Search

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.

Background: Acute eosinophilic pneumonia (AEP) is an idiopathic disease characterized by pulmonary eosinophilia. Because the fraction of exhaled nitric oxide (Feno) is a surrogate of eosinophilic inflammation, we evaluated the levels, changed treatments, and the diagnostic role of Feno in patients with AEP., Methods: Between June 2010 and March 2011, we prospectively enrolled patients at the Armed Forces Capital Hospital who had pulmonary infiltrates and a febrile illness and who were clinically suspected to have AEP. We measured Feno twice at the initial visit (pretreatment) and 2 weeks after the initial measurement (posttreatment)., Results: A total of 60 subjects were enrolled, and 31 were given a diagnosis of AEP. The pretreatment Feno levels of the patients with AEP were significantly higher than those of the patients without AEP (median, 48 parts per billion [ppb] [range, 10-138] vs 14 ppb [range, 5-41]; P < .001). The cut-off value (23.5 ppb) showed that the maximal area under the receiver operating characteristic curve predicted AEP with a sensitivity of 0.87 and a specificity of 0.83. The posttreatment Feno levels decreased significantly in the patients with AEP, and the levels were similar to the patients without AEP (median, 19 ppb [range, 7-44] vs 14 ppb [range, 1-58]; P = .21), Conclusions: The Feno level was significantly higher in patients with AEP than in those without AEP. Feno measurement can be used as a diagnostic tool to differentiate patients with AEP from those without AEP., Trial Registry: ClinicalTrials.gov; No.: NCT01152424; URL: www.clinicaltrials.gov.

Background and Purpose: The goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs)., Methods: A 24-week, prospective, open-label, single-arm, multicenter study was conducted from June 2009 to June 2010 in patients with probable AD. The enrolled patients had either a poor response or a decline in global function after treatment with oral ChEIs, or they were not able to tolerate treatment with oral ChEIs due to adverse events such as nausea or vomiting. A poor response was defined as a decrease of at least 2 points on the Korean version of the Mini-Mental State Examination (K-MMSE) within the previous 6 months (the decline in global function was determined by the investigator or caregiver). The efficacy of treatment was assessed using a follow-up Clinical Global Impression of Change (CGIC) assessment and K-MMSE conducted after 24 weeks, and safety was measured by the occurrence of adverse events and patient disposition., Results: In total, 164 patients aged 74.7±7.52 years (mean±SD) and with 5.12±3.64 years of education were included. The study was completed by 70% of the patients (n=116), with 12.2% discontinuing due to adverse events. The most frequently reported adverse events (11%) were skin lesions, such as erythema or itching, followed by gastrointestinal problems (1.2%). Either an improvement or no decline in CGIC scores was reported for 82% of the patients., Conclusions: The immediate switching of patients from an oral ChEI to the rivastigmine transdermal patch without a washout period was safe and well tolerated by the probable-AD patients in this study.

The purpose of this study was to investigate risk factors of postoperative pneumonia (POP) after lung cancer surgery. The 417 lung cancer patients who underwent surgical resection in a tertiary referral hospital were included. Clinical, radiological and laboratory data were reviewed retrospectively. Male and female ratio was 267:150 (median age, 65 yr). The incidence of POP was 6.2% (26 of 417) and in-hospital mortality was 27% among those patients. By univariate analysis, age ≥ 70 yr (P < 0.001), male sex (P = 0.002), ever-smoker (P < 0.001), anesthesia time ≥ 4.2 hr (P = 0.043), intraoperative red blood cells (RBC) transfusion (P = 0.004), presence of postoperative complications other than pneumonia (P = 0.020), forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) < 70% (P = 0.002), diffusing capacity of the lung for carbon monoxide < 80% predicted (P = 0.015) and preoperative levels of serum C-reactive protein ≥ 0.15 mg/dL (P = 0.001) were related with risk of POP. Multivariate analysis showed that age ≥ 70 yr (OR = 3.563, P = 0.014), intraoperative RBC transfusion (OR = 4.669, P = 0.033), the presence of postoperative complications other than pneumonia (OR = 3.032, P = 0.046), and FEV(1)/FVC < 70% (OR = 3.898, P = 0.011) were independent risk factors of POP. In conclusion, patients with advanced age, intraoperative RBC transfusion, postoperative complications other than pneumonia and a decreased FEV(1)/FVC ratio have a higher risk for pneumonia after lung cancer surgery.

Background: Patients with stage I-II non-small cell lung cancer (NSCLC) show variability in recurrence after curative resection. Several factors have been proposed as prognostic of recurrence in previous studies. However, because of the heterogeneity of the populations studied, these reports did not yield consistent results. The aim of our study was to identify risk factors for recurrence in patients with curatively resected stage I-II NSCLC., Methods: We reviewed the medical records of pathological stage I-II NSCLC patients after curative surgery performed in a tertiary referral center (Seoul National University Hospital) from January 2002 to December 2004. Demographic factors, radiological, histopathological, and laboratory findings, and surgery-related factors were analyzed. Patients with invasive cancer other than lung cancer that was present 5 years prior to surgery were excluded. The Cox proportional hazard regression model was used for multivariate analyses., Results: Three hundred and ten patients were included. Among them, local recurrence occurred in 27 patients (8.7%), whereas distant recurrence occurred in 79 patients (25.5%). Adenocarcinoma histology (OR, 2.74; 95% CI, 1.14-6.58; P=0.024), carcinoembryonic antigen (CEA) level>2.3 ng/mL (OR, 2.26; 95% CI, 1.02-5.00; P=0.045), and standard uptake values (SUV) of tumor in positron emission tomography (PET)>4.5 (OR, 5.45; 95% CI, 1.82-16.31; P=0.002) were independent predictors of recurrence in addition to TNM stage. We also constructed a recurrence prediction model based on these findings, which yielded better diagnostic performance than the TNM staging system., Conclusion: Adenocarcinoma histology, CEA level, and SUV of PET could be considered as prognostic factors for recurrence in patients with curatively resected stage I-II NSCLC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Interleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF., Methods: One promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay., Results: The minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002)., Conclusion: The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

Background: Delirium is a common problem and associated with poor outcomes in intensive care unit (ICU) patients. Diagnosis of delirium in ICU patients is limited and usually underdiagnosed by physicians. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is one of the most widely used screening methods for detection of ICU delirium. Our goal was to translate and validate the CAM-ICU for use in the Korean ICU setting., Methods: Translation of the CAM-ICU was done according to the guidelines suggested by the Translation and Cultural Adaptation Group. For validation and interrater reliability assessment of the Korean CAM-ICU, two nurses independently assessed delirium in ICU patients and the results were compared with the reference evaluation, which was done by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV)., Results: Twenty-two patients were evaluated by two nurses and one psychiatrist expert independently. During the study period, we have continuously educated study nurses. Based on DSM-IV criteria, 16 out of 22 (72.7%) patients developed delirium. The sensitivities of the two nurses' evaluations using the Korean CAM-ICU were 89.80% for nurse 1 and 77.40% for nurse 2. Their specificities were 72.40% and 75.80% and their overall accuracy was 83.33% and 88.37% respectively. The Korean CAM-ICU was done with reasonable interrater reliability between nurse 1 and nurse 2 (κ = 0.81, p < 0.001)., Conclusions: The Korean CAM-ICU showed good validity and could be incorporated into clinical practice in Korean ICUs., Trial Registration: ISRCTN: ISRCTN50265663.

