Korean Obstructive Lung Disease 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.

Association between Long-Term Exposure to PM2.5 and Lung Imaging Phenotype in CODA Cohort

Background and Aims: Ambient particulate matter (PM) is causing respiratory symptoms of individuals at all ages and reducing their lung functions. These individuals could develop chronic pulmonary disease. Recent studies have shown that short-term exposure to PM affects acute exacerbation of respiratory disease. However, evidence about the association between long-term exposure and progression of respiratory diseases remains insufficient. The purpose of this study was to examine the association between long-term exposure of air pollution (PM2.5) and the effect on lung imaging phenotype in dust-exposed Korean adults living near cement factories. Methods: We conducted a cross-sectional analysis on the Chronic Obstructive Pulmonary Disease (COPD) in Dusty Areas (CODA) cohort, which was recruited from 2012 to 2014. Emphysema index and mean wall area were measured using an in-house software program developed by the Korean obstructive lung disease study group based on chest CT scan. A satellite-based model was used to estimate the long-term PM2.5 concentration at each participant’s address. Results: Of 504 eligible participants, 400 participants were analyzed. Their mean age was 71.7 years. Most participants were men (N = 301, 75.3%). The emphysema index of the whole group was 6.63 ± 0.70, and the mean wall area was 68.8 ± 5.2. Image measurement and PM2.5 concentration showed no significant difference in the whole group; however, in the group of subjects with normal lung function, there were significant associations between long-term PM2.5 exposure and emphysema index measurement: 1-year (ß = 0.758, p = 0.021), 3-year (ß = 0.629, p = 0.038), and 5-year (ß = 0.544, p = 0.045). There was no significant association between long-term PM2.5 exposure and mean wall area measurement: 1-year (ß = −0.389, p = 0.832), 3-year (ß = −3.677, p = 0.170), and 5-year (ß = −3.769, p = 0.124). Conclusions: This study suggests that long-term exposure of PM2.5 may affect the emphysematous change in patients with normal lung functions.

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.

Clinical impact of long-term change in air trapping on pulmonary function and computed tomography parameters in chronic obstructive pulmonary disease.

Background/AimsAir trapping is associated with unfavorable outcomes in chronic obstructive pulmonary disease (COPD). The present study evaluated the association between longitudinal changes in air trapping with pulmonary function, computed tomography (CT) parameters and exacerbation.MethodsPatients enrolled in the Korean Obstructive Lung Disease (KOLD) study cohort from June 2005 to October 2015 were included. The study patients were categorized into four groups according to the change in residual volume to total lung capacity ratio (RV/TLC) over 3 years. The RV/TLC was considered abnormal when it was ≥ 40% and normal when it was < 40%.ResultsA total of 279 patients were categorized into four groups: 76 in the “normal to normal” (N→N) group, 34 in the “abnormal to normal” (A→N) group, 33 in the “normal to abnormal” (N→A) group, and 136 in the “abnormal to abnormal” (A→A) group. For forced expiratory volume in 1 second and forced vital capacity (FVC), respectively, group A→N showed a large increase of 266 mL (p < 0.001) and 381 mL (p < 0.001), group N→A showed a marked decrease of 216 mL (p < 0.001) and 332 mL(p = 0.029), and group A→A showed a decrease of 16 mL (p = 0.426) and 6 mL (p = 0.011) compared to group N→N. Group A→N showed a significant decrease of −0.013 in expiratory to inspiratory ratio of the mean lung density (p < 0.001), while group A→N showed an increase of 0.005 (p < 0.001).ConclusionsPatients with COPD whose RV/TLC changed from normal to abnormal showed deterioration of pulmonary function and worsening of CT parameters simultaneously.

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.

Mixed Phenotype of Emphysema and Airway Wall Thickening Is Associated with Frequent Exacerbation in Chronic Obstructive Pulmonary Disease Patients.

ObjectiveThe presence of both emphysema and airway wall thickening determined via volumetric computed tomography (CT) is defined as mixed phenotype. The long-term clinical course of this phenotype has not been studied in depth. This study compared the mixed phenotype to other phenotypes of chronic obstructive pulmonary disease (COPD) patients.MethodsCOPD patients enrolled in the Korean Obstructive Lung Disease (KOLD) study from June 2005 to October 2015 were evaluated. The emphysema index and the percentage of bronchial mean wall area were calculated from volumetric CT scans. Patients with COPD were classified into four phenotypes using two cutoffs: emphysema index of 15% and median value of mean wall area (MWA%).ResultsOf 435 patients with COPD, 99 (22.8%) were defined as CT-normal type, 119 (27.4%) as emphysema-dominant type, 113 (26.0%) as airway-dominant type, and 104 (23.9%) as mixed type. The mixed phenotype showed the highest baseline total COPD Assessment Test (CAT) and St. George’s Respiratory Questionnaire (SGRQ) scores. Moreover, it had the highest proportion of patients experiencing exacerbation of COPD (50.0%), and had the lowest baseline FEV1. Lower BMI, GOLD stages III–IV, and mixed phenotype were significant factors associated with severe exacerbation frequency in univariate analyses. Multivariate analyses showed that lower BMI and CT phenotype were significant factors associated with severe exacerbation frequency. Compared to the CT-normal phenotype, the mixed phenotype was significantly associated with more frequent severe exacerbation (IRR 4.134, 95% CI: 1.135–15.057, P=0.031).ConclusionPatients with mixed phenotype are more symptomatic, have poorer pulmonary function, and are associated with more frequent severe exacerbation.

Progression of erectile function in men with chronic obstructive pulmonary disease: a cohort study

BackgroundAlthough sexual function is a quality of life aspect that is markedly affected in males with chronic obstructive pulmonary disease (COPD), this topic has not attracted much attention and research on this matter is lacking. In this study, we investigated longitudinal changes in the erectile function of men with COPD in order to identify latent groups and influencing factors.MethodsA total of 185 men with COPD from the Korean Obstructive Lung Disease study, which was conducted from 2005 to 2013, were analyzed in this study. Data on their erectile function, based on the International Index of Erectile Function-5, were collected over a period of 4 years. Growth mixture modeling and logistic regression analysis were used to determine the factors predicting distinct erectile function changes over time.ResultsOverall, subjects’ erectile function slightly improved in the first year and then gradually worsened over time. Using growth mixture modeling, we identified four distinct latent groups, which we labeled as follows: “consistently maintained normal erectile function” (9.7%), “rapidly worsened and then rapidly improved” (9.2%), “gradually improved in the early stage and then gradually worsened” (36.8%), and “consistently maintained poor erectile function” (44.3%). Progression of erectile function was significantly associated with age, economic status, and self-rated health status.ConclusionsThis suggests that comprehensive patient care involving the management of COPD as well as erectile dysfunction in patients with chronic respiratory disease is important from a prophylactic perspective and should be developed in accordance with the characteristics of the disease process.

Change in inhaled corticosteroid treatment and COPD exacerbations: an analysis of real-world data from the KOLD/KOCOSS cohorts

BackgroundThis cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.MethodsA total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed. Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.ResultsICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead. Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period. The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs. 0.53, p < 0.001). Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs. 0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs. 0.12, p = 0.03).ConclusionsPrescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators. ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients’ characteristics.

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.