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Quercetin, a ubiquitous bioactive plant flavonoid, has shown to exert a broad range of activities, such as apoptotic, antioxidant, and anti-inflammatory effects. Thus, flavonoids can mediate both cell protection and cell injury. Recently, quercetin has been reported to prevent the progression of emphysema in animal models through antioxidant and antiinflammatory actions. These findings suggest that quercetin could be a potential treatment option for chronic obstructive pulmonary disease. Its clinical application, however, could be limited by the cytotoxicity of quercetin, and understanding of the apoptotic mechanisms of quercetin is a prerequisite to develop a therapeutic strategy with minimal cytotoxicity. We evaluated the apoptotic effect of quercetin and its molecular mechanisms in normal bronchial epithelial cells (BEAS-2B cells). Quercetin decreased the viability of BEAS-2B cells via apoptosis in a dose- and time-dependent manner. Quercetin activated JNK and increased the expression levels of c-Jun and p53-dependent Bax. Blockade of JNK activation by overexpression of dominant negative JNK1 suppressed apoptosis by quercetin via inhibition of caspase-3 activation and reduction of p53 and Bax expression. Simultaneously, quercetin inactivated glycogen synthase kinase (GSK)-3β, which is phosphatidylinositol 3-kinase/Akt dependent. Overexpression of a constitutively active GSK-3β mutant enhanced quercetin-induced JNK activation. In contrast, overexpression of enzymatically inert GSK-3β inhibited JNK activation, resulting in a suppression of apoptosis by quercetin. Taken together, the JNK-p53 pathway is involved in quercetin-induced apoptosis, and simultaneous inactivation of GSK-3β can attenuate apoptosis in normal bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Examines the effect of acetylsalicylic acid (ASA) on endogenous Interleukin-kappaB kinase activity in lung epithelial cells. ASA dosage; Western blot analysis; Immunofluorescent staining for nuclear factor-KappaB; Mechanism of anti-inflammatory action.

Investigates the effect of acetylsalicylic acid (ASA) on IkappaB kinase activity in lung epithelial cells. Mechanism of anti-inflammatory response of ASA; Induction of proinflammatory cytokine expression by interleukin-1beta and tumor necrosis factor (TNF)-alpha; Influence of ASA on proinflammatory cytokine expression; Role of ASA on TNF-induced IkappaB kinase activation.

Proteasome inhibitors (PIs) have been reported to induce apoptosis in many types of tumor. Their apoptotic activities have been suggested to be associated with the up-regulation of molecules implicated in pro-apoptotic cascades such as p53, p21Waf1, and p27Kip1. Moreover, the blocking of NF-κB nuclear translocation via the stabilization of IκB is an important mechanism of PI-induced apoptosis. However, we found that longterm incubation with PIs (PS-341 or MG132) increased NF-κB-regulated gene expression such as COX-2, cIAP2, XIAP, and IL-8 in a dose- and time-dependent manner, which was mediated by phosphorylation of IκBα and its subsequent degradation via the alternative route, lysosome. Overexpression of the IκBα superrepressor (IκBα-SR) blocked PI-induced NF-κB activation. Treatment with lysosomal inhibitors (ammonium chloride or chloroquine) or inhibitors of cathepsins (Z-FF-FMK or Z-FAFMK) or knock-down of LC3B expression by siRNAs suppressed PI-induced IκBα degradation. Furthermore, we found that both IKK-dependent and IKK-independent pathways were required for PI-induced IκBα degradation. Pretreatment with IKKβ specific inhibitor, SC-514, partially suppressed IκBα degradation and IL-8 production by PIs. Blockade of IKK activity using insolubilization by heat shock (HS) and knock-down by siRNAs for IKKβ only delayed IκBα degradation up to 8 h after treatment with PIs. In addition, PIs induced Akt-dependent inactivation of GSK-3β. Inactive GSK-3β accelerated PI-induced IκBα degradation. Overexpression of active GSK-3β (S9A) or knock-down of GSK-3βdelayed PI-induced IκBα degradation. Collectively, our data demonstrate that long-term incubation with PIs activates NF-κB, which is mediated by IκBα degradation via the lysosome in an IKK-dependent and IKK-independent manner. [ABSTRACT FROM AUTHOR]

