Eupatilin Alleviates Hyperlipidemia in Mice by Inhibiting HMG-CoA Reductase.

Artemisia princeps (family Asteraceae) is a natural product broadly used as an antioxidative, hepatoprotective, antibacterial, and anti-inflammatory agent in East Asia. In the present study, eupatilin, the main constituent of Artemisia princeps, was investigated as an antihyperlipidemic agent. Eupatilin inhibited 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HCR), an enzyme that is a therapeutic target for hyperlipidemia, in an ex vivo assay using rat liver. In addition, oral administration of eupatilin significantly lowered the serum levels of total cholesterol (TC) and triglycerides (TG) in corn oil-induced and Triton WR-1339-induced hyperlipidemic mice. These results suggest that eupatilin can alleviate hyperlipidemia by inhibiting HCR.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice.

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

The Impact of Inhaled Corticosteroids on the Prognosis of Chronic Obstructive Pulmonary Disease.

Background: A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world. Methods: We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years). Results: Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P<0.05). Hospitalization due to respiratory causes was also higher among ICS users (P<0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P<0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P<0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P<0.05). Conclusion: Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.

Increased hospitalizations and economic burden in COPD with bronchiectasis: a nationwide representative study.

With the increasing use of computed tomography, bronchiectasis has become a common finding in patients with chronic obstructive pulmonary disease (COPD). However, the clinical aspects and medical utilization of COPD with bronchiectasis (BE) remain unclear. We aimed to investigate the BE effect on prognosis and medical utilization in patients with COPD. Among 263,747 COPD patients, we excluded patients lacking chest X-ray, CT, or pulmonary function test codes and classified 2583 GOLD-C/D patients matched according to age, sex, and medical aid as having COPD-BE (447 [17.3%]) and COPD without BE (2136 [82.7%]). Patients with COPD-BE showed a higher rate of acute exacerbation requiring antibiotics than those without BE. Moreover, multivariable analysis showed that BE co-existence was a crucial factor for moderate-to-severe exacerbation (incidence rate ratio [IRR] 1.071; 95% CI 1.012-1.134; p = 0.019). Patients with COPD-BE had a significantly higher rate of exacerbations requiring antibiotics, as well as treatment cost and duration (meant as number of days using hospitalization plus outpatient appointment), than those with COPD without BE (52.64 ± 65.29 vs. 40.19 ± 50.02 days, p < 0.001; 5984.08 ± 8316.96 vs. 4453.40 ± 7291.03 USD, p < 0.001). Compared with patients with COPD without BE, patients with COPD-BE experienced more exacerbations requiring antibiotics, more hospitalizations, and a higher medical cost.

Does the Use of Asthma-Controller Medication in Accordance with Guidelines Reduce the Incidence of Acute Exacerbations and Healthcare Costs?

BACKGROUND: In asthma, consistent control of chronic airway inflammation is crucial, and the use of asthma-controller medication has been emphasized. Our purpose in this study is to compare the incidence of acute exacerbation and healthcare costs related to the use of asthma-controller medication. METHODS: By using data collected by the National Health Insurance Review and Assessment Service, we compared one-year clinical outcomes and medical costs from July 2014 to June 2015 (follow-up period) between two groups of patients with asthma who received different prescriptions for recommended asthma-controller medication (inhaled corticosteroids or leukotriene receptor antagonists) at least once from July 2013 to June 2014 (assessment period). RESULTS: There were 51,757 patients who satisfied our inclusion criteria. Among them, 13,702 patients (26.5%) were prescribed a recommended asthma-controller medication during the assessment period. In patients using a recommended asthma-controller medication, the frequency of acute exacerbations decreased in the follow-up period, from 2.7% to 1.1%. The total medical costs of the controller group decreased during the follow-up period compared to the assessment period, from $3,772,692 to $1,985,475. Only 50.9% of patients in the controller group used healthcare services in the follow-up period, and the use of asthma-controller medication decreased in the follow-up period. CONCLUSION: Overall, patients using a recommended asthma-controller medication showed decreased acute exacerbation and reduced total healthcare cost by half.

Chronic Obstructive Pulmonary Disease Is Not Associated with a Poor Prognosis in COVID-19.

