Cancer development in patients with COPD: a retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea.

BACKGROUND: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. METHODS: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7789), former smokers with COPD (N = 1085), and smokers with COPD (N = 2677). RESULTS: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among smokers, p <  0.01). Old age, male sex, lower BMI, low exercise level, history of diabetes mellitus, smoking, and COPD were independent factors associated with the development of lung cancer (p <  0.01). Multi-variable analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer, and colorectal cancer and liver cancer among other major cancers (p <  0.01). CONCLUSION: Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status.

Prevention of venous thromboembolism in medical intensive care unit: a multicenter observational study in Korea.

Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.

GSK3 inactivation is involved in mitochondrial complex IV defect in transforming growth factor (TGF) ß1-induced senescence.

Transforming growth factor ß1 (TGF ß1) induces Mv1Lu cell senescence by persistently producing mitochondrial reactive oxygen species (ROS) through decreased complex IV activity. Here, we investigated the molecular mechanism underlying the effect of TGF ß1 on mitochondrial complex IV activity. TGF ß1 progressively phosphorylated the negative regulatory sites of both glycogen synthase kinase 3 (GSK3) α and ß, corresponding well to the intracellular ROS generation profile. Pre-treatment of N-acetyl cysteine, an antioxidant, did not alter this GSK3 phosphorylation (inactivation), whereas pharmacological inhibition of GSK3 by SB415286 significantly increased mitochondrial ROS, implying that GSK3 phosphorylation is an upstream event of the ROS generation. GSK3 inhibition by SB415286 decreased complex IV activity and cellular O(2) consumption rate and eventually induced senescence of Mv1Lu cell. Similar results were obtained with siRNA-mediated knockdown of GSK3. Moreover, we found that GSK3 not only exists in cytosol but also in mitochondria of Mv1Lu cell and the mitochondrial GSK3 binds complex IV subunit 6b which has no electron carrier and is topologically located in the mitochondrial intermembrane space. Involvement of subunit 6b in controlling complex IV activity and overall respiration rate was proved with siRNA-mediated knockdown of subunit 6b. Finally, TGF ß1 treatment decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation. Taken together, our results suggest that GSK3 inactivation is importantly involved in TGF ß1-induced complex IV defects through decreasing phosphorylation of the subunit 6b, thereby contributing to senescence-associated mitochondrial ROS generation.

Biomechanical stability according to different configurations of screws and rods.

STUDY DESIGN: Comparison of biomechanical strength according to 2 different configurations of screws and rods. OBJECTIVE: To compare the biomechanical strength of different configurations of screws and rods composed of the same material and of the same size. SUMMARY OF BACKGROUND DATA: Many complications related to instrumentation have been reported. The incidence of metallic failure would differ according to the materials and configurations of the assembly of the screws and rods used. However, to our knowledge, the biomechanical effects of implant assembly rods and screws with different configurations and different contours have not been reported. METHODS: Biomechanical testing was conducted to compare top tightening (TT) screw-rod configuration with side tightening (ST) screw-rod configuration. All tests were conducted using a hydraulic all-purpose testing machine. All data were acquired at a rate of 10 Hz. Both screw systems used spinal rods of 6 mm diameter and were made of TiAl4V ELI material. Among 5 types of tests, 3 were conducted on the basis of American Society for Testing and Materials (ASTM) F 1798 to 97 and F1717-10. The other 2 tests were conducted for comparing the characteristics between TT and ST pedicle screws according to modified methods from ASTM F 1717-10 and ASTM F 1798-97. All results including axial gripping capacity and yield forces were obtained using the same methods on the basis of the mentioned ASTM standards. RESULTS: In the axial gripping capacity test, the mean axial gripping capacity of the TT screw-rod configuration was 3332 ± 118 N and that of ST was 2222 ± 147 N in straight rods (P = 0.019). In 15-degree contoured rods, TT was 2988 ± 199 N and ST was 2116 ± 423 N (P = 0.014). In 30-degree contoured rods, TT was 2227 ± 408 N and ST was 1814 ± 285 N (P = 0.009). In the pulling-out test, the pulling-out force of ST was 8695 ± 1616 N and that of TT was 6106 ± 195 N (P = 0.014). In the rod-pushing test, the failure force of ST was 4131 ± 205 N and that of TT was 5639 ± 105 N. In the compressive fatigue test, the maximum load was 145 N in ST and 119 N in TT. In the cycle fatigue test, the fatigue strength of ST was higher than that of TT. In the rod-pushing test, the failure force of ST was 4131 ± 205 N and that of TT was 5639 ± 105 N (P=0.046). CONCLUSIONS: Two different configurations of rod-screw systems found statistically significant differences with axial gripping, pulling out, and fatigue failures. ST constructs improved fixation stability over TT constructs. It was concluded that ST configuration may reduce complications related to implantation.

Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia: a randomized trial.

RATIONALE: Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial. OBJECTIVES: Evaluate the impact of adjunctive tifacogin on mortality in patients with sCAP. METHODS: A multicenter, randomized, placebo-controlled, double-blind, three-arm study was conducted from July 2005 to June 2008 at 188 centers in North and South America, Europe, South Africa, Asia, Australia, and New Zealand. Adults with sCAP were randomized to receive a continuous intravenous infusion of tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, or matching placebo over 96 hours. MEASUREMENTS AND MAIN RESULTS: Severity-adjusted 28-day all-cause mortality. Of 2,138 randomized patients, 946, 238, and 918 received tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, and placebo, respectively. Tifacogin 0.075 mg/kg/h was discontinued after the first interim analysis according to prespecified futility criterion. The 28-day all-cause mortality rates were similar between the 0.025 mg/kg/h (18%) and placebo groups (17.9%) (P = 0.56). Greater reduction in prothrombin fragment 1+2 and thrombin antithrombin complexes levels relative to baseline throughout the first 96 hours was found with tifacogin 0.025 mg/kg/h than with placebo. The incidence of adverse events and serious adverse events were comparable between the tifacogin 0.025 mg/kg/h and placebo groups. CONCLUSIONS: Tifacogin showed no mortality benefit in patients with sCAP despite evidence of biologic activity.

Emphysema as a risk factor for the outcome of surgical resection of 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.

Blood lead levels in relation to smoking and chronic obstructive pulmonary disease (COPD): a study from Korean National Health and Nutrition Examination Survey (KNHANES).

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. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD. METHODS: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010-2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels. RESULTS: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P<0.05). Multivariable regression analysis demonstrated that older age, male sex, smoking, occupation, and education level were independently associated with higher blood lead levels (P<0.05). CONCLUSIONS: Smoking status, occupation, and education level along with old age and male sex were independently associated with higher blood lead levels; however, COPD was not after adjustment of all confounding factors.

Acute hemodynamic effects of recruitment maneuvers in patients with acute respiratory distress syndrome.

BACKGROUND: The recruitment maneuver (RM) in acute respiratory distress syndrome (ARDS) can cause hemodynamic derangement. We evaluated circulatory and cardiac changes during RMs. METHODS: We performed sustained inflation (SI) with a pressure of 40 cm H(2)O for 30 seconds as an RM on 22 patients with ARDS. Blood pressure (BP) and heart rate were recorded immediately before, every 10 seconds during, and 30 seconds after the RM. Ventricular dimensions were obtained simultaneously using M-mode echocardiography, and tissue Doppler imaging was performed on the left ventricular wall. RESULTS: Mean, systolic, and diastolic BP decreased at 20 and 30 seconds during 30-second RMs (mean BP: 92 +/- 12 at baseline to 83 +/- 18 mm Hg at the end of the RM, P < .05) and subsequently recovered. Heart rate decreased at 10 and 20 seconds during the RM, and tended to increase afterward. Both ventricular dimensions decreased significantly during the RM. The left ventricular ejection fraction and peak velocity of the left ventricle during systole remained stable. The fractional changes in mean BP and left ventricular end-diastolic dimension during the RMs were correlated significantly with each other (r(s) = 0.59). Static compliance of the respiratory system (Crs) was lower in patients with mean BP change > or =15% than in patients in whom the change was <15% (P < .05). CONCLUSIONS: A transient decrease in mean BP was observed during the RM, and its degree was correlated with the preload decrease, while cardiac contractility was maintained.

