Mortality of patients with chronic obstructive pulmonary disease: a nationwide populationbased cohort study

BACKGROUND/AIMS: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality in the world. There are no population-based studies on longterm mortality in COPD patients in Korea. METHODS: Using the large, population-based, National Health Insurance Service- National Sample Cohort (NHIS-NSC), we identified COPD patients using the International Classification of Disease-Tenth Revision (ICD-10) and prescription details in the NHIS-NSC during 2003 to 2013. We analyzed the survival curves of COPD patients by sex, age, and cause of death. RESULTS: A total of 14,127 individuals older than 40 years were diagnosed with COPD. There were a total of 3,695 deaths (26.2%) in COPD patients during the study period. The 5-year mortality of COPD patients was 25.4% (29.9% in males and 19.1% in females). The mortality rate increased rapidly with age. The most common cause of death in COPD was chronic lower respiratory disease. CONCLUSION: This study described long-term mortality in COPD patients in Korea. Higher mortality was observed in males, and it was closely related to age.ope

Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease

BACKGROUND: Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort. METHODS: We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model. RESULTS: Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = - 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels. CONCLUSIONS: Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.ope

The Distribution of Multidrug-resistant Microorganisms and Treatment Status of Hospital-acquired Pneumonia/Ventilator-associated Pneumonia in Adult Intensive Care Units: a Prospective Cohort Observational Study

Background: It is essential to determine the distribution of the causative microorganisms in the region and the status of local antibiotic resistance for the proper treatment of hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). This study aimed to investigate the occurrence and causative strains of HAP/VAP, distribution of resistant bacteria, use of antibiotics, and the ensuing outcomes of patients in Korea. Methods: A multicenter prospective observational cohort study was conducted among patients with HAP/VAP admitted to the medical intensive care unit of 5 tertiary referral centers between August 2012 and June 2015. Patients' demographic and clinical data were collected. Results: A total of 381 patients were diagnosed with HAP/VAP. Their median age was 69 (59-76) years and 71% were males. A majority of the patients (88%) had late-onset (> 5 days) HAP/VAP. One-quarter of the patients (n = 99) had at least one risk factor for multidrug-resistant (MDR) pathogens, such as prior intravenous antibiotic use within the last 90 days. Microbiological specimens were mostly obtained noninvasively (87%) using sputum or endotracheal aspirates. Pathogens were identified in 235 (62%) of the 381 patients. The most common bacterial pathogen was Acinetobacter baumannii (n = 89), followed by Staphylococcus aureus (n = 52), Klebsiella pneumoniae (n = 25) and Pseudomonas aeruginosa (n = 22). Most of isolated A. baumannii (97%) and S. aureus (88%) were multidrug resistant. The most commonly used empirical antibiotic regimens were carbapenem-based antibiotics (38%), followed by extended-spectrum penicillin/β-lactamase inhibitor (34%). Glycopeptide or linezolid were also used in combination in 54% of patients. The 28-day mortality rate of the patients with HAP/VAP was 30% and the 60-day mortality was 46%. Patients who used empirical antibiotics appropriately had significantly lower mortality rates than those who did not (28-day mortality: 25% vs. 40%, P = 0.032; 60-day mortality: 41% vs. 55%, P = 0.032, respectively). Administration of appropriate empirical antibiotics (odds ratio [OR], 0.282; confidence interval [CI], 0.092-0.859; P = 0.026), Day 7 treatment failure (OR, 4.515; CI, 1.545-13.192; P = 0.006), and APACHE II score on day 1 (OR, 1.326; CI, 0.988-1.779; P = 0.012) were the factors that determined the 28-day mortality in patients with HAP who had identified bacteria as pathogens. Conclusion: In HAP/VAP patients, there was a large burden of MDR pathogens, and their associated mortality rate was high. Proper selection of empirical antibiotics was significantly associated with the patient's prognosis; however, there was a discrepancy between major pathogens and empirical antibiotic therapy.ope

Socioeconomic impact of asthma, chronic obstructive pulmonary disease and asthma-COPD overlap syndrome

Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is defined as having both features of asthma and COPD, which are airway hyper-responsiveness and incompletely reversible airway obstruction. However, socioeconomic impact of ACOS have not been well appreciated. Methods: Adults with available wheezing history and acceptable spirometry were selected from the fourth Korean National Health and Nutrition Examination Survey (KNHANES IV) in 2007-2009. Their data were merged with the Korean National Health Insurance claim data. 'Asthma group' was defined as having self-reported wheezing history and FEV1/FVC ≥0.7, 'COPD group' was defined as having FEV1/FVC <0.7 and no wheezing, 'ACOS group' was defined as having both wheezing and FEV1/FVC <0.7, and 'no airway disease (NAD) group' was defined as having no wheezing and FEV1/FVC ≥0.7. Results: Among a total of 11,656 subjects, ACOS comprise 2.2%; COPD, 8.4%; asthma, 5.8% and NAD, 83.6%. Total length of healthcare utilization and medical costs of ACOS group was the top among four groups (P<0.001), though inpatient medical cost was the highest in COPD group (P=0.025). Multiple linear regression analyses showed that ACOS group (β=12.63, P<0.001) and asthma group (β=6.14, P<0.001) were significantly associated with longer duration of healthcare utilization and ACOS group (β=350,475.88, P=0.008) and asthma group (β=386,876.81, P<0.001) were associated with higher medical costs. Conclusions: This study demonstrated that ACOS independently influences healthcare utilization after adjusting several factors. In order to utilize limited medical resources efficiently, it may be necessary to find and manage ACOS patients.ope