BACKGROUND: The effect of underlying chronic obstructive pulmonary disease (COPD) on coronavirus disease 2019 (COVID-19) during a pandemic is controversial. The purpose of this study was to examine the prognosis of COVID-19 according to the underlying COPD. METHODS: COVID-19 patients were assessed using nationwide health insurance data. Comorbidities were evaluated using the modified Charlson Comorbidity Index (mCCI) which excluded COPD from conventional CCI scores. Baseline characteristics were assessed. Univariable and multiple logistic and linear regression analyses were performed to determine effects of variables on clinical outcomes. Ages, sex, mCCI, socioeconomic status, and underlying COPD were selected as variables. RESULTS: COPD patients showed older age (71.3±11.6 years vs. 47.7±19.1 years, p<0.001), higher mCCI (2.6±1.9 vs. 0.8±1.3, p<0.001), and higher mortality (22.9% vs. 3.2%, p<0.001) than non-COPD patients. The intensive care unit admission rate and hospital length of stay were not significantly different between the two groups. All variables were associated with mortality in univariate analysis. However, underlying COPD was not associated with mortality unlike other variables in the adjusted analysis. Older age (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.11-1.14; p<0.001), male sex (OR, 2.29; 95% CI, 1.67-3.12; p<0.001), higher mCCI (OR, 1.30; 95% CI, 1.20-1.41; p<0.001), and medical aid insurance (OR, 1.55; 95% CI, 1.03-2.32; p=0.035) were associated with mortality. CONCLUSION: Underlying COPD is not associated with a poor prognosis of COVID-19.

Effect of low protein intake on acute exacerbations in mild to moderate chronic obstructive pulmonary disease: data from the 2007-2012 KNHANES.

BACKGROUND: Several researchers have reported that the amount of protein intake is associated with lung function and airflow obstruction. However, few studies have investigated the effect of low protein intake on acute exacerbations of chronic obstructive pulmonary disease. This study aimed to investigate the effect of low protein intake on exacerbations in mild to moderate chronic obstructive pulmonary disease. METHODS: We used data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES) between 2007 and 2012, linked to the National Health Insurance claims data. The clinical outcomes and the rate of exacerbation were retrospectively compared between the low protein intake group and the non-low protein intake group which was stratified by quartile categories of protein intake in 2,069 patients with mild to moderate chronic obstructive pulmonary disease. RESULTS: The low protein intake group was significantly associated with older age, women, never smoker, low household income, and low education level, compared with the non-low protein intake group. The low protein intake group was significantly associated with increased hospitalization (18.0% vs. 10.5%, P<0.001) and emergency department utilization (1.6±1.0 vs. 1.1±0.4, P=0.033) compared with the non-low protein intake group. In multivariate analysis, the low protein intake group was associated with hospitalization (odds ratio 1.46; 95% CI, 1.09-1.96; P=0.012). The multiple linear regression analysis revealed that the amount of protein intake was associated with FVC % predicted (ß=0.048, P<0.001) and FEV1% predicted (ß=0.022, P=0.015). CONCLUSIONS: Low protein intake was associated with an increased risk of exacerbations in mild to moderate chronic obstructive pulmonary disease. The data are available at the KNHANES website (https://knhanes.cdc.go.kr).

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

Inhaled corticosteroid is not associated with a poor prognosis in COVID-19.

Frequent Outpatient Visits Prevent Exacerbation of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease requiring frequent outpatient visits and lifelong management. We aimed to evaluate the roles of frequent outpatient visits in prognosis of COPD. We used claims data in the national medical insurance review system provided by the Health Insurance Review and Assessment Service of Korea from May 1, 2014 to April 30, 2015. A definition of COPD was used based on the diagnosis code and medication. Frequent visitors were defined as subjects who visited the outpatient clinic for COPD three or more times per year. Among 159,025 subjects, 117,483 (73.9%) were classified as frequent visitors. Frequent visitors underwent pulmonary function tests and used various inhalers more often than did infrequent visitors. The rates of COPD exacerbation requiring admission to a general ward, emergency room, or intensive care unit were significantly lower in frequent visitors than in infrequent visitors. In multivariable analysis, frequent visits were identified as an independent factor preventing COPD exacerbation that required admission to a ward (odds ratio [OR], 0.387), emergency room, (OR, 0.558), or intensive care unit (OR, 0.39) (all P < 0.001). In conclusion, we showed frequent outpatient visits reduce the risk of COPD exacerbation by 45-60%.

