Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-γ) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-γ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.
Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.
Background: A lung hyperinflation, or air trapping, caused by expiratory flow-limitation contributes to dyspnea in patients with chronic obstructive pulmonary disease (COPD). Forced expiratory volume in 1 second (FEV1) has served as an important diagnostic measurement of COPD, but does not correlate with patient-centered outcomes such as dyspnea. Therefore, this study was performed to investigate the role of radiologic quantity in evaluating the dyspnea in patients with COPD by measuring lung hyperinflation in chest x-ray and high resolution chest tomography (HRCT). Methods: Fifty patients with COPD were enrolled in this study. Their subjective dyspnea score (modified Borg scale dyspnea index), spirometry, and lung volume were measured. Simultaneous hyperinflations of chest x-ray score (“chest score”) and degree of emphysema of HRCT (“HRCT score”) were measured. The “chest score” were composed of lung length, retrosternal space width, and height of the arc of the diaphragm and “HRCT score” were composed of severity and extent of emphysema. Results: The mean age of patients was 69 years old and their mean FEV1 was 51.7%. The Borg score significantly correlated with parameters of spirometry and lung volume, including FVC, FEV1, FEV1/FVC, RV, RV/TLC, and DLCO. The Borg score correlated well with “HRCT score”, but did not correlate with “chest score”. Also, the Borg scale correlates inversely with body mass index. Conclusion: The quantity of emphysema on chest HRCT may serve as an objective marker of dyspnea in patients with COPD.
Background: There are various etiologies causing bronchiectasis, but the cases without definite causes account for a quite high proportion. It is also uncertain that immunoglobulin G subclass deficiency (IgGSD) is associated with bronchiectasis. Therefore, we tried to measure the frequency of IgGSD in patients with bronchiectasis of unclear etiology, and to observe the clinical features of those patients with bronchiectasis and IgGSD. Methods: For the outpatients of a university hospital who were diagnosed as bronchiectasis by chest CT, we produced comprehensive history taking and physical examinations, and finally selected 31 patients with bronchiectasis of unclear etiology. Results: Two patients had total immunoglobulin G deficiency. The frequency of IgGSD was comparatively high (n=14). When we compared IgGSD group to normal immunoglobulin G subclass group, there were no significant differences in sex, age, and the frequency of sinusitis, bronchial asthma, and the abnormal lung function. Conclusion: In cases of bronchiectasis without definite causes, it can be considered to measure the level of immunoglobulin G subclass. It is also probably worthwhile to further evaluate the relationship between IgGSD and bronchiectasis.
Background: The quality of care for patients with community acquired pneumonia needs to be improved; the factors affecting this care need to be analyzed. The objectives of this study were used to measure the performance of care processes of for patients with pneumonia and to determine those patient and hospital characteristics are associated with quality care. Methods: The analysis was performed using data from 21 hospitals that had over 500 beds for 1,001 patients, who were sampled randomly. All patients were born before 31 December 1989, and discharged between the two months’ August 2006 and October 2006. Performance process indicators were measured by respective hospital, and multivariate logistic regression was used to calculate associations between patients and hospital characteristics using 4 process indicators. Results: Performance rates in timely assessment of oxygenation assessments and blood cultures, correct administration of antibiotic medications, and blood culture performed prior to initial antibiotics were 69.4%, 79.1%, 82.5% and 60.5%, respectively. Age had a positive affect on oxygenation assessment within 24 hours. Bed number, number of nurses per bed, annual number of emergency department visits, average percentage of beds filled, location and arrival time, and site were factors associated with process indicators. Conclusion: It is necessary to make up for the weak points in the process of care for patients with community acquired pneumonia, by enforcing quality assurance. To reduce performance rate variation among hospitals, improvement in care protocols is required for hospitals that have poor quality of care levels.
There are several respiratory diseases that show chronic granulomatous inflammation for the histologic finding. Among them, sarcoidosis and tuberculosis are not easy to differentiate when the clinical and radiological features present similar patterns. The increasing incidence of nontuberculous mycobacteria pulmonary disease is making it more difficult for clinicians to arrive at a proper diagnosis. A 69 year old male patient visited our hospital with chronic cough as his chief compliant. His radiologic findings were multiple enlarged mediastinal lymphadenpathies with innumerable micronodules and multiple patch infiltrations. The spleen biopsy finding showed chronic granulomatous inflammation, and Mycobacterium avium was identified on the bronchoscopic culture. Because of these findings, we treated him with drugs for nontuberculous mycobacteria disease other than sarcoidosis. However, during the treatment, his symptoms and radiological features became aggravated. Thus, we reviewed the radiologic and pathologic findings and decided to treat him with steroid, which relieved his symptoms and improved the radiologic findings. We report here on a case of sarcoidosis that was initially misdiagnosed as nontuberculous mycobacteria pulmonary disease.
Hereditary hemorrhagic telangiectasia (HHT, also called Osler-Weber-Rendu Disease) is a rare systemic fibrovascular dysplasia characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations (AVMs). HHT is an autosomal dominant disease with a prevalence of 1 in 5,000∼8,000. Recurrent epistaxis is often the first and most common manifestation, and about 30% of patients reveal pulmonary AVM. Presently, we report a familial case of HHT. A 61-year-old male with asymptomatic multiple pulmonary AVMs was successfully treated with embolization. His older brother who presented with recurrent epistaxis and multiple telangiectasias was treated with laser ablation. Their pedigree revealed a family history of recurrent epistaxis.
The primary cause of hemoptysis is the bronchial artery. However, it should be noted that pulmonary artery and other vessels can cause hemoptysis. If the source of the bleeding is not determined after embolization, other evaluations are needed. Systemic-pulmonary anastomosis and pulmonary artery pseudo-aneurysm are rare vascular abnormalities with varying etiologies. An accurate and rapid diagnosis is needed in hemoptysis, since the cause may be life-threatening. We report a case of a 77-years-old man with persistent hemoptysis due to the right inferior phrenic artery - pulmonary artery anastomosis and pseudoaneurysm. After the embolization of the inferior phrenic artery, the hemoptysis was successfully treated.
The syndrome of inappropriate secretion of the antidiuretic hormone (SIADH) is a well recognized paraneoplastic phenomenon related to impaired water excretion, and can result in dilutional hyponatremia as well as central nervous system symptoms. It is characterized by a decrease in plasma osmolarity with inappropriately concentrated urine. The causes of SIADH are associated with pulmonary and endocrine disorders, central nervous system diseases, and malignancies, including lung cancer. The other causes of SIADH include some drugs, particularly chemotherapy agents. Anticancer drugs, such as cisplatin, vincristine, and cyclophosphamide are well known causes of SIADH but the mechanisms are unclear. Recently, we encountered a patient with advanced non-small cell lung cancer who suffered from general weakness and altered mentality after an intravenous carboplatin and gemcitabine combination.