Korean Obstructive Lung Disease Cohort Research Articles

Impact of Previous Occupational Exposure on Outcomes of Chronic Obstructive Pulmonary Disease.

: BackgroundOccupational exposures have been regarded as a risk factor for the development of chronic obstructive pulmonary disease (COPD). However, there is little knowledge regarding the effect of occupational exposure on the treatment outcomes of COPD. Therefore, the aim of this study was to evaluate the question of whether occupational exposure can have a potential impact on COPD outcomes. Methods: Information regarding self-reported occupational exposure for 312 patients with COPD from the Korean Obstructive Lung Disease (KOLD) Cohort were included. A comparison of the rate of acute exacerbation, annual lung function change, and quality of life according to the presence or absence of occupational exposure was performed. Results: Seventy-six patients (24.4%) had experienced occupational exposure; chemical materials were most common. At enrollment, a higher COPD-specific version of the St. George Respiratory Questionnaire total score (39.7 ± 18.8 vs. 33.1 ± 17.6, p = 0.005) and a higher exacerbation history in the past year (30.3% vs. 17.5%, p = 0.017) were observed for patients with occupational exposure compared to those without occupational exposure. Furthermore, in the follow-up period, after adjusting for potential confounders, a higher frequency of acute exacerbation (odd ratio, 1.418; 95% confidence interval, 1.027–1.956; p = 0.033) and a more rapid decline in forced expiratory volume in 1 s (p = 0.009) was observed for COPD patients with occupational exposure compared to those without occupational exposure. Conclusions: In the KOLD cohort, worse outcomes in terms of exacerbation rate and change in lung function were observed for COPD patients with occupational exposure compared to those without occupational exposure. These findings suggest that occupational exposure not only is a risk factor for COPD but also might have a prognostic impact on COPD.

Clinical Impact of the Bronchiectasis with Chronic Bronchitis Symptoms in COPD: Analysis of a Longitudinal Cohort.

PurposeBronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE.Patients and MethodsWe analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups.ResultsIn total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045).ConclusionBE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.

Deep radiomics-based survival prediction in patients with chronic obstructive pulmonary disease

Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642–0.8373) and 0.7156 (95% CI, 0.7024–0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.

Radiomics approach for survival prediction in chronic obstructive pulmonary disease

To apply radiomics analysis for overall survival prediction in chronic obstructive pulmonary disease (COPD), and evaluate the performance of the radiomics signature (RS). This study included 344 patients from the Korean Obstructive Lung Disease (KOLD) cohort. External validation was performed on a cohort of 112 patients. In total, 525 chest CT-based radiomics features were semi-automatically extracted. The five most useful features for survival prediction were selected by least absolute shrinkage and selection operation (LASSO) Cox regression analysis and used to generate a RS. The ability of the RS for classifying COPD patients into high or low mortality risk groups was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. The five features remaining after the LASSO analysis were %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm. The RS demonstrated a C-index of 0.774 in the discovery group and 0.805 in the validation group. Patients with a RS greater than 1.053 were classified into the high-risk group and demonstrated worse overall survival than those in the low-risk group in both the discovery (log-rank test, < 0.001; hazard ratio [HR], 5.265) and validation groups (log-rank test, < 0.001; HR, 5.223). For both groups, RS was significantly associated with overall survival after adjustments for patient age and body mass index. A radiomics approach for survival prediction and risk stratification in COPD patients is feasible, and the constructed radiomics model demonstrated acceptable performance. The RS derived from chest CT data of COPD patients was able to effectively identify those at increased risk of mortality. • A total of 525 chest CT-based radiomics features were extracted and the five radiomics features of %LAA-950, AWT_Pi10_6th, AWT_Pi10_heterogeneity, %WA_heterogeneity, and VA18mm were selected to generate a radiomics model. • A radiomics model for predicting survival of COPD patients demonstrated reliable performance with a C-index of 0.774 in the discovery group and 0.805 in the validation group. • Radiomics approach was able to effectively identify COPD patients with an increased risk of mortality, and patients assigned to the high-risk group demonstrated worse overall survival in both the discovery and validation groups.