Background: Carcinoma of unknown primary tumors (CUP) is present in 0.5%-9% of all patients with malignant neoplasms; only 20%-27% of primary sites are identified before the patients die. Currently, 18F-fluorodeoxy-glucose positron-emission tomography (18F-FDG PET) or PET combined with computed tomography (PET/CT) is widely used for the diagnosis of CUP. However, the diagnostic yield of the primary site varies. The aim of this study was to determine whether PET or PET/CT has additional advantages over the conventional diagnostic workup in detecting the primary origin of CUP., Findings: Twenty patients with unknown primary tumors that underwent PET or PET/CT were included in this study. For all patients, the conventional diagnostic workup was unsuccessful in detecting the primary sites. Among 20 patients, 11 had PET scans. The remaining nine patients had PET/CT. In all 20 patients, neither the PET nor PET/CT identified the primary site of the tumor, including six cases with cervical lymph node metastases. The PET and PET/CT revealed sites of FDG uptake other than those associated with known metastases in seven patients, but these findings did not influence patient management or therapy. Two patients had unnecessary invasive diagnostic procedures due to false positive results on the PET or PET/CT., Conclusions: Although it is inconclusive because of small sample size of the study, the additional value of PET or PET/CT for the detection of primary sites in patients with CUP might be less than expected; especially in patients that have already had extensive conventional diagnostic workups. Further study is needed to confirm this finding.

Glucocorticoids are effective for treating several respiratory diseases. However, they can cause hyperglycemia. This study determined the incidence and risk factors of steroid-induced diabetes mellitus (S-DM) in patients treated with glucocorticoid for respiratory diseases. A retrospective study examined patients with respiratory diseases treated with a prednisolone-equivalent glucocorticoid dose exceeding 20 mg/day for at least 4 weeks between January 2003 and December 2008. Patients whose initial random glucose level exceeded 200 mg/dL or who had pre-existing diabetes were excluded. S-DM was defined as a fasting glucose concentration exceeding 126 mg/dL or a random glucose concentration exceeding 200 mg/dL at least twice after beginning steroid treatment. A total of 231 patients with respiratory diseases met the inclusion criteria. Their median age was 55 yr, and 139 were female. The median cumulative prednisolone-equivalent glucocorticoid dose was 4,965 mg, and the median duration of steroid treatment was 193 days. S-DM was diagnosed in 34 (14.7%) of 231 patients. Multivariate logistic regression identified older age (odds ratio 1.05, 95% confidence interval 1.02-1.09) as a risk factor for S-DM. S-DM is frequent among patients with respiratory diseases treated with glucocorticoid. Clinicians should be aware of the possibility of S-DM, especially among elderly patients.

Because tuberculous (TB) involvement of mediastinal lymph nodes (LN) could cause false positive results in nodal staging of lung cancer, we examined the accuracy of nodal staging in lung cancer patients with radiographic sequelae of healed TB. A total of 54 lung cancer patients with radiographic TB sequelae in the lung parenchyma ipsilateral to the resected lung, who had undergone at least ipsilateral 4- and 7-lymph node dissection after both chest computed tomography (CT) and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT were included for the analysis. The median age of 54 subjects was 66 yr and 48 were males. Calcified nodules and fibrotic changes were the most common forms of healed parenchymal pulmonary TB. Enlarged mediastinal lymph nodes (short diameter > 1 cm) were identified in 21 patients and positive mediastinal lymph nodes were identified using FDG-PET/CT in 19 patients. The overall sensitivity and specificity for mediastinal node metastasis were 60.0% and 69.2% with CT and 46.7% and 69.2% with FDG-PET/CT, respectively. In conclusion, the accuracy of nodal staging using CT or FDG-PET/CT might be low in lung cancer patients with parenchymal TB sequelae, because of inactive TB lymph nodes without viable TB bacilli.

Background/aims: Many patients undergoing a flexible bronchoscopy (FB) experience anxiety and discomfort during the procedure. We assessed whether an additional patient visit after a FB would improve patient satisfaction., Methods: The study patients were randomly assigned to a control and post-visit groups. The physicians who were scheduled to perform the FB visited the study patients. The control group had one visit before the FB and the post-visit group had a before and after FB visit. The post-visit group received additional information and support during the second visit. Twenty-four hours after the FB, the participants completed questionnaires about discomfort and satisfaction with the procedure., Results: The control and post-visit groups included 151 and 153 patients, respectively. The post-visit group reported having more information after the FB than the control group. The additional post-bronchoscopy visit improved the general patient tolerability of the procedure. The willingness to return for another FB was not affected by the post-bronchoscopy patient visit., Conclusions: The post-bronchoscopy visit improved patient satisfaction and general tolerability to the procedure. Subjective patient tolerability with the FB may be improved through a post-bronchoscopy visit by providing more information and emotional support to patients.

Background and Objective: Accurate staging at the time of diagnosis is very important in deciding on the appropriate treatment for cancer patients. FDG PET indicates metabolic changes in cancer cells, enabling the early detection of lesions. This has the advantage of allowing more accurate staging than is possible with conventional staging tools, and has led to the incorporation of FDG PET in the initial work-up protocols for lung cancer patients. In this study, we evaluated the clinical impact of FDG PET as an initial staging tool, on the therapeutic management of patients with non-small cell lung cancer (NSCLC)., Methods: Patients diagnosed with NSCLC by histopathology were retrospectively identified and both chest CT and FDG PET were performed for initial staging. Information was collected regarding the results of conventional versus FDG PET staging, and any resulting modifications of treatment were evaluated., Results: Among the 537 patients who were evaluated FDG PET resulted in upstaging of the tumour in 91 (17%) and downstaging of the tumour in 68 (13%). Consequently, therapeutic management was modified in 118 patients (22%). Furthermore, use of FDG PET resulted in the detection of a second primary cancer in six patients., Conclusions: This study confirms that FDG PET has a considerable impact on the initial staging and therapeutic management of patients with NSCLC., (© 2010 The Authors. Journal compilation © 2010 Asian Pacific Society of Respirology.)

