Suboptimal peak inspiratory flow rate in dry-powder inhaler users for chronic obstructive pulmonary disease in Korea.

BACKGROUND: A suboptimal peak inspiratory flow rate (PIFR) in dry-powder inhaler (DPI) users can lead to insufficient therapeutic effects in the treatment of chronic obstructive pulmonary disease (COPD). However, few data on the prevalence of and factors associated with suboptimal PIFR in Korean patients with COPD are available. METHODS: We conducted a cross-sectional study of patients with COPD who had been using DPIs for more than three months. PIFR was measured using an In-Check DIAL G16 device. Suboptimal PIFR was defined as below the resistance-matched threshold. Multivariable logistic regression analysis was used to determine factors associated with suboptimal PIFR. RESULTS: Of 444 DPI users with COPD, the rate of suboptimal PIFR was 22.0 % (98/444). In a multivariable analysis, significant factors associated with suboptimal PIFR were age (adjusted odds ratio [aOR] = 1.06 by 1-year increase; 95 % confidence interval [CI] = 1.02-1.09), male sex (aOR = 0.28; 95 % CI = 0.11-0.73), body mass index (BMI) (aOR = 0.91 by 1 kg/m2 increase; 95 % CI = 0.85-0.99), post-bronchodilator forced vital capacity (FVC) %pred (aOR = 0.97 by 1%pred increase; 95 % CI = 0.95-0.99), and In-Check DIAL R2-type inhaler [medium-low resistance] use (aOR = 3.70 compared with R1-type inhalers [low resistance]; 95 % CI = 2.03-7.03). CONCLUSIONS: In Korea, more than one-fifth of DPI users with COPD had a suboptimal PIFR. The factors associated with suboptimal PIFR were age, female gender, low BMI, low FVC, and R2-type inhaler use. Therefore, clinicians should carefully evaluate the possibility of suboptimal PIFR when prescribing DPIs.

Components of the Chronic Obstructive Pulmonary Disease Assessment Test Associated with the Exacerbation of Severe Chronic Obstructive Pulmonary Disease 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 exacerbations 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.

Clinical significance of chronic bronchitis in different racial groups.

BACKGROUNDS: Limited data are available on racial differences in the clinical features of chronic bronchitis (CB) patients with chronic obstructive pulmonary disease (COPD). In this study, we aimed to compare clinical features among CB patients of different races. We also analyzed the clinical significance of CB, defined classically and based on the COPD Assessment Test (CAT), to validate the CAT-based definition. METHODS: We analyzed patient data extracted from the Korean COPD Subgroup Study (KOCOSS) cohort (2012-2021) and US Genetic Epidemiology of COPD (COPDGene) study (2008-2011). We compared clinical characteristics among CB and non-CB patients of three different races using two CB definitions. RESULTS: In this study, 3,462 patients were non-Hispanic white (NHW), 1,018 were African American (AA), and 1,793 were Asian. The proportions of NHW, AA, and Asian patients with CB according to the classic definition were 27.4%, 20.9%, and 10.7%, compared with 25.2%, 30.9%, and 23.0% according to the CAT-based definition, respectively. The risk of CB prevalence was highest in NHW and lowest in Asian COPD patients. Among all races, CB patients were more likely to be current smokers, have worse respiratory symptoms and poorer health-related quality of life (HrQoL), and to have decreased lung function and exercise capacity. Most of these characteristics showed similar associations with the outcomes between the two definitions of CB. A binominal regression model revealed that CB patients of all races had an increased risk of future exacerbations according to both CB definitions, except for Asian patients with classically defined CB. CONCLUSIONS: The presence of CB was associated with worse respiratory symptoms, HrQoL, exercise capacity and lung function, and more exacerbations, regardless of race or CB definition. The CAT-based definition may be more useful for assessing the risk of future exacerbations in Asian COPD patients.

