Clinical characteristics of chronic obstructive pulmonary disease patients with superoptimal peak inspiratory flow rate.

Characteristics of chronic obstructive pulmonary disease (COPD) patients with superoptimal peak inspiratory flow rates (PIFR) has not been thoroughly investigated. This study aimed to compare the characteristics between COPD patients with superoptimal PIFR and those with optimal and sub-optimal PIFR. PIFR was measured using In-Check DIAL G16 and categorized into sub-optimal (PIFR lower than that required by the patient's device), optimal, and superoptimal (peak PIFR ≥ 90 L/min). Considering COPD patients with sub-optimal PIFR as the reference group, analyses were performed to identify PIFR-related factors. Subgroup analysis was performed according to the forced expiratory volume in 1 s (FEV1) % of the predicted value (%pred). Among 444 post-bronchodilator-confirmed COPD patients from seven tertiary hospitals in South Korea, 98, 223, and 123 were classified into the sub-optimal, optimal, and superoptimal PIFR groups, respectively. The superoptimal PIFR group were younger, had an increased proportion of males, a higher body mass index, lowest number of comorbidities and less frequent exacerbation in the previous year, as well as the highest forced vital capacity %pred. The adjusted odds ratio for frequent exacerbation in the previous year was lower in the superoptimal PIFR group than in the sub-optimal PIFR group and was more pronounced in patients with an FEV1%pred of < 70%. COPD patients with superoptimal PIFR have clinical characteristics different from those patients with the sub-optimal and optimal PIFR. Having a high inspiratory flow may be a favorable trait in COPD.

Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial.

BACKGROUND: Acute bronchitis is the most common respiratory disease. Mixture of Ivy Leaf Extract and Coptidis rhizome syrup has shown good treatment efficacy against chronic bronchitis and acute respiratory infections. This study aimed to evaluate the efficacy and safety of Mixture of Ivy Leaf Extract and Coptidis rhizome compared with those of Pelargonium sidoides extract, for the treatment of acute bronchitis. METHODS: We performed a multicenter, randomized, double-blind, active-controlled, parallel phase III study in 220 patients with acute bronchitis. The participants were offered either Mixture of Ivy Leaf Extract and Coptidis rhizome syrup (AGS) and placebo of P. sidoides tablet or placebo syrup and active tablet of P. sidoides (AGU) for 7 days. The primary endpoint was the change in the Bronchitis Severity Score (BSS) from the baseline visit (visit 2) to day 7 (visit 3). RESULTS: For the primary outcome, there was no significant difference in the change of total BSS between visits 2 and 3 (-4.10 ± 1.93 vs. -4.24 ± 1.85, p = 0.5125), and since the upper limit of the confidence interval (1.00) was smaller than the predetermined non-inferiority margin (1.17), it was confirmed that the AGS group was non-inferior to the AGU group. The changes in each symptom in the BSS between visits 2 and 3 also showed no significant differences. The overall improvement rate measured by the investigator (91.7 vs. 89.7%; p = 0.3506) and the satisfaction rate of the participants at visit 3 also showed no significant differences (97.2 vs. 94.4%; p = 0.4388). Regarding safety issues, adverse reactions were noted in both groups similarly, with no serious adverse events (4.55 vs. 3.64%, p > 0.999). CONCLUSION: Mixture of Ivy Leaf Extract and Coptidis rhizome syrup is as effective and safe as P. sidoides in controlling symptoms of acute bronchitis.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

PURPOSE: Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. METHODS: We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. RESULTS: Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). CONCLUSIONS: SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

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.

Prevalences and Interrelationships of Post COVID-19 Fatigue, Sleep Disturbances, and Depression in Healthy Young and Middle-Aged Adults.

Background: An evaluation of the persistence of symptoms following COVID-19 in economically active young and middle-aged adults is crucial due to its significant socioeconomic impact resulting from compromised work performance. Methods: A prospective, multicenter study at 12 South Korean hospitals from January to December 2022 involved telephone interviews along with validated questionnaires. Results: Among 696 participants with a median age of 32 and no prior diagnoses, 30% of participants experienced persistent fatigue, while 21.4% suffered from sleep disturbance at 6 months following infection. Additionally, approximately 25% of the participants exhibited depression that endured for up to 6 months. Symptomatic individuals at 3 months exhibited a significantly higher prevalence of persistent fatigue, sleep disturbances, and depression at 6 months compared to those who remained asymptomatic. Notably, sleep disturbance and persistent fatigue at 3 months emerged as significant independent predictors of the presence of depression at 6 months. Conclusions: Even among young and middle-aged healthy adults, prolonged fatigue, sleep disturbance, and depression exhibit a significant prevalence and persisted for up to 6 months. Therefore, implementing a workplace management protocol for these symptoms is essential to mitigate the socioeconomic burden caused by the impairment of work efficiency.

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.

Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR).

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.

Application of the Lancet Commission COPD classification to COPD Cohort Population in South Korea.

The Lancet Commissions on COPD recommended a new classification based on five main risk factors. Patients with COPD were prospectively enrolled in a Korean COPD subgroup study cohort between April 2012 and June 2022. Patients were classified according to the etiologies (Type 1: Genetically determined (COPD-G), Type 2: Abnormal lung development (COPD-D), Type 3: Infections (COPD-I), Type 4: Cigarette smoking (COPD-C), Type 5: Biomass and pollution (COPD-P)). The database enrolled 3476 patients. Among 3392 patients, 52 (2 %), 1339 (39 %), 2930 (86 %), and 2221 (65 %) were compatible with type 2 (COPD-D), 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Most patients (71 %, 2405) had multiple risk factors contributing to their COPD. However, 93, 712, and 182 patients had only type 3 (COPD-I), 4 (COPD-C), and 5 (COPD-P), respectively. Type 3 (COPD-I) only patients were significantly younger, more often female, and had lower lung function. Both the rate and frequency of severe exacerbations were significantly higher in type 3 (COPD-I) only patients (p = 0.038 and p = 0.048, respectively). Compared with type 5 (COPD-P) only, type 3 (COPD-I) only was significantly associated with the risk of severe exacerbation (Odds ratio, 5.7 [95 % CI, 1.0-32.4]; P = 0.049, incident rate ratio, 8.7 [95 % CI, 1.7-44.0]; P = 0.009). Many patients were affected by multiple factors. Therefore, it is important to consider not only smoking history, but also other potential risk factors when evaluating patients with COPD. Further research is needed to explore the implications of this new COPD classification system for clinical practice and treatment strategies.

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.

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.

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.

Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

Background: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Short-acting ß2-agonist prescriptions in patients with asthma: findings from the South Korean cohort of SABINA III.

BACKGROUND/AIMS: Despite short-acting ß2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study. METHODS: This study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms. RESULTS: Data from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting ß2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation. CONCLUSION: SABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.

Pulmonary Rehabilitation Is Associated With Decreased Exacerbation and Mortality in Patients With COPD: A Nationwide Korean Study.

BACKGROUND: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019. RESEARCH QUESTION: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality? STUDY DESIGN AND METHODS: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed. RESULTS: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality. INTERPRETATION: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal.

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.