Expression of excision repair cross-complementation group 1 protein predicts poor outcome in patients with small cell lung cancer.

BACKGROUND: Alterations in apoptosis-related proteins and DNA damage repair proteins are associated with resistance to chemotherapy or radiotherapy, which is the most important cause of treatment failure in small cell lung cancer (SCLC). PATIENTS AND METHODS: Pretreatment tumor biopsy specimens from 77 patients with SCLC (limited stage: 40, extensive stage: 37) were analyzed for p53, bcl-2, bax and ERCC1 expression by immunohistochemistry. All patients were treated with platinum-based doublets. The most commonly used regimen was etoposide/cisplatin (50 patients). In patients with limited stage SCLC, thoracic irradiation was performed either concurrently with chemotherapy or sequentially. RESULTS: High expression of p53, bcl-2, bax and ERCC1 was observed in 40 (52%), 72 (94%), 38 (49%) and 13 (17%) patients, respectively. High expression of ERCC1 was associated with poor OS (1-year, 23% vs. 53%; p=0.026). When grouped according to stage, a significant correlation between high expression of ERCC1 and poor outcome was observed only in patients with limited stage SCLC (p=0.017). High expression of p53, bcl-2 and bax was not correlated with patient outcome. Multivariate analysis showed that extensive stage (p=0.006) and male gender (p=0.009) were independent predictors of poor OS, while high expression of ERCC1 failed to reach statistical significance despite a trend (p=0.057). In limited stage patients, high expression of ERCC1 was an independent prognostic factor for poor OS (p=0.046), along with male gender (p=0.033). CONCLUSIONS: High expression of ERCC1 protein may be a useful predictor of poor outcome in SCLC patients treated with chemotherapy with or without radiotherapy, especially in limited stage SCLC.

Evaluation of bronchoalveolar lavage fluid from ARDS patients with regard to apoptosis.

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-alpha (GRO-alpha), 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 (rs=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 (rs=0.57), GRO-alpha (rs=0.47), and TRAIL (rs=0.45). The BAL fluid IL-8 (rs=0.61), sFas (rs=0.57), G-CSF (rs=0.44), and TRAIL (rs=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 183.4 pg/mL (interquartile range 76.7-315.9) vs. 63.8 pg/mL (36.2-137.2); p<0.05]. The sFas levels were positively correlated with the PaO2/FiO2 ratio (rs=0.40), and the TRAIL levels were negatively correlated with the multiple organ dysfunction scores (rs=-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.

Low expression of Bax predicts poor prognosis in resected non-small cell lung cancer patients with non-squamous histology.

OBJECTIVE: The present study evaluated the prognostic significance of apoptosis-related proteins p53, Bax and galectin-3 in patients with non-small cell lung cancer (NSCLC) treated with surgical resection. METHODS: We investigated the expression of these proteins and their association with clinicopathologic characteristics including disease-free survival (DFS) and overall survival (OS) in 205 NSCLC patients who underwent surgical resection (Stage I, 97; II, 46; IIIA, 45; IIIB, 17) using immunohistochemistry. Eighty-eight patients (43%) received adjuvant treatment (chemotherapy: 8, radiotherapy: 24, both: 56). RESULTS: High expressions of Bax, p53 and galectin-3 were observed in 48 (23%), 81 (40%) and 105 (51%) patients, respectively. Low expression of Bax was significantly associated with male gender, squamous cell histology and low expression of galectin-3. Five-year DFS and OS of total patients were 37 and 46%, respectively. High expressions of p53 and galectin-3 were not associated with poor DFS or OS, and no significant correlation existed between low expression of Bax and outcome of patients. However, in patients with non-squamous histology (108 patients), low expression of Bax was a significant independent predictor of poor DFS (P = 0.017) and OS (P = 0.037). In addition, in patients with Stage II or III disease, low expression of Bax significantly correlated with poor DFS (P = 0.004). It was also the most significant independent poor prognostic factor second only to a large primary tumor size in Stage II or III patients with non-squamous histology. CONCLUSIONS: Low expression of Bax was significantly associated with poor prognosis in resected NSCLC patients with non-squamous histology.