Prescription Status and Clinical Outcomes of Methylxanthines and Leukotriene Receptor Antagonists in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Background: Methylxanthines and leukotriene receptor antagonists (LTRA) are not a first-line medical treatment for chronic obstructive pulmonary disease (COPD) but are frequently prescribed despite limited evidence. We aimed to elucidate the real prescribing status and clinical impacts of these agents in early COPD patients. Methods: Patients with mild-to-moderate COPD (FEV1>50%) were selected from the Korean National Health and Nutrition Examination Survey data between 2007 and 2012. Besides analyzing the prescription status of methylxanthines and LTRA and the contributing factors to the prescription, we evaluated the clinical impacts of these drugs on the exacerbation, hospitalization, and medical costs. Results: Of 2269 patients with mild-to-moderate COPD, 378 patients (16.7%) were under medical treatments, and the users of methylxanthines and/or LTRA were 279 patients (12.3%); however, only 139 patients (6.1%) were inhaler users. The contributing factors for the prescription of methylxanthines were a comorbidity of asthma or allergic disease, poor lung function, low quality of life, prescribing doctor from the specialty of internal medicine, and an institution type of private hospital. The prescription of LTRA was associated with the comorbidity of allergic disease. The methylxanthine and/or LTRA users had more hospital utilization but did not have significant differences in acute exacerbations and medical cost for hospital utilization, compared with the non-users. Conclusion: Methylxanthines and LTRA were used in a significant proportion of patients with mild-to-moderate COPD in real fields without favorable impacts on the exacerbations, hospitalizations, or medical costs. The use of more effective inhaled medications should be encouraged.

Comparative Effectiveness of Abdominal versus Laparoscopic Radical Hysterectomy for Cervical Cancer in the Postdissemination Era.

PURPOSE: Despite the benefits of minimally invasive surgery for cervical cancer, there are a lack of randomized trials comparing laparoscopic radical hysterectomy and abdominal radical hysterectomy. We compared morbidity, cost of care, and survival between abdominal radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer. MATERIALS AND METHODS: We used the Korean nationwide database to identify women with cervical cancer who underwent radical hysterectomy from January 1, 2011 to December 31, 2014. Patients who underwent abdominal radical hysterectomy were compared to those who underwent laparoscopic radical hysterectomy. Perioperative morbidity, the use of adjuvant therapy, and survival were evaluated after propensity score balancing. RESULTS: We identified 6,335 patients, including 3,235 who underwent abdominal radical hysterectomy and 3,100 who underwent laparoscopic radical hysterectomy. The use of laparoscopic radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who were younger, had a more recent year of diagnosis, and were treated in the metropolitan area were more likely to undergo a laparoscopic procedure (p < 0.001). Compared to abdominal radical hysterectomy, laparoscopic radical hysterectomy was associated with lower rates of complication, fewertransfusions, a shorter hospital stay, less adjuvant therapy, and reduced total medical costs (p < 0.001). Laparoscopic surgery was associated with a better overall survival than abdominal operation (hazard ratio, 0.74; 95% confidence interval, 0.64 to 0.85). CONCLUSION: In the postdissemination era, laparoscopic radical hysterectomy was associated with more favorable morbidity profiles, a lower cost of care, and comparable survival than abdominal radical hysterectomy.

