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Abstract Background Air pollution, notably particulate matter (PM), significantly impacts chronic respiratory disease such chronic obstructive pulmonary disease (COPD). Although asthma-COPD overlap (ACO), considered one of the COPD etiotype, is associated with greater severity in both symptoms and outcomes, effects of PM exposure remain unclear. Thus, this study aimed to evaluate impact of PM on chronic airway disease animal models. Methods We established two distinct COPD etiotypes, cigarette smoking-related COPD (COPD-C) and COPD with asthma (COPD-A), using porcine pancreatic elastase (PPE) for COPD-C and a combination of PPE with ovalbumin for COPD-A. To reflect smoking influence, cigarette smoking extract was administered to both disease models. To assess impact of PM exposure, bronchoalveolar lavage fluid (BALF), proinflammatory cytokines, lung histology, and cellular damage mechanisms were analyzed. Results In the COPD-A model, cell counts and type 2 cytokines were elevated in BALF independent of PM exposure. All models exhibited increased lung inflammation and emphysema due to PM exposure. Expression levels of apoptosis-related protein B-cell lymphoma protein 2 (Bcl-2) associated X (Bax) showed an inclination to increase with PM exposure. In the COPD-A model, decreased expression of basal nuclear factor erythroid-derived 2-like 2 (Nrf-2) and increased production of reactive oxygen species (ROS) due to PM exposure were noted. Conclusion We developed two distinct models for the etiotypes of COPD and found increased vulnerability to cell damage in COPD-A after PM exposure. Moreover, the control group displayed escalated airway inflammation and emphysema due to PM exposure, substantiating the risk of respiratory diseases.

Abstract Background The representativeness of cohort studies compared to nationwide data is a major concern. This study evaluated the similarity and seasonality of causative respiratory viruses for chronic obstructive pulmonary disease (COPD) and asthma exacerbations between retrospective multicenter cohort study and nationwide data. Methods We compared data from the retrospective multicenter cohort study with Korean Influenza and Respiratory Surveillance System data between 2015 and 2018. Correlation, dynamic time warping (DTW), and seasonal autoregressive integrated moving average (SARIMA) analyses were performed. Results Spearman correlation coefficients [ρ] indicated very strong (respiratory syncytial virus [RSV] [ρ = 0.8458] and influenza virus [IFV] [ρ = 0.8272]), strong (human metapneumovirus [HMPV] [ρ = 0.7177] and parainfluenza virus [PIV] [ρ = 0.6742]), and moderate (rhinovirus [RV] [ρ = 0.5850] and human coronavirus [HCoV] [ρ = 0.5158]) correlations. DTW analyses showed moderate (PIV) and high (IFV, RSV, and HMPV) synchronicity between the two datasets, while RV and HCoV showed low synchronicity. SARIMA analyses revealed 12-month seasonality for IFV, RSV, PIV, and HMPV. The peak season was winter for RSV and IFV, spring to summer for PIV, and spring for HMPV. Conclusions This was the first study to report the synchronicity between a retrospective multicenter cohort study of viruses that can cause COPD or asthma exacerbations and nationwide surveillance system data.

Abstract Background Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC)

Abstract Background A sub-analysis of the Korean population in the LIBERTY ASTHMA QUEST trial (NCT02414854) revealed that dupilumab effectively treated severe uncontrolled asthma. This study aimed to assess the cost-effectiveness of add-on therapy with dupilumab to background therapy in patients ≥ 12 years of age with uncontrolled severe asthma compared to that of background therapy in South Korea. Methods The cost-effectiveness analysis was conducted using a Markov model over a lifetime from the Korean healthcare system perspective. Clinical efficacy and utility weights were obtained from post-hoc analyses of the Korean population in the QUEST trial. Data on the costs and treatment setting of exacerbation in a real-world setting were retrospectively collected using the administrative medical database from a single tertiary hospital. Results The base-case results indicated that add-on dupilumab therapy increases costs ($112,924 for add-on dupilumab versus $29,545 for background therapy alone). However, add-on dupilumab increased quality-adjusted life years (QALYs, 8.03 versus 3.93, respectively), with fewer events of severe exacerbations per patient compared to using the background therapy alone (17.920 versus 19.911, respectively). The incremental cost-effectiveness ratio was $20,325 per QALY. Various sensitivity analyses supported the robustness of the base-case results. Probabilistic sensitivity analysis showed that the probability of add-on dupilumab being cost-effective was 87% at a threshold willingness-to-pay of $26,718 (KRW 35 million) per QALY gained. Conclusions Dupilumab is cost-effective for adolescents and adults with uncontrolled severe asthma in South Korea. Our study provides evidence to support clinicians and policymakers in making informed decisions for severe asthma management.