Clinical Characteristics and Frequency of Chronic Obstructive Pulmonary Disease Exacerbations in Korean Patients: Findings From the KOCOSS Cohort 2012-2021.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exert a substantial burden on patients and healthcare systems; however, data related to the frequency of AECOPD in the Korean population are limited. Therefore, this study aimed to describe the frequency of severe, and moderate or severe AECOPD, as well as clinical and demographic characteristics of patients with chronic obstructive pulmonary disease (COPD) in South Korea. METHODS: Data from patients aged > 40 years with post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ≤ 70% of the normal predicted value from the Korea COPD Subgroup Study database were analyzed (April 2012 to 2021). The protocol was based on the EXAcerbations of COPD and their OutcomeS International study. Data were collected retrospectively for year 0 (0-12 months before study enrollment) based on patient recall, and prospectively during years 1, 2, and 3 (0-12, 13-24, and 25-36 months after study enrollment, respectively). The data were summarized using descriptive statistics. RESULTS: Data from 3,477 Korean patients (mean age, 68.5 years) with COPD were analyzed. Overall, most patients were male (92.3%), former or current smokers (90.8%), had a modified Medical Research Council dyspnea scale score ≥ 1 (83.3%), and had moderate airflow limitation (54.4%). The mean body mass index (BMI) of the study population was 23.1 kg/m², and 27.6% were obese or overweight. Hypertension was the most common comorbidity (37.6%). The mean blood eosinophil count was 226.8 cells/µL, with 21.9% of patients having ≥ 300 cells/µL. A clinically insignificant change in FEV1 (+1.4%) was observed a year after enrollment. Overall, patients experienced a mean of 0.2 severe annual AECOPD and approximately 1.1 mean moderate or severe AECOPD. Notably, the rates of severe AECOPD remained generally consistent over time. Compared with patients with no exacerbations, patients who experienced severe exacerbations had a lower mean BMI (21.7 vs. 23.1 kg/m²; P < 0.001) and lower lung function parameters (all P values < 0.001), but reported high rates of depression (25.5% vs. 15.1%; P = 0.044) and anxiety (37.3% vs. 16.7%; P < 0.001) as a comorbidity. CONCLUSION: Findings from this Korean cohort of patients with COPD indicated a high exacerbation burden, which may be attributable to the unique characteristics of the study population and suboptimal disease management. This highlights the need to align clinical practices with the latest treatment recommendations to alleviate AECOPD burden in Korea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05750810.

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.

Effect of Broncho-Vaxom (OM-85) on the frequency of chronic obstructive pulmonary disease (COPD) exacerbations.

BACKGROUND: Efforts have been made to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations using a variety of measures. Broncho-Vaxom (BV) is an immunomodulating agent that has shown potential benefit by balancing between immune stimulation and regulation in patients with COPD. In this study, we evaluated the clinical efficacy of BV for reducing the risk of COPD exacerbations. METHODS: This study was based on the Korean National Health Insurance database, which contains reimbursement information for almost the entire population of South Korea. We extracted data from 2016 to 2019 for patients started on BV during 2017-2018. We collected baseline data on demographics, comorbidities, inhaler use, hospital type, and insurance type 1 year before starting BV. We also analyzed exacerbation history, starting from the year before BV initiation. RESULTS: In total, 238 patients were enrolled in this study. Their mean age was 69.2 ± 9.14 years, 79.8% were male, and 45% experienced at least one exacerbation. BV reduced the risk of moderate (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.38-0.91) and moderate-to-severe exacerbations compared to pre- and post-BV (OR = 0.571, 95% CI: 0.37-0.89). BV use also reduced the incidence of moderate and moderate-to-severe exacerbations (incidence rate ratio [IRR] = 0.75, p = 0.03; and IRR = 0.77, p = 0.03, respectively). The use of BV was significantly delayed moderate exacerbations (hazard ratio = 0.68, p = 0.02), but not with moderate-to-severe or severe exacerbations. CONCLUSION: The use of BV was associated with fewer moderate and moderate-to-severe exacerbations. Additionally, BV was associated with a delay in moderate COPD exacerbations.

