Differential decline of lung function in COPD patients according to structural abnormality in chest CT.

Background: Different progressions or prognoses of chronic obstructive pulmonary disease (COPD) have been reported according to structural abnormalities based on chest computed tomography (CT). This study aimed to investigate whether different structural abnormalities independently affect annual lung function changes and clinical prognosis in patients with COPD. Methods: This longitudinal multicenter observational study was conducted using the KOCOSS cohort (NCT02800499) database in Korea from January 2012 to December 2019. For COPD patients with chest CT findings at baseline enrolment and longitudinal spirometric data, annual forced expiratory volume in 1 s (FEV1) decline rate (mL/year) and clinical outcomes were compared according to structural abnormalities, including emphysema, bronchiectasis (BE), and tuberculosis-destroyed lung (TDL). We estimated the adjusted annual FEV1 changes using a mixed-effect linear regression model. Results: Among the enrolled 237 patients, 152 showed structural abnormalities. Emphysema, BE, and TDL were observed in 119 (78.3%), 28 (18.4%), and 27 (17.8%) patients, respectively. The annual decline in FEV1 was faster in COPD patients with structural abnormalities than those without (ß = -70.6 mL/year, P-value = 0.039). BE/TDL-dominant or emphysema-dominant structural abnormality contributed to an accelerated annual FEV1 decline compared to no structural abnormality (BE/TDL-dominant, ß = -103.7 mL/year, P-value = 0.043; emphysema-dominant, ß = -84.1 mL/year, P-value = 0.018). Structural abnormalities made no significant differences in acute exacerbation rate and mortality. Conclusion: The lung function decline rate in COPD differed according to structural abnormalities on CT. These findings may suggest that more focus should be placed on earlier intervention or regular follow-up with spirometry in COPD patients with BE or TDL on chest CT.

Components of the COPD assessment test associated with the exacerbation of severe COPD patients.

INTRODUCTION: The Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) score is widely used for evaluating the health status of patients diagnosed with COPD. The aim of this study was to identify which components of the CAT are associated with exacerbation in severe COPD patients. METHODS: Using data from the Korean COPD Subgroup Study (KOCOSS), we identified 3,440 COPD patients, among which 1,027 patients are classified as having severe COPD based on spirometry results. The CAT scores on 8 items were evaluated and classified into respiratory and non-respiratory categories. We analyzed the association between CAT item scores and moderate-to-severe exacerbations during study enrollment and the following years. RESULTS: Patients with a history of moderate-to-severe exacerbations had higher scores on non-respiratory CAT components. Longitudinal CAT scores on all items after enrollment were higher in the moderate-to-severe exacerbation group. Additionally, the frequency of severe exacerbations was associated with specific CAT components related to limited activities, confidence leaving home, sleeplessness, and energy. CONCLUSIONS: This study revealed that the non-respiratory CAT component scores were statistically significant factors for predicting the moderate-to-severe exacerbation of severe COPD patients. Non-respiratory symptoms and functional limitations should be considered in patients with severe COPD. Interventions, such as pulmonary rehabilitation, may be needed to improve patients' overall well-being and prevent exacerbations.

Spirometric Interpretation and Clinical Relevance According to Different Reference Equations.

BACKGROUND: Global Lung Function Initiative (GLI)-2012 reference equation is currently suggested for interpretation of spirometry results and a new local reference equation has been developed in South Korea. However, lung function profiles according to the different reference equations and their clinical relevance have not been identified in chronic obstructive pulmonary disease (COPD) patients. METHODS: Our cross-sectional study evaluated Choi's, Korean National Health and National Examination Survey (KNHANES)-VI, and GLI-2012 reference equations. We estimated the percentages of predictive forced expiratory volume in one second (FEV1) and airflow limitation severity according to reference equations and analyzed their associations with patient reported outcomes (PROs): COPD assessment test (CAT) score, St. George's Respiratory Questionnaire for COPD patients (SGRQ-C) score, and six minute walk distance (6MWD). RESULTS: In the eligible 2,180 COPD patients, lower predicted values of FEV1 and forced vital capacity (FVC) were found in GLI-2012 compared to Choi's and KNHANES-VI equations. GLI-2012 equation resulted in a lower proportion of patients being classified as FEV1 < 80% or FVC < 80% compared to the other equations. However, the Z-scores of FEV1 and FVC were similar between the KNHANES-VI and GLI-2012 equations. Three reference equations exhibited significant associations between FEV1 (%) and patient-reported outcomes (CAT score, SGRQ-C score, and 6MWD). CONCLUSION: GLI-2012 reference equation may not accurately reflect FEV1 (%) in the Korean population, but the Z-score using GLI-2012 equation can be a viable option for assessing FEV1 and airflow limitation in COPD patients. Similar to the other two equations, the GLI-2012 equation demonstrated significant associations with PROs.