Abstract 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

Abstract 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.

Exposure to fine particulate matter (PM2.5) and heavy metals (HMs) in the air is closely associated with the incidence and exacerbation of pulmonary fibrosis. Although the specific responses of alveolar epithelial cells (AECs) and lung fibroblasts to PM2.5 or HM exposure have been well defined, the cellular responses of lung fibroblasts to PM2.5 or HM exposure and the subsequent interactions with AECs remain poorly investigated. In this study, we demonstrated that human lung fibroblasts exposed to PM2.5 or lead (Pb) induced fibrotic changes and apoptosis in AECs. Lung fibroblasts exposed to PM2.5 induced fibrotic changes in AECs via a paracrine action. We further evaluated the detrimental effects of four HMs (cadmium, lead, arsenic, and manganese) present at the highest levels in the ambient air of South Korea, and investigated their paracrine effects on AECs. We found that long-term (14 passages) exposure to these HMs negatively affected the growth, migration, and survival of lung fibroblasts. Notably, manganese (Mn) significantly upregulated the expression of fibrotic markers with the activation of extracellular signal-regulated kinase (ERK) signaling in lung fibroblasts. However, treatment with conditioned medium (CM) collected from Mn-treated lung fibroblasts did not induce fibrotic changes in AECs. Interestingly, CM from Pb-treated lung fibroblasts significantly upregulated markers for fibrosis and apoptosis in AECs via activation of the ERK signaling pathway. These results suggest that understanding interactions between fibroblasts and AECs may provide useful strategies against PM or HM-induced injuries in alveolar tissue.

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

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

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Abstract Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic therapy. The aim of this study was to examine the prevalence of CKD and prescription status of pirfenidone in IPF patients and to analyze its impact on mortality. Data from the Korean National Health Insurance Service (NHIS) database between October 2015 and September 2021 were used. IPF and CKD were defined based on both International Classification of Diseases 10th Revision (ICD-10) codes and Rare Intractable Disease (RID) codes. The risk of mortality was assessed based on accompanying CKD with or without antifibrotic therapy. Among 5038 patients with IPF, 8.4% had comorbid CKD and 83.3% with CKD did not receive renal replacement therapy (RRT). Patients with IPF and CKD were older, predominantly male, and had more frequent comorbidities such as cardiovascular disease and diabetes mellitus than subjects without CKD. Pirfenidone was prescribed to 105 (24.6%) of 426 CKD patients, and 89.5% of them did not receive RRT. Pirfenidone was also prescribed to 775 (16.8%) of 4612 IPF patients without CKD. Significant difference was not found in all-cause mortality between the IPF patients with or without CKD regardless of pirfenidone treatment. The use of antifibrotics in IPF patients with CKD is limited due to CKD severity; however, evidence is lacking. Mortality did not increase with accompanying CKD regardless of antifibrotic use. Further research on IPF and CKD is needed.

Abstract 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.

Abstract 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.