Although Clara cell secretory protein (CC-10, CC-16 or uteroglobin, secretoglobin 1A1) has been ascribed anti-inflammatory, immunomodulatory and anti-cancer activity roles in lung diseases including lung cancer, its precise function remains unclear. The objective of the present study was to evaluate the role of CC-10 in the immunomodulation of human monocytes and dendritic cells (DCs). The human lung adenocarcinoma cell line A549, was used to examine PGE2 production after cyclooxygenase (COX) inhibition and adenovirus encoding human CC-10 cDNA (Ad-CC-10) transfection. Type I and II cytokines were measured from peripheral blood mononuclear cells (PBMCs) and DCs which were cultured with tumor supernatant (TSN) or Ad-CC-10 transfected TSN. When PBMCs were cultured with supernatant A549 (tumor supernatant, TSN), the levels of T-cell helper type 1 (Th1) and 2 (Th2) cytokines increased. However, CC-10 inhibited the induction of Th2 cytokines of PBMCs stimulated with TSN. In DCs, TSN inhibited Th1 type cytokines but induced Th2 type. In contrast, TSN treated with either CC-10 or NS398 (COX-2 inhibitor) stimulated Th1 type and inhibited Th2 type without any phenotypic changes. The supernatants generated in the presence of NS-398 or CC-10 prevented tumor-induced inhibition of allogeneic T-cell stimulation. While the level of interleukin (IL)-10 secretion from DC-Ad-CC-10 was decreased, the level of IL-12 secretion was increased by CC-10. Collectively our data suggest that a supernatant of NSCLC causes an imbalance in the immune response of PBMCs and DCs, which is reversed by CC-10. This suggests that CC-10 is a candidate for the development of a new immunotherapy for lung cancer.

Introduction: As the population of patients with lung cancer increases, the expenditure on lung cancer treatment will become a huge economic burden in many countries. To support public health services for the treatment of lung cancer, the calculation of lung cancer-specific costs is important., Methods: This study included newly diagnosed 76 lung cancer patients who had survived for at least 5 years after the diagnosis in a tertiary care hospital in South Korea. Direct medical costs were calculated from health care claims obtained from Seoul National University Hospital, which included out-of-pocket expenditures. Direct non-medical and indirect costs were calculated from national statistics., Results: Mean direct medical costs, direct non-medical costs, and indirect costs amounted to $21,321, $6444 and $4943 respectively, based on an exchange rate of Korean Won 1200=US $1. The average cost for treatment of one lung cancer patient for all 5 years was $32,708. This constituted 44.7% of the per capita income during the same 5-year period., Conclusion: The economic burden of lung cancer treatment is significant in Korea., (Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to determine candidemia incidence among patients in a medical intensive-care unit (MICU) and the associated mortality rate and to identify risk factors associated with candidemia. We retrospectively performed a 1:3 matched case-control study of MICU patients with candidemia. Controls were matched for sex, age, and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Candidemia incidence was 9.1 per 1,000 admissions. The most common pathogen was Candida albicans. Crude mortality was 96% among candidemia patients and 52% among controls (P<0.001). Mortality differed significantly between the groups according to Kaplan-Meier survival analysis (P=0.024). Multivariate analysis identified the following independent risk factors for candidemia: central venous catheterization (odds ratio [OR] = 3.2, 95% confidence interval [CI]=1.2-9.0), previous steroid therapy (OR=4.7, 95% CI=1.8-12.1), blood transfusion during the same admission period (OR=6.3, 95% CI=2.4-16.7), and hepatic failure upon MICU admission (OR=6.9, 95% CI=1.7-28.4). In conclusion, we identify an additional independent risk factor for candidemia, the presence of hepatic failure on MICU admission. Therefore, increased awareness of risk factors, including hepatic failure, is necessary for the management of candidemia.

Background/aims: The risk of venous thromboembolism (VTE), which encompasses deep vein thrombosis and pulmonary embolism (PE), increases in patients with cancer. Anticancer treatment is also associated with an increased risk for VTE. We conducted this study to investigate the clinical characteristics of patients with cancer and PE related to anticancer treatment in a tertiary care hospital in Korea., Methods: We retrospectively reviewed the clinical data of patients with an underlying malignancy who were diagnosed with PE by chest computed tomography (CT) with or without lower extremity CT angiography between January 2006 and December 2007 at Seoul National University Hospital., Results: Overall, 95 patients with malignancies among 168 with PE were analyzed. The median age was 64 years. The median time interval from the malignancy diagnosis to the PE diagnosis was 5.5 months. Lung cancer was the most common malignancy (23.0%), followed by pancreatobiliary cancer, stomach cancer, gynecological cancer, breast cancer, and hepatocellular carcinoma. Platinum-containing and pyrimidine analog-containing chemotherapeutic regimens were common., Conclusions: PE was diagnosed within 1 year after the cancer diagnosis in almost 70% of patients. Lung cancer was the most common underlying malignancy.

Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of M. abscessus lung disease can be problematic. Surgical resection has been tried for patients with localized M. abscessus lung disease refractory to medical treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease who had been diagnosed and treated three times for pulmonary tuberculosis. She was initially diagnosed as having M. intracellulare lung disease; however, M. abscessus was isolated after several months of medication. She had multiple bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly isolated from her sputa despite prolonged treatment with clarithromycin, ethambutol, moxifloxacin, and amikacin. She improved only after sequential bilateral lung resection. Based on the experience with this patient, we suggest that, if medical treatment fails, surgical resection of a diseased lung should be considered even in patients with bilateral lesions.

The aim of the present study was to confirm the association between the CD14-159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14-159C/T genotypes were determined by PCR - restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter-luciferase reporter constructs, including the -159T or -159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-gamma secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of -159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the -159T allele was higher than that of the -159C allele. Serum sCD14 levels were higher among tuberculosis patients with -159TT genotypes than among those with -159CC genotypes and interferon-gamma release by PBMCs was decreased in subjects with -159TT genotypes. In conclusion, the -159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the -159T allele, the higher level of sCD14, and the decreased interferon-gamma secretion in subjects with -159TT genotypes.

Objectives: The aim of this study was to analyze changes in the extent of radiographic lesions with treatment in patients with pulmonary tuberculosis (TB) and, further, to identify clinical and radiographic factors related to radiographic response., Methods: A prospective cohort study including patients with culture-proven pulmonary TB was performed. The posterior-anterior view films of the chest that had been taken at the time of diagnosis and at 6 months after the initiation of treatment were compared. We expressed the extents of the lesions as percentages involving the parenchyma compared with the remaining normal parenchyma., Results: Among 135 patients enrolled, three failed to achieve smear conversion of sputa after 6 months of treatment. The extent of radiographic lesions decreased from 22.8% at the time of diagnosis to 10.5% after 6 months of treatment. Through the multiple regression model, we found that increasing age (p=0.034), previous history of TB (p=0.016), presence of cavity (p=0.016) or fibrotic lesion (p=0.009), and multidrug-resistant TB (p=0.002) were significantly associated with a poor radiographic response., Conclusion: Patients with less-prominent radiographic improvement and sustained negative tuberculous cultures of the sputa could be closely observed without ordering unnecessary chest radiographs or mycobacterial cultures as well as prolonging treatment.