Carbon monoxide activates autophagy via mitochondrial reactive oxygen species formation

Autophagy, an autodigestive process that degrades cellular organelles and protein, plays an important role in maintaining cellular homeostasis during environmental stress. Carbon monoxide (CO), a toxic gas and candidate therapeutic molecule, confers cytoprotection in animal models of acute lung injury. The mechanisms underlying CO-dependent lung cell protection and the role of autophagy in this process remain unclear. Here, we demonstrate that CO exposure time-dependently increased the expression and activation of the autophagic protein, microtubule-associated protein-1 light chain-3B (LC3B) in mouse lung, and in cultured human alveolar (A549) or human bronchial epithelial cells. Furthermore, CO increased autophagosome formation in epithelial cells by electron microscopy and green fluorescent protein (GFP)-LC3 puncta assays. Recent studies indicate that reactive oxygen species (ROS) play an important role in the activation of autophagy. CO up-regulated mitochondria-dependent generation of ROS in epithelial cells, as assayed by MitoSOX fluorescence. Furthermore, CO-dependent induction of LC3B expression was inhibited by N-acetyl-L-cysteine and the mitochondria-targeting antioxidant, Mito-TEMPO. These data suggest that CO promotes the autophagic process through mitochondrial ROS generation. We investigated the relationships between autophagic proteins and CO-dependent cytoprotection using a model of hyperoxic stress. CO protected against hyperoxia-induced cell death, and inhibited hyperoxia-associated ROS production. The ability of CO to protect against hyperoxia-induced cell death and caspase-3 activation was compromised in epithelial cells infected with LC3B-small interfering (si)RNA, indicating a role for autophagic proteins. These studies uncover a new mechanism for the protective action of CO, in support of potential therapeutic application of this gas.ope

Effectiveness of bronchoscopic lung volume reduction using unilateral endobronchial valve: a systematic review and meta-analysis

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) can be suggested as an alternative for surgical lung volume reduction surgery for severe emphysema patients. This article intends to evaluate by systematic review the safety and effectiveness of BLVR using a one-way endobronchial valve. METHODS: A systematic search of electronic databases, including MEDLINE, EMBASE, and the Cochrane Library, as well as eight domestic databases up to December 2013, was performed. Two reviewers independently screened all references according to selection criteria. The Scottish Intercollegiate Guidelines Network criterion was used to assess quality of literature. Data from randomized controlled trials were combined and meta-analysis was performed. RESULTS: This review included 15 studies. Forced expiratory volume in 1 second (FEV1) improved in the intervention group compared with the control group (mean difference [MD]=6.71, 95% confidence interval [CI]: 3.31-10.11). Six-minute walking distance (MD=15.66, 95% CI: 1.69-29.64) and cycle workload (MD=4.43, 95% CI: 1.80-7.07) also improved. In addition, St George's Respiratory Questionnaire score decreased (MD=4.29, 95% CI: -6.87 to -1.71) in the intervention group. In a subgroup analysis of patients with complete fissure, the FEV1 change from baseline was higher in the BLVR group than in the control group for both 6 months (MD=15.28, P<0.001) and 12 months (MD=17.65, P<0.001), whereas for patients with incomplete fissure, FEV1 and 6-minute walking distance showed no change. One-year follow-up randomized controlled trials reported deaths, although the cause of death was not related to BLVR. Respiratory failure and pneumothorax incidence rates were relatively higher in the BLVR group, but the difference was not significant. CONCLUSION: BLVR may be an effective and safe procedure for the treatment of severe COPD patients with emphysema, based on existing studies.ope

Effects of dietary antioxidant vitamins on lung functions according to gender and smoking status in Korea: a population-based cross-sectional study

OBJECTIVE: Cigarette smoke-induced oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Dietary antioxidants are thought to prevent smoke-induced oxidative damage. The aim of this study was to investigate associations between lung function and the consumption of antioxidant vitamins in Korean adults. METHODS: In total, 21 148 participants from the Korean National Health and Nutrition Examination Survey (2007-2014) were divided into four groups based on smoking history and gender. Multivariate regression models were used to evaluate associations between lung function and intake of dietary antioxidants. RESULTS: Subjects in the highest intake quintile (Q5) of vitamin A, carotene and vitamin C intake had mean forced expiratory volume in 1 s (FEV1) measurements that were 30 mL, 32 mL and 36 mL higher than those of individuals in the lowest intake quintile (Q1), respectively (p for trend; p=0.008, p=0.010 and p20 pack-years had mean FEV1 measurements that were 192 mL, 149 mL and 177 mL higher than those of patients in Q1 (p for trend; p=0.018, p=0.024 and p=0.043, for vitamin A, carotene and vitamin C, respectively). CONCLUSIONS: These findings indicate that the influence of antioxidant vitamins on lung function depends on gender and smoking status in the Korean COPD population.ope