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. Methods A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. Results More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. Conclusion Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3–5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

Abstract Introduction Analysis of the National Health Insurance data has been actively carried out for the purpose of academic research and establishing scientific evidences for health care service policy in asthma. However, there has been a limitation for the accuracy of the data extracted through conventional operational definition. In this study, we verified the accuracy of conventional operational definition of asthma, by applying it to a real hospital setting. And by using a machine learning technique, we established an appropriate operational definition that predicts asthma more accurately. Methods We extracted asthma patients using the conventional operational definition of asthma at Seoul St. Mary’s hospital and St. Paul’s hospital at the Catholic University of Korea between January 2017 and January 2018. Among these extracted patients of asthma, 10% of patients were randomly sampled. We verified the accuracy of the conventional operational definition for asthma by matching actual diagnosis through medical chart review. And then we operated machine learning approaches to predict asthma more accurately. Results A total of 4,235 patients with asthma were identified using a conventional asthma definition during the study period. Of these, 353 patients were collected. The patients of asthma were 56% of study population, 44% of patients were not asthma. The use of machine learning techniques improved the overall accuracy. The XGBoost prediction model for asthma diagnosis showed an accuracy of 87.1%, an AUC of 93.0%, sensitivity of 82.5%, and specificity of 97.9%. Major explanatory variable were ICS/LABA,LAMA and LTRA for proper diagnosis of asthma. Conclusions The conventional operational definition of asthma has limitation to extract true asthma patients in real world. Therefore, it is necessary to establish an accurate standardized operational definition of asthma. In this study, machine learning approach could be a good option for building a relevant operational definition in research using claims data.

Abstract Few studies have directly compared the incidence of pneumonia in patients on common chronic obstructive pulmonary disease (COPD) treatments such as long-acting muscarinic antagonists (LAMA) with those on inhaled corticosteroids and long-acting β2-agonist (ICS/LABA). Moreover, risk factors for pneumonia in COPD are still unclear. We aimed to compare the incidence of pneumonia in COPD patients on LAMA and those on ICS/LABA and explored the risk factors associated with pneumonia. This nationwide cohort study used Korean National Health Insurance claim data from January 2002 to April 2016. Patients who received COPD medication, either LAMA or ICS/LABA, with the COPD diagnostic code, were selected. We enrolled patients with good compliance (medication possession ratio ≥ 80%). The primary outcome was pneumonia in COPD patients initiating LAMA or ICS/LABA. We investigated the risk factors associated with pneumonia, including the sub-types of ICS treatments. After propensity score matching, the incidence rate per 1000 person-years of pneumonia was 93.96 for LAMA (n = 1003) and 136.42 for ICS/LABA (n = 1003) patients (p

Background: This study aimed to investigate the efficacy and safety of digital therapeutics (DTx), EASYBREATH, for pulmonary rehabilitation (PR) in patients with chronic respiratory diseases (CRDs). Materials and Methods: This prospective randomized controlled trial was conducted at multiple centers. Participants were randomly allocated 1:1 to the DTx group (DTxG), provided with DTx using EASYBREATH. The DTxG underwent an 8-week PR program with evaluations conducted at baseline, four weeks, and eight weeks. The control group (CG) underwent one PR session and was advised to exercise and undergo the same evaluation. The primary outcome was the change in six-minute walking distance (6MWD) over eight weeks, and secondary outcomes included changes in scores of Modified Medical Research Council (mMRC), chronic obstructive pulmonary disease assessment test (CAT), and St. George’s respiratory questionnaire (SGRQ). Results: The change in 6MWD after eight weeks demonstrated a significant difference between the DTxG and CG (57.68 m vs. 21.71 m, p = 0.0008). The change in mMRC scores (p = 0.0008), CAT scores (p < 0.0001), and total SGRQ scores (p = 0.0003) also showed a significant difference between the groups after eight weeks. Conclusions: EASYBREATH significantly improved exercise capacity, alleviated dyspnea, and enhanced the overall quality of life at eight weeks. EASYBREATH is a highly accessible, time-efficient, and effective treatment option for CRD with high compliance.

Abstract Background Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO. Methods We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system. Results Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase–associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model. Conclusion We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.

