International Journal Of Chronic Obstructive Pulmonary Disease[JOURNAL]
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200 papers
Association Between Subsegmental Dosing Accuracy and Outcomes of Bronchoscopic Thermal Vapor Ablation: An Exploratory Retrospective Study in Severe Heterogeneous Emphysema.
Yang H, Chen S, Zheng X … +6 more , Cui N, Xie F, Hou H, Ye L, Herth FJF, Sun J
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41878299 · Full text
PURPOSE: Bronchoscopic thermal vapor ablation (BTVA) is a minimally invasive treatment for severe emphysema. However, the treatment doses are typically generated at the segmental level. In specific cases, treatment needs...
PURPOSE: Bronchoscopic thermal vapor ablation (BTVA) is a minimally invasive treatment for severe emphysema. However, the treatment doses are typically generated at the segmental level. In specific cases, treatment needs to be conducted at the subsegmental level, and the proportion can only be roughly allocated based on CT image review, potentially leading to dose mismatch. This retrospective exploratory study investigated the relationship between subsegmental dose accuracy (theoretical-to-actual matching) and clinical outcomes following BTVA. METHODS: Patients who underwent BTVA at the Shanghai Chest Hospital between 2023 and 2024 were analyzed. Subsegmental theoretical doses (BroncQCT software) were compared to previously administered actual treatment doses. Dose matching was defined as: 1) segmental treatments were presumed matched (uniform vapor assumption), 2) subsegmental treatments required ≤10% deviation between actual and theoretical dose ratios (|Actual ratio - Theoretical ratio| × 100%). Patients with >10% deviation or BroncQCT-identified nontarget subsegments were unmatched. Clinical parameters at 1, 3, 6, and 12 months after single treatment were compared. RESULTS: Among 21 patients (15 matched, 6 unmatched), the mean changes in FEV for the overall cohort were +70mL at 1 month (n = 19, = 0.018), +90mL at 3 months (n = 14, = 0.056), and +130mL at 6 months (n = 8, = 0.015). The matched group demonstrated superior median increases compared to unmatched patients (+150mL [n = 9] vs +10mL [n = 5]; = 0.012) at 3 months where between-group differences were maximal. Similar trends were observed at 1 month (median +110mL [n = 14] vs 0mL [n = 5]; = 0.044) and 6 months (median +150mL [n = 5] vs +60mL [n = 3]; = 0.036). Adverse events (including two late deaths in comorbid patients) were documented, though small sample sizes prevent definitive safety conclusions. CONCLUSION: This exploratory study found that subsegmental dose matching was associated with greater FEV changes after BTVA. These hypothesis-generating findings require prospective validation in a randomized controlled trial (NCT06152107).
Mechanisms, Efficacy, Safety, and Pharmacoeconomics of Low-Dose, Long-Term Macrolide Antibiotics in the Treatment of Chronic Obstructive Pulmonary Disease: A Review.
Wu J, Wu D, Wang H … +2 more , Liu J, Chen Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41878298 · Full text
Chronic Obstructive Pulmonary Disease (COPD) is usually associated with abnormal airways and/or alveoli caused by exposure to toxic particles or gases. In addition to their traditional anti-infective effects, macrolide a...
Chronic Obstructive Pulmonary Disease (COPD) is usually associated with abnormal airways and/or alveoli caused by exposure to toxic particles or gases. In addition to their traditional anti-infective effects, macrolide antibiotics, when administered for long courses, may improve respiratory function, clinical outcomes, and quality of life in COPD patients, as well as reduce the frequency of acute exacerbations of COPD. For example, continuous azithromycin treatment for 1 year can reduce the annual frequency of acute exacerbations from 1.83 to 1.48 episodes, making it of great value in the treatment of COPD. However, macrolide antibiotics have potential adverse drug reactions, such as cardiotoxicity, diarrhea, and hearing impairment. Long-term use can also induce antibiotic resistance, which limits their widespread application. This article reviews the research progress on the mechanism of action, clinical efficacy, safety, and pharmacoeconomics of macrolide antibiotics in the treatment of COPD, aiming to provide a theoretical basis for optimizing individualized treatment strategies for COPD. For patients with frequent acute exacerbations or severe COPD, long-term treatment with azithromycin (500 mg, three times a week) is recommended; for patients with comorbid cardiovascular disease risks, electrocardiographic monitoring and risk assessment before treatment are suggested. Elderly patients or those on long-term medication need regular hearing tests.