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). 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. 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. This study confirms that FDG PET has a considerable impact on the initial staging and therapeutic management of patients with NSCLC. F-FDG PET has a considerable impact on both initial staging and clinical decisions regarding therapeutic management in patients with non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article presents information on a study which elucidates the clinical characteristics and treatment responses of tuberculosis developing in patients receiving anticancer chemotherapy. Malignant disease and anticancer chemotherapy are risk factors for the development of tuberculosis or poor prognosis in tuberculosis patients. Impairment of host defense mechanisms, poor nutrition, and debility have been proposed as attributing factors for the higher incidence of tuberculosis in patients with some malignant diseases. The trend that the presence of healed scar suggesting previous tuberculosis on chest radiography is more common in tuberculosis patients receiving anticancer chemotherapy, and new lesions were extended from there or contained healed scar in the study, which suggests tuberculosis development by reactivation may reinforce the concept of anticancer chemotherapy as a risk factor for the development of tuberculosis.

Background: In many cases, physicians initiate anti-tuberculosis (TB) treatment based only on symptoms or radiographic findings without confirmation of pulmonary TB by acid-fast bacilli (AFB) smear. It has not been well known which clinical characteristics could be used as predictors for positive culture or real TB in patients with sputum smear-negative presumptive pulmonary TB. Objective: We tried to elucidate treatment outcomes in patients with sputum smear-negative presumptive pulmonary TB and to find predictors of positive culture results. Methods: We reviewed data of the patients who had been treated as presumptive TB with negative AFB smear on the basis of clinical and radiographic features from December 1998 to December 2000 at a university hospital in Korea. We reviewed medical records and radiographs of patients and analyzed possible predictors for positive culture. Results: One hundred and one patients were enrolled. Among them, pulmonary TB was confirmed by culture in 32 patients (31%). Thirty-one (96.9%) out of 32 culture-positive patients showed clinical or radiographic improvement as did 50 (72.5%) out of 69 culture-negative patients. The predictor for a positive culture result is the presence of patchy consolidation in an initial radiograph (p = 0.025; OR 2.89; 95% CI 1.14–7.28). Conclusions: The empirical anti-TB treatment in patients with sputum smear-negative presumptive pulmonary TB was effective and adequate, especially presented with patchy consolidation in initial chest radiographs in Korea. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

α1-Antitrypsin genotypes in Korean patients with chronic obstructive pulmonary diseaseKIM CH, YIM J-J, YOO C-G, LEE CT, KIM YW, HAN SK, SHIM Y-S.Respirology2005;10: 223–228α1-Antitrypsin (AAT) deficiency is a recognized susceptible factor for chronic obstructive pulmonary disease (COPD) in Western countries, but its importance in Korea is unclear. To date, no definitive case ofα1-antitrypsin deficiency has been reported in Korea. This study aimed to clarify whetherα1-antitrypsin deficiency exists and to determine the distribution ofα1-antitrypsin alleles in the Korean population.The serum concentrations ofα1-antitrypsin were determined and polymorphisms of theα1-antitrypsin gene in 114 COPD patients and in 196 healthy controls were examined. Phenotyping by isoelectric focusing and the genotyping ofα1-antitrypsin gene by polymerase chain reaction and restriction fragment length polymorphism were performed.Noα1-antitrypsin level abnormality was found in the patients.M1(Val)/M1(Val)was found to be the most frequent genotype in both groups (69.2% and 66.8%, respectively), andM1(Val)the most frequent allele. The distributions ofα1-antitrypsin alleles were similar in the patient and control groups, and noSorZallele was found.α1-Antitrypsin deficiency is unlikely to be an important cause of chronic obstructive pulmonary disease in the Korean population. [ABSTRACT FROM AUTHOR]