Abstract The effects of forced vital capacity (FVC) on clinical outcomes of asthma-chronic obstructive pulmonary diseases overlap (ACO) are still unknown. We conducted this study to examine the association of FVC on clinical outcomes in ACO. Data from the Korean COPD Subgroup Study cohort were analyzed. Patients who fulfilled the ACO criteria were included and grouped according to FVC changes, such as FVC-incline and FVC-decline. No significant differences were observed between the FVC-incline and FVC-decline groups in baseline clinical characteristics. In a year after, FVC-decline group experienced more moderate (47.1% vs. 36.8%, p = 0.02) and moderate-to-severe (49.8% vs. 39.6%, p = 0.03) acute exacerbations (AEs), compared to FVC-incline group. The frequency of moderate AEs (1.3 ± 2.1 vs. 0.9 ± 1.7, p = 0.03) and moderate-to-severe AEs (1.5 ± 2.5 vs. 1.1 ± 1.9, p = 0.04) were higher in the FVC-decline group than in the FVC-incline groups. After adjusting for confounding factors, FVC-decline group was associated with moderate AEs (odds ratio [OR] = 1.58; 95% confidence interval [CI] 1.02–2.44; p = 0.04), and moderate-to-severe AEs (OR = 1.56; 95% CI 1.01–2.41; p

Abstract 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.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation due to chronic airway inflammation and destruction of the alveolar structure from persistent exposure to oxidative stress. The body has various antioxidant mechanisms for efficiently coping with such oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) is a representative system. Dysregulation of the Nrf2-ARE pathway is responsible for the development and promotion of COPD. Furthermore, COPD severity is also closely related to this pathway. There has been a clinical impetus to use Nrf2 for diagnostic and therapeutic purposes. Therefore, in this work, we systematically reviewed the clinical significance of Nrf2 in COPD patients, and discuss the value of Nrf2 as a potential COPD biomarker.

Background We evaluated the effect of particulate matter (PM) and cigarette smoke extract (CSE) on bronchial epithelial cell survival, as well as oxidative stress and autophagy levels. Moreover, we aimed to assess the effect of the antioxidant N-acetylcysteine (NAC) on the adverse effects of PM and CSE exposure. Methods Normal human bronchial epithelial cells (BEAS-2B cells) were exposed to urban PM with or without CSE, after which cytotoxic effects, including oxidative stress and autophagy levels, were measured. After identifying the toxic effects of urban PM and CSE exposure, the effects of NAC treatment on cell damage were evaluated. Results Urban PM significantly decreased cell viability in a concentration-dependent manner, which was further aggravated by simultaneous treatment with CSE. Notably, pretreatment with NAC at 10 mM for 1 hour reversed the cytotoxic effects of PM and CSE co-exposure. Treatment with 1, 5, and 10 mM NAC was shown to decrease reactive oxygen species levels induced by exposure to both PM and CSE. Additionally, the autophagy response assessed via LC3B expression was increased by PM and CSE exposure, and this also attenuated by NAC treatment. Conclusion The toxic effects of PM and CSE co-exposure on human bronchial epithelial cells, including decreased cell viability and increased oxidative stress and autophagy levels, could be partly prevented by NAC treatment.

Abstract It is challenging to overcome difficult-to-treat asthma, and cell-based therapies are attracting increasing interest. We assessed the effects of mesenchymal stem cell (MSC) treatments using a murine model of chronic ovalbumin (OVA)-challenged asthma. We developed a murine model of chronic allergic asthma using OVA sensitization and challenge. Human adipose-derived MSCs (hADSCs) or human bone marrow-derived MSCs (hBMSCs) were administered. We measured the levels of resistin-like molecule-β (RELM-β). We also measured RELM-β in asthma patients and normal controls. OVA-challenged mice exhibited increased airway hyper-responsiveness, inflammation, and remodeling. hBMSC treatment remarkably decreased airway hyper-responsiveness but hADSC treatment did not. Both MSCs alleviated airway inflammation, but hBMSCs tended to have a more significant effect. hBMSC treatment reduced Th2-cytokine levels but hADSC treatment did not. Both treatments reduced airway remodeling. The RELM-β level decreased in the OVA-challenged control group, but increased in both treatment groups. We found that the serum level of RELM-β was lower in asthma patients than controls. MSC treatments alleviated the airway inflammation, hyper-responsiveness, and remodeling associated with chronic asthma. hBMSCs were more effective than hADSCs. The RELM-β levels increased in both treatment groups; the RELM-β level may serve as a biomarker of MSC treatment efficacy.

