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Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80–0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I–III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

Background: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. Methods: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George’s Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. Results: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37–88 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 ± 16.93 vs. end of study, 29.08 ± 15.16, p &lt, 0.0001) and a significant reduction in BSS (baseline, 7.16 ± 2.63 vs. end of study, 4.72 ± 2.45, 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. Conclusions: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.

Background: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure although the majority of lead poisonings originate from workplace exposures. We attempted to investigate the blood lead levels based on COPD and smoking status and the independent association between elevated blood lead levels and clinical variables. Methods: Our data were collected from Korean National Health and Nutrition Examination Survey (KNHANES) IV (n= 9744 in 2008, n= 10533 in 2009), V (n = 8518 in 2011), and VI (n = 8018 in 2013). Blood lead levels were analyzed based on clinical variables. Multivariate linear regression analyses were done to find variables associated with elevated blood lead levels. Results: Blood lead levels were higher in males, older age group, smokers, COPD, lower education group, and lower income group (p Conclusion: Smoking status and education level along with old age and male gender were independently associated with higher blood lead levels, however COPD was not, suggesting higher blood lead level in COPD should be attributed to other correlated clinical factors.

Yeon-Mok Oh,1,* Keu Sung Lee,2,* Yoonki Hong,3,* Sung Chul Hwang,2 Jae Yeol Kim,4 Deog Keom Kim,5 Kwang Ha Yoo,6 Ji-Hyun Lee,7 Tae-Hyung Kim,8 Seong Yong Lim,9 Chin Kook Rhee,10 Hyoung Kyu Yoon,11 Sang Yeub Lee,12 Yong Bum Park,13 Jin Hee Jung,14 Woo Jin Kim,3 Sang-Do Lee,1 Joo Hun Park2 1Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Korea; 3Department of Internal Medicine and Environmental Health Center, Kangwon National University, Kangwon National University Hospital, Chuncheon, Korea; 4Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea; 6Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea; 7Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 8Division of Pulmonology, Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea; 9Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University of Korea, Seoul, Korea; 11Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 12Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University Anam Hospital, Seoul, Korea; 13Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea; 14Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea *These authors contributed equally to this work Background: High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids. However, the prognostic role of blood eosinophil count remains underexplored. Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.Methods: Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital. The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%–5%), and low (

Background: Cardiovascular disease is the most common cause of death in chronic obstructive pulmonary disease (COPD). However, the impact of cardiovascular comorbidities on the prognosis of COPD is not well known. Objectives: This study was performed to investigate the effects of cardiovascular comorbidities on the prognosis of COPD. Methods: We enlisted 229 patients with COPD who underwent comprehensive cardiac evaluations including coronary angiography and echocardiography at Ajou University Hospital between January 2000 and December 2012. Survival analyses were performed in this retrospective cohort. Results: Kaplan-Meier analyses showed that COPD patients without left heart failure (mean survival = 12.5 ± 0.7 years) survived longer than COPD patients with left heart failure (mean survival = 6.7 ± 1.4 years; p = 0.003), and the survival period of nonanemic COPD patients (mean survival = 13.8 ± 0.8 years) was longer than that of anemic COPD patients (mean survival = 8.3 ± 0.8 years; p < 0.001). The survival period in COPD with coronary artery disease (CAD; mean survival = 11.37 ± 0.64 years) was not different from that in COPD without CAD (mean survival = 11.98 ± 0.98 years; p = 0.703). According to a multivariate Cox regression model, a lower hemoglobin level, a lower left ventricular ejection fraction, and the forced expiratory volume in 1 s (FEV1) were independently associated with higher mortality in the total COPD group (p < 0.05). Conclusions: Hemoglobin levels and left ventricular ejection fraction along with a lower FEV1 were identified as independent risk factors for mortality in COPD patients who underwent comprehensive cardiac evaluations, suggesting that multidisciplinary approaches are required in the care of COPD.