Background and Objective: More non-diagnostic pathology results may be reported following transthoracic needle lung biopsy (TTNB) when no on-site cytopathologist is available. This study was conducted to analyse the final outcomes in patients with non-diagnostic pathology results, and the factors related to the adequacy of specimens., Methods: The medical records of consecutive patients who had undergone TTNB from January 2004 to January 2005 were retrospectively analysed. Non-diagnostic pathology results were classified into three groups: (i) atypical cells, (ii) non-specific inflammation and (iii) inadequate specimen. The final diagnosis and clinical outcome for each patient were analysed after additional diagnostic studies and clinical follow up., Results: TTNB was performed on 291 patients. Specimens were adequate in 256 cases. The results were non-diagnostic for 103 patients, and the percentages of atypical cells, non-specific inflammation and inadequate specimen were 15.5% (16/103), 50.5% (52/103) and 40% (35/103), respectively. In 14 patients (87.5%) the diagnosis of atypical cells was confirmed, and in 10 (62.5%) these were due to malignancies. In two patients (3.8%) the lesions reported as non-specific inflammation were eventually confirmed as malignancies. After repeated attempts to confirm their diagnoses, 22 patients (62.9%) with initial reports of inadequate specimen were diagnosed with specific diseases. Specimen adequacy correlated with technical skill, size of the lesion, guidance method and biopsy method., Conclusions: Non-diagnostic pathology results from TTNB, in the absence of an on-site cytopathologist, are of value in assessing the clinical probability of malignancy and can be useful in the management of lung lesions. However, many other factors should be considered in patients with inadequate specimens.

Radiation is one of the main treatment modalities in lung cancer, but low sensitivity and acquired resistance of lung cancer cells to radiation frequently result in treatment failure. The activation of nuclear factor (NF)-κB is reportedly the main mechanism by which cancer cells exhibit resistance to external stresses, such as chemotherapy or radiation therapy. In this study, we blocked the activation of NF-κB by adenovirus-expressing IκBα-SR and investigated the effect this had on radiation sensitivity. Transduction with ad-IκBα effectively blocked the activation of NF-κB by radiation in all the cancer cell lines tested, except for NCI H460. Clonogenic assay after radiation demonstrated that ad-IκBα transduction enhanced the sensitivity to radiation of the lung cancer cell lines and HeLa cells, except for NCI H460. The radiosensitizing effect of IκBα was more potent in lung cancer cell lines with radioresistance (SKMESres) (sensitizer enhancement ratio 1:61). From these findings, NF-κB blockade by ad-IκBα enhanced the radiation sensitivity and also abolished the acquired radiation resistance of lung cancer cell lines. This study provides a therapeutic rationale for combining an NF-κB-blocking strategy with radiation to both increase sensitivity and overcome acquired resistance to radiation.

Extrapulmonary organ involvement in human immunodefiaency virus (HIV)-infected patients with pulmonary tuberculosis (TB) is reported to be 26%, however, the clinical predictors of extrapulmonary involvement in pulmonary TB patients has not been reported yet. We tried to determine the clinical predictors of presence of extrapulmonary involvement in patients with pulmonary TB. Cross-sectional study was performed including all adult patients with culture-proven pulmonary TB diagnosed between January 1, 2004 and July 30, 2006, at a tertiary referral hospital in South Korea. The presence of extra-pulmonary TB involvement was diagnosed based on bacteriological, pathological, or clinical evidence. Among 320 patients with a culture-proven pulmonary TB, 40 had extrapulmonary involvement. Patients with bilateral lung involvement were more likely to have extrapulmonary involvement, with an adjusted odds ratio (OR) of 4.21 (95% confidence interval [CI], 1.82-9.72), while patients older than 60 yr (adjusted OR, 0.27; 95% CI, 0.08-0.89), patients with cavitary lesions (adjusted OR, 0.37; 95% CI, 0.16-0.84), and with higher levels of serum albumin (adjusted OR, 0.45; 95% CI, 0.25-0.78) had less frequent involvement. Clinicians should be aware of the possibility of extrapulmonary involvement in TB patients with bilateral lung involvement without cavity formation or lower levels of serum albumin.

Bone scan (BS) and serum alkaline phosphatase (ALP) concentration are used to detect bone metastasis in malignancy, although whole-body fluoro-D-glucose positron emission tomography computed tomography (FDG PET/CT) is being used increasingly. But BS is still used for the detection of metastatic bone lesion. So we compared the usefulness of PET/CT, BS, and serum ALP in detecting bone metastases in patients with newly diagnosed lung cancer. The medical record database was queried to identify all patients with a new diagnosis of lung cancer between January 2004 and December 2005, who had a PET/CT, BS, and serum ALP before treatment. We retrospectively reviewed all patients' records and radiological reports. One hundred eighty-two patients met the inclusion criteria. Bone metastases were confirmed in 30 patients. The sensitivity values were 93.3% for PET/CT, 93.3% for BS, 26.7% for serum ALP concentration, and 26.7% for BS complemented with serum ALP concentration. The respective specificity values were 94.1%, 44.1%, 94.1%, and 97.3%. The kappa statistic suggested a poor agreement among the three modalities. FDG PET/CT and BS had similar sensitivity, but PET/CT had better specificity and accuracy than BS. PET/CT is more useful than BS for evaluating bone metastasis. However, in the advanced stage, because of its high specificity, BS complemented with serum ALP is a cost-effective modality to avoid having to use PET/CT.

Background and Objective: Connective tissue diseases are the most common disorders causing diffuse alveolar haemorrhage (DAH) confirmed by open lung biopsy. However, it is not known whether these diseases are also the most common causes of DAH in patients presenting with the features of ARDS/acute lung injury (ALI). This study evaluated the frequency of concomitant disease in patients with ARDS/ALI and DAH., Methods: The sampling frame comprised all patients in a tertiary referral hospital diagnosed with ARDS/ALI and who underwent BAL between January 2000 and July 2006. The medical records of those patients who had BAL fluid findings compatible with DAH were reviewed., Results: Of the 97 patients diagnosed with ARDS/ALI and who underwent BAL, 27 had BAL fluid findings compatible with DAH. Sixteen of the 27 patients did not have connective tissue diseases (59%); of these 12 patients had concomitant haematological malignancies or solid tumours. Of the seven patients who presented with DAH and no known underlying disease, only two were subsequently diagnosed with a connective tissue disorder. The in-hospital mortality rate was 55% and 63% for patients with DAH with and without connective tissue diseases, respectively (P = 0.710)., Conclusions: The majority of patients with DAH presenting with the features of ARDS/ALI did not have underlying connective tissue diseases. Concomitant malignancies were found frequently in these patients. The outcome did not differ between patients with DAH with or without connective tissue diseases.