The Remote Assessment of Physical Capacities of Patients with COPD, Feasibility and Learning Effect of the 5-Repetition Sit-to-Stand Test (5STS).
Moine E, Oliver N, Alexandre F … +4 more , Molinier V, Barbaste F, Hayot M, Heraud N
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41878297 · Full text
PURPOSE: With the rise of telehealth and telemonitoring respiratory chronic diseases, having a simple and reliable remote physical capacity assessment test is an important issue. The 5-repetition sit-to-stand test (5STS)...
PURPOSE: With the rise of telehealth and telemonitoring respiratory chronic diseases, having a simple and reliable remote physical capacity assessment test is an important issue. The 5-repetition sit-to-stand test (5STS) is a good candidate, but two aspects must be studied before considering its remote implementation, the assessment of a learning effect (LE) which conditions administration and interpretation of the test, and its feasibility via videoconference. PATIENTS AND METHODS: 40 stable patients with COPD were enrolled. From home, they performed 5STS tests during three visits (V1-V3) of five trials (T1-T5), each with a 5-min rest period. V2 took place 24-48h after V1 and V3 took place one month later. To assess remote feasibility, reasons for non-inclusion related to digital technology use, connection failures, adverse events, and patient satisfaction were recorded. LE was assessed by timing the 5STS tests performed at each visit and corresponds to an improvement in performance over repeated trials. RESULTS: No adverse events were reported. 19% of patients were not enrolled due to a hardware issue or insufficient computer skills. 3% of visits were cancelled due to connection/camera failure. Test acceptability showed an overall satisfaction rate of 96%. Repeatability was excellent with ICC [CI95] of 0.91 [0.85-0.95] at V1; 0.98 [0.96-0.99] at V2; and 0.95 [0.91-0.97] at V3. The smallest detectable change at 95% was 0.99 seconds. Friedman ANOVA of V1 confirmed a LE, with significant differences between the first trial (V1T1) and V1T3, V1T4 and V1T5, and between V1T2 and V1T5 (all p<0.01). The median difference between V1T1 and V1T5 was -1.50 [-2.09/-0.81] seconds. Inter-visit comparison between V1 and V2 showed no difference between V1T5 and any of the trials in V2, confirming a stabilisation of LE after five trials. CONCLUSION: The remote 5STS is a feasible, safe, and reliable test. Performing five trials is essential to monitor the LE and to avoid underestimating initial physical condition of COPD patients at the start of an exercise training programme. TRIAL REGISTRATION: NCT05852821.
Inverse Association Between Triglyceride-Glucose Index and Ischemic Stroke in Hospitalized Patients with Chronic Obstructive Pulmonary Disease and Atrial Fibrillation: A Retrospective Analysis.
Chen S, Luo C, You C … +4 more , Xiong Y, Ye X, Tang Y, Zhang X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868727 · Full text
PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) face elevated ischemic stroke (IS) risk. This study assessed the triglyceride-glucose (TyG) index as a metabolic marker for...
PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) face elevated ischemic stroke (IS) risk. This study assessed the triglyceride-glucose (TyG) index as a metabolic marker for IS risk in this population. PATIENTS AND METHODS: This retrospective analysis included 710 hospitalized patients with COPD and AF (2014-2024). The TyG index (ln[fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]) measured at admission was the exposure; new-onset IS occurring during the index hospitalization (median duration: 9 days, IQR: 6-13) was the outcome. Univariate and multivariate logistic regression (adjusting for age, sex, smoking, blood pressure, diabetes, lipids, prior stroke) identified associations. Nonlinearity was assessed using generalized additive models (GAM). Predictive performance was evaluated via ROC analysis (AUC). RESULTS: IS occurred in 32 patients (4.5%). Unexpectedly, and in contrast to findings in the general population, higher TyG index was associated with lower IS risk in univariate analysis (OR=0.49, 95% CI:0.26-0.94). After full adjustment, each unit increase in TyG index was associated with lower IS risk (aOR=0.24, 95% CI:0.10-0.57, =0.001). However, the wide confidence interval and limited events (n=32) indicate this large effect estimate should be interpreted cautiously, as it may reflect statistical instability. The finding suggests a potential metabolic paradox in this population. GAM confirmed a linear inverse relationship after adjusting for stroke history (OR=0.50, 95% CI:0.30-0.90, P=0.032). The TyG index predicted IS with an AUC of 0.614 (95% CI:0.513-0.715). CONCLUSION: Contrary to observations in the general population, in hospitalized COPD and AF patients, a higher TyG index was associated with lower short-term ischemic stroke risk. However, this inverse association could reflect either a true inverse metabolic relationship or reverse causality whereby low TyG marks disease severity (malnutrition, poor metabolic reserve, chronic inflammation). Lack of comprehensive disease severity and nutritional assessments limits causal inference. The TyG index may serve as a potential biomarker in hospitalized patients, but population-based studies are essential to address selection bias.