The role of peroxiredoxin III in the ototoxic drug-induced mitochondrial apoptosis of cochlear hair cells.

CONCLUSION: Peroxiredoxin (Prx) III plays a protective role in cisplatin- and gentamicin-induced apoptosis via a mitochondria-dependent pathway in cochlear hair cells. OBJECTIVES: The aim of the present study was to investigate the effects of the depletion of endogenous Prx III on oxidative damage to mitochondrial components and on apoptotic events with the use of RNA interference. MATERIALS AND METHOD: . Depletion of Prx III was done by RNA interference in cochlear hair cells (UB/OC-1), and cells were exposed to ototoxic drugs (cisplatin or gentamicin). We then compared the apoptotic signaling between Prx III-depleted and control cells. RESULTS: The depletion of Prx III resulted in increased intracellular ROS levels accompanied by enhanced apoptosis by ototoxic drugs. The Prx III-depleted cells showed mitochondrial membrane potential collapse, cytochrome c release, and caspase activation.

Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells.

Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2O2, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H2O2. Uptake of ChitoPEGse nanoparticles by CT26 cells significantly increased in acidic and redox state. PL-incorporated ChitoPEGse nanoparticles (PL NPs) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and antimetastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered to cancer cells with an acidic- or redox state-sensitive manner and then efficiently targeted pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have dual pH- and redox-responsiveness.

Blood eosinophil count as a prognostic biomarker in COPD.

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 (<2%). RESULTS: The high group had longer six-minute walk distance (high =445.8±81.4, middle =428.5±88.0, and low =414.7±86.3 m), higher body mass index (23.3±3.1, 23.1±3.1, and 22.5±3.2 kg/m2), lower emphysema index (18.5±14.1, 22.2±15.3, and 23.7±16.3), and higher inspiratory capacity/total lung capacity ratio (32.6±7.4, 32.4±9.2, and 29.9% ± 8.9%) (P<0.05). The survival period increased with increasing blood eosinophil count (high =9.52±0.23, middle =8.47±1.94, and low =7.42±0.27 years, P<0.05). Multivariate linear regression analysis revealed that the emphysema index was independently and negatively correlated with blood eosinophil count (P<0.05). CONCLUSION: In COPD, the severity of emphysema was independently linked with low blood eosinophil count and the longer survival period was associated with increased blood eosinophil count, though it was not proven in the multivariate analysis.

Serum angiopoietin-2 as a clinical marker for lung cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p < 0.001) and VEGF (542.9 +/- 445.8 pg/mL vs 364.7 +/- 185.9 pg/mL, p < 0.05) [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, p < 0.001), specifically in non-small cell lung cancer (NSCLC) [n = 110; r = 0.34; p < 0.001] 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 (p < 0.005). 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; p < 0.05), 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. CONCLUSIONS: Our study suggests that serum angiopoietin-2 is a useful clinical marker for detecting NSCLC with distant metastasis and is of potential prognostic value.

Short-term Evaluation of a Comprehensive Education Program Including Inhaler Training and Disease Management on Chronic Obstructive Pulmonary Disease.

BACKGROUND: Proper education regarding inhaler usage and optimal management of chronic obstructive pulmonary disease (COPD) is essential for effectively treating patients with COPD. This study was conducted to evaluate the effects of a comprehensive education program including inhaler training and COPD management. METHODS: We enlisted 127 patients with COPD on an outpatient basis at 43 private clinics in Korea. The patients were educated on inhaler usage and disease management for three visits across 2 weeks. Physicians and patients were administered a COPD assessment test (CAT) and questionnaires about the correct usage of inhalers and management of COPD before commencement of this program and after their third visit. RESULTS: The outcomes of 127 COPD patients were analyzed. CAT scores (19.6±12.5 vs. 15.1±12.3) improved significantly after this program (p<0.05). Patients with improved CAT scores of 4 points or more had a better understanding of COPD management and the correct technique for using inhalers than those who did not have improved CAT scores (p<0.05). CONCLUSION: A comprehensive education program including inhaler training and COPD management at a primary care setting improved CAT scores and led to patients' better understanding of COPD management.

Anemia as a clinical marker of stable chronic obstructive pulmonary disease in the Korean obstructive lung disease cohort.