Background: In COPD, coronary artery disease (CAD) is a frequent co-morbidity and cardiovascular disease is the most common cause of death. When coronary angiography was performed, the Gensini score is used for the assessment of CAD severity. This study was performed to evaluate the clinical impact of Gensini score in COPD. Methods: We retrospectively reviewed 191 patients with COPD (male 90.1%, mean age 68.5 ± 8.9 years, smoker 86.2%) who had undergone coronary angiography in Ajou University Hospital from Jan 2000 to Dec 2012. The extent of CAD in the entire coronary arterial tree was assessed by Gensini score. Comparative analyses between high Gensini group (≥4 points; median value or more) and low Gensini group ( Results: High Gensini group was more frequently associated with triple vessel CAD (37.2% vs. 1.0%, p 1 (66.4 ± 16.9 vs 64. 9 ± 19.0, p=0.583) and prevalence of hypertension (59.6% vs. 57.7%, p=0.796) did not differ between two groups. High Gensini group was independently related to triple vessel CAD (OR 3.51, 95% CI 1.77 – 6.94) and myocardial infarction (OR 5.38, 95% CI 1.83 – 15.82). Conclusion: Our data suggest that high Gensini score in COPD was independently associated with cardiac co-morbidities such as triple vessel CAD and myocardial infarction.

Cell-mediated immunity plays an important role in the pathobiology of tuberculosis (TB). The ligands for CXC chemokine receptor 3 (CXCR3) activate the T-helper type 1 lymphocyte pathway. The CXCR3 ligands are reportedly useful clinical markers for the diagnosis and follow-up of TB. The objective of this study was to assess the utility of CXCR3 ligands for evaluating early treatment responses in TB. We recruited 88 patients who underwent antituberculous chemotherapy. The serum levels of interferon (IFN)-γ and the CXCR3 ligands CXCL9 (monokine induced by IFN-γ [MIG]), CXCL10 (IFN-γ-inducible 10-kDa protein [IP-10]), and CXCL11 (IFN-inducible T-cell α chemoattractant [I-TAC]) were measured before and 2 months after the start of treatment. Treatment responses were divided into “fast” and “slow” based on the clinical, radiological, and bacteriological improvement at 2 months. A change in level of 20% or more at 2 months was defined as “significant.” In patients with treatment success, 58 patients exhibited a fast response and 20 patients exhibited a slow response. Treatment failure occurred in 5 patients, and the diagnoses were changed to non-TB diseases in 5 patients. The levels of all CXCR3 ligands significantly decreased in the fast-response group (P

Information about the QT interval from surface electrocardiograms (ECGs) is essential for surveillance of the proarrhythmia potential of marketed drugs. However, ECG records obtained in daily practice cannot be easily used for this purpose without labor-intensive manual effort. This study was aimed at constructing an open-access QT database, the Electrocardiogram Vigilance with Electronic Data Warehouse (ECG-ViEW). This longitudinal observational database contains 710,369 measurements of QT and associated clinical data from 371,401 patients. The de-identified database is freely available at http://www.ecgview.org.

SummaryBackgroundsEpithelial cell apoptosis plays an important role in the pathogenesis of idiopathic interstitial pneumonia (IIP).MethodsSerum levels of caspase-cleaved cytokeratin-18 (M30) were measured in 55 patients with IIP and 34 healthy controls using enzyme-linked immunosorbent assays. The IIP cases included usual interstitial pneumonia (UIP; n = 30), nonspecific interstitial pneumonia (NSIP; n = 15), and cryptogenic organizing pneumonia (COP; n = 10). The radiological scoring was performed based on high-resolution computed tomography (HRCT) findings.ResultsPatients with IIP had higher serum M30 levels than did the control group (178.6 ± 91.5 vs. 113.7 ± 46.8 U/L, p