Evaluating Arrhythmia Risk in Patients with Chronic Obstructive Pulmonary Disease Treated with Aclidinium/Formoterol Fumarate and Other Inhaled Bronchodilators: A Post-Authorization Safety Study.
Rebordosa C, Aguado J, Bartsch J … +7 more , Saigi-Morgui N, Carsin AE, Garcia-Esteban R, Ignatova E, Freedman D, Perez-Gutthann S, Rivero-Ferrer E
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868726 · Full text
PURPOSE: A post-authorization safety study program examined the cardiovascular safety of the long-acting muscarinic antagonist (LAMA) aclidinium bromide monotherapy and the LAMA/long-acting β-agonist (LABA) aclidinium br...
PURPOSE: A post-authorization safety study program examined the cardiovascular safety of the long-acting muscarinic antagonist (LAMA) aclidinium bromide monotherapy and the LAMA/long-acting β-agonist (LABA) aclidinium bromide/formoterol fumarate. We assessed frequency and risk of any cardiac arrhythmias (CA), atrial fibrillation (AF), and serious ventricular arrhythmias (SVA) in aclidinium and aclidinium/formoterol users. PATIENTS AND METHODS: This population-based cohort study included adults with chronic obstructive pulmonary disease (COPD) initiating COPD medications in the UK Clinical Practice Research Datalink Aurum database (Jan 2015-Mar 2021). CA, AF, and SVA incidence rate ratios (IRR) were estimated using Poisson regression models for continuous current users initiating aclidinium and aclidinium/formoterol versus LABA, and during the first episode of current single use for aclidinium versus LAMA and aclidinium/formoterol versus LAMA/LABA, adjusting for clinically relevant covariables. RESULTS: The study included a total of 248,148 initiators. For CA and AF, respectively, adjusted IRRs (95% confidence intervals [CIs]) ranged from 0.98 (0.69-1.41) for LAMA/LABA to 2.08 (1.36-3.18) for aclidinium/formoterol and from 0.83 (0.55-1.24) for LAMA/LABA to 1.85 (1.15-3.00) for aclidinium/formoterol versus current LABA use. For current single use (first episode), adjusted IRRs (95% CIs) for CA and AF were 1.46 (0.93-2.29) and 1.57 (0.94-2.62) for aclidinium versus other LAMAs, and 2.15 (1.33-3.49) and 1.79 (0.96-3.33) for aclidinium/formoterol versus LAMA/LABA, respectively. There were few SVA events. CONCLUSION: CA and AF risks were increased for most study medications compared with LABA. Increased risks of CA and AF for several medications relative to LABA, LAMA, or LAMA/LABA may be driven by differences in baseline characteristics (eg, COPD severity).
Evaluation of Clinical Characteristics and Lung Function Trajectories in Young COPD Patients Within the General Population.
Nam JH, Rhee CK, Jo YS … +5 more , Kim S, Kim YS, Kim SH, Kim KH, Choi JY
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868725 · Full text
PURPOSE: Young chronic obstructive pulmonary disease (COPD), distinct from COPD in older individuals, often remains underdiagnosed despite its potential for early interventions. This study aimed to identify the character...