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 (FEV 1 )/forced vital capacity (FVC) ratio

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

Abstract With the increasing use of computed tomography, bronchiectasis has become a common finding in patients with chronic obstructive pulmonary disease (COPD). However, the clinical aspects and medical utilization of COPD with bronchiectasis (BE) remain unclear. We aimed to investigate the BE effect on prognosis and medical utilization in patients with COPD. Among 263,747 COPD patients, we excluded patients lacking chest X-ray, CT, or pulmonary function test codes and classified 2583 GOLD-C/D patients matched according to age, sex, and medical aid as having COPD-BE (447 [17.3%]) and COPD without BE (2136 [82.7%]). Patients with COPD-BE showed a higher rate of acute exacerbation requiring antibiotics than those without BE. Moreover, multivariable analysis showed that BE co-existence was a crucial factor for moderate-to-severe exacerbation (incidence rate ratio [IRR] 1.071; 95% CI 1.012–1.134; p = 0.019). Patients with COPD-BE had a significantly higher rate of exacerbations requiring antibiotics, as well as treatment cost and duration (meant as number of days using hospitalization plus outpatient appointment), than those with COPD without BE (52.64 ± 65.29 vs. 40.19 ± 50.02 days, p

Abstract 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.

Abstract 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

Background Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea. Methods A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement). Results The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers. Conclusion Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Background We evaluated the long-term effects of domiciliary noninvasive positive-pressure ventilation (NIPPV) used to treat patients with chronic obstructive pulmonary disease (COPD). Methods Databases were searched to identify randomized controlled trials of COPD with NIPPV for longer than 1 year. Mortality rates were the primary outcome in this meta-analysis. The eight trials included in this study comprised data from 913 patients. Results The mortality rates for the NIPPV and control groups were 29% (118/414) and 36% (151/419), suggesting a statistically significant difference (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.65–0.95). Mortality rates were reduced with NIPPV in four trials that included stable COPD patients. There was no difference in admission, acute exacerbation and quality of life between the NIPPV and control groups. There was no significant difference in withdrawal rates between the two groups (RR, 0.99; 95% CI, 0.72–1.36; p=0.94). Conclusion Maintaining long-term nocturnal NIPPV for more than 1 year, especially in patients with stable COPD, decreased the mortality rate, without increasing the withdrawal rate compared with long-term oxygen treatment.

Background Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. Results We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Background The effect of underlying chronic obstructive pulmonary disease (COPD) on coronavirus disease 2019 (COVID-19) during a pandemic is controversial. The purpose of this study was to examine the prognosis of COVID-19 according to the underlying COPD. Methods COVID-19 patients were assessed using nationwide health insurance data. Comorbidities were evaluated using the modified Charlson Comorbidity Index (mCCI) which excluded COPD from conventional CCI scores. Baseline characteristics were assessed. Univariable and multiple logistic and linear regression analyses were performed to determine effects of variables on clinical outcomes. Ages, sex, mCCI, socioeconomic status, and underlying COPD were selected as variables. Results COPD patients showed older age (71.3±11.6 years vs. 47.7±19.1 years, p