Factors Associated with the Discrepancy between Exercise Capacity and Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Exercise capacity is associated with lung function decline in chronic obstructive pulmonary disease (COPD) patients, but a discrepancy between exercise capacity and airflow limitation exists. This study aimed to explore factors contributing to this discrepancy in COPD patients. METHODS: Data for this prospective study were obtained from the Korean COPD Subgroup Study. The exercise capacity and airflow limitation were assessed using the 6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1). Participants were divided into four groups: FEV1 >50%+6-MWD >350, FEV1 >50%+6- MWD ≤350, FEV1 ≤50%+6-MWD >350, and FEV1 ≤50%+6-MWD ≤350 and their clinical characteristics were compared. RESULTS: A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) were enrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, and among 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multiple regression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval [CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178 to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008) were significantly associated with discrepancies in exercise capacity and airflow limitation in patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusion capacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantly associated with discrepancies between exercise capacity and airflow limitation. CONCLUSION: The exercise capacity of COPD patients may be influenced by factors other than airflow limitation, so these aspects should be considered when assessing and treating patients.

Predictive Role of White Blood Cell Differential Count for the Development of Acute Exacerbation in Korean Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic inflammation. Acute exacerbation of COPD (AECOPD) manifests as acute worsening of respiratory symptoms and is associated with high morbidity and mortality. The aim of the present study was to evaluate the predictive value of white blood count (WBC) and its derived inflammatory biomarkers for AECOPD. Methods: From the Korean COPD Subgroup Study cohort, a prospective and multicenter observational study, 826 patients who had baseline complete blood count (CBC) and 3-year AECOPD data were included. Follow-up CBC data at 1 (n = 385), 2 (n = 294), and 3 (n = 231) years were collected for available patients. The primary outcome was the occurrence of AECOPD at 3 years. The risk of AECOPD was evaluated using a binary logistic analysis. Results: The cumulative incidences of 12-, 24-, and 36-month AECOPD were 47.6%, 60.5%, and 67.6%, respectively. Patients with AECOPD at 3 years had higher baseline WBC counts, neutrophil counts, neutrophil/lymphocyte ratio (NLR), and neutrophil/monocyte ratio than those without AECOPD. Higher WBC count, neutrophil count, and NLR were associated with the 3-year occurrence of AECOPD in the univariate analysis, but only the higher neutrophil count was a significant risk factor (odds ratio [OR] = 1.468; 95% confidence interval [CI]: 1.024-2.104) in the covariates-adjusted analysis. In the analysis of changes in inflammatory parameters, a decrease in the platelet count (OR = 0.502; 95% CI: 0.280-0.902) and NLR (OR = 0.535; 95% CI: 0.294-0.974) at 2 years and an increase in the eosinophil count (OR = 2.130; 95% CI: 1.027-4.416) at 3 years were significantly associated with AECOPD in the adjusted analysis. Conclusion: Our data suggest that a high baseline WBC count, particularly neutrophil count, was associated with a higher incidence of long-term AECOPD.

Roles of Inflammatory Biomarkers in Exhaled Breath Condensates in Respiratory Clinical Fields.

BACKGROUND: Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. METHODS: We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. RESULTS: Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). CONCLUSION: Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.

Clinical implications of wheezing in patients with chronic obstructive pulmonary disease.

