Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence.

This study aimed to evaluate the efficacy of the 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for endometrial cancer (EC). Additionally, a novel risk category incorporating clinicopathological and molecular factors was introduced. The predictive value of this new category for recurrence and survival in Korean patients with EC was assessed, and comparisons were made with the 2013 and 2016 European Society of Medical Oncology (ESMO) risk classifications. Patients with EC were categorized into the POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes. Recurrence, survival, and adjuvant therapy were assessed according to each classification. Notably, patients with the POLEmut subtype showed no relapse, while patients with the P53abn subtype exhibited higher recurrence (31.8%) and mortality rates (31.8%). Regarding adjuvant therapy, 33.3% of low-risk patients were overtreated according to the 2020 ESGO/ESTRO/ESP guidelines. Overall and progression-free survival differed significantly across molecular classifications, with the POLEmut subtype showing the best and the P53abn subtype showing the worst outcomes. The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

Associations of Night Shift Status During Pregnancy With Small for Gestational Age and Preterm Births.

BACKGROUND: Shift work, including night shift work, during pregnancy has been associated with adverse birth outcomes such as small for gestational age (SGA) infants and preterm births. This study, conducted in South Korea using the Korean CHildren's ENvironmental health Study (Ko-CHENS) cohort, aimed to investigate the association between shift work and night shift status during pregnancy and adverse birth outcomes. METHODS: The Korean Ko-CHENS is a nationwide prospective birth cohort study of children's environmental diseases, conducted by the Ministry of Environment and the National Institute of Environmental Research. This study included pregnant women recruited from 2015 to 2020 for Ko-CHENS Core Cohorts, and 4,944 out of a total of 5,213 pregnant women were selected as final subjects. A logistic regression model was used to identify the risk factors affecting SGA births, preterm births, and low-birth-weight infants, and the odds ratio (OR) was adjusted. This was confirmed by calculating ORs. Maternal age, infant sex, maternal educational status, body mass index, smoking status, alcohol consumption status, parity, gestational diabetes mellitus, preeclampsia, and abortion history were used as adjusted variables. RESULTS: No statistically significant differences were observed in the birth outcomes or maternal working patterns. There were no significant differences in the adjusted odds ratios (aORs) of SGA and preterm births between the non-worker, day worker, and shift worker. However, there was a significant difference in the aORs of SGA between non-workers and night shift workers. (aORs [95% confidence interval], 2.643 [1.193-5.859]). CONCLUSION: Working during pregnancy did not increase the risk of SGA or preterm birth, and night shift work did not increase the risk of preterm birth. However, night-shift work increases the risk of SGA.

Effects of heavy metal exposure during pregnancy on birth outcomes.

Exposure to heavy metals such as lead, cadmium, and mercury poses serious health risks to pregnant women because of their high toxicity. In this study, we investigated the associations of heavy metal exposure with birth outcomes of Korean infants. Data of 5,215 women between 2015 and 2019 were analyzed. This study was part of the Korean Children's Environmental Health (Ko-CHENS) study. Linear regression and logistic regression analyses were used to examine effects of concentrations of lead, cadmium, and mercury on birth weight, small for gestational age, and large for gestational age after adjusting for maternal age groups, parity, infant sex, education, income, smoking, drinking, body mass index, stillbirth, premature birth, diabetes, hypertension, and gestational diabetes. Besides adjusting for these covariates, each metal was mutually adjusted to estimate birth weight and large for gestational age status. Maternal cadmium concentrations during early pregnancy (ß = - 39.96; 95% confidence interval (CI): - 63.76, - 16.17) and late pregnancy (ß = - 37.24; 95% CI - 61.63, - 12.84) were significantly associated with birth weight. Cadmium levels during early pregnancy (adjusted OR = 0.637; 95% CI 0.444, 0.912) were also associated with large for gestational age status. Our findings suggest that prenatal cadmium exposure, even at a low level of exposure, is significantly associated with low birth weight.

CT-Derived Deep Learning-Based Quantification of Body Composition Associated with Disease Severity in Chronic Obstructive Pulmonary Disease.