Summary Background Apoptosis is thought to play an important role in the development of acute respiratory distress syndrome (ARDS). We evaluated the bronchoalveolar lavage (BAL) fluid from ARDS patients focusing on apoptosis. Methods The study enrolled 31 ARDS patients and 20 healthy controls. BAL fluid levels of caspase-cleaved cytokeratin-18 (CK-18) and soluble mediators such as interleukin-8 (IL-8), soluble Fas (sFas), soluble Fas ligand (sFasL), growth-related oncogene-α (GRO-α), granulocyte colony-stimulating factor (G-CSF), and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) were measured using enzyme-linked immunosorbent assay (ELISA). Results The BAL fluid caspase-cleaved CK-18 levels in ARDS patients were higher than those in controls, reflecting increased epithelial apoptosis, and were correlated with lung injury scores ( r s =0.49). The BAL fluid levels of all mediators were significantly higher in ARDS patients than in controls. In ARDS patients, the BAL fluid IL-8 level was positively correlated with the levels of sFas ( r s =0.57), GRO-α ( r s =0.47), and TRAIL ( r s =0.45). The BAL fluid IL-8 ( r s =0.61), sFas ( r s =0.57), G-CSF ( r s =0.44), and TRAIL ( r s =0.33) levels were correlated with the BAL fluid neutrophil count. The G-CSF levels were significantly higher in non-surviving than in surviving ARDS patients [median 183.4pg/mL (interquartile range 76.7–315.9) vs. 63.8pg/mL (36.2–137.2); p P aO 2 / F iO 2 ratio ( r s =0.40), and the TRAIL levels were negatively correlated with the multiple organ dysfunction scores ( r s =−0.37). Conclusions Among the mediators in BAL fluid from ARDS patients, G-CSF had the most significant prognostic implications, and the sFas and TRAIL levels were correlated with clinical severity.

Background: The T-helper type 1(Th1) lymphocytes is important in pathogenesis of tuberculosis. So, we evaluated for significance of interferon (IFN)-γ and IFN-inducible chemokines in pleural effusions. Methods: A total of 276 subjects were enrolled. The study population comprised 80 patients with tuberculous effusions, 68 patients with malignant effusions, 53 patients with parapneumonic effusions, 27 patients with transudates, and 48 patients with miscellaneous effusions. In serum and effusion samples from patients with pleural effusions, the levels of IFN-γ, IFN-inducible T-cell alpha chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG) were measured by enzyme-linked immunosorbent assay (ELISA) and the levels of adenosine deaminase (ADA) were measured by colorimetry. Receiver operating characteristic (ROC) analysis was performed. Results: The levels of IFN-γ, I-TAC, MIG and ADA in the pleural effusions were significantly increased in the tuberculous effusions ( p Conclusions: All the IFN-γinducible chemokines along with and ADA showed high discriminating powers for tuberculous effusion, especially IFN-γ in effusion, and MIG in serum. Those chemokines can be useful surrogate markers in diagnosis of pleural effusion.

Background: Buckwheat flour (BF) is known as a potent food allergen. Sensitization to it usually occurs by ingestion but also by inhalation in occupational or domestic exposure. Buckwheat chaff-stuffed pillows (BCP) can be contaminated with BF during the process of pilling, and many Korean children and adults use BCP for health reasons. Methods and Results: We here present three cases of BF allergy in children using BCP, who had been treated as nonatopic asthmatics after undergoing the routine allergy skin tests and serologic tests. We took careful clinical histories, and performed skin prick tests (SPT), the radioimmunoassay (RIA) for specific IgE, the BCP-elimination test, the BF bronchial provocation test, and IgE Western blot. All three children showed positive skin reactions to BF, but none of them had positive reactions to house-dust mites. Nocturnal asthmatic symptoms were improved during 7 days of BCP elimination, and asthmatic responses were observed by bronchial provocation tests with homemade BF extract. Serum BF-specific IgE antibodies and several IgE-binding proteins were detected by RIA and Western blot analysis, respectively. Conclusions: Thus, a small amount of BF attached to BCP can induce BF sensitization, and BCP should be considered a main cause of childhood nocturnal asthma in those asthmatics exposed to these pillows.