PURPOSE: Young chronic obstructive pulmonary disease (COPD), distinct from COPD in older individuals, often remains underdiagnosed despite its potential for early interventions. This study aimed to identify the characteristics of young COPD patients and the patterns of lung function trajectory. PATIENTS AND METHODS: This study was based on a large community-based cohort database in Korea. Young COPD was defined as COPD diagnosed in patients aged ≤ 50 years. We analyzed the clinical characteristics and lung function changes over 12 years, comparing young and old COPD patients. RESULTS: Among the 9,577 patients enrolled in this study, 815 (8.5%) were diagnosed with COPD. The young COPD group had a higher proportion of females, never-smokers and a higher body mass index (BMI), compared to the older COPD group. The prevalence of young COPD increased from 117 (3.64%) to 334 (6.88%) according to the lower limit of normal (LLN) criteria. Analysis of lung function over 12 years revealed that the rate of decline in FEV1 (L), FEF25-75% (L), and FEV1/FVC ratio was slower in young COPD than in old COPD. Multivariate Cox analysis identified female sex, higher FEV1 (%), and young COPD as independent predictive factors for time-to-first normalization of airflow obstruction. Old COPD and low FEV1 (%) were identified as independent risk factors for time-to-first dyspnea. CONCLUSION: Young COPD is characterized by a higher proportion of females, non-smokers, and elevated BMI compared to old COPD. It has potential for lung function recovery and serves as an independent prognostic factor for the normalization of airflow obstruction.
Epidemiological Trends and Projections of PM.-Attributable COPD Burden in China Over 1990-2035.
Li M, Wang L, Amhare AF … +5 more , Song Y, Wan P, Shi S, Qiao L, Guo Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868724 · Full text
OBJECTIVE: This study investigated long-term trends in the burden of chronic obstructive pulmonary disease (COPD) attributable to PM in China from 1990 to 2021 and projected future patterns through 2035. METHODS: Data we...
OBJECTIVE: This study investigated long-term trends in the burden of chronic obstructive pulmonary disease (COPD) attributable to PM in China from 1990 to 2021 and projected future patterns through 2035. METHODS: Data were obtained from the Global Burden of Disease Study 2021. Key indicators included disability-adjusted life years (DALYs), deaths, age-standardized disability-adjusted life years rates (ASDR), and age-standardized mortality rates (ASMR), which together characterize both individual-level and population-level disease burden. Analyses were stratified by sex and age group. Future trends were projected using a Bayesian age-period-cohort (BAPC) model. RESULTS: From 1990 to 2021, the COPD burden in China showed a sustained downward trend. The overall ASDR decreased from 2692.65 to 473.09 per 100,000 population (approximately an 82.4% reduction), while the ASMR declined from 162.33 to 28.22 per 100,000 population (approximately an 82.6% reduction). More pronounced declines were observed during the mid-1990s to early 2000s. A modest increase in PM-attributable COPD burden was noted in 2020, which may be associated with disruptions related to the COVID-19 pandemic. In 2021, COPD attributable to PM accounted for an estimated 9.16 million DALYs and 497,000 deaths, with a consistently higher burden observed among males. Projections indicate a continued overall decline in COPD burden by 2035, although a slight upward trend in ASMR is projected among males. CONCLUSION: COPD attributable to PM continues to impose a substantial public health burden in China. Despite long-term declines in age-standardized rates, the observed fluctuation in 2020 suggests ongoing vulnerability among individuals with chronic respiratory diseases. Continued efforts targeting air quality improvement and smoking reduction may contribute to further mitigation of COPD burden, particularly among high-risk populations.
Infection and Risk of Chronic Obstructive Pulmonary Disease: A Meta-Analysis and Mendelian Randomization Study.
Xu Y, Li J, He C … +7 more , Su A, Jiang H, Ma B, Zhu L, Yang Z, Wu F, Liu J
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868723 · Full text
BACKGROUND: () infection and chronic obstructive pulmonary disease (COPD) are both common global public health burdens. Current evidence suggests that infection may be associated with the development and progression of...
BACKGROUND: () infection and chronic obstructive pulmonary disease (COPD) are both common global public health burdens. Current evidence suggests that infection may be associated with the development and progression of COPD. METHODS: This study conducted a meta-analysis to systematically evaluate the association between infection and COPD risk. Eight Chinese and English databases were searched through September 2025. We then performed two-sample Mendelian randomization (MR) using genetic instruments for antibody phenotypes and COPD GWAS summary statistics to test bidirectional causality. RESULTS: A total of 27 studies were included, comprising 7159 participants. Compared with controls, COPD patients had a higher positivity rate (RR = 1.43, 95% CI: 1.25-1.60, < 0.00001). Among COPD patients, positivity was associated with poorer lung function (FEV/FVC: MD = -6.75, 95% CI: -9.17 to -4.34, < 0.00001; FEV%: MD = -9.34, 95% CI: -12.61 to -6.07, < 0.00001; FEV: MD = -0.16, 95% CI: -0.23 to -0.09, < 0.00001; FVC%: MD = -5.29, 95% CI: -9.76 to -0.81, = 0.02; FVC: MD = -0.15, 95% CI: -0.28 to -0.01, = 0.03). Compared with patients with severe-to-very severe COPD, those with mild-to-moderate COPD had a lower prevalence of infection (RR = 0.75, 95% CI: 0.59-0.96; P = 0.02). However, the two-sample MR analysis did not find evidence of a bidirectional causal relationship between antibodies and COPD. CONCLUSION: The study shows that infection is more prevalent among patients with COPD and is associated with reduced lung function and greater disease severity, but no genetic evidence of causality was identified. Therefore, based on current evidence, routine screening or eradication therapy is not recommended in the general COPD population.