Purpose: Our study aimed to evaluate the association between automated quantified body composition on CT and pulmonary function or quantitative lung features in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods: A total of 290 patients with COPD were enrolled in this study. The volume of muscle and subcutaneous fat, area of muscle and subcutaneous fat at T12, and bone attenuation at T12 were obtained from chest CT using a deep learning-based body segmentation algorithm. Parametric response mapping-derived emphysema (PRMemph), PRM-derived functional small airway disease (PRMfSAD), and airway wall thickness (AWT)-Pi10 were quantitatively assessed. The association between body composition and outcomes was evaluated using Pearson's correlation analysis. Results: The volume and area of muscle and subcutaneous fat were negatively associated with PRMemph and PRMfSAD (p < 0.05). Bone density at T12 was negatively associated with PRMemph (r = -0.1828, p = 0.002). The volume and area of subcutaneous fat and bone density at T12 were positively correlated with AWT-Pi10 (r = 0.1287, p = 0.030; r = 0.1668, p = 0.005; r = 0.1279, p = 0.031). However, muscle volume was negatively correlated with the AWT-Pi10 (r = -0.1966, p = 0.001). Muscle volume was significantly associated with pulmonary function (p < 0.001). Conclusion: Body composition, automatically assessed using chest CT, is associated with the phenotype and severity of COPD.

A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase.

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

Required biological time for lung maturation and duration of invasive ventilation: a Korean cohort study of very low birth weight infants.

Background: We investigated the duration of invasive ventilation among very low birth weight (VLBW) infants to evaluate the current minimum time required for lung maturation to breathe without ventilator assistance after preterm birth. Methods: A total of 14,658 VLBW infants born at ≤32+6 weeks between 2013 and 2020 were enrolled. Clinical data were collected from the Korean Neonatal Network, a national prospective cohort registry of VLBW infants from 70 neonatal intensive care units. Differences in the duration of invasive ventilation according to gestational age and birth weight were investigated. Recent trends and changes in assisted ventilation duration and associated perinatal factors between 2017-20 and 2013-16 were compared. Risk factors related to the duration of assisted ventilation were also identified. Results: The overall duration of invasive ventilation was 16.3 days and the estimated minimum time required corresponded to 30+4 weeks of gestation. The median duration of invasive ventilation was 28.0, 13.0, 3.0, and 1.0 days at <26, 26-27, 28-29, and 30-32 weeks of gestation, respectively. In each gestational age group, the estimated minimum weaning points from the assisted ventilator were 29+5, 30+2, 30+2, and 31+5 weeks of gestation. The duration of non-invasive ventilation (17.9 vs. 22.5 days) and the incidence of bronchopulmonary dysplasia (28.1% vs. 31.9%) increased in 2017-20 (n = 7,221) than in 2013-16 (n = 7,437). In contrast, the duration of invasive ventilation and overall survival rate did not change during the periods 2017-20 and 2013-16. Surfactant treatment and air leaks were associated with increased duration of invasive ventilation (inverse hazard ratio 1.50, 95% CI, 1.04-2.15; inverse hazard ratio 1.62, 95% CI, 1.29-2.04). We expressed the incidence proportion of ventilator weaning according to the invasive ventilation duration using Kaplan-Meier survival curves. The slope of the curve slowly decreased as gestational age and birth weight were low and risk factors were present. Conclusions: This population-based data on invasive ventilation duration among VLBW infants suggest the present limitation of postnatal lung maturation under specific perinatal conditions after preterm birth. Furthermore, this study provides detailed references for designing and/or assessing earlier ventilator weaning protocols and lung protection strategies by comparing populations or neonatal networks.

Metabolomics Reveals Dysregulated Sphingolipid and Amino Acid Metabolism Associated with Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD-related phenotypes in a Korean cohort. Patients and Methods: Blood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS/MS analysis. Results: Among the evaluated plasma sphingolipids, an increase in the metabolism of two specific sphingomyelins, SM (d18:1/24:0) and SM (d18:1/24:1) were significantly associated with COPD. There was no significant correlation between any of the SMs and the emphysema index, FVC and FEV1 in the COPD cohort. Meanwhile, Cer (d18:1/18:0) and Cer (d18:1/24:1) were significantly associated with reduced FEV1. Furthermore, the levels of several amino acids were altered in the COPD group compared to that in the non-COPD group; glutamate and alpha AAA were substantial associated with emphysema in COPD. Kynurenine was the only amino acid significantly associated with reduced FEV1 in COPD. In contrast, there was no correlation between FVC and the elevated metabolites. Conclusion: Our results provide dysregulated plasma metabolites impacting COPD phenotypes, although more studies are needed to explore the underlying mechanism related to COPD pathogenesis.