BACKGROUND The ligands for CXC chemokine receptor 3 (CXCR3) recruit T-helper type 1 cells, which play a major role in cell-mediated immunity in TB. METHODS A total of 409 subjects were enrolled. The study population comprised 186 patients with active TB, 58 patients with non-TB pulmonary diseases, 50 control subjects with a positive interferon (IFN)-γ release assay (IGRA) result, and 115 control subjects with a negative IGRA result. Whole-blood samples were collected using IGRA methodology. After incubation, plasma IFN-γ levels and two CXCR3 ligands, IFN-inducible T-cell α-chemoattractant (I-TAC, CXCL11) and monokine induced by IFN-γ (MIG, CXCL9), were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was performed. Sensitivity and specificity were based on cutoff values selected to maximize the Youden index. RESULTS The TB antigen-stimulated levels of IFN-γ, I-TAC, and MIG were significantly increased in the active pulmonary TB group compared with all other groups. From ROC analysis, for the diagnosis of active TB, I-TAC and MIG outperformed IFN-γ in all comparisons with the IGRA-positive and -negative control groups and the non-TB pulmonary disease group. The areas under the curve (95% CI) for differentiating active pulmonary TB from all other groups were 0.893 (0.864-0.924) for IFN-γ, 0.962 (0.946-0.978) for I-TAC, and 0.944 (0.922-0.965) for MIG. Sensitivity and specificity were 90.3% and 90.7%, respectively, for I-TAC; 92.5% and 85.2% for MIG; and 84.9% and 79.8% for IFN-γ. CONCLUSIONS TB antigen-stimulated assays of I-TAC and MIG may be useful surrogate markers in the diagnosis of active pulmonary TB.

article i nfo Purpose: The Sequential Organ Failure Assessment (SOFA) score, originally developed to assess organ failure status, is widely used as a prognostic indicator in intensive care unit patients. Additional prognostic factors, such as age and comorbidities, may complement the predictive performance of the SOFA. Methods: In total, 1049 consecutive patients were enrolled prospectively. SOFA and other admission-based intensive care unit scores were recorded during the first 24 hours. A complemented SOFA (cSOFA) score model was constructed by adding age and comorbidity scores to the original SOFA score, based on logistic regression analysis. The predictive performance was evaluated with regard to hospital mortality by receiver operating characteristics analysis. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of the model, and leave-one-out cross-validation was performed. Results: The cSOFA score (maximum 30 points) was calculated as the SOFA score (24 points) + age score (2 points) + comorbidity score (4 points). The cSOFA score model showed satisfactory calibration and cross- validation performance. The AUC (95% CI) of the cSOFA score (0.812 (0.787-0.835)) was higher than the SOFA score (0.743 (0.715-0.769), P b .0001). Conclusion: The performance of the SOFA score to predict hospital mortality can be improved by considering age and comorbidity factors.

Autologous fat grafting to the breast for breast reconstruction and cosmetic breast augmentation has gained much attention recently. However, its efficacy and the severities of its associated complications are of concern. The authors experienced one case of multiple breast abscesses after augmentation mammoplasty by autologous fat grafting.A 42-year-old woman presented to the authors' emergency department reporting tenderness, swelling, and a sensation of heat in both breasts. The patient had undergone augmentation mammoplasty by autologous fat grafting 7 days previously. Abscess formation was suspected based on the patient's history, physical examination, laboratory findings, and image study.Incision and drainage were performed immediately with the patient under general anesthesia, and 500 ml of a foul, brown, turbid, purulent fluid containing necrotic fat debris was drained from each breast. Empiric antibiotics were started on the first hospital day, and betadine and saline-irrigation were administered daily for 2 weeks. Incisions were closed on hospital day 19 when laboratory data and local infection signs had improved. At the patient's 9-month follow-up assessment, breast contours were found to be well preserved, and scarring was minimal.Immediate complications such as edema, hematoma, and infection require serious consideration after autologous fat grafting in the breast. In particular, infection probably is the most serious complication because the volume of the fat injected is large and can induce systemic infections such as sepsis and distort the contours of the breast. To avoid such infections, systemic and multicenter studies are required to determine how fat grafting should be performed to minimize the risks of fat necrosis and infection.