Background/Aims Hypoxemia in chronic obstructive pulmonary disease (COPD) leads to reduced ability to exercise, decreased quality of life, and, eventually, increased mortality. Home oxygen therapy in patients with severe COPD reduces distress symptoms and mortality rates. However, there have been few studies on physicians’ prescription behavior toward home oxygen therapy. Therefore, we investigated the respiratory specialists’ perspective on home oxygen therapy. Methods In this cross-sectional, study, a questionnaire was completed by 30 pulmonary specialists who worked in tertiary hospitals and prescribed home oxygen therapy. The questionnaire consisted of 28 items, including 15 items on oxygen prescription for outpatients, four for inpatients, and nine on service improvement. Results All physicians were prescribing less than 2 L/min of oxygen for either 24 (n = 10, 33.3%) or 15 hours (n = 9, 30.3%). All (n = 30) used pulse oximetry, 26 (86.7%) analyzed arterial blood gas. Thirteen physicians had imposed restrictions and recommended oxygen use only during exercise or sleep. Sixteen (53.3%) physicians were educating their patients about home oxygen therapy. Furthermore, physicians prescribed home oxygen to patients that did not fit the typical criteria for long-term oxygen therapy, with 30 prescribing it for acute relief and 17 for patients with borderline hypoxemia. Conclusions This study identified the prescription pattern of home oxygen therapy in Korea. Respiratory physicians prescribe home oxygen therapy to hypoxemic COPD patients for at least 15 hours/day, and at a rate of less than 2 L/min. More research is needed to provide evidence for establishing policies on oxygen therapy in COPD patients.

Abstract 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

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient’s quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Background The Korea National Health and Nutrition Examination Survey (KNHANES) is a well-designed survey to collect national data, which many researchers have used for their studies. In KNHANES, although portable spirometry was used, its reliability has not been verified. Methods We prospectively enrolled 58 participants from four Korean institutions. The participants were classified into normal pattern, obstructive pattern, and restrictive pattern groups according to their previous spirometry results. Lung function was estimated by conventional spirometry and portable spirometry, and the results were compared. Results The intraclass correlation coefficients of forced vital capacity (FVC) (coefficient, 9.993; 95% confidence interval [CI], 0.988–0.996), forced expiratory volume in 1 second (FEV1) (coefficient, 0.997; 95% CI, 0.995–0.998), FEV1/FVC ratio (coefficient, 0.995; 95% CI, 0.992–0.997), and forced expiratory flow at 25–75% (FEF25–75%; coefficient, 0.991; 95% CI, 0.984–0.994) were excellent (all p

Abstract Cigarette smoking is a risk factor of mortality and morbidity from various cancerous, respiratory, and myocardial diseases. Nicotine dependence is assessed based on the degree of physical dependence. We aimed to determine the clinical, socioeconomic and psychological factors associated with the smoking status and degree of nicotine dependence of smokers. From April 2009 to September 2010, we retrospectively collected data from 17,577 subjects aged ≥ 18 years who had undergone a general health examination at a health promotion center. The instruments used included the Fagerström Tolerance Questionnaire (FTQ), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Stress Response Inventory (SRI), and Alcohol Use Disorder Identification Test (AUDIT). Of the current smokers (N = 3946), 2345 (59%), 1154 (29%), and 447 (12%) had low, moderate, and high nicotine dependence, respectively. In multiple logistic analysis, predictors of high nicotine dependence were male sex (odds ratio [OR] 3.705, 95% confidence interval [CI] 1.997–6.945), older age (≥ 65 years) (OR 1.016, 95% CI 1.004–1.029), higher body mass index (BMI) (OR 1.048, 95% CI 1.018–1.078), diabetes (OR 1.870, 95% CI 1.251–2.794), single marital status (OR 1.575, 95% CI 1.186–2.092), lower education level (OR 1.887, 95% CI 1.463–2.433), and a higher stress level (OR 1.018, 95% CI 1.997–6.945). Thus, clinical, psychological, socioeconomic status including male, older age, higher BMI, diabetes, single marital status, lower education, and higher stress should be taken into consideration by promoting smoking cessation.