Structural and functional alterations of subjects with cement dust exposure: A longitudinal quantitative computed tomography-based study.

Cement dust exposure (CDE) can be a risk factor for pulmonary disease, causing changes in segmental airways and parenchymal lungs. This study investigates longitudinal alterations in quantitative computed tomography (CT)-based metrics due to CDE. We obtained CT-based airway structural and lung functional metrics from CDE subjects with baseline CT and follow-up CT scans performed three years later. From the CT, we extracted wall thickness (WT) and bifurcation angle (θ) at total lung capacity (TLC) and functional residual capacity (FRC), respectively. We also computed air volume (Vair), tissue volume (Vtissue), global lung shape, percentage of emphysema (Emph%), and more. Clinical measures were used to associate with CT-based metrics. Three years after their baseline, the pulmonary function tests of CDE subjects were similar or improved, but there were significant alterations in the CT-based structural and functional metrics. The follow-up CT scans showed changes in θ at most of the central airways; increased WT at the subgroup bronchi; smaller Vair at TLC at all except the right upper and lower lobes; smaller Vtissue at all lobes in TLC and FRC except for the upper lobes in FRC; smaller global lung shape; and greater Emph% at the right upper and lower lobes. CT-based structural and functional variables are more sensitive to the early identification of CDE subjects, while most clinical lung function changes were not noticeable. We speculate that the significant long-term changes in CT are uniquely observed in CDE subjects, different from smoking-induced structural changes.

Quantitative assessment the longitudinal changes of pulmonary vascular counts in chronic obstructive pulmonary disease.

BACKGROUND: Chest computed tomography (CT) is a widely used method to assess morphological and dynamic abnormalities in chronic obstructive pulmonary disease (COPD). The small pulmonary vascular cross-section (CSA), quantitatively extracted from volumetric CT, is a reliable indicator for predicting pulmonary vascular changes. CSA is associated with the severity of symptoms, pulmonary function tests (PFT) and emphysema and in COPD patients the severity increases over time. We analyzed the correlation longitudinal changes in pulmonary vascular parameters with clinical parameters in COPD patients. MATERIALS AND METHODS: A total of 288 subjects with COPD were investigated during follow up period up to 6 years. CT images were classified into five subtypes from normal to severe emphysema according to percentage of low-attenuation areas less than -950 and -856 Hounsfield units (HU) on inspiratory and expiratory CT (LAA-950, LAA-856exp). Total number of vessels (Ntotal) and total number of vessels with area less than 5 mm2 (N<5 mm) per 1 cm2 of lung surface area (LSA) were measured at 6 mm from the pleural surface. RESULTS: Ntotal/LSA and N<5 mm/LSA changed from 1.16 ± 0.27 to 0.87 ± 0.2 and from 1.02 ± 0.22 to 0.78 ± 0.22, respectively, during Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage progression. Both parameters changed from normal to severe emphysema according to CT subtype from 1.39 ± 0.21 to 0.74 ± 0.17 and from 1.18 ± 0.19 to 0.67 ± 0.15, respectively. LAA-950 and LAA-856exp were negatively correlated with Ntotal/LSA (r = - 0.738, - 0.529) and N<5 mm /LSA (r = - 0.729, -- .497). On the other hand, pulmonary function test (PFT) results showed a weak correlation with Ntotal/LSA and N<5 mm/LSA (r = 0.205, 0.210). The depth in CT subtypes for longitudinal change both Ntotal/LSA and N<5 mm/LSA was (- 0.032, - 0.023) and (- 0.027) in normal and SAD, respectively. CONCLUSIONS: Quantitative computed tomography features faithfully reflected pulmonary vessel alterations, showing in particular that pulmonary vascular alteration started.

