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Background@#Surgical resection is the standard treatment for early-stage lung cancer. Since postoperative lung function is related to mortality, predicted postoperative lung function is used to determine the treatment modality. The aim of this study was to evaluate the predictive performance of linear regression and machine learning models. @*Methods@#We extracted data from the Clinical Data Warehouse and developed three sets: set I, the linear regression model; set II, machine learning models omitting the missing data: and set III, machine learning models imputing the missing data. Six machine learning models, the least absolute shrinkage and selection operator (LASSO), Ridge regression, ElasticNet, Random Forest, eXtreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM) were implemented. The forced expiratory volume in 1 second measured 6 months after surgery was defined as the outcome. Five-fold cross-validation was performed for hyperparameter tuning of the machine learning models. The dataset was split into training and test datasets at a 70:30 ratio. Implementation was done after dataset splitting in set III. Predictive performance was evaluated by R2 and mean squared error (MSE) in the three sets. @*Results@#A total of 1,487 patients were included in sets I and III and 896 patients were included in set II. In set I, the R2 value was 0.27 and in set II, LightGBM was the best model with the highest R2 value of 0.5 and the lowest MSE of 154.95. In set III, LightGBM was the best model with the highest R2 value of 0.56 and the lowest MSE of 174.07. @*Conclusion@#The LightGBM model showed the best performance in predicting postoperative lung function.
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Background/Aims@#Obstructive sleep apnea (OSA) is prevalent in older patients with idiopathic pulmonary fibrosis (IPF); however, it is underrecognized. OSA is characterized by intermittent hypoxia (IH) and sleep fragmentation. In this study, we evaluated the effects of IH in an older mouse model of bleomycin-induced lung fibrosis. @*Methods@#Bleomycin-induced mice (C57BL/6, female) were randomly divided into four groups of young vs. old and room air (RA)-exposed vs. IH-exposed. Mice were exposed to RA or IH (20 cycles/h, FiO2 nadir 7 ± 0.5%, 8 h/day) for four weeks. The mice were sacrificed on day 28, and blood, bronchoalveolar lavage (BAL) fluid, and lung tissue samples were obtained. @*Results@#The bleomycin-induced IH-exposed (EBI) older group showed more severe inflammation, fibrosis, and oxidative stress than the other groups. The levels of inflammatory cytokines in the serum and BAL fluid increased in the EBI group. Hydroxyproline levels in the lung tissue increased markedly in the EBI group. @*Conclusions@#This study demonstrates the possible harmful impact of OSA in an elderly mouse model of lung fibrosis. This study further suggests that older patients with IPF and OSA may be more of a concern than younger patients with IPF. Further research is required in this area.
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Background@#Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. @*Methods@#We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. @*Results@#While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003–2005 to 468 in 2018–2020, that of other institutions increased from 0 to 238.The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%.The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, r s = −0.740, P = 0.003) and recent administrative difficulties were encountered (r s = −0.616, P = 0.019). @*Conclusion@#This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.
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Obesity hypoventilation syndrome (OHS) is defined as the triad of obesity (body mass index, [BMI] ≥ 30 kg/m 2 ), daytime hypercapnia (PaCO2 ≥ 45 mm Hg), and sleep breathing disorder, after excluding other causes for hypoventilation. As the obese population increases worldwide, the prevalence of OHS is also on the rise. Patients with OHS have poor quality of life, high risk of frequent hospitalization and increased cardiopulmonary mortality. However, most patients with OHS remain undiagnosed and untreated. The diagnosis typically occurs during the 5th and 6th decades of life and frequently first diagnosed in emergency rooms as a result of acute-on-chronic hypercapnic respiratory failure. Due to the high mortality rate in patients with OHS who do not receive treatment or have developed respiratory failure, early recognition and effective treatment is essential for improving outcomes. Positive airway pressure (PAP) therapy including continuous PAP (CPAP) or noninvasive ventilation (NIV) is the primary management option for OHS. Changes in lifestyle, rehabilitation program, weight loss and bariatric surgery should be also considered.
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Background@#This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. @*Methods@#We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. @*Results@#The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users.EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). @*Conclusions@#Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.