Comparison of the end-of-life decisions of patients with hospital-acquired pneumonia after the enforcement of the life-sustaining treatment decision act in Korea.

BACKGROUND: Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. METHODS: This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan-Meier curve analyses for survival were performed. RESULTS: Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63-81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan-Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). CONCLUSIONS: After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed.

Risk of Rapid Lung Function Decline in Young Adults With Chronic Obstructive Pulmonary Disease: A Community-Based Prospective Cohort Study.

It is unclear whether young adults with chronic obstructive pulmonary disease (COPD) are at an increased risk of rapid lung function decline. A total of 2,934 Korean adults aged 40-49 years who had consecutive lung function measurements were included. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity < lower limit of normal. The risk of rapid decline in FEV1, defined as ≥ 60 mL/year, was assessed using multivariable logistic regression analysis. In the multivariable model, a significantly higher risk of rapid decline in FEV1 was observed for the COPD group compared with the non-COPD group (adjusted odds ratio, 1.89; 95% confidence interval, 1.18-2.95), which was especially significant in subjects with FEV1 less than the median value (< 110%pred) (Pinteraction = 0.017) and inactive physical activity (Pinteraction = 0.039). In conclusion, the risk of rapid FEV1 decline was higher in young adults with COPD than in those without COPD, especially in those with FEV1 less than the median value and inactive physical activity.

Recent Prevalence of and Factors Associated With Chronic Obstructive Pulmonary Disease in a Rapidly Aging Society: Korea National Health and Nutrition Examination Survey 2015-2019.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) increases with age, and aging is an important risk factor for COPD development. In the era of global aging, demographic information about the prevalence of and factors associated with COPD are important to establish COPD care plans. However, limited information is available in rapidly aging societies, including Korea. METHODS: We conducted a cross-sectional observational study using Korea National Health and Nutrition Examination Survey data from 2015-2019. We included 15,613 participants and analyzed trends of and factors associated with COPD. RESULTS: During the study period, the overall prevalence of COPD was 12.9%. Over five years, the yearly prevalence of COPD was fairly constant, ranging from 11.5% to 13.6%. Among individuals aged ≥ 70 years, nearly one-third met COPD diagnostic criteria. In the multivariable analysis, age 70 years or older was the most strong factor associated with COPD (adjusted odds ratio [aOR], 17.86; 95% confidence interval [CI], 14.16-22.52; compared with age 40-49), followed by asthma (aOR, 3.39; 95% CI, 2.44-4.71), male sex (aOR, 2.64; 95% CI, 2.18-3.19), and current smokers (aOR, 2.60; 95% CI, 2.08-3.25). Additionally, ex-smokers, low income, decreased forced expiratory volume in 1 second %pred, and a history of pulmonary tuberculosis were associated with COPD. On the other hand, body mass index (BMI) ≥ 25 kg/m² (aOR, 0.62; 95% CI, 0.54-0.71; compared with BMI 18.5-24.9 kg/m²) had an inverse association with COPD. CONCLUSION: Recent trends in the prevalence of COPD in South Korea are relatively stable. Approximately one-third of participants aged 70 years and older had COPD. Aging was the most important factor associated with COPD.

Empiric Anti-Pseudomonal ß-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching.

BACKGROUND: There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric anti-pseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP. METHODS: This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019. Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem ß-lactam monotherapy and fluoroquinolone combination therapy groups. Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias. RESULTS: In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286). There was no significant difference in 30-day mortality between the two groups (16.8% vs. 18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782-3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups. CONCLUSION: Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to ß-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.