Correlation between Telomere Length and Chronic Obstructive Pulmonary Disease-Related Phenotypes: Results from the Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) Cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with increased prevalence in the elderly. Telomeres are repetitive DNA sequences found at the end of the chromosome, which progressively shorten as cells divide. Telomere length is known to be a molecular marker of aging. This study aimed to assess the relationship between telomere length and the risk of COPD, lung function, respiratory symptoms, and emphysema index in Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) cohort. METHODS: We extracted DNA from the peripheral blood samples of 446 participants, including 285 COPD patients and 161 control participants. We measured absolute telomere length using quantitative real-time polymerase chain reaction. All participants underwent spirometry and quantitative computed tomography scan. Questionnaires assessing respiratory symptoms and the COPD Assessment Test was filled by all the participants. RESULTS: The mean age of participants at the baseline visit was 72.5±7.1 years. Males accounted for 72% (321 participants) of the all participants. The mean telomere length was lower in the COPD group compared to the non-COPD group (COPD, 16.81±13.90 kb; non-COPD, 21.97±14.43 kb). In COPD patients, 112 (75.7%) were distributed as tertile 1 (shortest), 91 (61.1%) as tertile 2 and 82 (55%) as tertile 3 (longest). We did not find significant associations between telomere length and lung function, exacerbation, airway wall thickness, and emphysema index after adjusting for sex, age, and smoking status. CONCLUSION: In this study, the relationship between various COPD phenotypes and telomere length was analyzed, but no significant statistical associations were shown.

Computed tomography-based visual assessment of chronic obstructive pulmonary disease: comparison with pulmonary function test and quantitative computed tomography.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has variable subtypes involving mixture of large airway inflammation, small airway disease, and emphysema. This study evaluated the relationship between visually assessed computed tomography (CT) subtypes and clinical/imaging characteristics. METHODS: In total, 452 participants were enrolled in this study between 2012 and 2017. Seven subtypes were defined by visual evaluation of CT images using Fleischner Society classification: normal, paraseptal emphysema (PSE), bronchial disease, and centrilobular emphysema (trace, mild, moderate and confluent/advanced destructive). The differences in several variables, including clinical, laboratory, spirometric, and quantitative CT features among CT-based visual subtypes, were compared using the chi-square tests and one-way analysis of variance. RESULTS: Subjects who had PSE had better forced expiratory volume in 1 second (FEV1) (P=0.03) percentage and higher lung density (P<0.05) than those with moderate to confluent/advanced destructive centrilobular emphysema. As the visual grade of centrilobular emphysema worsened, pulmonary function declined and modified Medical Research Council, COPD assessment test (CAT) score, and quantitative assessment (emphysema index and air trapping) increased. The bronchial subtype was associated with higher body mass index (BMI), better lung function and higher lung density. Participants with trace emphysema showed a rapid increase in functional small airway disease. CONCLUSIONS: Classifying subtypes using visual CT imaging features can reflect heterogeneity and pathological processes of COPD.

Quantitative computed tomography features and clinical manifestations associated with the extent of bronchiectasis in patients with moderate-to-severe COPD.

Background: Few studies have investigated the quantitative computed tomography (CT) features associated with the severity of bronchiectasis in COPD patients. The purpose of this study was to identify the quantitative CT features and clinical values to determine the extent of bronchiectasis in moderate-to-severe COPD patients. Methods: A total of 127 moderate-to-severe COPD patients were selected from the cohort of COPD in Dusty Areas (CODA). The study subjects were classified into three groups according to the extent of bronchiectasis on CT: no bronchiectasis, mild bronchiectasis, and moderate-to-severe bronchiectasis. The three groups were compared with respect to demographic data, symptoms, medical history, serum inflammatory markers, pulmonary function, and quantitative CT values. Results: Among 127 moderate-to-severe COPD subjects, 73 patients (57.5%) were detected to have bronchiectasis, 51 patients (40.2%) to have mild bronchiectasis, and 22 patients (17.3%) to have moderate-to-severe bronchiectasis. Compared with COPD patients without bronchiectasis, those with bronchiectasis were older and had higher frequency of prior tuberculosis, lower prevalence of bronchodilator reversibility (BDR), and more severe air trapping (P < 0.05). Moderate-to-severe bronchiectasis patients had lower body mass index (BMI), higher frequency of prior tuberculosis, lower prevalence of BDR, worse pulmonary function, and more severe air trapping (P < 0.05) than those in the mild bronchiectasis group. Conclusion: Moderate-to-severe bronchiectasis was associated with a history of pulmonary tuberculosis, lower BMI, severe airflow obstruction, and lower BDR in moderate-to-severe COPD patients. Quantitative analysis of CT showed that severe air trapping was associated with the extent of bronchiectasis in these patients.

Epidemiological study of PM2.5 and risk of COPD-related hospital visits in association with particle constituents in Chuncheon, Korea.