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Background/Aims@#As there is insufficient evidence for a relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA), we investigated whether OSA diagnosed by polysomnography (PSG) is related to GERD. @*Methods@#A total of 402 subjects was evaluated. Overnight PSG was performed and a few questionnaires on GERD, anxiety, depression, and daytime sleepiness were administered. An apnea-hypopnea index < 5 was the classification criterion for subjects without OSA.Subjects with heartburn or acid regurgitation at least once a week were classified as having GERD. @*Results@#Among the 402 subjects, 318 had OSA and 84 did not. The prevalence of GERD was 12.9% among patients with OSA and 10.7% among those without (P = 0.590). The prevalence of GERD did not correlate with OSA severity (P = 0.474). Patients with OSA with GERD had higher Stanford Sleepiness Scale (P = 0.004), Epworth Sleepiness Scale (P = 0.001), and depression (P < 0.001) scores than patients with OSA without GERD. Subjects with nocturnal gastroesophageal reflux symptoms had a higher body mass index, waist-to-height ratio, and waist circumference-to-height index than those without symptoms. Multiple logistic regression showed that higher Epworth Sleepiness Scale and depression scores were independent factors associated with GERD in patients with OSA. @*Conclusions@#The prevalence of GERD in patients with OSA was 12.9%. The prevalence of GERD did not correlate with OSA severity. Daytime sleepiness and depression seem to be associated with GERD in patients with OSA, while nocturnal reflux symptoms seem to be related to obesity in OSA.
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Background/Aims@#As there is insufficient evidence for a relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA), we investigated whether OSA diagnosed by polysomnography (PSG) is related to GERD. @*Methods@#A total of 402 subjects was evaluated. Overnight PSG was performed and a few questionnaires on GERD, anxiety, depression, and daytime sleepiness were administered. An apnea-hypopnea index < 5 was the classification criterion for subjects without OSA.Subjects with heartburn or acid regurgitation at least once a week were classified as having GERD. @*Results@#Among the 402 subjects, 318 had OSA and 84 did not. The prevalence of GERD was 12.9% among patients with OSA and 10.7% among those without (P = 0.590). The prevalence of GERD did not correlate with OSA severity (P = 0.474). Patients with OSA with GERD had higher Stanford Sleepiness Scale (P = 0.004), Epworth Sleepiness Scale (P = 0.001), and depression (P < 0.001) scores than patients with OSA without GERD. Subjects with nocturnal gastroesophageal reflux symptoms had a higher body mass index, waist-to-height ratio, and waist circumference-to-height index than those without symptoms. Multiple logistic regression showed that higher Epworth Sleepiness Scale and depression scores were independent factors associated with GERD in patients with OSA. @*Conclusions@#The prevalence of GERD in patients with OSA was 12.9%. The prevalence of GERD did not correlate with OSA severity. Daytime sleepiness and depression seem to be associated with GERD in patients with OSA, while nocturnal reflux symptoms seem to be related to obesity in OSA.
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Background@#Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once-daily in COPD patients in Korea. @*Methods@#This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once-daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted postbronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV1 at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment. @*Results@#Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV1 versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, –0.81), and rescue medication use (Δ, –0.09 puffs/day). Both treatments were well tolerated by patients. @*Conclusion@#A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.
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Background@#E-cigarettes are steadily gaining popularity in Korea. However, the characteristics of e-cigarette smokers, especially nicotine dependence and stress susceptibility, have not been evaluated in comparison to those of nonsmokers or combustible cigarette smokers in Korea. @*Methods@#In this study, 28,059 participants from the Korea National Health and Nutrition Examination Survey (2013–2017) were classified into the following three groups: non-smokers, smokers (current smokers and ex-smokers of combustible cigarettes only), and e-smokers (current smokers and ex-smokers of e-cigarettes regardless of combustible cigarette use). @*Results@#Among the participants, 16,980 (60.5%), 9,247 (33.0%), and 1,832 (6.4%) subjects were non-smokers, smokers, and e-smokers, respectively. E-smokers were younger, more educated, and had a higher household income than nonsmokers or smokers. The number of e-smokers who smoked within 5 minutes of waking up (31.5% vs. 19.8%, p<0.001) and who planned to quit smoking within 6 months (39.1% vs. 35.7%, p<0.05) was greater than that of smokers. E-smokers perceived stress as “very much” (7.0% vs. 4.4%, p<0.001) and “a lot” (29.1% vs. 20.5%, p<0.001) compared to non-smokers. Suicidal ideation (6.5% vs. 4.7%, p<0.001), plans (2.4% vs. 1.3%, p<0.001), and attempts (1.1% vs. 0.5%, p<0.001) were higher in e-smokers than in non-smokers. Depressive episodes in 1 year (14.2% vs. 11.4%, p<0.05) and suicidal plans (2.4% vs. 1.8%, p<0.05) were more frequent among e-smokers than among smokers. @*Conclusion@#E-smokers were younger, more educated, and had a higher income, but they were more dependent on nicotine and susceptible to stress than non-smokers and smokers. Smoking cessation counseling should be tailored according to the characteristics of e-smokers.