Background: Studies on the prevalence of wheezing in both the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) and non-ACO groups, as well as the clinical characteristics of wheezing patients in each group, are rare. We examined the prevalence of wheezing in ACO patients and non-ACO patients, respectively. In addition, we aimed to determine clinical characteristics of patients with wheezing compared to those without wheezing in the ACO and non-ACO groups. Methods: We analyzed the data from the Korean COPD Subgroup Study (KOCOSS), a multicenter prospective cohort. We classified patients into four groups according to whether they were ACO patients or had self-reported wheezing based on the patient's answer to the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C): ACO with wheezing, ACO without wheezing, non-ACO with wheezing, and non-ACO without wheezing. Clinical characteristics and exacerbations during 1-year follow up were compared among four groups. Results: Wheezing was present in about 56% of patients in the ACO and non-ACO groups. In both groups, patients with wheezing exhibited more severe symptoms, worse lung function, and a higher risk of exacerbation than those without wheezing. There was no association between blood eosinophil count and wheezing in both the ACO and non-ACO groups. During 1-year follow-up, the ACO with wheezing group experienced exacerbations the most frequently, followed by the non-ACO with wheezing group. Moreover, wheezing was an independent predictor of the risk of exacerbation in patients with COPD, irrespective of both the ACO phenotype and the severity of airflow limitation. The exacerbation risk was higher in COPD patients who experienced wheezing more frequently. Conclusions: Wheezing, reflecting more prominent airflow limitation and predicting exacerbation development, may serve as a severe phenotype of COPD rather than being indicative of an ACO phenotype.

Associations between depression and anxiety index and frequency of acute exacerbation in chronic obstructive pulmonary disease.

BACKGROUND: Comorbidities of chronic obstructive pulmonary disease (COPD) influence clinical characteristics and prognosis. OBJECTIVES: This study compared the clinical characteristics and exacerbation rate of COPD according to the presence of depression or anxiety. DESIGN: This study used data from The Korea COPD Subgroup Study (KOCOSS) cohort, a nationwide prospective cohort from 54 medical centers, between April 2012 and 2019. METHODS: Depression and anxiety were diagnosed with the Beck Depression Inventory and Beck Anxiety Inventory. Negative binomial regression analysis was performed to analyze the frequency of exacerbations in depressed patients and anxiety. Differences in lung function trajectory according to presence of depression/anxiety were analyzed using a linear mixed model. RESULTS: In all, 2147 patients were enrolled. Depressed patients or anxiety had lower lung function, higher modified Medical Research Council (mMRC) grade, St. George Respiratory Questionnaire (SGRQ) score, and COPD assessment test score, and higher rates of exacerbation in the past year than those without depression/anxiety. Depressed patients had a higher frequency of moderate to severe exacerbations [Incidence Rate Ratio (IRR): 1.57, CI: 1.17-2.11, p = 0.002] and those with anxiety had higher frequencies of moderate to severe (IRR: 1.52, CI: 1.03-2.27, p = 0.038) and severe exacerbations (IRR: 2.13, CI: 1.09-4.15, p = 0.025) during 1-year follow-up compared to those without these comorbidities. The differences in the change in annual forced expiratory volume in 1 seconds (FEV1) over 3 years according to the presence of depression or anxiety were not statistically significant. CONCLUSION: Depressed and anxious patients showed increased respiratory symptoms and exacerbation rate as well as reduced health-related quality of life, whereas there were no significant differences in changes in lung function between groups with and without depression/anxiety.

Development of a daily predictive model for the exacerbation of chronic obstructive pulmonary disease.

Acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) compromises health status; it increases disease progression and the risk of future exacerbations. We aimed to develop a model to predict COPD exacerbation. We merged the Korean COPD subgroup study (KOCOSS) dataset with nationwide medical claims data, information regarding weather, air pollution, and epidemic respiratory virus data. The Korean National Health and Nutrition Examination Survey (KNHANES) dataset was used for validation. Several machine learning methods were employed to increase the predictive power. The development dataset consisted of 590 COPD patients enrolled in the KOCOSS cohort; these were randomly divided into training and internal validation subsets on the basis of the individual claims data. We selected demographic and spirometry data, medications for COPD and hospital visit for AE, air pollution data and meteorological data, and influenza virus data as contributing factors for the final model. Six machine learning and logistic regression tools were used to evaluate the performance of the model. A light gradient boosted machine (LGBM) afforded the best predictive power with an area under the curve (AUC) of 0.935 and an F1 score of 0.653. Similar favorable predictive performance was observed for the 2151 individuals in the external validation dataset. Daily prediction of the COPD exacerbation risk may help patients to rapidly assess their risk of exacerbation and will guide them to take appropriate intervention in advance. This might lead to reduction of the personal and socioeconomic burdens associated with exacerbation.