Study objectives: To evaluate the incidence and clinical significance of delayed pneumothorax, and to analyze the influence of multiple variables on the rate of delayed pneumothorax associated with transthoracic needle biopsy (TTNB) of the lung. Study design: Prospective study. Setting: Tertiary care university hospital. Study subjects: Adult patients underwent TTNB from June 2001 to June 2002. Measurements and results: Among the 458 patients included in this study, 280 fluoroscopicguided, 21 CT-guided, and 157 ultrasonography-guided lung biopsies were performed. A follow-up chest radiograph was obtained immediately, and 3 h, 8 h, and 24 h after the biopsy procedure. Pneumothorax that had not developed up to 3 h but developed later was defined as a delayed pneumothorax. Patients with a symptomatic or enlarged pneumothorax were treated using a pigtail catheter or chest tube. Variables such as age, gender, lesion size, location, presence of an emphysematous change, biopsy guidance methods, and biopsy devices were analyzed. Pneumothorax developed in 100 of the 458 patients (21.8%), and delayed pneumothorax developed in 15 patients (3.3%). Seventeen patients, including 3 patients with delayed pneumothorax, required a pigtail catheter or a chest tube insertion. The pigtail catheter or chest tube insertion rate in delayed pneumothorax was 20% (3 of 15 patients). Female gender and the absence of an emphysematous change correlated with an increased rate of delayed pneumothorax (p < 0.05). Lesion size, location, biopsy guidance methods, devices, and underlying diseases were not correlated with the delayed pneumothorax rate. Conclusions: The incidence of delayed pneumothorax was 3.3% of all TTNBs. Female gender and the absence of an emphysematous change were identified as risk factors for delayed pneumothorax. Delayed pneumothorax is clinically important because of its considerable incidence and the necessity for pigtail catheterization or chest tube insertion in these patients. [ABSTRACT FROM AUTHOR]

Silicone fluid (polymethylsiloxane) is a liquid polymer that had been widely used in breast augmentation and other cosmetic procedures. However, many adverse reactions after silicone injections into human beings have been reported including adverse pulmonary sequelae. We report a case of a 46-year-old woman who suffered from acute pneumonitis that was induced by illicit injection of silicone into the vaginal wall for colpoplasty. The pulmonary involvement was documented by transbronchial lung biopsy and bronchoalveolar lavage where examination with the electron microscope disclosed the presence of large quantities of pleomorphic cytoplasmic inclusions in alveolar macrophages. Clinicians should be aware of this unusual complication of injection of silicone. [ABSTRACT FROM AUTHOR]

Objectives: Prone position ventilation improves oxygenation and reduces the mortality of patients with severe acute respiratory distress syndrome. However, there is limited evidence about which patients would gain most survival benefit from prone positioning. Herein, we investigated whether the improvement in oxygenation after prone positioning is associated with survival and aimed to identify patients who will gain most survival benefit from prone positioning in patients with acute respiratory distress syndrome.Design: A retrospective cohort study.Setting: Medical ICU at a tertiary academic hospital between 2014 and 2020.Patients: Adult patients receiving prone positioning for moderate-to-severe acute respiratory distress syndrome.Interventions: None.Measurements and Main Results: The main outcomes were ICU and 28-day mortality. A total of 116 patients receiving prone positioning were included, of whom 45 (38.8%) were ICU survivors. Although there was no difference in PaO2:FIO2 ratio before the first prone session between ICU survivors and nonsurvivors, ICU survivors had a higher PaO2:FIO2 ratio after prone positioning than nonsurvivors, with significant between-group difference (p < 0.001). The area under the receiver operating characteristic curve of the percentage change in the PaO2:FIO2 ratio between the baseline and 8-12 hours after the first prone positioning to predict ICU mortality was 0.87 (95% CI, 0.80-0.94), with an optimal cutoff value of 53.5% (sensitivity, 91.5%; specificity, 73.3%). Prone responders were defined as an increase in PaO2:FIO2 ratio of greater than or equal to 53.5%. In the multivariate Cox regression analysis, prone responders (hazard ratio, 0.11; 95% CI, 0.05-0.25), immunocompromised condition (hazard ratio, 2.15; 95% CI, 1.15-4.03), and Sequential Organ Failure Assessment score (hazard ratio, 1.16; 95% CI, 1.06-1.27) were significantly associated with 28-day mortality.Conclusions: The PaO2:FIO2 ratio after the first prone positioning differed significantly between ICU survivors and nonsurvivors. The improvement in oxygenation after the first prone positioning was a significant predictor of survival in patients with moderate-to-severe acute respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that a high-flow nasal cannula (HFNC) could help to remove carbon dioxide (CO2) from anatomical dead spaces, but evidence to support that is lacking. The objective of this study was to elucidate whether use of an HFNC could reduce the arterial partial pressure of CO2 (PaCO2) in patients with acute hypercapnic respiratory failure who are receiving conventional oxygen (O2) therapy. Methods: A propensity score-matched observational study was conducted to evaluate patients treated with an HFNC for acute hypercapnic respiratory failure from 2015 to 2016. The hypercapnia group was defined as patients with a PaCO2 >50 mm Hg and arterial pH <7.35. Results: Eighteen patients in the hypercapnia group and 177 patients in the nonhypercapnia group were eligible for the present study. Eighteen patients in each group were matched by propensity score. Decreased PaCO2 and consequent pH normalization over time occurred in the hypercapnia group (P=0.002 and P=0.005, respectively). The initial PaCO2 level correlated linearly with PaCO2 removal after the use of an HFNC (R2=0.378, P=0.010). The fraction of inspired O2 used in the intensive care unit was consistently higher for 48 hours in the nonhypercapnia group. Physiological parameters such as respiratory rate and arterial partial pressure of O2 improved over time in both groups. Conclusions: Physiological parameters can improve after the use of an HFNC in patients with acute hypercapnic respiratory failure given low-flow O2 therapy via a facial mask. Further studies are needed to identify which hypercapnic patients might benefit from an HFNC. [ABSTRACT FROM AUTHOR]