Significant predictors of medically diagnosed chronic obstructive pulmonary disease in patients with preserved ratio impaired spirometry: a 3-year cohort study.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is an incompletely understood respiratory condition. We investigated the incidence and significant predictive factors of chronic obstructive pulmonary disease (COPD) in PRISm patients. METHODS: From 11,922 subjects registered in the Korea National Health and Nutrition Examination Survey, never or light smokers, young subjects, and those already medically diagnosed with COPD (defined by ICD-10 code and prescribed medication) were excluded. The 2666 remaining subjects were categorized into PRISm (normal forced expiratory volume in the first second [FEV1]/force vital capacity [FVC] [≥ 0.7] and low FEV1 (< 80%); n = 313); normal (n = 1666); and unrevealed COPD groups (FEV1/FVC ratio <  0.7; n = 687). These groups were compared using matched Health Insurance Review and Assessment Service data over a 3-year follow-up. RESULTS: COPD incidence in PRISm patients (17/1000 person-year [PY]) was higher than that in normal subjects (4.3/1000 PY; P <  0.001), but lower than that in unrevealed COPD patients (45/1000 PY; P < 0.001). PRISm patients visited hospitals, took COPD medication, and incurred hospitalization costs more frequently than normal subjects, but less frequently than unrevealed COPD patients. In the overall sample, age, FVC, FEV1, dyspnea, and wheezing were significant predictors of COPD, but in PRISm patients, only age (OR, 1.14; P = 0.002) and wheezing (OR, 4.56; P = 0.04) were significant predictors. CONCLUSION: PRISm patients are likely to develop COPD, and should be monitored carefully, especially older patients and those with wheezing, regardless of lung function.

Impact of BMI on exacerbation and medical care expenses in subjects with mild to moderate airflow obstruction.

Background and objective: The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown. We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs. Methods: We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data. COPD was confirmed by spirometry. BMI was used to stratify patients into four categories: underweight (BMI <18.5 kg/m2), normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2). Results: Of the 1,320 patients with COPD with mild to moderate airflow obstruction, 27.8% had a BMI ≥25 kg/m2. Compared with normal-weight patients, obese patients tended to experience fewer exacerbations (incidence rate ratio [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not significant in a multivariable analysis. COPD-related health-care utilization and medical expenses were higher among underweight patients than the other groups. After adjustment, the risk of COPD-related hospitalization was highest among underweight and higher among overweight patients vs normal-weight patients (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight, and obese groups, respectively; P = 0.01). Conclusion: Decreased weight tends to negatively influence prognosis of COPD with mild to moderate airflow obstruction, whereas higher BMI was not significantly related to worse outcomes.

Regular follow-up visits reduce the risk for asthma exacerbation requiring admission in Korean adults with asthma.

BACKGROUND: Asthma requires regular follow-up visits and sustained medication use. Although several studies have reported the importance of adherence to medication and compliance with the treatment, none to date have reported the importance of regular follow-up visits. We investigated the effects of regular clinical visits on asthma exacerbation. METHODS: We used claims data in the national medical insurance review system provided by the Health Insurance Review and Assessment Service of Korea. We included subjects aged ≥ 15 years with a diagnosis of asthma, and who were prescribed asthma-related medication, from July 2013 to June 2014. Regular visitors (frequent visitors) were defined as subjects who visited the hospital for follow-up of asthma three or more times per year. RESULTS: Among 729,343 subjects, 496,560 (68.1%) were classified as regular visitors. Old age, male sex, lack of medical aid insurance, attendance of a tertiary hospital, a high Charlson comorbidity index, and a history of admission for exacerbated asthma in the previous year were significant determining factors for regular visitor status. When we adjusted for all these factors, frequent visitors showed a lower risk of asthma exacerbation requiring general ward admission (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.47-0.50; P < 0.001), emergency room admission (OR 0.83; 95% CI 0.79-0.86; P < 0.001), and intensive care unit admission (OR 0.49; 95% CI 0.44-0.54; P < 0.001) than infrequent visitors. CONCLUSIONS: Regular clinical visits are significantly associated with a reduced risk of asthma exacerbation requiring hospital admission in Korean adults with asthma.

Heterogeneity of asthma and COPD overlap.