Purpose: We evaluated the clinical significance of angiopoietins and vascular endothelial growth factor (VEGF) in patients with resected early stage lung cancer. Patients and methods: The study enrolled 101 patients with completely resected non-small cell lung cancer (NSCLC) of stage I or II, along with 70 healthy volunteers. Serum concentrations of angiopoietin1, angiopoietin-2, and VEGF were measured with an ELISA. Immunohistochemical expression of angiopoietin-1 was compared with the microvessel density on the lung cancer tissues. Results: The patients had lower serum angiopoietin-1 (32.1 ± 9.9 ng/mL vs. 39.0 ± 10.8 ng/mL, p < 0.001), higher angiopoietin-2 (1949.2 ± 1099.4 pg/mL vs. 1498.6 ± 650.0 pg/mL, p < 0.01), and higher VEGF (565.1 ± 406.3 pg/ mL vs. 404.6 ± 254.8 pg/mL, p < 0.01) levels than the controls. The angiopoietin-2 level was higher in stage II than in stage I patients (p < 0.05). The levels of angiopoietin-1 (r = 0.28) and angiopoietin-2 (r = 0.36) each correlated with the VEGF level. Patients with a higher level of angiopoietin-1 (≥31.2 ng/mL) had better disease-specific and relapse-free survival than those with a lower angiopoietin-1 level (

Angiopoietins play a critical role in the angiogenesis related to tumor growth in concert with vascular endothelial growth factor (VEGF), and enhanced expression of angiopoietin-2 has been reported in lung cancer tissue.Patients with lung cancer (n = 136) and healthy volunteers (n = 40) were enrolled. Serum angiopoietin-2 and VEGF concentrations were measured using enzyme-linked immunosorbent assay.Patients with lung cancer had higher serum angiopoietin-2 (2,046.3 +/- 1,171.3 pg/mL vs 1,269.8 +/- 494.1 pg/mL, p0.001) and VEGF (542.9 +/- 445.8 pg/mL vs 364.7 +/- 185.9 pg/mL, p0.05) [mean +/- SD] levels than the control group. Serum angiopoietin-2 and VEGF levels correlated with each other in patients with lung cancer (Spearman r = 0.30, p0.001), specifically in non-small cell lung cancer (NSCLC) [n = 110; r = 0.34; p0.001] but not in small cell lung cancer (n = 26). With stage progression in NSCLC, serum angiopoietin-2 levels increased, and patients with distant metastasis had higher levels than those without metastasis (p0.005). By contrast, serum VEGF level did not increase with stage progression, and only had a trend toward elevation in distant metastasis (p = 0.05). In NSCLC, the low angiopoietin-2 group (1,605.5 pg/mL) had a better overall survival compared to the high angiopoietin-2 group (or = 1,605.5 pg/mL; p0.05), although this survival benefit was not maintained after controlling for stage in a multivariate analysis. The angiopoietin-2 levels were higher in NSCLC patients with postoperative recurrence than in those without.Our study suggests that serum angiopoietin-2 is a useful clinical marker for detecting NSCLC with distant metastasis and is of potential prognostic value.

Nitric oxide (NO) inhalation therapy has been employed in the management of acute respiratory distress syndrome (ARDS), in order to improve oxygenation. Several factors have been implicated as being responsible for the action of inhaled NO. Alveolar recruitment methods, such as prone positioning and a sufficient positive end expiratory pressure (PEEP), have been identified as having a positive impact on the NO response. A Recruitment maneuver (RM) was introduced for the treatment of ARDS, along with a lung protective strategy. Here, we hypothesized that a RM may further augment the oxygenation of patients treated with NO inhalation. Therefore, the effects of the inhalation of NO, either in combination with a RM, or separately, were evaluated on patients with ARDS for their enhancing action. 23 patients with ARDS were enrolled, and divided into three groups. The patients in group 1 (n=11) were treated with 5 ppm NO via inhalation, followed by a RM, applying a sustained inflation pressure of 30 - 35 cmH2O for 30 seconds. Group 2 (n=6) received a RM alone, while group 3 (n=3) was treated with NO inhalation alone. The oxygenation and hemodynamic parameters were obtained prior to, and 2, 12, and 24 h after, the respective treatment procedures. For group 1, the PaO2/FiO2 increased from its initial value of 171.8 +/- 67.8 to 203.2 +/- 90.0 2 h after NO inhalation. Further improvement was noted with the continual application of the RM reaching, 215.5 +/- 74.6 (p=0.05) and 254.2 +/- 109.5 (p < 0.05), after 12 and 24 h, respectively. Initially 7 of the subjects did not respond to NO inhalation, but 3 of these non-responders changed into responders 12 h after the RM. The changes in the PaO2/FiO2 from baseline at each time period were greater in group 1 than in the other groups, but with no statistical significance. The hemodynamics of the patients was not significantly altered during the entire study period. We conclude that the combined application of NO inhalation and a RM could be beneficial and safe for patients with ARDS, showing an enhancing effect in improvement of oxygenation.