Purpose Screening for lung cancer in high-risk patients using the National Lung Screening Trial (NLST) criteria resulted in a decreased lung cancer-related mortality rate. However, whether these criteria are applicable to the Korean has not been investigated thus far. Therefore, we estimated the utility of the NLST criteria as a screening tool for lung cancer in the Korean population. Materials and Methods The total number of newly diagnosed lung cancer cases in 2013 was obtained from the Korea National Statistical Office. The proportion of newly diagnosed lung cancer cases that met the NLST criteria was calculated via a retrospective cohort of a tertiary referral hospital. We estimated the nationwide proportion of patients who met the NLST criteria using the 5th Korea National Health and Nutrition Examination Survey conducted during 2010-2012 (KNHANES V). Results Using KNHANES V data, we found that approximately 6.92% of the general population of Korea would meet the NLST criteria. In the tertiary referral hospital, 29.6% of the 2,689 newly diagnosed lung cancer patients met the NLST criteria. In 2013, the total number of newly diagnosed lung cancer cases in Korea was 23,177. The estimated nationwide proportions of lung cancer patients who met and did not meet the NLST criteria were 0.37% and 0.06%, respectively, yielding a ratio of 5.78. Conclusion The NLST criteria demonstrated sound clinical utility for lung cancer screening of high-risk patients in Korea. [ABSTRACT FROM AUTHOR]

An imbalance between oxidative stress and antioxidant activity plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke, a major risk factor of COPD, induces cellular oxidative stress, but levels of antioxidants such as heme oxygenase-1 (HO-1) are reduced in individuals with severe COPD. In this study, we evaluated the molecular mechanism of reduced HO-1 expression in human bronchial epithelial cells. We found that cigarette smoke extract (CSE) increases HO-1 levels via activation of NFE2-related factor 2 (Nrf2). However, pretreating cells with the protease neutrophil elastase (NE) suppressed the CSE-induced expression of HO-1 mRNA and protein. NE also decreased the sirtuin 1 (SIRT1) level, but did not inhibit CSE-induced nuclear translocation and DNA-binding activity of Nrf2. Transfection of cells with a Myc/His-tagged SIRT1 expression vector completely blocked the NE-mediated suppression of HO-1 expression. We further noted that the NE-induced down-regulation of SIRT1 was not due to decreased transcription or proteasomal/ lysosomal degradation or loss of solubility. Immunofluorescence staining revealed that NE enters the cell cytoplasm, and we observed that NE directly cleaved SIRT1 in vitro, indicating that SIRT1 levels are decreased via direct degradation by internalized NE. Of note, we observed decreased SIRT1 levels in NE-treated primary human bronchial epithelial cells and in lung homogenates from both smokers and patients with COPD. In conclusion, NE suppresses CSE-induced HO-1 expression by cleaving SIRT1. This finding indicates the importance of crosstalk between oxidative stress and protease responses in the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients.Methods: Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models.Results: Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants.Conclusions: Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS. Methods: We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching. Results: A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001). Conclusions: ACE inhibitor or ARB may have beneficial effect on ARDS patients. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the development of leukopenia during treatment with first-line drugs.