Subtypes of Patients with Mild to Moderate Airflow Limitation as Predictors of Chronic Obstructive Pulmonary Disease Exacerbation.

COPD is a heterogeneous disease, and its acute exacerbation is a major prognostic factor. We used cluster analysis to predict COPD exacerbation due to subtypes of mild-moderate airflow limitation. In all, 924 patients from the Korea COPD Subgroup Study cohort, with a forced expiratory volume (FEV1) ≥ 50% and documented age, body mass index (BMI), smoking status, smoking pack-years, COPD assessment test (CAT) score, predicted post-bronchodilator FEV1, were enrolled. Four groups, putative chronic bronchitis (n = 224), emphysema (n = 235), young smokers (n = 248), and near normal (n = 217), were identified. The chronic bronchitis group had the highest BMI, and the one with emphysema had the oldest age, lowest BMI, and highest smoking pack-years. The young smokers group had the youngest age and the highest proportion of current smokers. The near-normal group had the highest proportion of never-smokers and near-normal lung function. When compared with the near-normal group, the emphysema group had a higher risk of acute exacerbation (OR: 1.93, 95% CI: 1.29-2.88). However, multiple logistic regression showed that chronic bronchitis (OR: 2.887, 95% CI: 1.065-8.192), predicted functional residual capacity (OR: 1.023, 95% CI: 1.007-1.040), fibrinogen (OR: 1.004, 95% CI: 1.001-1.008), and gastroesophageal reflux disease were independent predictors of exacerbation (OR: 2.646, 95% CI: 1.142-6.181). The exacerbation-susceptible subtypes require more aggressive prevention strategies.

When is LABA/LAMA Better than LAMA in GOLD Group B or D Patients for Reducing Acute Exacerbations of COPD?

Long-acting ß2-agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown. With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095-0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749). The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms.

Clinical Characteristics and Medical Utilization of Smokers with Preserved Ratio Impaired Spirometry.

Purpose: To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm). Patients and Methods: We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD). Results: A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV1 and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV1 and FVC % predicted were factors associated with medical utilization in PRISm. Conclusion: Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV1 and FVC might need close observation and early treatment.

Clinical significance of normalized airflow obstruction in patients with chronic obstructive pulmonary disease.

BACKGROUND: There is ongoing debate regarding the diagnostic criteria for chronic obstructive pulmonary disease (COPD); recent studies have focused on the early COPD detection and management. Here, we compared clinical features and prognosis in patients with FEV1/FVC<0.70 at baseline, according to normalized airflow obstruction status during follow-up. METHODS: We used the Korea COPD Subgroup Study (KOCOSS) cohort database, a prospective nationwide observational COPD study. Normalized obstruction (NO) was defined as FEV1/FVC ≥0.7 in the 2-year follow-up period, whereas fixed obstruction (FO) was defined as FEV1/FVC <0.7. Demographic and clinical data, 1-year exacerbation risk and difference in FEV1 decline over 2 years were compared between NO and FO groups. RESULTS: Among the 670 COPD patients with post-bronchodilator FEV1/FVC <0.7 in this study, 95 (14.2%) displayed NO. Compared with the FO group, the NO group had higher FEV1, and DLCO, body mass index, as well as lower Saint George Respiratory Questionnaire, Beck Depression Index, and Beck Anxiety Index. Blood eosinophil count, IgE level, and FeNO did not significantly differ between two groups. There was no significant difference in exacerbation frequency between the two groups, but the NO group had a significant increase in FEV1 compared with the FO group during follow-up. CONCLUSION: Transient airflow obstruction in the NO group may represent a clinical manifestation of early COPD; close monitoring is needed for such patients.

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

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

Airflow obstruction and chronic obstructive pulmonary disease are common in pulmonary tuberculosis even without sequelae findings on chest X-ray.