The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was defined as RV/TLC ≥ 40%. Multivariate logistic regression analysis demonstrated that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV1) (P < 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019), and higher emphysema index (P = 0.010) were associated independently with resting hyperinflation. Multivariate Cox regression model that included age, gender, dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter 6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all-cause mortality. Our data showed that older age, higher emphysema index, higher SGRQ score, and lower FEV1 were associated independently with resting pulmonary hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause mortality in COPD. Graphical Abstract

Unilateral or bilateral non-Hodgkin's lymphomas arising primarily in the adrenal glands are extremely rare. These lymphomas are usually present with large, bilateral adrenal masses with or without lymphadenopathy, and may be accompanied by adrenal insufficiency in some cases. A review of the literature indicates that patients with primary lymphoma of the adrenal glands usually do not have disease elsewhere, and if present, it is frequently extranodal. We report here an unusual case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.

Background: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. Methods: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. Results: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1±1,467.3 U/mL) than in patients with lung cancer (956.5±618.5 U/mL), parapneumonic effusion (689.9±413.6 U/mL), and transudates (273.6±144.5 U/mL; all p

Background: Adequate assessment and control of sedation play crucial roles in the proper performance of mechanical ventilation. Methods: A total of 30 patients with various pulmonary diseases were prospectively enrolled. The study population was randomized into two groups. The sedation assessment group (SAG) received active protocol-based control of sedation, and in the empiric control group (ECG), the sedation levels were empirically adjusted. Subsequently, daily interruption of sedation (DIS) was conducted in the SAG. Results: In the SAG, the dose of midazolam was significantly reduced by control of sedation (day 1, 1.3±0.5 μg/kg/min; day 2, 0.9±0.4μg/kg/min; p＜0.01), and was significantly lower than the ECG on day 2 (p＜0.01). Likewise, on day 2, sedation levels were significantly lower in the SAG than in the ECG. Significant relationship was found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS; rs=−0.57), Ramsay Sedation Scale and Bispectral Index (BIS; rs=0.77), and RASS and BIS (rs=−0.79). In 10 patients, who didn't require re-sedation after DIS, BIS showed the earliest and most significant changes among the sedation scales. Ventilatory parameters showed significant but less prominent changes, and hemodynamic parameters didn't show significant changes. No seriously adverse events ensued after the implementation of DIS. Conclusion: Active assessment and control of sedation significantly reduced the dosage of sedatives in patients receiving mechanical ventilation. DIS, conducted in limited cases, suggested its potential efficacy and tolerability.

Background: Adaptive support ventilation (ASV), an automated closed-loop ventilation mode, adapts to the mechanical characteristics of the respiratory system by continuous measurement and adjustment of the respiratory parameters. The adequacy of ASV was evaluated in the patients with acute lung injury (ALI). Methods: A total of 36 patients (19 normal lungs and 17 ALIs) were enrolled. The patients' breathing patterns and respiratory mechanics parameters were recorded under the passive ventilation using the ASV mode. Results: The ALI patients showed lower tidal volumes and higher respiratory rates (RR) compared to patients with normal lungs (7.1±0.9 mL/kg vs. 8.6±1.3 mL/kg IBW; 19.7±4.8 b/min vs. 14.6±4.6 b/min; p＜0.05, respectively). The expiratory time constant (RCe) was lower in ALI patients than in those with normal lungs, and the expiratory time/RCe was maintained above 3 in both groups. In all patients, RR was correlated with RCe and peak inspiratory flow ( rs=−0.40; rs=0.43; p＜0.05, respectively). In ALI patients, significant correlations were found between RR and RCe (rs=−0.76, p＜0.01), peak inspiratory flow and RR (rs=−0.53, p＜0.05), and RCe and peak inspiratory flow (rs=−0.53, p＜0.05). Conclusion: ASV was found to operate adequately according to the respiratory mechanical characteristics in the ALI patients. Discrepancies with the ARDS Network recommendations, such as a somewhat higher tidal volume, have yet to be addressed in further studies.