Predicting long-term mortality with two different criteria of exercise-induced desaturation in COPD

BackgroundThere are few reports on exercise-induced desaturation (EID) as a predictor of mortality in chronic obstructive pulmonary disease (COPD). However, the definitions of EID vary in published reports. The main purpose was to evaluate the association between EID and long-term mortality by applying two criteria of EID. MethodsA total of 507 subjects were selected from the Korean Obstructive Lung Disease cohort. EID was assessed using the 6-min walk test (6MWT) and defined using two different criteria [1]: post-6MWT oxygen saturation (SpO2) of ≤88% (criterion A) and [2] post-6MWT SpO2 < 90% or a decrease of ≥4% compared to baseline (criterion B). ResultsThe prevalence of EID was 5.1% based on criterion A and 13.0% based on criterion B. Regardless of the criteria used, mortality was higher in the EID group than in the non-EID group (A: 50 vs. 11.4%, B: 33.3 vs. 10.4%) during up to 161 months of follow-up. COPD patients without EID survived significantly longer than those with EID (A: 143.5 vs. 92.9, B: 144.8 vs. 115.2 months). Multivariate Cox regression analysis revealed that COPD patients with EID had a 2.4-fold increased risk of death by criterion A (adjusted HR 2.375; 95% CI: 1.217–4.637; P = 0.011). The risk of death increased in COPD patients with EID by criterion B, but the difference was not statistically significant. ConclusionsCOPD patients with EID demonstrated significantly higher long-term mortality than those without EID. The EID criterion A has a better predictive value for mortality in COPD.

A comparative study of chest CT findings regarding the effects of regional dust exposure on patients with COPD living in urban areas and rural areas near cement plants

BackgroundThe clinical and radiological presentation of chronic obstructive pulmonary disease (COPD) is heterogenous depending on the characterized sources of inflammation. This study aimed to evaluate COPD phenotypes associated with specific dust exposure.MethodsThis study was designed to compare the characteristics, clinical outcomes and radiological findings between two prospective COPD cohorts representing two distinguishing regions in the Republic of Korea; COPD in Dusty Area (CODA) and the Korean Obstructive Lung Disease (KOLD) cohort. A total of 733 participants (n = 186 for CODA, and n = 547 for KOLD) were included finally. A multivariate analysis to compare lung function and computed tomography (CT) measurements of both cohort studies after adjusting for age, sex, education, body mass index, smoking status, and pack-year, Charlson comorbidity index, and frequency of exacerbation were performed by entering the level of FEV1(%), biomass exposure and COPD medication into the model in stepwise.ResultsThe mean wall area (MWA, %) became significantly lower in COPD patients in KOLD from urban and metropolitan area than those in CODA cohort from cement dust area (mean ± standard deviation [SD]; 70.2 ± 1.21% in CODA vs. 66.8 ± 0.88% in KOLD, p = 0.028) after including FEV1 in the model. COPD subjects in KOLD cohort had higher CT-emphysema index (EI, 6.07 ± 3.06 in CODA vs. 20.0 ± 2.21 in KOLD, p < 0.001, respectively). The difference in the EI (%) was consistently significant even after further adjustment of FEV1 (6.12 ± 2.88% in CODA vs. 17.3 ± 2.10% in KOLD, p = 0.002, respectively). However, there was no difference in the ratio of mean lung density (MLD) between the two cohorts (p = 0.077). Additional adjustment for biomass parameters and medication for COPD did not alter the statistical significance after entering into the analysis with COPD medication.ConclusionsHigher MWA and lower EI were observed in COPD patients from the region with dust exposure. These results suggest that the imaging phenotype of COPD is influenced by specific environmental exposure.

Impact of Body Mass Index Change on the Prognosis of Chronic Obstructive Pulmonary Disease