Background and objective: Aside from smoking, which is already recognized as a strong risk factor for COPD, interest in the impact of particulate matter (PM) on COPD is increasing. This study aimed to investigate the effect of PM, especially with an aerodynamic diameter ≤2.5 µm (PM2.5), and its chemical constituents on the exacerbation of COPD. Methods: Data on hospital visits including admission and outpatient clinic visits for exacerbation of COPD in Chuncheon, Korea, between 2006 and 2012 were extracted from the National Health Insurance Service database. PM2.5 and its chemical constituents were measured on the roof of the four-story Kangwon National University Natural Sciences building once every 3 days. Meteorological data were provided by the Korean Meteorological Administration. Results: During the study period, the mean level of PM2.5 was 35.0±25.2 µg/m3, and the number of daily hospital visits were 6.42±4.28 and 2.07±1.93 for males and females, respectively. The number of COPD-related hospital visits increased with increasing PM2.5 after adjusting for meteorological covariates and females tended to be more affected sooner than males. Among the PM2.5 constituents, Al, Si, and elemental carbon were associated with increased hospital visits and there was a difference according to sex. In males, some constituents of PM2.5 were related to an increased risk of a hospital visit, mainly on the first and second days of measurement (Lag1 and Lag2). In contrast, there was no significant increase in the risk of hospital visits due to any of the PM2.5 constituents in females. Conclusion: Concentrations of PM2.5 mass and some of the PM2.5 constituents were associated with increased COPD-related hospital visits in Chuncheon.

Differences in chronic obstructive pulmonary disease phenotypes between non-smokers and smokers.

INTRODUCTION AND OBJECTIVES: Although tobacco smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), more than one-fourth of COPD patients are non-smokers. In this cross-sectional study, the differences in COPD phenotypes between non-smokers and smokers in male subjects were investigated and were focused on structural lung changes using a quantitative assessment of computed tomography (CT) images. METHODS: They divided male participants with COPD, from a Korean cohort near a cement plant, into non-smokers and smokers by a cutoff of a 5 pack-year smoking history. Clinical characteristics, including age, body mass index (BMI), spirometry results, history of biomass smoke exposure, and CT measurements, were compared between the two groups. Emphysema index (EI) and mean wall area percentage (MWA %) were used to evaluate the structural lung changes on volumetric CT scans. RESULTS: The non-smoker group (n = 49) had younger patients and had a greater BMI than the smoker group (n = 113) (P < .05). Spirometry results, including post-bronchodilator forced expiratory volume in 1 s, were comparable between the two groups. More smokers had emphysema than non-smokers (EI 10.0 vs. 6.5, P < .001), but after accounting the potential confounders in model analysis, the difference was borderline significance (P = .051). In the subgroup of biomass smoke-exposed subjects, MWA% was significantly greater in smokers than in non-smokers (MWA 69.1 vs. 65.3, P = .03), while EI was not statistically different (EI 7.1 vs. 10.4, P = .52). CONCLUSIONS: Non-smoker males with COPD were younger and had a greater BMI than the smokers. Tobacco smoke exposure seemed to be associated with an emphysema-predominant phenotype, while biomass smoke exposure exhibited a significant interaction with tobacco smoking in an airway-predominant phenotype.

Inflammatory biomarkers and radiologic measurements in never-smokers with COPD: A cross-sectional study from the CODA cohort.

Various biomarkers have emerged as potential surrogates to represent various subgroups of chronic obstructive pulmonary disease (COPD), which manifest with different phenotypes. However, the biomarkers representing never-smokers with COPD have not yet been well elucidated. The aim of this study was to evaluate the associations of certain serum and radiological biomarkers with the presence of COPD in never-smokers. To explore the associations of serum and radiological biomarkers with the presence of COPD in never-smokers, we conducted a cross-sectional patient cohort study composed of never-smokers from the COPD in Dusty Areas (CODA) cohort, consisting of subjects living in dusty areas near cement plants in South Korea. Of the 131 never-smokers in the cohort, 77 (58.8%) had COPD. There were no significant differences in the number of subjects with high levels of inflammatory biomarkers (>90th percentile of never-smokers without COPD), including white blood cell count, total bilirubin, interleukin (IL)-6, IL-8, and C-reactive protein, or radiologic measurements (including emphysema index and mean wall area percentage) between never-smokers with COPD and those without COPD. However, the number of subjects with high uric acid was significantly higher in never-smokers with COPD than never-smokers without COPD (31.2% (24/77) vs. 11.1% (6/54); p = 0.013). In addition, multivariate analysis revealed that high uric acid was significantly associated with the presence of COPD in never-smokers (adjusted relative risk: 1.63; 95% confidence interval: 1.21, 2.18; p = 0.001). Our study suggests that high serum levels of uric acid might be a potential biomarker for assessing the presence of COPD in never-smokers.