Burden of Disease Analysis of COPD Attributable to Occupational PGFs in the BRICS Countries, 1990-2021.
Zeng J, Xie J, Huang S … +2 more , Cheng J, Zeng Q
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868722 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The BRICS countries (Brazil, Russia, India, China, and South Africa), which are undergoing rapid industrialization,...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The BRICS countries (Brazil, Russia, India, China, and South Africa), which are undergoing rapid industrialization, face significant occupational exposures to particulate matter, gases, and fumes (PGFs)-important risk factors for COPD. This study aims to assess the disease burden of COPD attributable to occupational PGFs in the BRICS countries from 1990 to 2021. METHODS: This analysis was based on data from the Global Burden of Disease (GBD) 2021 database, covering the period from 1990 to 2021 for the BRICS countries. The study examined the burden of COPD attributable to occupational PGFs by assessing absolute counts and age-standardized rates (ASRs) for deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs); estimated annual percentage changes (EAPCs) were also calculated for these metrics. Furthermore, a decomposition analysis was performed to identify contributors to changes in COPD burden, stratified by the Sociodemographic Index (SDI). Forecasting of disease burden trends was carried out using exponential smoothing (ES) and autoregressive integrated moving average (ARIMA) models. RESULTS: From 1990 to 2021, the BRICS countries experienced a decline in ASRs for deaths, DALYs, and YLLs from COPD attributable to occupational PGFs. In contrast, the ASR for YLDs showed an increase. However, the absolute numbers of all outcomes rose. This divergence was primarily driven by population growth, which accounted for 85.2% of the rise in DALYs, far outweighing the effects of population aging (8.7%) and changes in age-specific rates (6.1%). By 2021, the absolute burden amounted to 12.60 million DALYs, 585,451 deaths, 10.55 million YLLs, and 2.05 million YLDs. Trend analysis confirmed this pattern, with significant negative estimated annual percentage changes (EAPCs) for DALYs, deaths, and YLLs, but a positive EAPC for YLDs. The burden was highest among men and the elderly (65-79 years) within BRICS, and in low- and middle-income regions globally. CONCLUSION: Despite declining age-standardized rates, the increasing absolute burden of COPD attributable to occupational PGFs in BRICS countries underscores the urgent need for workplace-focused interventions. Priority should be given to engineering controls, improved ventilation, respiratory protection programs, and occupational health standards in high-risk industries to reduce PGFs exposure at its source.
Integrating Multi-Omics Data to Uncover Causal Links Between Mitochondria-Related Genes and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study.
Hong E, Mao J, Ke Z … +1 more , Wu Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868721 · Full text
BACKGROUND: As a relatively common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high incidence and mortality rate. Mitochondrial dysfunction has been implicated in COPD pathogenesis, but the ca...