Background: Low body mass index (BMI) is an important prognostic factor in chronic obstructive pulmonary disease (COPD). However, the prognostic value of longitudinal BMI change in COPD has not been well studied. Objective: We aimed to evaluate the association between longitudinal change of BMI and prognosis of COPD in Korean COPD cohort. Methods: This study was conducted in a prospective Korean Obstructive Lung Disease (KOLD) cohort where COPD patients were recruited on an outpatient basis at 17 hospitals in South Korea. Annual BMI was measured over a period of 3 years or more. All patients were categorized into underweight (UW), normal weight (NW), and overweight (OW) groups by BMI. Clinical characteristics and outcomes including exacerbation and mortality were compared based on initial BMI grade and longitudinal change of BMI. Results: This analysis included 537 COPD patients (mean age = 67.4 ± 7.9 years, male = 97.0%, mean BMI = 23.0 ± 3.1) of KOLD cohort. The proportions of UW, NW, and OW groups were 6.9% (n = 37), 68.9% (n = 370), and 24.2% (n = 130) respectively. The UW group showed lower forced expiratory volume in 1 s (FEV₁) (p < 0.001), shorter 6-minute walk distance (p < 0.001), higher modified Medical Research Council score (p = 0.002), higher St. George Respiratory Questionnaire score (p < 0.001), higher emphysema index (p < 0.001) and air-trapping index (p < 0.001), and more frequent (p < 0.001) and severe exacerbations (p = 0.003). Multivariable analyses demonstrated that decrease of BMI (hazard ratio [HR] = 0.786, p = 0.038) and the descent of BMI group (HR = 3.167, p = 0.016) at 3-year follow-up along with age, initial BMI, post-bronchodilator FEV₁, and severe exacerbations were significantly associated with mortality. Conclusions: This study demonstrated that BMI decrease during follow-up was independently associated with exacerbation and higher mortality of COPD, suggesting BMI reduction in COPD should be carefully managed.

Low serum lymphocyte level is associated with poor exercise capacity and quality of life in chronic obstructive pulmonary disease

The purpose of this study was to evaluate the association of serum lymphocyte level with several clinical parameters in COPD. The study population included 451 COPD patients from the Korean Obstructive Lung Disease cohort study. Serum lymphocyte level was measured every year along with various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life using COPD assessment test (CAT) and St. George's Respiratory Questionnaire (SGRQ) scores, exacerbations, and survival. Serum lymphocyte level less than 20% was considered as a low lymphocyte level. Normal lymphocyte and low lymphocyte groups comprised of 409 (90.7%) and 42 (9.3%) patients, respectively. Clustered analysis showed that patients in low lymphocyte group had a lower post-bronchodilator forced expiratory volume in 1 s % predicted (estimated mean = − 5.70%; P = 0.001), a lower forced vital capacity % predicted (estimated mean = − 5.63%; P = 0.005), a shorter 6 MW distance (estimated mean = − 41.31 m; P < 0.001), a higher CAT score (estimated mean = 2.62; P = 0.013), and a higher SGRQ score (estimated mean = 10.10; P < 0.001). Serum lymphocyte level was not associated with frequent acute exacerbations nor mortality. Low serum lymphocyte group showed poorer pulmonary function, lower 6 MW distance, and worse quality of life. Serum lymphocyte levels could be a simple and widely available predictive marker for variable clinical outcomes in COPD patients.

Decline in Carbon Monoxide Transfer Coefficient in Chronic Obstructive Pulmonary Disease.

Background: Although a reduced carbon monoxide transfer coefficient (Kco) is an important feature in chronic obstructive pulmonary disease (COPD), how it changes over time and its relationship with other clinical outcomes remain unclear. This study evaluated longitudinal changes in Kco and their relationship with other clinical outcomes. Methods: We evaluated patients with COPD from the Korean Obstructive Lung Disease cohort, followed up for up to ten years. Random coefficient models were used to assess the annual change in Kco over time. Participants were categorized into tertiles according to Kco decline rate. Baseline characteristics and outcomes, including changes in FEV1 and emphysema index, incidence of exacerbations, and mortality, were compared between categories. Results: A decline in Kco was observed in 92.9% of the 211 enrolled participants with COPD. Those with the most rapid decline (tertile 1) had a lower FEV1/FVC% (tertile 1: 43.8% ± 9.7%, tertile 2: 46.4% ± 10.5%, tertile 3: 49.2% ± 10.4%, p = 0.008) and a higher emphysema index at baseline (27.7 ± 14.8, 22.4 ± 16.1, 18.1 ± 14.5, respectively, p = 0.001). Tertile 3 showed a lower decline rate in FEV1 (16.3 vs. 27.1 mL/yr, p = 0.017) and a lower incidence of exacerbations (incidence rate ratio = 0.66, 95% CI = 0.44–0.99) than tertile 1. There were no differences in the change in emphysema index and mortality between categories. Conclusion: Most patients with COPD experienced Kco decline over time, which was greater in patients with more severe airflow limitation and emphysema. Decline in Kco was associated with an accelerated decline in FEV1 and more frequent exacerbations; hence, this should be considered as an important outcome measure in further studies.

Severe vitamin D deficiency is associated with emphysema progression in male patients with COPD.

