The Effects of Nuclear Factor-kappa B Decoy Oligodeoxynucleotide on Lipopolysaccharide-Induced Direct Acute Lung Injury / 결핵및호흡기질환

BACKGROUND: The pathophysiologic mechanisms of early acute lung injury (ALI) differ according to the type of primary insult. It is important to differentiate between direct and indirect pathophysiologic pathways, and this may influence the approach to treatment strategies. NF-kappa B decoy oligodeoxynucleotide (ODN) is a useful tool for the blockade of the expression of NF-kappa B-dependent proinflammatory mediators and has been reported to be effective in indirect ALI. The purpose of this study was to investigate the effect of NF-kappa B decoy ODN in the lipopolysaccharide (LPS)-induced direct ALI model. METHODS: Five-week-old specific pathogen-free male BALB/c mice were used for the experiment. In the preliminary studies, tumor necrosis factor (TNF)-alpha, interleukine (IL)-6 and NF-kappa B activity peaked at 6 hours after LPS administration. Myeloperoxidase (MPO) activity and ALI score were highest at 36 and 48 hours, respectively. Therefore, it was decided to measure each parameter at the time of its highest level. The study mice were randomly divided into three experimental groups: (1) control group which was administered 50 microliter of saline and treated with intratracheal administration of 200 microliter DW containing only hemagglutinating virus of Japan (HVJ) vector (n=24); (2) LPS group in which LPS-induced ALI mice were treated with intratracheal administration of 200 microliter DW containing only HVJ vector (n=24); (3) LPS+ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 microliter DW containing 160 microgram of NF-kappa B decoy ODN and HVJ vector (n=24). Each group was subdivided into four experimental subgroups: (1) tissue subgroup for histopathological examination for ALI at 48 hours (n=6); (2) 6-hour bronchoalveolar lavage (BAL) subgroup for measurement of TNF-alpha and IL-6 in BAL fluid (BALF) (n=6); (3) 36-hour BAL subgroup for MPO activity assays in BALF (n=6); and (4) tissue homogenate subgroup for measurement of NF-kappa B activity in lung tissue homogenates at 6 hours (n=6). RESULTS: NF-kappa B decoy ODN treatment significantly decreased NF-kappa B activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-alpha and interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score. CONCLUSION: NF-kappa B decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.

Clinical Characteristics of Smoking Asthmatics / 결핵및호흡기질환

BACKGROUND: The smoking prevalence in asthma patients are similar to those in the general population. Asthma and active cigarette smoking can interact to create more severe symptoms, an accelerated decline in lung function and impaired therapeutic responses. Accordingly, asthmatics with a history of smoking were examined to define the clinical characteristics and lung function of smoking asthmatics. METHODS: The medical records of 142 asthmatics with a known smoking history were reviewed. The patients were divided into three groups according to their smoking history - current smokers, former smokers and non-smokers. The clinical characteristics, lung function, and annual declines of the forced expiratory volume in one second (FEV1) were compared. RESULTS: Fifty-three of the 142 patients (37%) were current smokers, 24 were former smokers (17%) and 65 were non-smokers (45%). The patients with a hospital admission history during the previous year included 16 current smokers (30%), 4 former smokers (17%) and 7 non-smokers (11%) (p=0.02). The mean FEV1 (% predicted) was 76.8+/-19.8%, 71.6+/-21.1% and 87.9+/-18.7% for current smokers, former smokers and non-smokers, respectively (p<0.001). The FEV1/forced vital capacity (FVC) (ratio, %) values were 63.6+/-12.6%, 59.3+/-14.9% and 72.1+/-11.8% in current smokers, former smokers and non-smokers, respectively (p<0.001). The corresponding mean values for the individual FEV1 slopes were not significant (p=0.33). CONCLUSION: Asthmatic smokers demonstrated higher hospital admission rates and lower lung function. These findings suggest that the smoking history is an important predictor of a poor clinical outcome in asthma patients.

ANCA-negative limited Wegener's granulomatosis / 대한내과학회지

Wegener's granulomatosis is a very rare autoimmune disease that forms inflammatory granulomas of the upper and lower respiratory tract, and causes necrotizing vasculitis by invading small vessels. Its etiology is uncertain, but antineutrophil cytoplasmic antibody (ANCA) is thought to play an important role in causing the inflammatory granuloma formation and vasculitis. The detection of ANCA is a valuable finding in diagnosing Wegener's granulomatosis. However, in the limited type of Wegener's granulomatosis, which lacks accompanying constitutional symptoms, the diagnostic value of ANCA is minimal, requiring careful interpretation of ANCA-negativity. We report a case diagnosed as limited-type Wegener's granulomatosis through repeated biopsies despite ANCA negativity.

Bilateral Pulmonary Infiltrate with Milky BAL Fluid / 결핵및호흡기질환

Exogenous lipoid pneumonia is an uncommon disease that's caused by aspirating lipid formulations. Squalene, obtained from shark liver oil, is one of the causative agent and this is commonly used by some Koreans as a health promoting medication. We report here on a case of exogenous lipoid pneumonia that developed after ingestion of squalene capsules. The case showed milky BAL fluid and multiple pulmonary consolidations.

Phase II Trial of Irinotecan plus Cisplatin Combination as First Line Therapy for Patients with Small cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. METHODS: The study was conducted between January 2002 and June 2004. Patients were treated with 60mg/m2 irinotecan on day 1, 8, 15 and 60mg/m2 cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to 40mg/m2. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. RESULTS: Median ages of LD- and ED-SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1-year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1-year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. CONCLUSION: Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED-SCLC.