BACKGROUND: Anemia is a major co-morbidity in chronic obstructive pulmonary disease (COPD). However, the mechanism of development for anemia and the impact of anemia on the prognosis of COPD remain poorly understood. Therefore, this study attempted to evaluate the prognostic role of anemia on the clinical course of COPD and investigate the factors linked with the serum hemoglobin level in COPD. METHODS: We analyzed 407 COPD patients enrolled in the Korean obstructive lung disease (KOLD) cohort at 16 hospitals in Korea recruited over 9 years. Multivariate Cox regression analysis was performed to find independent predictors of survival and multivariate logistic regression analyses were done to find independent factors. RESULTS: Anemic COPD were older with lower body mass index (BMI) (P<0.001), lower serum cholesterol level (P=0.001), lower serum albumin level (P<0.001), and shorter 6-minute walking distance (P=0.046) compared to non-anemic COPD. A multivariate Cox regression analysis revealed that age (P=0.002), BMI (P=0.001), post-bronchodilator forced expiratory volume in 1 second (FEV1) (P=0.007), 6-minute walk distance (P=0.008), anemia (P=0.025) were significant predictors for all-cause mortality. In multivariate regression analysis, older age (P<0.001), female gender (P=0.001), lower BMI (P=0.016), and lower serum albumin level (P<0.001) were independent factors associated with lower serum hemoglobin level. CONCLUSIONS: Our data showed that anemia was an independent risk factor for mortality in COPD, and aging, lower serum albumin level, and lower BMI were independent factors associated with lower serum hemoglobin level.

TGF beta1 induces prolonged mitochondrial ROS generation through decreased complex IV activity with senescent arrest in Mv1Lu cells.

Transforming growth factor beta1 (TGF beta1) is a well-characterized cytokine that suppresses epithelial cell growth. We report here that TGF beta1 arrested lung epithelial Mv1Lu cells at G1 phase of the cell cycle with acquisition of senescent phenotypes in the presence of 10% serum, whereas it gradually induced apoptosis with lower concentrations of serum. The senescent arrest was accompanied by prolonged generation of reactive oxygen species (ROS) and persistent disruption of mitochondrial membrane potential (DeltaPsim). We demonstrated that the sustained ROS overproduction was derived from mitochondrial respiratory defect via decreased complex IV activity and was involved in the arrest. Moreover, we verified that hepatocyte growth factor released Mv1Lu cells from the arrest by protecting mitochondrial respiration, thereby preventing both the DeltaPsim disruption and the ROS generation. Our present results suggest the TGF beta1-induced senescent arrest as another plausible mechanism to suppress cellular growth in vivo and provide a new biochemical association between the mitochondrial functional defects and the cytokine-induced senescent arrest, emphasizing the importance of maintenance of mitochondrial function in cellular protection from the arrest.

Computerized physician order entry and electronic medical record systems in Korean teaching and general hospitals: results of a 2004 survey.

OBJECTIVE: To determine the availability of computerized physician order entry (CPOE) and electronic medical record (EMR) systems in teaching and general hospitals in the Republic of Korea. DESIGN: A combined mail and telephone survey of 283 hospitals. MEASUREMENTS: The surveys assessed the availability of CPOE and EMRs in the hospitals, as well as inducement, participation, and saturation regarding CPOE use by physicians. RESULTS: A total of 122 (43.1%) hospitals responded to the survey. The complete form of CPOE was available in 98 (80.3%) hospitals. The use of CPOE was mandatory in 92 (86.0%) of the 107 hospitals that responded to the questions regarding the requirement of CPOE use. In 85 (79.4%) of the hospitals in which CPOE was in use, more than 90% of physicians used the system. In addition, physicians entered more than 90% of their total orders through CPOE in 87 (81.3%) hospitals. In contrast, a complete EMR system was available in only 11 (9.0%) of the hospitals. CONCLUSION: Of the teaching and general hospitals in the Republic of Korea that responded to the survey, the majority (80.3%) have CPOE systems, and a complete EMR system is available in only 9%.

Combined effects of inhaled nitric oxide and a recruitment maneuver in patients with acute respiratory distress syndrome.

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.