PURPOSE: Pulmonary tuberculosis (TB) is a well-known risk factor for airflow obstruction and chronic obstructive pulmonary disease (COPD). The prognosis of TB without sequelae on chest X-ray (CXR) remains uncertain. METHODS: We used the 2008-2009 Korea National Health and Nutrition Examination Survey (KNHANES) data and 2007-2012 KNHANES-matched Health Insurance Review and Assessment Service cohort data. Airflow obstruction was assessed using a pulmonary function test. COPD was defined using diagnostic codes and the use of COPD medication for 3-year. We classified subjects into three groups based on TB history and sequelae on CXR. RESULTS: In 4911 subjects, the CXR(-) (no TB sequelae on CXR) post-TB group (n = 134) showed similar characteristics and normal lung function compared to that of the control group (n = 4,405), while the CXR(+) (TB sequelae on CXR) post-TB group (n = 372) showed different characteristics and reduced lung function. The prevalence of airflow obstruction was 9.3%, 13.4%, and 26.6% in control, CXR(-) post-TB, and CXR(+) post-TB groups, respectively. COPD was more common in the post-TB with CXR(+) (6.5%) or without CXR (-) (4.5%) groups, than in the control group (1.8%). Compared to the CXR(-) post-TB group, the control group showed a lower risk for airflow obstruction (OR, 0.774; p = .008). The CXR(+) post-TB group showed a higher risk for airflow obstruction (OR, 1.456; p = .011). The Control group also showed a lower risk for the development of COPD than the CXR(-) post-TB group (OR, 0.496; p = .011). CONCLUSIONS: We need to educate TB patients that airway obstruction and COPD can easily develop, even if TB sequelae are not observed on CXR.

Heterogeneity of asthma-chronic obstructive pulmonary disease (COPD) overlap from a cohort of patients with severe asthma and COPD.

BACKGROUND: A considerable proportion of patients have features of both asthma and chronic obstructive pulmonary disease (COPD) simultaneously, called asthma-COPD overlap (ACO). OBJECTIVES: The aim of this study was to identify heterogeneity of ACO from a cohort of patients with severe asthma and COPD using the same diagnostic criteria. DESIGN: We used the International Severe Asthma Registry (ISAR) and the Korean COPD Subgroup Study (KOCOSS) to evaluate clinical characteristics of ACO from each cohort. METHODS: We classified subjects into four groups: (1) pure severe asthma, (2) ACO from the severe asthma cohort, (3) ACO from the COPD cohort, and (4) pure COPD. ACO was defined by satisfying extreme bronchodilator response (BDR) >15% and 400 ml and/or blood eosinophil count ⩾300 /µL in patients aged 40 years or older and post-BD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. RESULTS: The ACO group had 25 (23%) of 111 in the ISAR cohort and 403 (23%) of 1781 in the KOCOSS cohort. The ACO from the COPD cohort was older with more males and more smokers, but had similar degree of airflow limitation compared with the ACO from the severe asthma cohort. ICS-containing inhaler treatment was prescribed for all severe asthma subjects, but only for 43.9% of ACO subjects from the COPD cohort. Compared with patients having pure severe asthma, the risk for exacerbation was comparable in ACO either from severe asthma or COPD cohort [adjusted odds ratio (aOR): 1.54, 95% CI: 0.22-10.95 or aOR: 2.15, 95% CI: 0.59-7.85]. CONCLUSION: The prevalence of ACO was similar in severe asthma and COPD cohorts applying identical diagnostic criteria. ACO from the severe asthma cohort was similar to ACO from the COPD cohort in terms of lung function and exacerbation risk.

Association between Serum Levels of Interleukin-25/Thymic Stromal Lymphopoietin and the Risk of Exacerbation of Chronic Obstructive Pulmonary Disease.

Th2 inflammation is associated with various characteristics of patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed the COPD exacerbation risk associated with serum levels of interleukin (IL)-25/thymic stromal lymphopoietin (TSLP) and eosinophils. We studied the KOCOSS cohort, a multicenter COPD cohort created by 54 medical centers in South Korea. We extracted data collected between April 2012 and August 2020. We measured serum levels of TSLP and IL-25 in those who agreed to provide blood, and assessed exacerbation risk according to each. In all, 562 patients were enrolled. The IL-25-high group had a lower St. George's Respiratory Questionnaire score than others, and the TSLP-high group had a poorer exercise capacity than the TSLP-low group. There were no significant differences in the forced expiratory volume in 1 s (FEV1), the levels of Th2 inflammatory biomarkers, or the exacerbation histories between the two groups. The 3-year decline in FEV1 was not significantly affected by IL-25 or TSLP levels. In terms of 1-year exacerbation risk, individuals in the IL-25-high group were at lower risk for moderate-to-severe exacerbation than others. A high TSLP level was associated with a lower risk of severe exacerbation but only in the eosinophil-low group. Serum levels of IL-25 are negatively correlated with moderate-to-severe exacerbation risk in this cohort. A negative correlation between severe exacerbation risk and TSLP level was apparent only in the eosinophil-low group.

