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.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To 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. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This 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. Results: Overall, 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 <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

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.

Efficacy of Digital Therapeutics for Pulmonary Rehabilitation: A Multi-Center, Randomized Controlled Trial.

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.

Differential response to roflumilast in patients with chronic obstructive pulmonary disease: real-world evidence.

Background: Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD. Methods: A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period. The primary outcome was to estimate the ratio of hazard ratio (RHR) of roflumilast for moderate-to-severe exacerbation in prespecified subgroups. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) for moderate-to-severe exacerbations. Results: Among 823,862 patients with COPD, 0.6% used roflumilast. The adjusted HR of roflumilast for moderate-to-severe exacerbations was reduced when treated for ≥3 months (RHR =0.558). Interaction effects of the variables on the HR of roflumilast for moderate-to-severe exacerbation were identified. The adjusted HR of roflumilast for moderate-to-severe exacerbation was significantly reduced in several subgroups: older age (65 years > age ≥50 years, RHR =0.838; age ≥65 years, RHR =0.818), a higher Charlson comorbidity index (1, RHR =0.832; 2, RHR =0.798; ≥3, RHR =0.790), history of exacerbation (RHR =0.886), bronchiectasis (RHR =0.774), chronic bronchitis (RHR =0.793), inhaled therapy [mono-bronchodilator, RHR =0.824; inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), RHR =0.591; LABA/long-acting muscarinic antagonist (LAMA), RHR =0.822; ICS/LABA/LAMA, RHR =0.570], methylxanthine (RHR =0.853), and statin (RHR =0.888). Conclusions: The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD. Personalised approaches to roflumilast based on clinical phenotypes would be effective for COPD.

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbations rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients ≥ 18 years of age who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naïve model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

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.

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.

Human Pluripotent Stem Cell-Derived Alveolar Organoids: Cellular Heterogeneity and Maturity.

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.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

BACKGROUND: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. OBJECTIVE: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. METHODS: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) between May 2017 and January 2023. Change in 4 asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to 1 year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and nonresponders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/y; asthma control: well controlled to uncontrolled; LTOCS: 0 to >30 mg/d; percent-predicted forced expiratory volume in 1 second [ppFEV1]: <50% to ≥80%). RESULTS: Percentage of biologic responders (ie, those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2% to 90.0% for exacerbation rate, 46.3% to 52.3% for asthma control, 31.1% to 58.5% for LTOCS daily dose, and 35.8% to 50.6% for ppFEV1. The proportion of patients having improvement post-biologic tended to be greater for anti-IL-5/5R compared with for anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. CONCLUSION: Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multidimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies. TRIAL REGISTRATION: The ISAR database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization studies (ENCEPP/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EUPAS38288) and with all applicable local and international laws and regulation, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=38289). Governance was provided by ADEPT (registration number: ADEPT1220).

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

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

Long-term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography and laboratory analyses every 6 months for 5 years. Radiological findings were categorized based on the Lugano classification as complete response (CR), partial response, stable disease (SD), or progressive disease. RESULTS: Initial treatment included observation (n=2), surgical resection (n=6), or systemic chemotherapy (n=34). Patients treated surgically had localized disease and achieved initial and long-term CR. Of the 34 patients who underwent chemotherapy, 30 achieved CR, 2 achieved SD, and 2 died. Overall and progression-free survival (PFS) rates were 93.9% and 54.3%, respectively. Multivariate analysis indicated that PFS was lower in patients with modified Ann Arbor stage III-IV lymphoma and those who did not achieve CR. CONCLUSIONS: Optimized treatment based on anatomical location, pulmonary function, and disease stage can improve long-term survival in patients with pulmonary MALT lymphoma.

Effects of comorbid chronic kidney disease on mortality in idiopathic pulmonary fibrosis patients and influence of pirfenidone.

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.

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

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

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

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

Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

The Complex Association between COPD and COVID-19.

Chronic obstructive pulmonary disease (COPD) is significant cause of morbidity and mortality worldwide. There is mounting evidence suggesting that COPD patients are at increased risk of severe COVID-19 outcomes; however, it remains unclear whether they are more susceptible to acquiring SARS-CoV-2 infection. In this comprehensive review, we aim to provide an up-to-date perspective of the intricate relationship between COPD and COVID-19. We conducted a thorough review of the literature to examine the evidence regarding the susceptibility of COPD patients to COVID-19 infection and the severity of their disease outcomes. While most studies have found that pre-existing COPD is associated with worse COVID-19 outcomes, some have yielded conflicting results. We also discuss confounding factors such as cigarette smoking, inhaled corticosteroids, and socioeconomic and genetic factors that may influence this association. Furthermore, we review acute COVID-19 management, treatment, rehabilitation, and recovery in COPD patients and how public health measures impact their care. In conclusion, while the association between COPD and COVID-19 is complex and requires further investigation, this review highlights the need for careful management of COPD patients during the pandemic to minimize the risk of severe COVID-19 outcomes.

The burden of systemic corticosteroid use in asthma management in Asia.

For most patients, asthma can be effectively managed using inhaled medications. However, patients who have severe and/or uncontrolled asthma, or who experience exacerbations, may require systemic corticosteroids (SCSs) to maintain asthma control. Although SCS are highly effective in this regard, even modest exposure to these medications can increase the risk for long-term, adverse health outcomes, such as type 2 diabetes, renal impairment, cardiovascular disease and overall mortality. Clinical and real-world data from studies investigating asthma severity, control and treatment practices around the globe have suggested that SCS are overused in asthma management, adding to the already substantial healthcare burden experienced by patients. Throughout Asia, although data on asthma severity, control and SCS usage are limited and vary widely among countries, available data strongly suggest a pattern of overuse consistent with the broader global trend. Coordinated changes at the patient, provider, institutional and policy levels, such as increasing disease awareness, promoting better adherence to treatment guidelines and increasing availability of safe and effective alternatives to SCS, are likely necessary to reduce the SCS burden for patients with asthma in Asia.