Effect of a New Spirometric Reference Equation on the Interpretation of Spirometric Patterns and Disease Severity

Background: A spirometric reference equation was recently developed for the general population in Korea. The applicability of the new Korean equation to clinical practice was examined by comparing it with the Morris equation, which is one of the most popular reference equations used for interpreting the spirometric patterns and for grading the disease severity in Korea. Methods: Spirometry was performed on 926 men and 694 women, aged 20 years or older, in November 2004 at the Asan Medical Center, Seoul, Korea. The subjects' age, gender, height, weight, and spirometric values (FEV1 [forced expiratory volume in one second], FVC [forced vital capacity], and FEV1/FVC) were obtained. The spirometric patterns and disease severity were evaluated using both equations, and the results of the Korean equation were compared with the Morris equation. The spirometric patterns were defined as normal, restrictive, obstructive, and undetermined according to the level of FEV1/FVC and FVC. The disease severity was defined according to the level of FEV1 level for subjects with an airflow limitation, and according to the FVC level for those subjects without an airflow limitation. Results: Spirometric patterns were differently interpreted in 22.5% (208/926) of the men and 24.8% (172/694) of the women after the application of the Korean equation compared with the Morris equation. Of the subjects with airflow limitation, disease severity was differently graded in 30.2% (114/378) of the men and 39.4% (37/94) of the women after the application of the Korean equation. Of the subjects without airflow limitation, disease severity was differently graded in 27.9% (153/548) of the men and 30.2% (181/600) of the women after the application of the Korean equation. Conclusion: Achange in the reference equation for spirometry could have an effect on the interpretation of spirometric patterns and on the grading of disease severity.ope

Health-related Quality of Life Measurement with St. George's Respiratory Questionnaire in Post-tuberculous Destroyed Lung

BACKGROUND: The control of active pulmonary tuberculosis is still an issue in community medicine. But there are also considerable needs for supportive management of symptomatic patients with post-tuberculous destroyed lung. Few studies have evaluated clinical characteristics and health-related quality of life in patients with post-tuberculous destroyed lung. METHODS: We evaluated lung function, exercise tolerance, HRCT and health-related quality of life measurements using the Korean version of St. George's Respiratory Questionnaire (SGRQ) in 22 patients with parenchymal damage to more than a half of one lung due to pulmonary tuberculosis. RESULTS: In the pulmonary function test, mixed defects and obstructive defects were observed in 10 (45.0%) and 9 (40.9%) of patients, respectively. In the cardiopulmonary exercise test, the mean VO2max% predicted (39.0%+/-10.9%) and O2 pulse% predicted (61.3%+/-13.6%) were markedly decreased. In the SGRQ, the impact score (mean 27.8+/-18.5) was significantly lower than the symptom score (mean 53.9+/-20.9) or activity score (mean 50.8+/-27.3) (p<0.05, p<0.01). Cronbach's alpha coefficient value for reliability was more than 0.7 for each subscale and total score. The total score showed a significant negative correlation with FEV1% predicted (r=-0.46, p<0.05) and SaO2 (r=-0.60, p<0.05). On HRCT, a median of 9 (range 5~15) bronchopulmonary segments were destroyed by less than half, which significantly correlated with SGRQ total score (r=-0.52, p=0.02). CONCLUSION: The reliability and validity of the Korean version of the SGRQ was acceptable for the measurement of health-related quality of life in patients with post-tuberculous destroyed lung.ope

Treatment of acute respiratory failure: invasive mechanical ventilation

Background: Acute respiratory failure is a condition in which gas exchange functions decrease due to various causes. Respiratory failure is one of the most common causes of intensive care unit admissions, and most cases require invasive mechanical ventilation. Current Concepts: Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. Invasive mechanical ventilation is commonly used to replace the functions of spontaneous breathing, either fully or partially, by performing the breathing function for the lungs. It is also indicated in patients who require airway protection or have neuromuscular diseases. Invasive mechanical ventilation should not be delayed until the need becomes urgent. There is no universal set of ventilation protocols established as ideal for all patients. It is essential that doctors understand and apply the necessary methods to protect the lungs from injury associated with invasive mechanical ventilation. Discussion and Conclusion: The primary goals of mechanical ventilation are to optimize oxygenation while avoiding ventilator-induced lung injury. In patients with acute respiratory failure, the mortality rate has reduced dramatically with the application of the lung-protective ventilation strategy. Patients undergoing invasive mechanical ventilation will survive if they are treated and monitored according to this principle, but damage to the lungs may occur if the guidelines are not followed. Therefore, it is essential to know and adhere to the initial setup and monitoring principles.ope