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Background/Aims@#This study evaluated the validity and reliability of the Korean version of the Wisconsin Smoking Withdrawal Scale (WSWS-K) for use in clinical practice and research on Korean smokers. @*Methods@#The Wisconsin Smoking Withdrawal Scale was translated into Korean and then back-translated into English. The authors reviewed the translation and back-translation and approved the final questionnaire draft. The validity and reliability of the WSWS-K were evaluated based on data collected from 300 participants. Construct validity was evaluated with a confirmatory factor analysis.Criterion-related validity was assessed by examining the relationships between the subscales of the WSWS-K and the matched items of the Korean version of the Minnesota Nicotine Withdrawal Scale (MNWS-K). @*Results@#The participants were predominantly male (93.6%) and the mean age was 59.23 ± 15.19 years. The confirmatory factor analysis revealed that fit indices (namely, the goodness-of-fit index, adjusted goodness-of-fit index, comparative f it index, and the normed f it index) exceeded or approached 0.9. Cronbach’s alpha for the entire scale was 0.87. The total score of the WSWS-K had a statistically significant positive correlation with that of the MNWS-K (Pearson’s correlation coefficient, 0.768; p < 0.01). Additionally, we performed linear regression between the WSWS-K and MNWS-K scores after adjusting for age, gender, comorbidity, and smoking history. After this adjustment, the p value of the WSWS-K was < 0.001. @*Conclusions@#The WSWS-K had satisfactory validity and reliability. The WSWS-K can be used with acceptable validity and reliability in research and clinical evaluation of Korean smokers.
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Background/Aims@#Many chronic obstructive pulmonary disease (COPD) patientshave physical limitations. We investigated EuroQol five-dimensions five-level (EQ-5D-5L) of COPD patients to assess quality of life, and assessed indirect burden including time expenditure to visit doctor, home care rate, and caregiver related burden. @*Methods@#We recruited 355 COPD patients according to severity of airflow limitationthat severity was set at 10% mild, 40% moderate, 30% severe, and 20% very severe in two primary and 11 secondary/tertiary hospitals. Eligible patients were aged ≥ 40 years, who have been diagnosed with COPD for more than 1 year. Patients were recruited between June 2015 and October 2016. @*Results@#The quality of life tended to decline with age, from mild to very severe impairment, as revealed by the EQ-5D-5L scores and the EQ visual analog scale.Family caregivers accompanied 22.6% of patients who visited outpatient clinics,and 25% of stage IV COPD patients. During emergency visits and hospitalization,this figure increased to > 60%. The home care rates were 28.5% for stage I patients, and 34.4, 31.8, and 52% for stage II to IV patients, respectively. The percentage of caregivers who stopped working was 13.6%. The EQ-5D index was strongly associated with the dyspnea scale (r = –0.64, p < 0.001). The average required time to see a doctor and visit the pharmacy was 154 minutes. @*Conclusions@#In patients with COPD, the EQ-5D index decreased and disease-relatedhome caregiving increased with airflow limitation. We considered the caregiver-related burden when making a strategy for COPD managemen
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Subject(s)
Female , Humans , Asthma , Bronchitis , Cohort Studies , Cough , Diagnosis , Disease Management , Eosinophils , Epidemiology , Gastroesophageal Reflux , Korea , Lung Diseases , Multivariate Analysis , Observational Study , Pregnant Women , Retrospective Studies , TuberculosisABSTRACT
BACKGROUND@#Chronic cough is defined as a cough lasting more than 8 weeks and socio-economic burden of chronic cough is enormous. The characteristics of chronic cough in Korea are not well understood. The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) published guidelines on cough management in 2014. The current study evaluated the clinical characteristics of chronic cough in Korea and the efficacy of the KATRD guidelines.@*METHODS@#This was a multi-center, retrospective observational study conducted in Korea. The participants were over 18 years of age. They had coughs lasting more than 8 weeks. Subjects with current pulmonary diseases, smokers, ex-smokers with more than 10 pack-years or who quit within the past 1 year, pregnant women, and users of cough-inducing medications were excluded. Evaluation and management of cough followed the KATRD cough-management guidelines.@*RESULTS@#Participants with chronic cough in Korea showed age in the late forties and cough duration of more than 1 year. Upper airway cough syndrome was the most common cause of cough, followed by cough-variant asthma (CVA). Gastro-esophageal reflux diseases and eosinophilic bronchitis were less frequently observed. Following the KATRD cough-management guidelines, 91.2% of the subjects improved after 4 weeks of treatment. Responders were younger, had a longer duration of cough, and an initial impression of CVA. In univariate and multivariate analyses, an initial impression of CVA was the only factor related to better treatment response.@*CONCLUSION@#The causes of chronic cough in Korea differed from those reported in other countries. The current Korean guidelines proved efficient for treating Korean patients with chronic cough.