Differences in clinical significance of bronchodilator responses measured by forced expiratory volume in 1 second and forced vital capacity.

BACKGROUND: The clinical implication of bronchodilator response (BDR) is not fully understood. However, BDR is frequently present in patients with chronic obstructive pulmonary disease (COPD). We identified the differences in clinical features regarding BDR. In addition, we divided BDR into BDR for forced expiratory volume in 1 s (FEV1) and BDR for forced vital capacity (FVC; i.e., BDR-FEV1 and BDR-FVC, respectively) and analyzed clinical significance. METHODS: We used data from the Korea COPD Subgroup Study, a multicenter cohort study of COPD patients recruited from 54 centers in South Korea since April 2012. We analyzed differences in baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline between BDR negative and positive patients. Moreover, we analyzed the differences in clinical features between BDR-FEV1 positive and negative patients and between BDR-FVC positive and negative patients. RESULTS: Of the 2,181 patients enrolled in this study, 366 (16.8%) were BDR positive. BDR positive patients were more likely to be ever-smokers and to have a lower body mass index and higher symptom scores compared to BDR negative patients. Baseline FEV1 and FEV1/FVC were lower in the BDR positive compared to the BDR negative group (1.7 ± 0.6 and 1.6 ± 0.5, respectively, p < 0.01; 50.9 ± 12.1 and 46.5 ± 14.8, respectively, p < 0.01). BDR positive patients were more likely to have been diagnosed with asthma-COPD overlap and to receive inhaled corticosteroids (ICS) than BDR negative patients. BDR-FVC patients were more likely to be smokers, suffer from worse symptoms and have lower lung function than those with no BDR-FVC. BDR had no significant effect on 1-year moderate to severe or severe exacerbation rates or 3-year annual FEV1 decline. Interactive effects of ICS and BDR on the exacerbation rate were not significant in any group. CONCLUSIONS: In this study, BDR positive patients were more likely to be ever-smokers and to have worse symptoms and lung function than BDR negative patients. BDR-FVC was associated with worse symptom control and lung function compared to BDR-FEV1. However, there were no significant differences in exacerbation rate or decline in lung function in any BDR group. In addition, the effects of ICS on exacerbations were not significant in any group.

Risk Factors of Rapid FEV1 Decline in a Real-World Chronic Obstructive Pulmonary Disease Cohort.

BACKGROUND: Rapid forced expiratory volume in 1 s (FEV1) decliners have been considered a unique subgroup of patients with chronic obstructive pulmonary disease (COPD). Rapid FEV1 decline manifests early and is associated with poor prognosis. This necessitates the pre-emptive identification of risk factors for rapid FEV1 decline. OBJECTIVES: We aimed to determine the risk factors and clinical outcomes in patients with COPD. METHODS: This longitudinal, observational study was based on the Korea COPD Subgroup Study cohort (NCT02800499) from January 2012 to December 2019 across 54 medical centers in South Korea. Eligible patients were followed up for 3 years with serial spirometric tests. We calculated the annualized percentage change in FEV1 from baseline. Rapid decliners were defined as the quartile of patients with the highest annualized percentage FEV1 decline. RESULTS: Of the 518 patients, 130 were rapid decliners who lost 6.2%/year and 100 mL/year of FEV1. The multivariable logistic regression identified male sex, current smoking, blood eosinophil count <150/µL, and high forced vital capacity as the independent risk factors for rapid FEV1 decline. Among rapid decliners, the lung function deteriorated more rapidly in current smokers and patients with severe dyspnea, while triple combination therapy attenuated lung function decline in comparison with mono-bronchodilator therapy. Rapid decliners had a higher rate of severe exacerbation than nonrapid decliners (0.2/year vs. 0.1/year, p value = 0.032). CONCLUSIONS: We identified the independent risk factors for rapid FEV1 decline. This information may assist physicians in the early detection and pertinent management of rapid decline among patients with COPD.