Abstract Background It is important to assess the prognosis of patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation of COPD (AECOPD). Recently, it was suggested that diffusing capacity of the lung for carbon monoxide (DLCO) should be added to multidimensional tools for assessing COPD. This study aimed to compare the DLCO and forced expiratory volume in one second (FEV1) to identify better prognostic factors for admitted patients with AECOPD. Methods We retrospectively analyzed 342 patients with AECOPD receiving inpatient treatment. We classified 342 severe AECOPD patients by severity of DLCO and FEV1 (≤ vs. > 50% predicted). We tested the association of FEV1 and DLCO with the following outcomes: in-hospital mortality, need for mechanical ventilation, need for intensive care unit (ICU) care. We analyzed the prognostic factors by multivariate analysis using logistic regression. In addition, we conducted a correlation analysis and receiver operating characteristic (ROC) curve analysis. Results In multivariate analyses, DLCO was associated with mortality (odds ratio = 4.408; 95% CI 1.070–18.167; P = 0.040) and need for mechanical ventilation (odds ratio = 2.855; 95% CI 1.216–6.704; P = 0.016) and ICU care (odds ratios = 2.685; 95% CI 1.290–5.590; P = 0.008). However, there was no statistically significant difference in mortality rate when using FEV1 classification (P = 0.075). In multivariate linear regression analyses, DLCO (B = − 0.542 ± 0.121, P

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

Background/Aims Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than 0.7 using spirometry is the golden standard to diagnose airf low limitation of chronic obstructive pulmonary disease (COPD). Recently, measuring FEV6 has been suggested as an alternative to measure FVC. Studies about the cut-off value for FEV1/FEV6 to diagnose airflow limitation have shown variable results, with values between 0.7 and 0.8. The purpose of this study was to determine the best cut-off value of FEV1/FEV6 to detect airflow limitation using handheld spirometry. Methods We recruited subjects over 40 years of age with smoking history over 10 pack-years. Participants underwent measurements with both handheld spirometry and conventional spirometry. We calculated the sensitivity and specificity of the value of FEV1/FEV6 using receiver-operating characteristic (ROC) curve analysis to obtain the diagnostic accuracy of handheld spirometry to detect airflow limitation. Results A total of 290 subjects were enrolled. Their mean age and smoking amount were 63.1 years and 31.6 pack-years, respectively. According to our ROC curve analysis, when FEV1/FEV6 ratio was 73%, sensitivity and specificity were the maximum and the area under the ROC curve was 0.93, showing an excellent diagnostic accuracy. Sensitivity, specificity, positive predictive value, and negative predictive value were 86.7%, 89.7%, 88.0%, and 88.5%, respectively. Participants with FEV1/FEV6 ≤ 73% had lower FEV1 predicted value compared to those with FEV1/FEV6 > 73% (65.4% vs. 86.5%, p < 0.001). Conclusions In summary, we demonstrate that the value of 73% in FEV1/FEV6 using handheld spirometry has the best sensitivity and specificity to detect airflow limitation in subjects with risk of COPD.

Background/Aims Current asthma therapies remain unsatisfactory for controlling airway remodelling in asthma. MicroRNA-21 is a key player in asthma pathogenesis, but the molecular mechanisms underlying its effects on airway remodelling are not completely understood. We investigated the effects of inhibition of microRNA-21 on allergic airway inflammation and remodelling. Methods Female BALB/c mice were divided into four groups: control, ovalbumin-sensitized and -challenged for 3 months, microRNA-negative control-treated ovalbumin-treated, and microRNA-21 inhibitor-treated ovalbumin-treated groups. Parameters related to airway remodelling, cytokine production, airway inflammation, and airway hyperresponsiveness were compared between groups. Human bronchial smooth muscle cells were used in a mechanism study. Results In this asthma model, ovalbumin-sensitized and -challenged mice exhibited allergic airway inflammation and airway remodelling. MicroRNA-21 inhibitor-treated mice had fewer inflammatory cells, lower TH2 cytokine production, and suppressed parameters related to remodelling such as goblet cell hyperplasia, collagen deposition, hydroxyproline content, and expression of smooth muscle actin. Inhibition of microRNA-21 decreased transforming growth factor β1 expression and induced Smad7 expression in lung tissue. In human bronchial smooth muscle cells stimulated with transforming growth factor β1, microRNA-21 inhibition upregulated Smad7 expression and decreased markers of airway remodelling. Conclusions Inhibition of microRNA-21 had both anti-inflammatory and anti-remodelling effects in this model of ovalbumin-induced chronic asthma. Our data suggest that the microRNA-21–transforming growth factor β1–Smad7 axis modulates the pathogenesis of ovalbumin-induced chronic asthma and in human bronchial smooth muscle cells. MicroRNA-21 inhibitors may be a novel therapeutic target in patients with allergic asthma, especially those with airway remodelling.