A cluster analysis of chronic obstructive pulmonary disease in dusty areas cohort identified three subgroups.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses. In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up. METHODS: We analyzed dusty areas cohort comprising 272 patients with COPD. The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline. The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data. The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups. RESULTS: PCA revealed that six independent components accounted for 77.3% of variance. Three distinct subgroups were identified through the cluster analysis. Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up. Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up. Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization. CONCLUSIONS: Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes. These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.

Which bronchodilator reversibility criteria can predict severe acute exacerbation in chronic obstructive pulmonary disease patients?

BACKGROUND: It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients. METHODS: Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models. RESULTS: Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants. CONCLUSIONS: Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship.

Implications of the pulmonary artery to ascending aortic ratio in patients with relatively mild chronic obstructive pulmonary disease.

BACKGROUND: Identifying markers for predicting the course and outcome of chronic obstructive pulmonary disease (COPD) remains important. The relative pulmonary artery enlargement to aorta ratio (PA-A ratio), which is measured using computed tomography (CT), is a reported predictor for COPD exacerbation and mortality. However, little is known about the implications of the PA-A ratio in patients with mild COPD. METHODS: We investigated the utility of the PA-A ratio as a biomarker in patients with relatively mild COPD. A total of 131 patients with mild to moderate COPD [post-bronchodilator forced expiratory volume in 1 sec (FEV1)/forced vital capacity (FVC) 61.6±6.4, mean post-bronchodilator FEV1 83%±17.8% of predicted value] were selected from a Korean COPD cohort (from 2012 until the end of 2014) and analyzed retrospectively. We determined the correlation between the PA-A ratio and clinical parameters using a linear regression model. RESULTS: The COPD assessment test (P=0.04), FEV1 (P=0.03), and a history of exacerbation in the last year (P=0.03) were significant factors in the univariate linear regression analysis. Post-bronchodilator FEV1 was most significantly associated with the PA-A ratio in the multivariate analysis (P=0.01). CONCLUSIONS: The PA-A ratio evaluated by CT imaging was independently correlated with a representative pulmonary function factor (FEV1) in patients with relatively mild COPD. The results suggest that the PA-A ratio may be an important biomarker for clinical outcome in patients with mild COPD.

Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. METHODS: Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. RESULTS: There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. CONCLUSION: Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients.

Comparison of serum biomarkers between patients with asthma and with chronic obstructive pulmonary disease.

OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) have distinct pathophysiological mechanisms but sometimes share similar clinical manifestations. Distinguishing between these diseases is important. This study compared the profiles of serum biomarkers between patients with asthma and those with COPD. METHODS: Serum levels of the chitinase like protein YKL-40, periostin, interleukin (IL)-18, and chemokine (C--C motif) ligand 18 (CCL18) were measured in asthma patients (n = 20), COPD patients (n = 16), and normal controls (n = 20). RESULTS: Serum levels of YKL-40 were higher in COPD patients [median (range), 55 (17-565) versus 208 (74-922) ng/mL, p < 0.0001], but no differences were observed between asthma and COPD patients after adjusting for age and forced expiratory volume in 1 s (FEV1). No differences in serum levels of periostin, IL-18, or CCL18 were observed between the patient groups. Total IgE and airway hypersensitivity were negatively correlated (r = -0.485, p = 0.007). CCL18 levels were related to patients' age in asthmatic patients (r = -0.562, p = 0.010). Serum levels of CCL18 and IL-18 were positively correlated in patients with COPD (r = 0.696, p = 0.003). CONCLUSIONS: No differences in the serum profiles of periostin, IL-18, or CCL18 were observed between patients with asthma and those with COPD. Serum levels of YKL-40 were not different between asthma and COPD patients after adjusting for age and FEV1. There were negative correlation between CCL18 and age in patients with asthma and positive correlation between IL-18 and CCL18 in patients with COPD.