Background and Objective: The growing burden of COPD in the Asia-Pacific region supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its causes, to ensure the development of effective national health policies and to facilitate equitable deployment of finite health-care resources in the prevention and management of COPD. This study estimated and compared COPD mortality and hospital morbidity rates and trends in these rates over time across countries and regions of Asia-Pacific., Methods: Data consistent with standard definitions of COPD (ICD-9/ICD-10) for the period 1991-2004 were obtained from national health statistics agencies. For countries/regions with complete national mortality and hospitalization data (Australia, Pacific Canada (British Columbia, Hong Kong, South Korea and Taiwan), annual age-standardized mortality and hospitalization rates were calculated for men and women aged >or= 40 years. Negative binomial regression modelling was used to estimate rate ratios for country/region, gender and age differences and general trends over time., Results: Mortality rates per 10,000 population ranged 6.4-9.2 in men, 2.1-3.5 in women and 3.7-5.3 overall in 2003. Corresponding ranges for morbidity were 32.6-334.7, 21.2-129 and 28.1-207.3 per 10 000. Trend analysis of data since 1997 produced annual percentage changes in mortality versus hospitalization of -4.4% versus -0.7% in Australia, -3.6% versus 7.5% in Pacific Canada (British Columbia), -7.15% versus -5.6% in Hong Kong and -2.9% versus -4.2% in Taiwan., Conclusions: In Asia-Pacific, overall mortality and morbidity rates are high and trends in mortality and morbidity vary between countries/regions. Differences in rates and trends for men and women most likely reflect the different trends in historical and prevalent smoking profiles for COPD in the different countries and regions.

Increased levels of matrix metalloproteinase-9 (MMP-9) in patients with tuberculous meningitis, tuberculous pleuritis, and advanced pulmonary tuberculosis (TB) suggest a pivotal role for MMP-9 in the development of pulmonary TB and its clinical manifestations. The present study was performed to evaluate the role of the -1562C/T single nucleotide polymorphism (SNP) in the promoter region of the human MMP-9 gene in development of pulmonary TB and its radiographic characteristics. A case-control study was performed with a study population of 205 patients with pulmonary TB and 223 healthy controls. Differences were explored in the allele and genotype distributions of the -1562C/T polymorphism between patients with pulmonary TB and healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavities. The -1562C/C genotype was more common in patients with multi-lobe involvement than in those with single-lobe involvement (81.8 vs. 67.6%, P=0.03). However, there were no significant differences in the distribution between patients with pulmonary TB and healthy controls (P=0.40) or between patients with and without cavities (P=0.18). These results suggest that the -1562C/C genotype is associated with the intrapulmonary spread of TB rather than its development.

Background: The measurement of carbohydrate antigen 19-9 (CA 19-9) is recommended for the diagnosis and follow-up of pancreatic cancer. However, increased CA 19-9 has also been reported in patients with various benign diseases of the lung. We aimed to elucidate the pulmonary radiographic abnormalities and laboratory results associated with increased concentrations of CA 19-9., Methods: This study was performed using a case-controlled design. Cases included all participants in a cancer screening program who had an increased CA 19-9 concentration (>37 U/mL), but without a diagnosis of malignancy. Age- and sex-matched participants with normal CA 19-9 levels were enrolled as controls. Laboratory results and radiographic features were compared., Results: In total, 119 participants with increased CA 19-9 concentrations and 476 controls were included. A higher erythrocyte sedimentation rate (ESR) [adjusted odd ratio (aOR), 1.03; 95% confidence interval (CI), 1.01-1.05], higher hemoglobin A(1c) (HbA(1c)) (aOR, 1.28; 95% CI, 1.05-1.56), bronchiectasis (aOR, 2.48; 95% CI, 1.22-5.02), bronchiolitis (aOR, 3.93; 95% CI, 1.88-8.22), emphysema (aOR, 2.67; 95% CI, 1.32-5.40), and interstitial fibrosis (aOR, 10.62; 95% CI, 2.03-55.44) were independent factors for increased CA 19-9., Conclusions: CA 19-9 concentrations, as well as increased ESR and HbA(1c), can be increased in patients with various lung abnormalities.

Good's syndrome is extremely rare. This adult-onset condition is characterized by a thymoma with immunodeficiency, low B- and T-cell counts, and hypo-gammaglobulinemia. The initial clinical presentation is either a mass-lesion thymoma or a recurrent infection. Patients with Good's syndrome are very susceptible to infections; common respiratory and opportunistic infections can be life-threatening. There are no reports of granulomatous lung disease in patients with Good's syndrome, although it has been observed in patients with common variable immunodeficiency, of which Good's syndrome is a subset. We describe a 53-year-old male thymoma patient who presented with respiratory symptoms caused by granulomatous lung disease and an opportunistic infection. He died of uncontrolled fungal infection despite repeated intravenous immunoglobulin and supportive care. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with severe recurrent infections, especially opportunistic infections.

Background: Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules., Methods: We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea., Results: We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age 25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB., Conclusion: Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.

Although it is not rare to find sputum that is positive acid-fast bacilli (AFB) smear but subsequent culture fails to isolate mycobacteria in clinical practice, the incidence and clinical implication of those sputa from new patients has not been clearly elucidated. The aim of this study was to determine the incidence and clinical implication of sputum with positive AFB smear but negative in mycobacterial culture. All sputa that were positive AFB smear requested during diagnostic work up for new patients visiting Seoul National University Hospital from 1 January 2005 through 31 December 2006 were included. Sputa producing a positive AFB smear but negative mycobacterial culture were classified into one of four categories: laboratory failure to isolate mycobacteria, false positive AFB smear, pathogen may show a positive AFB smear other than mycobacteria, and indeterminate results. Out of 447 sputa with a positive AFB smear, 29 (6.5%) failed to culture any organism. Among these 29 sputa, 18 were caused by laboratory failure to isolate mycobacteria, six were false positive smears, and five indeterminate. Although most sputum with a positive AFB smear but negative culture could be classified as a laboratory failure, clinicians should consider the possibility of false positive AFB smear.

Background and Objective: The effective control of tuberculosis (TB) requires that people at high risk for the reactivation of TB are identified. Haematological malignancy has been shown to be a risk factor for the development of TB, either through immune suppression by the tumour or through the effects of chemotherapy. This study assessed the hypothesis that solid-organ malignancy is a risk factor for the development of TB., Methods: A retrospective cohort study was performed to determine the incidence of TB in patients with solid-organ malignancy and in control subjects without malignancy. Risk factors for the development of TB among patients with cancer were also assessed., Results: The study recruited 1809 cases with cancer and 1809 control subjects and followed them for 3 years. The incidence of active TB per 1000 person-years was 3.07 in patients with cancer and 0.77 in controls (P = 0.009). Compared with the control group, patients with cancer had an increased risk of developing TB (incidence rate ratio (IRR) 4.69, 95% CI: 1.52-14.46). Proportional hazards regression analysis showed that the risk factors for development of TB were chronic renal failure (IRR 9.91, 95% CI: 1.17-83.60), old healed TB on CXR (IRR 45.05, 95% CI: 5.74-353.88), and anticancer chemotherapy (IRR 4.32, 95% CI: 1.10-16.89). An interaction between old healed TB and anticancer chemotherapy was observed., Conclusion: These findings indicate that immune suppression by cancer or by anticancer chemotherapy increases vulnerability to reactivation of TB, especially in cancer patients with old healed TB.