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of vitamin D deficiency. Vitamin D levels also correlate with lung function in patients with COPD. However, there are few reports on vitamin D deficiency and emphysema severity in COPD. This study aimed to investigate the effects of plasma 25-hydroxyvitamin D (25-OHD) level on emphysema severity in male COPD patients. A total of 151 male subjects were selected from the Korean Obstructive Lung Disease (KOLD) cohort. Subjects were subdivided into four subgroups according to their baseline plasma 25-OHD level: sufficiency (≥20ng/ml), mild deficiency (15-20ng/ml), moderate deficiency (10-15ng/ml), and severe deficiency (<10ng/ml). Baseline computed tomography (CT) emphysema indices revealed significant differences among the subgroups (p=0.034). A statistically significant difference was also observed among the subgroups regarding change in the CT emphysema index over 3 years (p=0.047). The annual increase in emphysema index was more prominent in the severe deficiency group (1.34% per year) than in the other groups (0.41% per year) (p=0.003). This study demonstrates that CT emphysema indices were different among the four subgroups and supports that severe vitamin D deficiency is associated with rapid progression of emphysema in male patients with COPD.

Quantitative Vertebral Bone Density Seen on Chest CT in Chronic Obstructive Pulmonary Disease Patients: Association with Mortality in the Korean Obstructive Lung Disease Cohort.

ObjectivePatients with chronic obstructive pulmonary disease (COPD) are known to be at risk of osteoporosis. The purpose of this study was to evaluate the association between thoracic vertebral bone density measured on chest CT (DThorax) and clinical variables, including survival, in patients with COPD.Materials and MethodsA total of 322 patients with COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. DThorax was measured by averaging the CT values of three consecutive vertebral bodies at the level of the left main coronary artery with a round region of interest as large as possible within the anterior column of each vertebral body using an in-house software. Associations between DThorax and clinical variables, including survival, pulmonary function test (PFT) results, and CT densitometry, were evaluated.ResultsThe median follow-up time was 7.3 years (range: 0.1–12.4 years). Fifty-six patients (17.4%) died. DThroax differed significantly between the different Global Initiative for Chronic Obstructive Lung Disease stages. DThroax correlated positively with body mass index (BMI), some PFT results, and the six-minute walk distance, and correlated negatively with the emphysema index (EI) (all p < 0.05). In the univariate Cox analysis, older age (hazard ratio [HR], 3.617; 95% confidence interval [CI], 2.119–6.173, p < 0.001), lower BMI (HR, 3.589; 95% CI, 2.122–6.071, p < 0.001), lower forced expiratory volume in one second (FEV1) (HR, 2.975; 95% CI, 1.682–5.262, p < 0.001), lower diffusing capacity of the lung for carbon monoxide corrected with hemoglobin (DLCO) (HR, 4.595; 95% CI, 2.665–7.924, p < 0.001), higher EI (HR, 3.722; 95% CI, 2.192–6.319, p < 0.001), presence of vertebral fractures (HR, 2.062; 95% CI, 1.154–3.683, p = 0.015), and lower DThorax (HR, 2.773; 95% CI, 1.620–4.746, p < 0.001) were significantly associated with all-cause mortality and lung-related mortality. In the multivariate Cox analysis, lower DThorax (HR, 1.957; 95% CI, 1.075–3.563, p = 0.028) along with older age, lower BMI, lower FEV1, and lower DLCO were independent predictors of all-cause mortality.ConclusionThe thoracic vertebral bone density measured on chest CT demonstrated significant associations with the patients' mortality and clinical variables of disease severity in the COPD patients included in KOLD cohort.