Prevalence, characteristics, and risk of exacerbation in young patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Early identification of chronic obstructive pulmonary disease (COPD) in young individuals could be beneficial to attempt preventive interventions. The objective of this study was to investigate clinical features and outcomes of young individuals with COPD from the general population cohort. METHODS: We included individuals from the Korean National Health and Nutrition Examination Survey (KNHANES) with spirometry and identifiable smoking status. Young subjects with COPD were defined as aged between 40 and 50 years and had baseline forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] ratio less than 0.7. Outcomes include the risk of exacerbation and medical expenses during 3 years of follow-up. RESULTS: Among 2236 individuals aged between 40 and 50 years, 95 (4.2%) had COPD, including 36 who were never-smokers and 59 who were ever-smokers. Approximately 98% of COPD subjects had mild to moderate airflow limitation. Inhaler treatment was given to only 6.3% patients in the COPD group. The risk of exacerbation for a 3-year period was analyzed using the never-smoker, non-COPD group as a comparator. Hazards ratio for exacerbation was 1.60 (95% confidence interval [CI] 0.18-14.20) in the never-smoker COPD group and 1.94 (95% CI 0.31-12.07) in the ever-smoker COPD group of young subjects. COPD related medical costs were not significantly different between non-COPD and COPD groups of young individuals. CONCLUSIONS: The risk of exacerbation showed an increasing trend in COPD patients regardless of smoking status compared to non-COPD. More attention to early identification and provision of preventive measures are needed to reduce disease progression and improve outcome.

Association of body mass index and COPD exacerbation among patients with chronic bronchitis.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) patients with a body mass index (BMI) < 25 kg/m2 are prone to develop adverse event of pharmacological treatment for frequent exacerbation. As chronic bronchitis (CB) is one of the strong risk factors of exacerbation, we investigated the associations between BMI and COPD exacerbations in patients with CB. METHODS: Patients with COPD were included from the Korean COPD Subgroup Study (KOCOSS), a multicenter observational cohort study. CB was defined using the St. George's Respiratory Questionnaire and the participants were categorized according to BMI cut-off of 25 kg/m2. Exacerbations during a 1-year follow-up were compared among four groups: non-CB with BMI ≥ 25 kg/m2, non-CB with BMI < 25 kg/m2, CB with BMI ≥ 25 kg/m2, and CB with BMI < 25 kg/m2. RESULTS: Among the 1264 patients with COPD, 451 (35.7%) had CB and 353 (27.9%) had both CB and BMI < 25 kg/m2. The COPD exacerbation risk increased across the non-CB with BMI < 25 kg/m2, CB with BMI ≥ 25 kg/m2, and CB with BMI < 25 kg/m2 groups (adjusted incidence rate ratio [95% confidence interval] 1.21 [0.89-1.62], 1.20 [0.77-1.88], and 1.41 [1.02-1.91], respectively, compared to the non-CB with BMI ≥ 25 kg/m2 group). CONCLUSIONS: COPD patients having both CB and a BMI < 25 kg/m2 are at higher risk of exacerbations. Considering that a BMI < 25 kg/m2 often limits treatment options preventing exacerbations, modified guidelines might be needed for non-obese CB patients in Asia.

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.

Comparison of clinical characteristics between chronic bronchitis and non-chronic bronchitis in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores. METHODS: This study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB. RESULTS: Among the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB. CONCLUSIONS: CB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Longitudinal changes in forced expiratory volume in 1 s in patients with eosinophilic chronic obstructive pulmonary disease.

BACKGROUND: Data on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV1) and effects of inhaled corticosteroid (ICS) in Korean COPD patients. METHODS: Stable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/µL). FEV1 changes were analyzed over a 3-year follow-up period. RESULTS: Of 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10-2.03). An accelerated FEV1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV1 change: - 12.2 mL/y and - 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (- 19.2 mL/y and - 4.5 mL/y, with and without ICS therapy, respectively). CONCLUSIONS: The annual rate of decline in FEV1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV1.