Background: The number of elderly patients admitted to intensive care units (ICUs) is growing with the increasing proportion of elderly persons in the Korean general population. It is often difficult to make decisions about ICU care for elderly patients, especially when they are in their 90s. Data regarding the proportion of elderly patients in their 90s along with their clinical characteristics in ICU are scarce. Methods: The records of Korean patients ≥ 90 years old who were admitted to the medical ICU in a tertiary referral hospital between January 2005 and December 2014 were retrospectively reviewed. We compared the trend in ICU use and characteristics of these el- derly patients between 2005-2009 and 2010-2014. Results: Among 6,186 referred patients, 55 aged ≥ 90 years were admitted to the medical ICU from 2005 to 2014. About 58.2% of these patients were male, and their mean age was 92.7 years. Their median Charlson comorbidity index score was 2 (IQR 1-3) and their mean APACHE II score was 25.0 (IQR 19.0-34.0). The most common reason for ICU care was acute respiratory failure. There were no dif- ferences in the survival rates between the earlier and more recent cohorts. However, after excluding patients who had specified "do not resuscitate" (DNR), the more recent group showed a significantly higher survival rate (53.8% mortality for the earlier group and 0% mortality for the recent group). Among the survivors, over half were discharged to their homes. More patients in the recent cohort (n=26 [78.8%]) specified DNR than in the earlier cohort (n=7 [35.0%], p=0.004). The number and proportion of patients ≥ 90 years old among patients using ICU during the 2005-2014 study period did not differ. Conclusions: The use of ICU care by elderly patients ≥ 90 years old was consistent from 2005-2014. The overall mortality rate tended to decrease, but this was not statistically significant. However, the proportion of patients specifying DNR was higher among more recent patients, and the recent group showed an even better survivorship after sensitivity analysis excluded patients specifying DNR. [ABSTRACT FROM AUTHOR]

Inflammation by IL-8-induced neutrophil recruitment and apoptosis of epithelial cells by decreased expression of VEGF have been suggested as one of the complicated pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). The role of neutrophil elastase (NE) in the development of COPD is also well known. However, little is known about how they interact. The objective of this study was to elucidate the effect of NE on cigarette smoke extract (CSE)-induced IL-8 and VEGF production and its molecular mechanism in bronchial epithelial cells. CSE increased both IL-8 and VEGF production in human bronchial epithelial cells (BEAS-2B). Although NE significantly enhanced CSE-induced IL-8 production, it suppressed VEGF production. This differential regulation was not CSE-specific. The effect of NE on IL-8 production, but not VEGF, was ERK-dependent. Interestingly, in contrast to decreased VEGF protein expression, NE accelerated VEGF transcription by CSE, suggesting post-translational modification. When cells were incubated with purified NE, it was detected in the cytoplasm, suggesting the intracellular translocation of NE. Furthermore, NE fragmented recombinant human VEGF in vitro but not recombinant human IL-8. These results indicate that VEGF down-regulation is due to direct degradation by NE, which is translocated into cells. Similar to in vitro cell experiments, elastase treatment increased CSE-induced IL-8; however, it suppressed VEGF production in bronchoalveolar lavage fluid of CSE-treated mice. Moreover, elastase treatment enhanced CSE-induced emphysema in mice. Considering the actions of IL-8 and VEGF, our results suggest that NE contributes to the pathogenesis of COPD by enhancing inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Background: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IκBα)/nuclear factor-kappa B (NF-κB) pathway in RAW 264.7 cells. Methods: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IκBα and nuclear translocation of NF-κB p65 were measured by Western blotting, and IκB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IκBα/NF-κB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. Results: The increase of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IκBα degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-κB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IκBα degradation and NF-κB transcription by AVP was abolished by tolvaptan treatment. Conclusions: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IκBα/NF-κB cascade in mouse macrophages via V2 receptors. [ABSTRACT FROM AUTHOR]

The article investigates the clinical course of idiopathic pulmonary fibrosis (IPF) among Korean patients. Topics discussed include the effectiveness of the gender, age and physiologic (GAP) model in predicting mortality rates among IPF patients, the prognosis and median survival rate of IPF and the reasons behind the difficulties in charting the progression of the disease.