Background: Recently, serious concerns about extensively drug-resistant tuberculosis (XDR-TB), which shows resistance to second-line anti-TB drugs in addition to isoniazid and rifampicin, have been raised. The aim of this study was to elucidate the impact of extensive drug resistance on treatment outcomes in non-human immunodeficiency virus (HIV)-infected patients with multidrug-resistant tuberculosis (MDR-TB)., Methods: Patients who received the diagnosis of and treatment as having MDR-TB at Seoul National University Hospital (Seoul, Republic of Korea) between January 1996 and December 2005 were included. The definition of XDR-TB was TB caused by bacilli showing resistance to both isoniazid and rifampicin and also showing resistance to any fluoroquinolone and to at least 1 of the following 3 injectable anti-TB drugs: capreomycin, kanamycin, and amikacin. To identify the impact of extensive drug resistance on treatment outcomes, univariate comparison and multiple logistic regression were performed., Results: A total of 211 non-HIV-infected patients with MDR-TB were included in the final analysis. Among them, 43 patients (20.4%) had XDR-TB. Treatment failure was observed in 19 patients (44.2%) with XDR-TB, whereas treatment of 46 patients (27.4%) with non-XDR-TB failed (P=.057). The presence of extensive drug resistance (adjusted odds ratio [OR], 4.46; 95% confidence interval [CI], 1.35-14.74) and underlying comorbidity (adjusted OR, 2.62; 95% CI, 1.00-6.87) were independent risk factors for treatment failure. However, a higher level of albumin was inversely associated with treatment failure (adjusted OR, 0.87; 95% CI, 0.77-0.97)., Conclusion: The presence of extensive drug resistance, the presence of comorbidity, and hypoalbuminemia were independent poor prognostic factors in non-HIV-infected patients with MDR-TB.

Background and Objectives: Rapid and accurate diagnosis of latent tuberculosis infection (LTBI) is crucial in military settings. This study aimed to detect the prevalence of LTBI using a whole-blood interferon-gamma assay based on Mycobacterium tuberculosis-specific antigens, and to identify risk factors for LTBI among military personnel in contact with patients with active pulmonary TB., Methods: This prospective study investigated contacts in military camps in South Korea of soldiers with active pulmonary TB. The whole-blood interferon-gamma assay was performed using QuantiFERON TB-Gold., Results: Among the 175 contacts, 25 (14.3%) showed positive results to the assay. Long duration of exposure (OR 2.83; 95% CI: 1.63-4.91), laryngeal TB (OR 6.04; 95% CI: 1.54-23.67) and intensive exposure (OR 5.13; 95% CI: 1.63-16.12) were associated with a positive result., Conclusions: A relatively small number of TB contacts in a military setting had LTBI.

Because additive effects of inhaled corticosteroids and long-acting anticholinergics are unclear, we undertook this study to compare the efficacy of tiotropium alone and tiotropium plus budesonide in patients with chronic obstructive pulmonary disease. The study subjects were randomized to receive either tiotropium 18 microg once daily with or without budesonide 200 microg twice daily for 6 weeks. The efficacy variables were changes in trough forced expiratory volume in one second (FEV1), St. George's Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and use of rescue medication. One hundred patients were randomized and 81 completed the study. The mean age was 64.0 yr, and the mean FEV1 was 39.7% predicted. Compared with tiotropium alone (N=40), the tiotropium/budesonide combination (N=41) was related to an improvement in the SGRQ total score (tiotropium -2.8 units and tiotropium/budesonide -5.6 units, p=0.003). 6MWD was improved by 13.5 m in the tiotropium group and by 22.5 m in the tiotropium/budesonide group (p=0.031). Changes in trough FEV1 and the use of rescue medication were similar between two groups. In conclusion, compared with tiotropium alone, the tiotropium/budesonide combination was related to an improved health-related quality of life. These data support that low-dose budesonide may enhance the efficacy of tiotropium.

Purposes: The aim of this study was to evaluate the usefulness of the whole-blood interferon-gamma assay (enzyme-linked immunosorbent assay [ELISA]) and interferon-gamma enzyme-linked immunospot assay (ELISPOT) based on early secretory antigenic target 6 and culture filtrate protein 10 in the diagnosis of active pulmonary tuberculosis (TB) in routine clinical practice., Method: We conducted a prospective study enrolling 144 participants with suspected pulmonary TB in a tertiary referral hospital in Seoul, South Korea, to investigate the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these tests. Clinical assessment, tuberculin skin test (TST), whole-blood interferon-gamma ELISA (QuantiFERON-TB Gold [QFT-G]; Cellestis Ltd; Victoria, Australia), and an ELISPOT assay (T SPOT.TB; Oxford Immunotec; Oxford, UK) were performed. Test results were compared with the final confirmed diagnoses., Results: Active pulmonary TB was diagnosed in 67 of 144 participants (47%). Sensitivities of QFT-G and T SPOT.TB for active pulmonary TB were 89% (95% confidence interval [CI], 79 to 96%) and 92% (95% CI, 83 to 97%), respectively; and specificities were 49% (95% CI, 37 to 61%) and 47% (95% CI, 36 to 59%). NPVs of QFT-G (84%; 95% CI, 69 to 93%) and T SPOT.TB (87%; 95% CI, 73 to 96%) were higher than that of TST (64%; 95% CI, 51 to 76%) [p = 0.001 and p < 0.001, respectively]., Conclusion: High NPVs of QFT-G and T SPOT.TB for the diagnosis of active TB suggest the supplementary role of these tests for the diagnostic exclusion of active TB, although the low PPV limits their usefulness in routine clinical practice in South Korea, where the prevalence of latent TB infection is considerable.

We aimed to determine the outcome of small (<10 mm) solid noncalcified pulmonary nodules detected by chest computed tomography (CT) scans. Reports of low-dose chest CT scans performed from October 2003 to April 2005 at the Seoul National University Hospital Healthcare System Gangnam Center were reviewed to identify patients with solid noncalcified pulmonary nodules smaller than 10 mm. Partly solid and nonsolid nodules or nodules without follow-up imaging within 1 year were excluded. Records were studied to determine if the initial nodules had changed in size. A total of 3478 chest CT examinations were performed, with 232 patients having small noncalcified nodules (6.7%). One hundred and thirty-eight patients met the criteria (104 men and 34 women) and 213 nodules were identified. The median age was 54 years (range 32-80) and at least 86 patients (62%) were at low to intermediate risk for developing lung cancer. The largest nodule was less than 5 mm in diameter in 87 patients (63%) and 5 mm or more in 51 patients (37%). None of the nodules grew and 29 (14%) decreased in size at follow-up CT scans performed within 12 months. When those individuals at low to intermediate risk for lung cancer were included, solid noncalcified subcentimeter nodules were less frequently found in low-dose CT screening and were nearly unchanged in size when a follow-up CT scan was done within 12 months.