Background Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily in COPD patients in Korea. Methods This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity

Abstract Background Blood eosinophil count may predict treatment response in patients with chronic obstructive pulmonary disease (COPD) during acute exacerbations (AE). However, the ability and thresholds of blood eosinophil counts in stable status to predict eosinophilic AECOPD have not been completely investigated. Methods This was a retrospective multicenter study performed January 2010 to December 2014. COPD subjects hospitalized with exacerbations, were included. Blood samples were obtained at the time of AE and stable disease at outpatient clinic before or after admission. We identified a blood eosinophil count cut-off point at stable COPD, either taken as a percentage or as absolute value, for identification of eosinophilic exacerbation. Results There was significant positive correlation of eosinophil counts between stable COPD and AECOPD. The best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation based on blood eosinophil count ≥ 2% was 300 cells/µL (area under the ROC curve [AUC] 0.614, P = 0.001, 39% sensitivity, 83.8% specificity). When the eosinophilic COPD exacerbation was based on blood eosinophil count ≥ 300 cells/µL, the best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation was also 300 cells/uL (AUC 0.634, P = 0.046, 45.8% sensitivity, 80.9% specificity). Conclusions We demonstrated association between blood eosinophil counts at stable COPD and those with AECOPD. The thresholds of blood counts at stable COPD to predict eosinophilic exacerbations was 300 cells/µL. Further and prospective studies in other populations should validate our results.

Abstract Background The role of interleukin (IL)-33 in patients with chronic obstructive pulmonary disease (COPD) has not been well elucidated. The aim of this study is to analyze the association between plasma IL-33 level and acute exacerbation of COPD. Methods Plasma IL-33 was measured in 62 COPD patients during their stable state. Patients were prospectively followed up for 1 year. The expression of IL-33 was measured in lung tissue obtained from 38 patients who underwent surgery. Results The number of exacerbations was significantly higher in the high plasma IL-33 group compared with the low plasma IL-33 group. On Poisson regression analysis, high plasma IL-33 was associated with increased risk of exacerbation (incidence rate ratio = 2.166, P = 0.043). The expression of IL-33 in the lung was higher in COPD patients than in controls. The expression of IL-33 was significantly correlated with smoking pack years (R = 0.45, P

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.

Background and AimsAir trapping is a predictive index for a decline in lung function and mortality in patients with chronic obstructive pulmonary disease (COPD). However, the role of air trapping in COPD exacerbation has rarely been studied. Therefore, this study aimed to investigate the impact of air trapping as a continuous parameter on COPD exacerbation.Materials and MethodsTo evaluate air trapping, we identified the ratio of residual volume (RV) to total lung capacity (TLC) of patients with COPD from the Korean COPD Subgroup Study (KOCOSS) cohort, which is a multicenter-based, prospective, consecutive cohort in Korea. The primary outcome was a development of COPD exacerbation during 3 years of follow-up.ResultsOf 2,181 participants, 902 patients measured the RV/TLC ratio in the baseline enrollment, and 410 were evaluated for assessing the development of COPD exacerbation. Of 410 patients, the rate of moderate to severe exacerbation and severe exacerbation was 70.7% and 25.9%. A 10% increase of RV/TLC ratio increased the risk of the moderate to severe exacerbation by 35% and severe exacerbation by 36%. In subgroup analysis, an interaction effect between triple inhaled therapy and the RV/TLC ratio for severe exacerbation nullified the association between the RV/TLC ratio and severe exacerbation (p for interaction = 0.002).ConclusionsIn this prospective cohort study, we found that air trapping (representing RV/TLC ratio as a continuous parameter) showed an association with an increased risk of COPD exacerbation, particularly in patients who have not undergone triple inhaler therapy.