Phase II Trial of Irinotecan plus Cisplatin Combination as First Line Therapy for Patients with Small cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. METHODS: The study was conducted between January 2002 and June 2004. Patients were treated with 60mg/m2 irinotecan on day 1, 8, 15 and 60mg/m2 cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to 40mg/m2. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. RESULTS: Median ages of LD- and ED-SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1-year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1-year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. CONCLUSION: Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED-SCLC.

Teratoma Presenting as An Unilateral Mediastinal Mass with Contralateral Pleural Effusion / 결핵및호흡기질환

A teratoma is the most common benign germ cell tumor that develops in the mediastinum. Patients with a mediastinal teratoma are usually asymptomatic. However, a spontaneous rupture of a mediastinal teratoma into the pleural cavity or adjacent organs can cause severe chest pain, hemoptysis, acute dyspnea, etc. Complications such as recurrent pneumonia, pericardial effusion, pleural effusion and great vessel invasion can sometimes occur. We encountered a case of a patient with an abrupt onset of dyspnea after persistent shoulder pain for one month. The X-ray examinations revealed a unilateral mediastinal mass with contralateral pleural effusion. Subsequent evaluations confirmed a spontaneous rupture of the teratoma into the contralateral pleural cavity.

Two Cases of Transfusion Related Acute Lung Injury / 결핵및호흡기질환

Transfusion related acute lung injury (TRALI) is a serious, potentially life-threatening complication of transfusion therapy that is sometimes under diagnosed and under reported. Patients with TRALI present with dyspnea/respiratory distress and fever. The symptoms, signs and chest radiological findings in TRALI are similar to transfusion associated circulatory overload, which makes it is difficult to distinguish it from circulatory overload. Although the mortality rate in cases of TRALI is relatively low, TRALI is the third most common cause of fatal transfusion reactions next to ABO blood type incompatibility and hepatitis. Mild-to-moderate cases of TRALI may be misdiagnosed as volume overload. Recently, we encountered two cases where the patients suffered from dyspnea and fever after a transfusion. and review of the relevant literature.

A Case of Passive Smoking Induced Respiratory Bronchiolitis Associated Interstitial Lung Disease / 결핵및호흡기질환

Respiratory bronchiolitis associated interstitial lung disease is a rare condition among current or ex-smokers, which has features consistent with interstitial lung disease. The presentations are non-specific, but symptoms generally include a cough and dyspnea on exertion, and its pathology is characterized by the accumulation of pigmented macrophages within the respiratory bronchioles and adjacent air spaces, and is associated with mild thickening of the peribronchiolar interstitium. Recently, the case of a 54-year-old woman passive smoker, diagnosed as having respiratory bronchiolitis associated interstitial lung disease, was experienced at our institution.

A Case of Peripheral T-cell Lymphoma with Diffuse Bilateral Pulmonary Infiltration and Whole Body Rash / 결핵및호흡기질환

Primary pulmonary non-Hodgkin's lymphoma (NHL) account for 0.4% of all types of lymphoma. Most cases are of the mucosa-associated lymphoid tissue (MALT) type, low grade B-cell lymphoma, but cases of the T-cell type are rare. The radiological findings frequently show hilar or mediastinal lymphadenopathy, but lung parenchymal involvement is uncommon. Here, a case of a patient, who presented with fever, generalized erythema, diffuse pulmonary infiltration and pleural effusion, diagnosed as a peripheral T-cell lymphoma, is reported.

The effect of Combination Therapy of Inhaled Corticosteroids and Long-acting Beta2-agonists on Acute Exacerbation in Moderate to Severe COPD Patients / 결핵및호흡기질환

BACKGROUND: The role of combination therapy of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) in asthma is well established, but nor much is known about this treatment in COPD. Recent studies have revealed that combining therapy is associated with fewer acute exacerbations in COPD, but in most of the studies, high-dose combination therapies have been employed. The current study assessed the effect of moderate or high-dose combination therapy of ICS plus LABA on the frequency of acute exacerbations in COPD. METHODS: Between January 1, 2001 and August 31, 2004, 46 patients with COPD (moderate, severe, very severe) were enrolled who received either fluticasone/salmeterol (flu/sal) 250 microgram/50 microgram twice a day (group A) or flu/sal 500 microgram/50 microgram twice a day (group B) for more than a year. We divided them into two groups depending on the dosage of ICS plus LABA. Effect of drugs was compared based on the factors such as symptom aggravation, number of admission, and time to first exacerbation during a year after use. RESULTS: Eleven of twenty-six patients in group A (42.3%) experienced acute exacerbation and eleven of twenty patients in group B (55%) experienced acute exacerbation during 1 year. Mean exacerbation rate of Group A was 0.96 and Group B was 1.05. Mean admission rate was 0.15 and 0.30, respectively. There was no statistically significant difference of aggravation rate, number of administration and time to first exacerbation between the two treatment groups. CONCLUSION: There was no significant difference between moderate and high dose combined inhaler therapy to reduce acute exacerbation in COPD patients (moderate, severe, very severe). Hence, the effective dose of combination therapy needs further study in patients with COPD.

The Relationship between Expression of EGFR, MMP-9, and C-erbB-2 and Survival Time in Resected Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. METHODS: Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC. Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. RESULTS: When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test). The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months , when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. CONCLUSION: In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.