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

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

Resting hyperinflation and emphysema on the clinical course of COPD

The aim of this study is to clarify whether the combined evaluation of resting hyperinflation and emphysema confers any additional advantages in terms of predicting clinical outcomes in chronic obstructive pulmonary disease (COPD) patients. We included COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. Patients with a residual volume/total lung capacity (RV/TLC) over the upper limit of normal were defined as having resting hyperinflation, and those with an emphysema index >10% were defined as having emphysema. We investigated the impacts of resting hyperinflation and emphysema on exacerbations and mortality. A total of 310 COPD patients were analyzed over a mean of 61.1 months. After adjustment for covariates, resting hyperinflation was an independent predictor of earlier exacerbation (HR = 1.66, CI = 1.24–2.22), more frequent exacerbation (IRR = 1.35, CI = 1.01–1.81), and higher mortality (HR = 2.45, CI = 1.16–5.17) risk. Emphysema was also significantly associated with earlier exacerbation (HR = 1.64, CI = 1.15–2.35), and higher mortality (HR = 3.13, CI = 1.06–9.27) risk. Participants with both resting hyperinflation and emphysema had an additively higher risk of earlier exacerbations (HR = 1.71, 95% CI = 1.26–2.33) and mortality (HR = 3.75, 95% CI = 1.81–7.73) compared with those in other groups. In conclusion, resting hyperinflation and emphysema had additional worse impacts on exacerbations and mortality in COPD patients.

Prediction of Treatment Response in Patients with Chronic Obstructive Pulmonary Disease by Determination of Airway Dimensions with Baseline Computed Tomography.

ObjectiveTo determine the predictive factors for treatment responsiveness in patients with chronic obstructive pulmonary disease (COPD) at 1-year follow-up by performing quantitative analyses of baseline CT scans.Materials and MethodsCOPD patients (n = 226; 212 men, 14 women) were recruited from the Korean Obstructive Lung Disease cohort. Patients received a combination of inhaled long-acting beta-agonists and corticosteroids twice daily for 3 months and subsequently received medications according to the practicing clinician's decision. The emphysema index, air-trapping indices, and airway parameter (Pi10), calculated using both full-width-half-maximum and integral-based half-band (IBHB) methods, were obtained with baseline CT scans. Clinically meaningful treatment response was defined as an absolute increase of ≥ 0.225 L in the forced expiratory volume in 1 second (FEV1) at the one-year follow-up. Multivariate logistic regression analysis was performed to investigate the predictors of an increase in FEV1, and receiver operating characteristic (ROC) analysis was performed to evaluate the performance of the suggested models.ResultsTreatment response was noted in 47 patients (20.8%). The mean FEV1 increase in responders was 0.36 ± 0.10 L. On univariate analysis, the air-trapping index (ATI) obtained by the subtraction method, ATI of the emphysematous area, and IBHB-measured Pi10 parameter differed significantly between treatment responders and non-responders (p = 0.048, 0.042, and 0.002, respectively). Multivariate analysis revealed that the IBHB-measured Pi10 was the only independent variable predictive of an FEV1 increase (p = 0.003). The adjusted odds ratio was 1.787 (95% confidence interval: 1.220–2.619). The area under the ROC curve was 0.641.ConclusionMeasurement of standardized airway dimensions on baseline CT by using a recently validated quantification method can predict treatment responsiveness in COPD patients.

Hybrid Airway Segmentation Using Multi-Scale Tubular Structure Filters and Texture Analysis on 3D Chest CT Scans.

Airway diseases are frequently related to morphological changes that may influence lung physiology. Accurate airway region segmentation may be useful for quantitative evaluation of disease prognosis and therapy efficacy. The information can also be applied to understand the fundamental mechanisms of various lung diseases. We present a hybrid method to automatically segment the airway regions on 3D volume chest computed tomography (CT) scans. This method uses multi-scale filtering and support vector machine (SVM) classification. The proposed scheme is comprised of two hybrid steps. First, a tubular structure-based multi-scale filter is applied to find the initial candidate airway regions. Second, for identifying candidate airway regions using the fuzzy connectedness technique, the small and disconnected branches of airway regions are detected using SVM classification trained to differentiate between airway and non-airway regions through texture analysis of user-defined landmark points. For development and evaluation of the method, two datasets were incorporated: (1) 55 lung-CT volumes from the Korean Obstructive Lung Disease (KOLD) Cohort Study and (2) 20 cases from the publicly open database (EXACT'09). The average tree-length detection rates of EXACT'09 and KOLD were 56.9 ± 11.0 and 70.5 ± 8.98, respectively. Comparison of the results for the EXACT'09 data set between the presented method and other methods revealed that our approach was a high performer. The method limitations were higher false-positive rates than those of the other methods and risk of leakage. In future studies, application of a convolutional neural network will help overcome these shortcomings.

Blood eosinophil count as a prognostic biomarker in COPD.