BACKGROUND: As a relatively common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high incidence and mortality rate. Mitochondrial dysfunction has been implicated in COPD pathogenesis, but the causal genes and underlying molecular mechanisms remain unclear. METHODS: We performed a summary data-based Mendelian Randomization (SMR) study integrating summary data from genome-wide association studies (GWAS) with blood-based methylation (mQTL), expression (eQTL), and protein quantitative trait loci (pQTL) to identify mitochondrial-related genes causally associated with COPD. Significant findings were validated using two-sample MR, independent lung tissue transcriptomic data (GSE76925), and weighted gene co-expression network analysis (WGCNA) to assess transcriptional consistency and functional convergence. RESULTS: Our integrative SMR and colocalization analyses identified 77 mitochondrial genes linked to COPD risk, including , and . A methylation-to-expression regulatory cascade was observed, with hypermethylation at cg24011261 associated with increased gene expression and higher COPD risk-despite its role as an antioxidant enzyme. Two-sample MR confirmed robust causal effects of and expression on COPD. These findings were replicated in lung tissue: , and were significantly upregulated in COPD patients (GSE76925). WGCNA revealed that these genes reside within a highly interconnected turquoise module strongly correlated with COPD status (r = 0.43, p < 0.001) and enriched in oxidative phosphorylation and mitochondrial energy metabolism pathways. CONCLUSION: This study provides systematic genetic and transcriptomic evidence that mitochondrial-related genes, particularly and , exert causal effects on COPD risk through regulatory cascades and coordinated network dysregulation. The convergence of genetic, epigenetic, and co-expression evidence underscores mitochondrial dysfunction as a central mechanism in COPD pathogenesis and highlights potential targets for future therapeutic development.
The Association Between Glycemic Variability and In-Hospital Mortality in Patients with Chronic Obstructive Pulmonary Disease: A MIMIC-IV Database-Based Retrospective Cohort Study.
He J, Chen Y, Wang Q … +2 more , Yu W, Zhang Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868720 · Full text
PURPOSE: The association between glycemic variability (GV) and the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD) remains uncertain. This study aimed to assess the connection between GV a...
PURPOSE: The association between glycemic variability (GV) and the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD) remains uncertain. This study aimed to assess the connection between GV and hospital mortality among hospitalized COPD patients. PATIENTS AND METHODS: Data from the MIMIC-IV database were used in this study. GV was analyzed as a continuous variable and in quartiles. Cox proportional hazards modeling with stepwise adjustment was used to assess the link between GV and in-hospital mortality, and HRs and 95% CIs were calculated. A restricted cubic spline model was applied to explore non-linear associations. Survival curves and Log rank tests were performed to assess survival differences. Subgroup analyses and interaction tests were conducted to determine the relationship across diverse populations. RESULTS: Our analysis encompassed 11873 patients, among whom 838 individuals died during their hospitalization. A significant association between GV and in-hospital mortality in COPD patients was found across all Cox proportional hazards models: the unadjusted model (HR [95% CI]: 1.849 [1.409, 2.427], P < 0.001), the partially adjusted model (HR [95% CI]: 1.880 [1.432, 2.468], P < 0.001), and the fully adjusted model (HR [95% CI]: 1.551 [1.110, 2.167], P = 0.01). The restricted cubic spline (RCS) models revealed a significant non-linear relationship (P-nonlinear < 0.001). Survival curves demonstrated significant differences in in-hospital survival rates across varying GV levels (log-rank P < 0.0001). CONCLUSION: GV exhibited a strong association with in-hospital mortality among COPD patients, and significant differences were observed in in-hospital survival rates across varying GV levels.
Moving Past Just Confidence Intervals: Why We Need Stronger Heterogeneity Assessment in Lung Cancer Meta-Analyses? [Letter].
Cherif H, Maazaoui S, Dziri C
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868719 · Full text
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Why the COPD Microbiome Matters: How Airway Microbes Shape Disease Severity and Treatment Response.
Jia S, Liu P, Zhang H … +3 more , Zeng H, Chen G, Zhao L
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41868718 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by multiple factors, with diverse clinical manifestations leading to varying treatment outcomes. Dysbiosis of the respiratory mic...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by multiple factors, with diverse clinical manifestations leading to varying treatment outcomes. Dysbiosis of the respiratory microbiome is one of the key contributors to this variability. OBJECTIVE AND METHODS: Due to differences in microbial detection technologies and sample collection methods, studies on the characteristics of respiratory prokaryotic microbiota and how these microbes influence host functions in COPD patients have yielded variable results. In this review, we conducted a comprehensive search of relevant literature from PubMed, ScienceDirect, and Elsevier, summarizing studies on the characteristics and functional analyses of prokaryotic microbiota under various technical approaches. The goal was to identify common patterns of microbiota changes in COPD across different disease states, as well as individual microbial influences on host functions. RESULTS: Compared with healthy adults, in stable-phase COPD patients, the relative abundance of species in the Bacteroidetes phylum is significantly reduced. During acute exacerbations, the predominant microbiota is composed of , and species from the Proteobacteria and Firmicutes phyla. Clinical indicators in COPD patients are correlated with the abundance of (Firmicutes) and (Bacteroidetes) species. