wedge resection. We report this case of the patient.

Diagnostic Performance of Routine Objective Tests and Cost-Effective Approach for Chronic Cough / 결핵및호흡기질환

BACKGROUND: Despite the clinical clues of bronchial asthma, some chronic coughers fail to be diagnosed due to negative test results. This study was aimed at evaluating the diagnostic performance of routine objective tests and identifying a cost-effective approach for asthmatics with a chronic cough. METHODS: Patients with a chronic cough of more than 3 weeks duration, and showing normal chest radiograph and spirometry were enrolled. On the first visit, objective tests, composed of serum total IgE, peripheral blood eosinophil count, spontaneous sputum eosinophil count, methacholine bronchial provocation test (MBPT) and paranasal sinus radiograph, were performed, with the simultaneous administration of oral prednisolone (0.5mg/kg) for one week. The final diagnoses were made on the basis of the test results, and the patients grouped according to their steroid responsiveness. The role of the etiologic diagnosis tests was evaluated, and the medical costs of the final management plan simulated with respect to three assumed models. RESULTS: Sixty chronic coughers were finally analyzed. The final diagnoses were as follows: bronchial asthma 21.7%, eosinophilic bronchitis 6.7%, paranasal sinusitis 18.3%, presumptive allergy 8.3% and non-diagnostic case 45.0%. Ninety percent were steroid responder. With the bronchial asthma cases, the positive rate of MBPT was 38.5%, with sputum eosinophil count in 84.6%, serum total IgE in 38.5%, and a peripheral blood eosinophil count rate of 30.8%. When the test results and steroid responsiveness data were applied to the 3 models, the chest radiograph, spirometry, sputum eosinophil count and paranasal sinus radiograph test results, and simultaneous short term steroid treatment seemed to have acceptable diagnostic performances, which could be used as a further guide to cost-effective planning. Conclusion:Objective tests, composed of chest radiograph, spirometry, paranasal sinus radiograph and sputum eosinophil count, with simultaneous short term steroid treatment, are suggested as cost-effective approaches for asthmatics with a chronic cough.

A Case of Chemical Pneumonitis Caused by Nitric Acid Fume Inhalation / 결핵

Chemical pneumonitis is caused by the inhalation of noxious chemical substances and is a cause of occupational lung disease. Nitric acid, which is a one of the common air pollutants and a potential oxidant for refining and cleansing of metals, has a chance for occupational and environmental exposure. A 52-year-old man visited our hospital due to coughing and dyspnea after the inhalation of nitric acid fumes at his workplace. He had conditions of tachypnea (respiratory rate 26 /min) and hypoxemia (PaO2 42.6 mmHg, SaO2 80.2% in room air) in our emergency department. The chest radiographs showed diffuse interstitial infiltrates and ground glass opacity in both lungs. The patient made improvements in clinical symptoms and chest radiography after being given a supply of oxygen, antibiotics, and bronchodilator therapy without systemic glucocorticoid therapy. On his follow up visit after 4 weeks, he showed no symptoms and sequelae, and the pulmonary function test showed a normal pulmonary function.

Occurrence of tuberculous pleurisy associated with infliximab therapy / 대한내과학회지

Infliximab is a chimeric antibody against tumor necrosis factor-alpha and it can be used in the treatment of ankylosing spondylitis. Tumor necorosis factor-alpha is a potent proinflammatory cytokine and plays a key role in the host response against tuberculosis. Infliximab is known to be effective on active ankylosing spondylitis but it can also cause reactivation of latent tuberculosis. Physicians should screen patients for latent tuberculous infection or disease before prescribing the drug. We experienced a case of tuberculous pleurisy after taking infliximab in a patient suffering from ankylosing spondylitis. We present the case with a review of literature.

Clinical Investigation of Recurrent Pneumonia in Adults: Analysis of Patients From Hallym University Medical Center / 결핵및호흡기질환

BACKGROUND: Recurrent pneumonia in adults is not uncommon. However, there is no domestic data about recurrent pneumonia in adults. Therefore, we investigated the associated diseases and clinical findings of recurrent pneumonia in adults. METHODS: Among 5513 patients who were treated in five teaching hospitals of Hallym medical center?over a 5-year period, we retrospectively reviewed the medical records of the 58 who were compatible with diagnostic criteria of recurrent pneumonia. RESULTS: The number of patients with recurrent pneumonia was 58 (1.05%, 58/5513) during the 5 years. Thirty- seven patients were male and 21 were female. Mean age was 66.4 (+/-14.9) years. Median interval between each pneumonic episode was 18.5 months. Associated diseases were 25 cases of respiratory diseases, 13 of heart diseases, 13 of diabetes mellitus, 7 of lung malignancies, 11 of malignancies other than lung, 7 of neurologic disease, and 8 of miscellaneous diseases. Three cases had no underlying illness. Of the 8 cases with 2 or more times of recurrence, 4 were associated with respiratory diseases, 2 with aspiration pneumonia due to neurologic diseases, 1 with heart disease and 1 with no underlying illness. Recurrent pneumonic episodes affecting the same location were 30 of the total recurrent pneumonic episodes (30/67, 47.8%) and common associated diseases were respiratory diseases including lung malignancies. The etiology of recurrent pneumonia was Streptococcus pneumoniae, methicillin- resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, atypical organisms, etc. CONCLUSION: Recurrent pneumonia in adults had a low incidence rate compared with children, but most cases had associated illness. Respiratory diseases including lung cancer were the most common associated illness of recurrent pneumonia.

The SOFA Score to Evaluate Organ Failure and Prognosis in the Intensive Care Unit Patients / 결핵및호흡기질환

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score can help to assess organ failure over time and is useful to evaluate morbidity. The aim of this study is to evaluate the performance of SOFA score as a descriptor of multiple organ failure in critically ill patients in a local unit hospital, and to compare with APACHE III scoring system. METHODS: This study was carried out prospectively. A total of ninety one patients were included who admitted to the medical intensive care unit (ICU) in Chuncheon Sacred Heart Hospital from May 1 through June 30, 2000. We excluded patients with a length of stay in the ICU less than 2 days following scheduled procedure, admissions for ECG monitoring, other department and patients transferred to other hospital. The SOFA score and APACHE III score were calculated on admission and then consecutively every 24 hours until ICU discharge. RESULTS: The ICU mortality rate was 20%. The non-survivors had a higher SOFA score within 24 hours after admission. The number of organ failure was associated with increased mortality. The evaluation of a subgroup of 74 patients who stayed in the ICU for at least 48 hours showed that survivors and non-survivors followed a different course. In this subgroup, the total SOFA score increased in 81% of the non-survivors but in only 21% of the survivors. Conversely, the total SOFA score decreased in 48% of the survivors compared with 6% of the non-survivors. The non-survivors also had a higher APACHE III score within 24 hours and there was a correlation between SOFA score and APACHE III score. CONCLUSION: The SOFA score is a simple, but effective method to assess organ failure and to predict mortality in critically ill patients. Regular and repeated scoring enables patient's condition and clinical course to be monitored and better understood. The SOFA score well correlates with APACHE III score.

A Case of Massive Pulmonary Gangrene Complicated by Klebsiella Pneumonia / 결핵및호흡기질환

Pulmonary gangrene is a rare and severe complication of bacterial pneumonia, where a pulmonary segment or lobe is sloughed due to parenchymal devitalization of the parenchyma, with secondary anaerobic infection and necrosis caused by pulmonary vascular thrombosis. Prior to the antibiotic era, massive pulmonary gangrene was potentially fatal. Herein, a case of pulmonary gangrene in a 67-year-old man is reported. He complained of fever, chills, dyspnea and purulent sputum of 5 days duration. The plain chest radiograph showed well-marginated right upper lobe consolidation, with bulging minor fissure, suggestive of a Klebsiella infection. A contrast CT scan demonstrated consolidation of the right upper lobe, with a central necrotizing portion. Klebsiella species was confirmed from both sputum and blood cultures. After appropriate antibiotics, the chest X-ray and CT scan 3 weeks later showed a large cavity with an air-fluid level, sloughing-off and extrusion of necrotic lung tissue, suggestive of pulmonary gangrene. Seven months later, the right gangrenous lung showed severe volume loss on a chest radiograph. The management of pulmonary gangrene has been somewhat controversial. Herein, it was managed without surgical drainage or resection. If the antibiotic therapy had failed, then a surgical approach would have been considered.

The Early Prognosis of Burn Patients with Elevated Initial Arterial Carboxyhemoglobin Level / 결핵

BACKGROUND: Smoke inhalation injury is an important determinant of mortality in burn patients. The early detection of inhalation injury in burn patients is important because the incidence of respiratory failure after inhalation injury was known to be high, with hypoxemia, pneumonia, and prolonged ventilatory support being commonplace. Acute carbon monoxide poisoning was one feature of smoke inhalation. The purpose of our study were to investigate the clinical characteristics of burn patients whose initial arterial carboxyhemoglobin (COHb) level had been elevated, to assess the clinical impact of COHb for smoke inhalation injury. METHODS: Among 1,416 burn patients had been admitted at our institution from August 1, 2001 to July 31, 2002, 39 patients whose initial arterial COHb level have been more than 5% were included. We compared clinical scoring system for inhalation injury, percent total body surface area (%TBSA) burn, initial chest X-ray findings, APACHE II scores and SAPS II scores between survivors (n=27) and non-survivors (n=12) retrospectively. RESULTS: COHb level were 9.7(5.71% and 10.3(8.81% in survivors and in non-survivors (p>0.05). Mean %TBSA burn of survivors and non-survivors were 16.6+/-17.8% and 60.7+/-28.8% (p<0.001). We did not find any difference in clinical scoring system, initial chest X-ray findings in survivors and in non-survivors. But %TBSA burn, APACHE II and SAPS II scores were high in non-survivors than in survivors significantly. Important factors associated with death were %TBSA burn, APACHE II scores, SAPS II scores, and the most important factor in predicting mortality was %TBSA burn. CONCLUSION: Burn patients with elevated initial arterial COHb level showed poor prognosis, but further study may be performed to know that the effect of COHb on prognosis in burn patients accompanying smoke inhalation.