BackgroundHigh blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids. However, the prognostic role of blood eosinophil count remains underexplored. Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.MethodsPatients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital. The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%–5%), and low (<2%).ResultsThe high group had longer six-minute walk distance (high =445.8±81.4, middle =428.5±88.0, and low =414.7±86.3 m), higher body mass index (23.3±3.1, 23.1±3.1, and 22.5±3.2 kg/m2), lower emphysema index (18.5±14.1, 22.2±15.3, and 23.7±16.3), and higher inspiratory capacity/total lung capacity ratio (32.6±7.4, 32.4±9.2, and 29.9% ± 8.9%) (P<0.05). The survival period increased with increasing blood eosinophil count (high =9.52±0.23, middle =8.47±1.94, and low =7.42±0.27 years, P<0.05). Multivariate linear regression analysis revealed that the emphysema index was independently and negatively correlated with blood eosinophil count (P<0.05).ConclusionIn COPD, the severity of emphysema was independently linked with low blood eosinophil count and the longer survival period was associated with increased blood eosinophil count, though it was not proven in the multivariate analysis.

Serial blood eosinophils and clinical outcome in patients with chronic obstructive pulmonary disease

BackgroundBlood eosinophils have been suggested as a potential biomarker in chronic obstructive pulmonary disease (COPD), and their stability over time has been investigated in a few studies. However, the association between the stability of blood eosinophils and long-term clinical outcomes in COPD patients has yet to be fully elucidated. This study aimed to evaluate the stability of blood eosinophils and its association with clinical outcomes in COPD patients.MethodsIn total, 299 COPD patients from the Korean Obstructive Lung Disease cohort with at least two blood eosinophil measurements were included. Patients were stratified according to a cut-off of 300 cells/μL, and the association between eosinophil changes and all-cause mortality was analysed. The annual decline in forced expiratory volume in 1 s (FEV1), serial changes in St George’s Respiratory Questionnaire score (SGRQ), and exacerbations during follow-up were compared among eosinophil groups.ResultsPatients were stratified into three groups according to the blood eosinophil cut-off: persistently < 300 cells/μL (PL; n = 175), variable (V; n = 68), and persistently ≥300 cells/μL (PH; n = 56). There were no significant differences in baseline characteristics (age, sex, smoking, body mass index, use of inhaled corticosteroids, exacerbations in the previous year, FEV1 (L or % predicted), or emphysema score) among the groups. During a median follow-up of 6.0 years, the PH group had a better survival rate than the PL group (adjusted mortality rate ratio, 0.29; 95% confidence interval, 0.09–0.97; P = 0.045). The PH group also showed improved symptoms and impact domains of SGRQ score compared to the PL group. No difference was found in annual FEV1 decline or exacerbations during follow-up among the groups.ConclusionsPatients with persistently high blood eosinophils had a better survival rate than those with persistently low blood eosinophils. Serial follow-up of blood eosinophils could help to predict outcomes in COPD patients.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort

BackgroundThe recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD.MethodsCOPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/μL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope.ResultsAmong 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting β2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (− 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline.ConclusionPatients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.

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

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

Urinary desmosine is associated with emphysema severity and frequent exacerbation in patients with COPD.

Matrix degradation is a key feature of chronic obstructive pulmonary disease (COPD). Desmosine and isodesmosine (desmosines) are excreted in urine following matrix degradation. The main purpose of this study was to investigate the association between computed tomography (CT) emphysema indices and urinary desmosines in patients with COPD. A total of 152 subjects were selected from the Korean Obstructive Lung Disease cohort. Their urine samples were assayed for desmosines using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The cohort was divided into emphysema-dominant (n = 80) and non-emphysema dominant- (n = 72) groups according to the CT emphysema index. The level of urinary desmosines was significantly higher in the emphysema-dominant group. Significant differences were also observed between the two groups for body mass index and lung function. Multivariate analysis indicated that a high level of urinary desmosines was a significant independent predictor of emphysema (relative risk: 2.6; 95% CI: 1.11-6.09; P = 0.028). The percentage of frequent exacerbators was significantly higher in the high urinary desmosine group in the first year of follow-up (P = 0.041). The mean number of exacerbations was higher in the high urinary desmosine group, although this difference was not statistically significant (P = 0.067). The changes in emphysema index did not differ between the two urinary desmosine groups over 3 years of follow-up. This study indicates that the level of urinary desmosines measured by LC-MS/MS methods is associated with the CT emphysema index. Urinary desmosine can be a useful predictor in identifying frequent exacerbators.