The Effectiveness and Harms of Screening for Chronic Obstructive Pulmonary Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to perform meta-analyses to update a previous systematic review (SR) conducted by the US Preventive Services Task Force (USPSTF) to evaluate the benefits and harms of screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults. METHODS: MEDLINE, EMBASE, Cochrane Library, and regional databases were searched from their inception to January 2020. Studies for diagnostic accuracy, preventive services effect, treatment efficacy, and treatment harms were included. RESULTS: Eighteen studies were included, and twelve of these were newly added in this update. In meta-analyses, the pooled sensitivity and specificity for COPD diagnosis using spirometry were 73.4% and 89.0%, respectively. The relative effect of smoking cessation intervention with screening spirometry, presented as abstinence rate, was not statistically significant (risk ratio [RR], 1.21; 95% confidence interval [CI], 0.87-1.67) when all selected studies were pooled, but screening on smoking cessation was effective (RR, 1.58; 95% CI, 1.14-2.19) when limited to studies with smoking cessation programs that provided smoking cessation medicines or intensive counseling at public health centers or medical institutions. CONCLUSION: In this study, no direct evidence for the impact on health outcomes of screening asymptomatic adults for COPD was identified similar to the previous SR. Further research is necessary to confirm the benefits of COPD screening.

Phenotype of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype. METHODS: Patients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/µL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/µL). RESULTS: The prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) - 9.1%; group B (light smoker with low BEC) - 3.7%; group C (moderate to heavy smoker with high BEC) - 73.8%; and group D (moderate to heavy smoker with low BEC) - 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups. CONCLUSION: The prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.

Clinical Characteristics of Non-Smoking Chronic Obstructive Pulmonary Disease Patients: Findings from the KOCOSS Cohort.

Chronic obstructive pulmonary disease (COPD) has been regarded as a disease of smokers, but the prevalence of non-smoking COPD patients have been reported to be considerable. We investigated differences in clinical characteristics between smoking and non-smoking COPD patients. We used data from the Korea COPD Subgroup Study (KOCOSS) database, which is a multicenter cohort that recruits patients from 54 medical centres in Korea. Comprehensive comparisons of smoking and non-smoking COPD patients were performed based on general characteristics, exacerbations, symptom scores, radiological findings, and lung-function tests. Of the 2477 patients included in the study, 8.1% were non-smokers and 91.9% were smokers. Non-smoking COPD patients were more likely to be female and to have a higher body mass index and lower level of education. Non-smoking COPD patients had more comorbidities, including hypertension, osteoporosis, and gastroesophageal reflux disease, and experienced more respiratory and allergic diseases. No significant differences in exacerbation rates, symptom scores, or exercise capacity scores were observed between the two groups. Smoking COPD patients had more emphysematous lung according to the radiological findings, and non-smoking patients had more tuberculosis-destroyed lung and bronchiectasis. Lung-function testing revealed no significant difference in the forced expiratory capacity in 1 sec between the two groups, but smokers had more rapid lung-function decline in the 5 years of follow-up data. We found differences in general characteristics and radiological findings between smoking and non-smoking COPD patients. No significant differences in exacerbation or symptom scores were observed, but decline in lung function was less steep in non-smoking patients.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2053088 .

Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. OBJECTIVE: To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. METHODS: Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. RESULTS: In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03-12.9). CONCLUSION: Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.

Characteristics of Specialist-Diagnosed Asthma-COPD Overlap in Severe Asthma: Observations from the Korean Severe Asthma Registry (KoSAR).

BACKGROUND: While the clinical characteristics and outcomes of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the prevalence and features of ACO in patients with severe asthma are unclear. OBJECTIVES: Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry. METHODS: At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non-ACO groups, and the demographic and clinical characteristics of these two groups were compared. RESULTS: Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex- or current smokers (P < .001) compared with those in the non-ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non-ACO group. The ACO group used more inhaled long-acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006). CONCLUSION: Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.