The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/ T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex-matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans.

In Korea, the Mycobacterium tuberculosis K-strain is the most prevalent clinical isolates and belongs to the Beijing family. In this study, we conducted comparative porteomics of expressed proteins of clinical isolates of the K-strain with H37Rv, H37Ra as well as the vaccine strain of Mycobacterium bovis BCG following phagocytosis by the human monocytic cell line U-937. Proteins were analyzed by 2-D PAGE and MALDITOF-MS. Two proteins, Mb1363 (probable glycogen phosphorylase GlgP) and MT2656 (Haloalkane dehalogenase LinB) were most abundant after phagocytosis of M. tuberculosis K-strain. This approach provides a method to determine specific proteins that may have critical roles in tuberculosis pathogenesis.

Background and Objectives: Patients with liver cirrhosis are likely to be susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of this study was to elucidate the clinical characteristics and treatment responses in TB patients with cirrhosis., Methods: Cases were patients with TB detected during their follow up for liver cirrhosis over a 4-year period. Controls were randomly selected patients with TB but no liver disease, matched to cases by age and gender in a 3:1 ratio., Results: Thirty-six cases and 108 controls were enrolled. Extrapulmonary TB was more common in cases than controls (31% vs 12%, P = 0.02). Clinical and radiographic manifestations and response to treatment did not differ between the two groups. The frequency of hepatotoxicity was higher in the cases than in the controls who were treated with a regimen containing rifampicin and isoniazid, although the difference was not statistically significant (27% vs 10%, P = 0.079)., Conclusions: TB patients with liver cirrhosis show extrapulmonary involvement more frequently. Patients with pulmonary TB and cirrhosis usually respond well to anti-TB treatment although appear to present more frequently with treatment-related hepatotoxicity.

RNA interference is a phenomenon whereby small double-stranded RNA knocks down the expression of a sequence-specific gene. Double-stranded siRNA transfection, as currently used, is considered to have transient and low transfection efficiency. We constructed an adenoviral vector-based short hair-pin(sh)RNA system to overcome the limitations of the genetic blockade of IGF-1R, one of most important cancer therapy targets. We constructed three different IGF-1R specific shRNAs (612, 801, and 3425) and generated three ad-shIGF-1Rs using BD Adeno-X expression system. We assessed the effect of ad-shIGF-1R on signal transduction, induction of apoptosis, and in vitro tumorigenicity of lung cancer cell lines. Western blot and FACS assays demonstrated that endogenous IGF-1R expression was efficiently suppressed after transduction of lung cancer cell lines with the three different ad-shIGF-1Rs. IGF-1R blockade by ad-shIGF-1R inhibited ligand induced phosphorylation of pAkt and pErk, and ad-shIGF-1R effectively blocked the in vitro tumorigenicity of lung cancer cell lines. Moreover, the transduction of a human lung cancer cell line with ad-IGF-1R(3425) enhanced chemosensitivity to anticancer drugs. We conclude that the adenoviral vector-based approach to the RNA interference of IGF-1R induced effective IGF-1R silencing in lung cancer cell lines as manifested by effective blocking of the downstream pathway of IGF-1R and by an antitumor effect. We believe that this system can be usefully applied to other cancer targets.

Background and Objective: The need for routine use of bronchial washing in addition to forceps biopsy has been debated in the diagnosis of endoscopically visible lung tumours. Moreover, the optimal sequence for obtaining bronchial washing and forceps biopsy specimens from endoscopically visible tumours through a flexible bronchoscope has not been well established., Methods: A multicentre 13-month prospective randomized study was performed. Two hundred and thirty consecutive patients with endoscopically visible tumours were randomly assigned into a bronchial washing before forceps biopsy (pre-biopsy) group and a bronchial washing after forceps biopsy (post-biopsy) group. Bronchial washing and forceps biopsy were performed according to the assigned sequence., Results: Two hundred and seven patients with a definite cytological or histological diagnosis of lung cancer were included in the analyses. One hundred and three were in the pre-biopsy group and 104 were in the post-biopsy group. The diagnostic yield of bronchial washing was 57.3% (59/103) in the pre-biopsy group and 55.8% (58/104) in the post-biopsy group (P = 0.88). In addition, bronchial washing provided the diagnosis in six patients without definite diagnosis from forceps biopsy, and its addition to forceps biopsy significantly increased the overall diagnostic yield of bronchoscopy from 93.7% to 96.6% (P = 0.03)., Conclusion: The sequence for performing bronchial washing before or after forceps biopsy did not affect the diagnostic yield of bronchial washing in patients with endoscopically visible lung cancers. However, bronchial washing led to a significant increase in the overall diagnostic yield of bronchoscopy in patients with lung cancers.

Although mycobacterial culture and the subsequent drug-susceptibility test (DST) for anti-tuberculosis (TB) drugs take several months to complete using solid media, there are no reports on the turnaround times of these tests under clinical conditions. The aim of this study was to determine the interval between initiation of anti-TB treatment and receipt of DST requested at an outpatient clinic. We prospectively enrolled patients with culture-positive pulmonary TB at Seoul National University Hospital from September 2002 to December 2004. Patients were followed up monthly. Mycobacterial cultures were done using Ogawa media at Seoul National University Hospital. DST were performed at the Korean Institute of Tuberculosis. Of the 104 patients enrolled, 54 were male. The median age was 41 yr. The median interval from initiation of anti-TB treatment to receipt of mycobacterial culture results by clinicians was 37 days (range, 0-89 days). The median interval from initiation of treatment to confirmation of DST by requesting clinicians was 80.5 days (range, 28-145 days). Clinicians only received the results of DST more than two months after initiation of treatment when they followed up patients monthly and mycobacterial culture was performed using solid media.

Background and Objective: The genetic factors for the development of bronchiectasis are not well understood in most patients. The aim of this study was to elucidate the possible association between bronchiectasis and guanine-thymine (GT) repeat polymorphism in intron 2 of the human Toll-like receptor 2 (TLR2), which has a crucial role in adaptive as well as innate immunity., Methods: A total of 194 patients with bronchiectasis and the same number of age- and gender-matched healthy blood donors were prospectively enrolled. The numbers of GT repeats were determined by PCR and gene scans. For further analysis, the alleles were classified into three subclasses: 12-16 GT repeats, short alleles (S allele); 17-22 repeats, medium-length alleles (M allele); and 23-27 repeats, long alleles (L allele)., Results: The overall distribution of alleles was not different between patient and control groups (P = 0.71). In addition, the frequencies of genotypes including short alleles were not different between patient and control groups (P = 0.92). Extent of bronchiectasis (P = 0.92) and bacterial colonization (P = 0.48) were not associated with any subclass genotype., Conclusions: Alleles and genotype including the shorter GT repeats in intron 2 of the TLR2, were not associated with the development, extent and bacterial colonization of bronchiectasis in Koreans.