Background There have been few studies of pulmonary actinomycosis, which is an uncommon anaerobic infection. Consequently, the optimal therapeutic regimen, appropriate duration of treatment, long-term prognosis, and factors predicting prognosis are not well established. Methods We retrospectively reviewed the medical records of histopathologically confirmed cases of pulmonary actinomycosis seen between November 2003 and December 2012. Results The study included 68 patients with a mean age of 58.4 ± 11.6 years. Of the 68, initial surgery was performed in 15 patients (22.1%), while the remaining 53 (77.9%) received antibiotic therapy initially. In the initial antibiotic group, 45/53 (84.9%) were cured without relapse (median antibiotic duration 5.3 months). 5/53 (9.4%) patients were refractory medically (median antibiotic duration 9.7 months), and 3/53 (5.7%) experienced a recurrence (median time to relapse 35.3 months). In the initial surgery group, 14/15 (93.3%) were cured and treatment failure occurred in one (6.7%). In the multivariate analysis, the absence of an antibiotic response at 1 month was the only independent factor associated with a poor treatment outcome, with an adjusted odds ratio of 49.2 (95% CI, 3.34–724.30). There was no significant difference in treatment outcome based on the size of the parenchymal lesion, comorbidities, whether intravenous antibiotics were used, antibiotic therapy duration, or whether the initial treatment was surgical. Conclusions Antibiotic treatment with or without surgery was effective for treatment of pulmonary actinomycosis. Nevertheless, treatment failure or recurrence occurred in a considerable proportion of patients, especially those resistant to the initial antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: There have been few studies of pulmonary actinomycosis, which is an uncommon anaerobic infection. Consequently, the optimal therapeutic regimen, appropriate duration of treatment, long-term prognosis, and factors predicting prognosis are not well established. Methods: We retrospectively reviewed the medical records of histopathologically confirmed cases of pulmonary actinomycosis seen between November 2003 and December 2012. Results: The study included 68 patients with a mean age of 58.4 ± 11.6 years. Of the 68, initial surgery was performed in 15 patients (22.1%), while the remaining 53 (77.9%) received antibiotic therapy initially. In the initial antibiotic group, 45/53 (84.9%) were cured without relapse (median antibiotic duration 5.3 months). 5/53 (9.4%) patients were refractory medically (median antibiotic duration 9.7 months), and 3/53 (5.7%) experienced a recurrence (median time to relapse 35.3 months). In the initial surgery group, 14/15 (93.3%) were cured and treatment failure occurred in one (6.7%). In the multivariate analysis, the absence of an antibiotic response at 1 month was the only independent factor associated with a poor treatment outcome, with an adjusted odds ratio of 49.2 (95% CI, 3.34-724.30). There was no significant difference in treatment outcome based on the size of the parenchymal lesion, comorbidities, whether intravenous antibiotics were used, antibiotic therapy duration, or whether the initial treatment was surgical. Conclusions: Antibiotic treatment with or without surgery was effective for treatment of pulmonary actinomycosis. Nevertheless, treatment failure or recurrence occurred in a considerable proportion of patients, especially those resistant to the initial antibiotic treatment. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effectiveness of interferon-γ (IFN-γ) release assays (IGRAs) in detecting latent tuberculosis (TB) infection in health-care workers (HCWs). The study involved HCWs in contact with TB patients in South Korea and they all underwent monthly physical examination and QuantiFERON TB Gold In-Tube assay (QFT-GIT) for a year. Monthly testing was found to be associated with fluctuation in IGRA findings among HCWs.

Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries. A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re-identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute. Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species ( n = 91 + 17), Haemophilus influenzae ( n = 71), Pseudomonas aeruginosa ( n = 63), Streptococcus pneumoniae ( n = 32), Acinetobacter baumannii ( n = 22) and Moraxella catarrhalis ( n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate. Gram-negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB. With the wide variations in the bacteria isolated across Asia, western COPD guidelines for antibiotic therapy may not be readily applicable and surveillance of the local prevalence and antibiotic resistance is important to guide management of acute exacerbations of COPD in these countries. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Pp.057 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. [ABSTRACT FROM AUTHOR]

When a patient with cT1–2N0M0 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 N0 and M0 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 T1–2N0M0, and tried to identify clinical and radiologic factors predictive of malignancy. The study population consisted of 39 patients with T1–2N0M0 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 N0 or M0 NSCLCs. [ABSTRACT FROM AUTHOR]