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Background@#Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. @*Methods@#Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. @*Results@#In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. @*Conclusion@#CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.
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BACKGROUND@#Chronic cough is defined as a cough lasting more than 8 weeks and socio-economic burden of chronic cough is enormous. The characteristics of chronic cough in Korea are not well understood. The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) published guidelines on cough management in 2014. The current study evaluated the clinical characteristics of chronic cough in Korea and the efficacy of the KATRD guidelines.@*METHODS@#This was a multi-center, retrospective observational study conducted in Korea. The participants were over 18 years of age. They had coughs lasting more than 8 weeks. Subjects with current pulmonary diseases, smokers, ex-smokers with more than 10 pack-years or who quit within the past 1 year, pregnant women, and users of cough-inducing medications were excluded. Evaluation and management of cough followed the KATRD cough-management guidelines.@*RESULTS@#Participants with chronic cough in Korea showed age in the late forties and cough duration of more than 1 year. Upper airway cough syndrome was the most common cause of cough, followed by cough-variant asthma (CVA). Gastro-esophageal reflux diseases and eosinophilic bronchitis were less frequently observed. Following the KATRD cough-management guidelines, 91.2% of the subjects improved after 4 weeks of treatment. Responders were younger, had a longer duration of cough, and an initial impression of CVA. In univariate and multivariate analyses, an initial impression of CVA was the only factor related to better treatment response.@*CONCLUSION@#The causes of chronic cough in Korea differed from those reported in other countries. The current Korean guidelines proved efficient for treating Korean patients with chronic cough.
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Background@#Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. @*Methods@#Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. @*Results@#In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. @*Conclusion@#CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.
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BACKGROUND: Understanding the burden of disease is important to establish cost-effective treatment strategies and to allocate healthcare resources appropriately. However, little reliable information is available regarding the overall economic burden imposed by chronic obstructive pulmonary disease (COPD) in Korea. METHODS: This study is a multicenter observational research on the COPD burden in Korea. Total COPD costs were comprised of three categories: direct medical, direct non-medical, and indirect costs. For direct medical costs, institutional investigation was performed at 13 medical facilities mainly based on the claims data. For direct non-medical and indirect costs, site-based surveys were administered to the COPD patients during routine visits. Total costs were estimated using the COPD population defined in the recent report. RESULTS: The estimated total costs were approximately 1,245 million US dollar (1,408 billion Korean won). Direct medical costs comprised approximately 20% of the total estimated costs. Of these, formal medical costs held more than 80%. As direct non-medical costs, nursing costs made up the largest percentage (39%) of the total estimated costs. Costs for COPD-related loss of productivity formed four fifths of indirect costs, and accounted for up to 33% of the total costs. CONCLUSION: This study shows for the first time the direct and indirect costs of COPD in Korea. The total costs were enormous, and the costs of nursing and lost productivity comprised approximately 70% of total costs. The results provide insight for an effective allocation of healthcare resources and to inform establishment of strategies to reduce national burden of COPD.
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Humans , Delivery of Health Care , Efficiency , Health Care Costs , Korea , Nursing , Pulmonary Disease, Chronic ObstructiveABSTRACT
PURPOSE: In the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO. METHODS: SIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12–75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β2-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/µL. This subgroup analysis evaluated Korean patients from this group. RESULTS: Of 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/µL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13–0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06–0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039–0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143–0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (−0.27 [95% CI, −0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, −0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms. CONCLUSIONS: Benralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.
Subject(s)
Humans , Arm , Asthma , Eosinophils , Forced Expiratory Volume , Korea , Lung , Receptors, Interleukin-5ABSTRACT
BACKGROUND/AIMS: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = –0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = –0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. CONCLUSIONS: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.
Subject(s)
Humans , Biomarkers , C-Reactive Protein , Forced Expiratory Volume , Inflammation , Interleukin-6 , Korea , Lung Diseases , NF-E2-Related Factor 2 , Plasma , Pulmonary Disease, Chronic Obstructive , Pulmonary Surfactant-Associated Protein D , Respiratory Function Tests , Vital CapacityABSTRACT
BACKGROUND/AIMS: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. METHODS: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. RESULTS: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. CONCLUSIONS: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.