Ground-glass opacity (GGO) attracts attention because of the possibility of early lung cancer. However, some lesions are reduced in size or disappear at follow-up. This study was designed to explore the natural history of solitary GGO, to determine the prevalence of malignancy and to identify factors predictive of benignity or malignancy. Solitary and focal GGO lesions [pGGO (p=pure) and mGGO (m=mixed) based on the presence of a solid component] of less than 3 cm were included. Lesions of less than 1cm were followed up by chest HRCT 3 months later and lesions over 1cm were investigated by percutaneous needle biopsy (PCNB). One hundred and eighty-six patients (69 pGGO and 117 mGGO) were enrolled. Of the 69 pGGO lesions, 7 were diagnosed as pre-malignant or malignant lesions, 3 as benign lesions and 26 pGGO lesions (37.6%) were reduced or disappeared (transient lesions) at follow-up chest HRCT. The other 33 lesions showed no significant change during follow-up. Thus, the probability of malignancy in pGGO was 7/36 (19.4%). On the other hand, of the 117 mGGO lesions, 26 were found to be malignant, 3 were diagnosed as benign and 57 lesions (48.7%) were reduced or had disappeared at follow-up chest HRCT. The other 31 lesions showed no change during follow-up, and thus the probability of malignancy in mGGO was 26/86 (30.2%). A female sex and a spiculated mGGO border were found to be related with malignancy. However, a high blood eosinophil count was strongly associated with regressing or transient mGGO, suggesting that pulmonary infiltrate with eosinophilia (PIE) might have been responsible. We recommend short-term follow-up by chest HRCT be conducted for mGGO lesions in the presence of high eosinophilia--regardless of lesion size.

Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (< or =65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8+/-113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment.

Objective and Background: Costs associated with multidrug-resistant tuberculosis (MDR-TB) are higher than those associated with drug-susceptible TB because of the higher prices of second-line anti-TB drugs, the prolonged duration of treatment, greater productivity loss and higher mortality. The aim of this study was to estimate the cost of treatment for MDR-TB according to the treatment strategy and prognosis in South Korea., Methods: We estimated the direct (medical and non-medical) and indirect cost for the treatment of MDR-TB according to the treatment strategies and prognosis: in medically treated, surgically treated and deceased patients groups. The same analyses were undertaken for drug-susceptible TB for comparison. The patients with MDR-TB or drug-susceptible TB were randomly selected from the TB cohort of Seoul National University Hospital, Seoul, South Korea., Results: Direct costs per person were US$4000 (US$2527-4841) in the medically treated group, US$17,457 (US$10,133-26,418) in the surgically treated group and US$33,362 (US$25 386-40 338) in the deceased group. Total costs per person were US$15,856 (US$10,752-38,421), US$47,159 (US$20,587-77,622) and US$478,357 (US$257,377-777,778), respectively. For the patients with drug-susceptible TB, the total cost ranged from US$1680 to US$7637 (median US$2166)., Conclusions: The cost for the treatment of MDR-TB is seven to 22 times that of managing the drug-susceptible TB in South Korea. Considering the high cost, transmissibility and considerable fatality of MDR-TB, there is a need to provide specific separate funding for multidrug-resistant tuberculosis.

Hypoxia confers protection against apoptosis in cancer cells, and this hypoxia-induced resistance to apoptosis has been suggested to be associated with genetic and adaptive changes. However, it is not clear whether survival signals, such as the PI3K/Akt and ERK pathways are involved. We investigated the roles of these pathways in hypoxia-induced protection against apoptosis in lung cancer cells. Treatment of cells with either ultraviolet (UV) or etoposide induced apoptosis time-dependently in A549 and NCI-H157 cells. However, though hypoxia alone neither induced apoptosis nor reduced cell survival, it suppressed the apoptosis induced by UV or etoposide. Moreover, hypoxia activated the PI3K/Akt and ERK pathways, and blocking the activation of either pathway reversed resistance to UV- and etoposide-induced apoptosis in response to hypoxia. These results suggest that hypoxia confers resistance to UV- or etoposide-mediated apoptosis in lung cancer cells via the activations of the PI3K/Akt and the ERK pathways.

Objective: Although extrapulmonary organs are involved in 20% of patients with tuberculosis, the host genetic factors associated with the extrapulmonary dissemination of tuberculosis are not yet known. The aim of this study was to identify the host genetic factors associated with the extrapulmonary dissemination of tuberculosis by comparing gene expression profiles of patients who had recovered from extrapulmonary tuberculosis and those who had recovered from pulmonary tuberculosis., Methods: Five patients from each group were enrolled. Total RNA was extracted from peripheral blood mononuclear cells that had been incubated for 48 h with whole lysate of Mycobacterium tuberculosis (H37Rv, 0.5 microg/mL). Gene expression profiles were acquired using the GeneChip array and its applied systems. Gene expression profiles from five patients with previous extrapulmonary tuberculosis and one pooled control sample from five patients with previous pulmonary tuberculosis were analysed and compared. Genes that were expressed concordantly in more than 80% of arrays and that showed more than twofold changes in at least one array among samples from patients who had recovered from extrapulmonary tuberculosis were identified., Results: Compared with the control sample, the expression of 16 genes, including those for tumour necrosis factor (TNF)-alpha and cathepsin W, was increased, and the expression of 45 genes including that for TNF-receptor superfamily member 7 (TNFRSF7), was decreased in the extrapulmonary tuberculosis patients. The altered expression of the TNF-alpha, cathepsin W and TNFRSF7 genes was confirmed by quantitative RT-PCR., Conclusions: Altered expression of the genes for TNF-alpha, cathepsin W and TNFRSF7 may be risk factors for the extrapulmonary dissemination of tuberculosis in humans.

When a patient with cT(1-2)N(0)M(0) stage non-small-cell lung cancer (NSCLC) has a second small nodule(s), the treatment plan and prognosis depend largely on whether the nodule is benign or malignant. However, the incidence of malignancy of nodules associated with N(0) and M(0) NSCLC is unknown. Furthermore, predictive factors of malignancy have not been defined. Thus, we evaluated the nature of nodules that were less than 15 mm in diameter associated with stage T(1-2)N(0)M(0), and tried to identify clinical and radiologic factors predictive of malignancy. The study population consisted of 39 patients with T(1-2)N(0)M(0) NSCLC and a second nodule(s) less than 1.5 cm and who had received curative resection. Medical records and radiologic findings, including CT scans of the chest, were retrospectively reviewed. Nodules were finally diagnosed as benign in 85% and malignant in 15%. No significant differences in terms of gender, age, preoperative carcinoembryonic antigen (CEA) level, cell type, pathologic stages, shape, size, location and number of nodules, or the presence of calcification around nodules was observed between benign and malignant groups. We suggest that if primary NSCLC is resectable, an effort should be made to confirm the pathologic diagnosis of nodules. If histologic findings in nodules are not available, surgical resection should be actively considered, especially when nodules < 1.5 cm are associated with N(0) or M(0) NSCLCs.