BACKGROUND/AIMS Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer. METHODS To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-β(1), tumor necrosis factor-α, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells. RESULTS Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells. CONCLUSIONS Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.

It is unclear whether emphysema, regardless of airflow limitation, is a predictive factor associated with survival after lung cancer resection. Therefore, we investigated whether emphysema was a risk factor associated with the outcome after resection for lung cancer. This study enrolled 237 patients with non small cell lung cancer with stage I or II who had surgical removal. Patient outcome was analyzed based on emphysema. Emphysema was found in 43.4% of all patients. Patients with emphysema were predominantly men and smokers, and had a lower body mass index than the patients without emphysema. The patients without emphysema (n=133) survived longer (mean 51.2+/-3.0 vs. 40.6+/-3.1 months, P=0.042) than those with emphysema (n=104). The univariate analysis showed a younger age, higher FEV(1)/FVC, higher body mass index, cancer stage I, and a lower emphysema score were significant predictors of better survival. The multivariate analysis revealed a younger age, higher body mass index, and cancer stage I were independent parameters associated with better survival, however, emphysema was not. This study suggests that unfavorable outcomes after surgical resection of lung cancer should not be attributed to emphysema itself.

Background: The nitric oxide (NO) released by inducible NO synthase (iNOS) plays an important role in the pathophysiology of sepsis. Corticosteroids also play a role in the hemodynamic and inflammatory reactions in sepsis. Both have been shown to have a relationship theoretically, but their correlation and clinical impacts have rarely been evaluated. Methods: 26 patients with sepsis and 14 healthy controls were enrolled in this study. The initial random plasma total NO and the serum cortisol levels were measured. The same measurements were serially carried out on the , , and days. Results: The initial total plasma levels of NO and cortisol were higher in the patients with sepsis than in the healthy controls. The total NO levels were higher in patients with severe sepsis than in the those with mild sepsis. There was a correlation between the total NO and cortisol level throughout the study. Conclusion: In patients with sepsis, the levels of plasma NO and cortisol were well correlated during the first week of sepsis, which suggests an interrelationship. However, the clinical and pathogenetic implications await further evaluation.

Background: Corticosteroids are known to be significant prognostic parameters in sepsis. Recently, an absolute and relative insufficiency of the corticosteroids system has often been reported to often develop particularly in severe sepsis. Degree of such an adrenal insufficiency not only has prognostic implications but also can be used to guide corticosteroids replacement therapy. The 24-hour urinary cortisol levels as well as serum cortisol concentrations were measured to assess the clinical significance and their relationship with the other parameters of sepsis, and also evaluated the clinical implications of the relative adrenal insufficiency. Methods: 26 consecutive patients with sepsis were enrolled. The basal random serum cortisol, ACTH, ADH, lactate levels and 24-hour urinary free cortisol amount were measured. The rapid ACTH (250 μg) stimulation test was also performed. Results: Basal serum cortisol levels were higher in the non-survivors than in the survivors. The 24-hour urinary free cortisol levels were higher in the patients with severe sepsis than in those without. The serum cortisol levels strongly correlated with the serum ADH and lactate levels. The 24-hour urinary free cortisol levels strongly correlated with the serum cortisol and lactate levels. The fractional changes in the cortisol levels after the rapid ACTH stimulation tests correlated with the serum cortisol, ADH, and lactate levels. Conclusion: Both the serum cortisol and 24-hour urinary cortisol were found to be significant prognostic factors in sepsis, and showed a strong correlation with the other parameters. The relative adrenal insufficiency might also be an important clinical parameter. (Tuberc Respir Dis 2006; 61: 356-365)