BACKGROUND: Asthma and COPD are heterogeneous diseases. Patients with both disease features (asthma-COPD overlap [ACO]) are common. However, clinical characteristics and socio-economic burden of ACO are still controversial. The aim of this study was to identify the heterogeneity of ACO and to find out the subtypes with clinical impact among ACO subtypes. METHODS: In the Korean National Health and Nutrition Examination Survey (KNHANES) conducted between 2007 and 2012, subjects who were ≥40 years and had prebronchodilator FEV1/FVC <0.7 and FEV1 ≥50% predicted were included. The presence or absence of self-reported wheezing was indicated by W+ or W- and used as an index of airway hyper-responsiveness. S+/S- was defined as subjects who were smokers/never smokers. The subjects were divided into the following four groups: W-S-, W-S+, W+S-, and W+S+. W+S- and W+S+ were asthma-predominant ACO and COPD-predominant ACO, respectively. KNHANES and linked National Health Insurance data were analyzed. RESULTS: The asthma-predominant ACO group showed the lowest socioeconomic status, FEV1, FVC% predicted, and quality of life (QoL) levels. The COPD-predominant ACO group showed the highest hospitalization rate, outpatient medical cost, and total and outpatient health care utilization. COPD-predominant ACO was associated with exacerbations compared to the W-S- group (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.12-2.85; P=0.015) and W-S+ group (OR 2.11; 95% CI 1.43-3.10; P<0.001). COPD-predominant ACO was associated with increased medical cost. CONCLUSION: Asthma-predominant ACO individuals displayed poorer socioeconomic status and QoL compared to the COPD-predominant ACO group. The COPD-predominant ACO group displayed more frequent exacerbations and greater medical costs. Considering the heterogeneity of ACO, it is desirable to identify subtypes of ACO patients and appropriately allocate limited medical resources.

Comparative study on medical utilization and costs of chronic obstructive pulmonary disease with good lung function.

INTRODUCTION: Patients with mild to moderate chronic obstructive pulmonary disease (COPD) are underdiagnosed and undertreated due to the asymptomatic nature of the disease. Previous studies on patients with mild COPD have focused on symptomatic patients. Therefore, in this study, we evaluated the treatment status of patients with early COPD in Korea. MATERIALS AND METHODS: We compared hospital visits, medical costs per person, and COPD medication use by patients with COPD screened from the general population and COPD cohort patients. Patients with COPD aged ≥40 years with the value of forced expiratory volume in 1 s (FEV1) ≥60% were selected from the 2007 to 2012 Korea National Health and Nutrition Examination Survey (KNHANES) data. Data including the number of outpatient clinic visits, admission to hospitals, COPD-related medications, and medical costs were obtained from the Health Insurance Review and Assessment Service and were compared with the data of patients with COPD with FEV1 ≥60% from the Korean COPD Subtype Study (KOCOSS) cohort. RESULTS: Based on EuroQol 5-dimension questionnaire index scores of 0.9±0.14, we found that patients with COPD from the KNHANES group showed few symptoms compared to those from the KOCOSS cohort. In 2007, among the patients with COPD with an FEV1 value of ≥60%, only 3.6% from the KNHANES group and 30% from the KOCOSS cohort visited medical facilities. Total medical cost per person per year increased from 264.37±663.41 US Dollars (USD) in 2007 to 797.00±2,724.21 USD in 2012 for the KNHANES group. In 2012, only 20.7% of the patients from KNHANES database received long-acting muscarinic agonists (LAMA), whereas 78.7% of the patients from KOCOSS database received LAMA. CONCLUSION: Medical resource utilization and medical costs per person for patients with early COPD in Korea increased. However, asymptomatic patients with COPD represented by the KNHANES group do not receive adequate long-term treatment compared to relatively symptomatic patients, and require more clinical attention from physicians.

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 (ß=12.63, P<0.001) and asthma group (ß=6.14, P<0.001) were significantly associated with longer duration of healthcare utilization and ACOS group (ß=350,475.88, P=0.008) and asthma group (ß=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.

Identification of subtypes in subjects with mild-to-moderate airflow limitation and its clinical and socioeconomic implications.