Objective and background: Atypical—but not definitely malignant—cells in cytological examinations of sputum are usually associated with lung cancers. However, atypical cells are occasionally identified in patients without lung cancer. The aim of this study was to determine the clinical implication of the atypical cells from sputum in patients without lung cancer or other malignancies. Methodology: All patients with atypical cells observed following cytological examination of sputum on one or more occasion over a 2-year period in Seoul National University Hospital were enrolled. After exclusion of patients followed up for less than 6 months, their clinical data were reviewed retrospectively. Results: Among 601 enrolled patients with atypical cells, lung cancers were diagnosed within 30 days of identification of atypical cells in 542 (90.2%) patients. Five out of 59 patients who had no evidence of lung cancer, were subsequently diagnosed with lung cancer or other malignancies following a mean observation of 164 days. In the other 54 patients without subsequent malignancies, the most common respiratory diseases were pneumonia including tuberculosis. Conclusions: The subsequent development of malignancy in patients with atypical cells in sputum despite a thorough evaluation was rare, and close observation without invasive diagnostic procedures might be simply required in these patients. [ABSTRACT FROM AUTHOR]

Heat shock (HS) activates mitogen-activated protein (MAP) kinases. Although prior exposure to nonlethal HS makes cells refractory to the lethal effect of a subsequent HS, it is unclear whether this also occurs in MAP kinase activation. This study was undertaken to evaluate the effect of a heat pretreatment on MAP kinase activation by a subsequent HS and to elucidate its possible mechanism. Preheating did not make BEAS-2B cells refractory to extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) activation by a second HS but accelerated their inactivation after HS. The rapid inactivation of ERK and JNK was dependent on de novo protein synthesis and associated with the up-regulation of heat shock protein 70 (HSP70). Moreover, the inhibition of phosphatase activity reversed this rapid inactivation. MAP kinase phosphatase-1 (MKP-1) expression was increased by HS, and the presence of its phosphorylated form (p-MKP-1) correlated with the observed rapid ERK and JNK inactivation. Blocking induction of p-MKP-1 with antisense MKP-1 oligonucleotides suppressed the rapid inactivation of ERK and JNK in preheated cells. HSP70 overexpression caused the early phosphorylation of MKP-1. Moreover, MPK-1 phosphorylation and the rapid inactivation of ERK were inhibited by blocking HSP70 induction in preheated cells. In addition, MKP-1 was insolubilized by HS, and HSP70 associated physically with MKP-1, suggesting that a chaperone effect of HSP70 might have caused the early phosphorylation of MKP-1. These results indicate that preheating accelerated MAP kinase inactivation after a second HS and that this is related to a HSP70-mediated increase in p-MKP-1. [ABSTRACT FROM AUTHOR]

Study objectives: To assess the clinical characteristics of fever after fiberoptic bronchoscopy (FOB) and to identify the independent risk factors of postbronchoscopy fever. Study design: Prospective study. Setting: Tertiary care university hospital. Study subjects: Immunocompetent adults undergoing FOB between July 2001 and April 2002. Measurements and results: Five hundred eighteen adults were included in this study. The incidence of postbronchoscopy fever was 5%, and the mean onset time of the fever was 8.7 ± 1.1 h after FOB (mean ± SEM). In most cases, the fever subsided spontaneously within a day, with a mean fever duration of 14.0 ± 3.1 h. No organisms were isolated from blood culture specimens drawn at the time of fever, although significant increases in total leukocytes and neutrophil counts were observed in the peripheral blood at the time of fever compared to levels prior to FOB. Univariate analysis showed that fever was related to multiple factors, such as the radiologic extent of involvement, consolidation, abnormal bronchoscopic findings, biopsy, lavage, the amount of saline solution or drug administered, the duration of the procedure, the severity of bleeding, and a final diagnosis of pulmonary tuberculosis. However, after multivariate analysis, the final diagnosis of pulmonary tuberculosis and the severity of bleeding were identified as independent risk factors. Conclusions: Fever after FOB occurs relatively frequently but transiently in immunocompetent adults. Independent risk factors for the development of this complication seem to be related to the diagnosis of pulmonary tuberculosis and the severity of bleeding during FOB. [ABSTRACT FROM AUTHOR]