PURPOSE: The purpose of this study was to identify subtypes in patients with mild-to-moderate airflow limitation and to appreciate their clinical and socioeconomic implications. METHODS: Subjects who were aged ≥20 years and had forced expiratory volume in 1 second (FEV1) ≥60% predicted and FEV1/forced vital capacity <0.7 were selected from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) in 2007-2012. The data were merged to the National Health Insurance reimbursement database during the same period. k-Means clustering was performed to explore subtypes. For clustering analysis, six key input variables - age, body mass index (BMI), FEV1% predicted, the presence or absence of self-reported wheezing, smoking status, and pack-years of smoking - were selected. RESULTS: Among a total of 2,140 subjects, five groups were identified through k-means clustering, namely putative "near-normal (n=232)," "asthmatic (n=392)," "chronic obstructive pulmonary disease (COPD) (n=37)," "asthmatic-overlap (n=893)," and "COPD-overlap (n=586)" subtypes. Near-normal group showed the oldest mean age (72±7 years) and highest FEV1 (102%±8% predicted), and asthmatic group was the youngest (46±9 years). COPD and COPD-overlap groups were male predominant and all current or ex-smokers. While asthmatic group had the lowest prescription rate despite the highest proportion of self-reported wheezing, COPD, asthmatic-overlap, and COPD-overlap groups showed high prescription rate of respiratory medicine. Although COPD group formed only 1.7% of total subjects, they showed the highest mean medical cost and health care utilization, comprising 5.3% of the total medical cost. When calculating a ratio of total medical expense to household income, the mean ratio was highest in the COPD group. CONCLUSION: Clinical and epidemiological heterogeneities of subjects with mild-to-moderate airflow limitation and a different level of health care utilization by each subtype are shown. Identification of a subtype with high health care demand could be a priority for effective utilization of limited resources.

Natural course of early COPD.

BACKGROUND AND OBJECTIVE: Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for early COPD during a 6-year period. METHODS: Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES) data. We linked the KNHANES data of patients with early COPD to National Health Insurance data. RESULTS: A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV1) was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D) index value was 0.9. In total, 110 patients utilized health care for COPD in 2007, and this number increased to 179 in 2012. The total mean number of days used per person increased from 4.9 in 2007 to 7.8 in 2012. The total medical cost per person also increased from 248.8 US dollar (USD) in 2007 to 780.6 USD in 2013. A multiple linear regression revealed that age, lower body mass index, lower FEV1 (%), and lower EQ-5D score were significantly associated with medical costs. CONCLUSION: Even in early COPD patients, some of them eventually progressed and utilized health care for COPD.

Patterns and determinants of COPD-related healthcare utilization by severity of airway obstruction in Korea.

BACKGROUND: We investigated patients with chronic obstructive pulmonary disease (COPD) to analyze patterns and identify determinants of healthcare use, according to the severity of airflow obstruction. We used retrospective cohort data from a combination of the 4th Korea National Health and Nutritional Examination Survey (KNHANES) and Korean National Health Insurance (NHI) claims. METHODS: Demographic and medical claims data were retrospectively analyzed from the 4th KNHANES along with NHI claims. Eligible patients were aged ≥40 years, who underwent complete pulmonary function tests (PFTs), and had at least one inpatient or outpatient claim coded as COPD between January 1, 2007 and December 31, 2010. RESULTS: Among 6,663 eligible participants, 897 (13.5%) had airway obstruction. Self-reported physician-diagnosed COPD comprised only 3%, and there were 870 undiagnosed COPD patients (97%). Self-reported physician-diagnosed asthma made up 3.7%. Of the 897 respondents, 244 (27.2%) used COPD-related healthcare services. The frequency of healthcare visits increased with increasing severity of airway obstruction. After a 3-year follow-up period, 646 (74.2% of those initially undiagnosed) remained undiagnosed and only 224 (25.8%) were diagnosed and treated for COPD. Only 27.5% of the 244 participants with airway obstruction who used COPD-related healthcare underwent PFTs during the study period. The percentage of prescribed medications associated with COPD increased in accordance with the severity of the COPD. Inhaled long-acting anticholinergics were prescribed for 10.9% of patients with moderate airway obstruction and for 52.4% of patients with severe obstruction. Inhaled long-acting ß-agonists combined with corticosteroids were prescribed for 50% of patients with severe airway obstruction. Conversely, 44.6% of healthcare users were prescribed oral theophylline for COPD treatment, and 21.7% were also prescribed an oral corticosteroid. The determinants of COPD-associated healthcare use in respondents with obstructive lung disease were advanced age, severe airflow limitation, presence of comorbidities, and self-reported physician diagnosis of COPD. CONCLUSIONS: This study ascertained marked underdiagnosed COPD. Although the percentage of prescribed medication used to treat COPD increased with the severity of the COPD, medications primarily prescribed such as oral theophylline or oral corticosteroids are inappropriate for first-line COPD treatment.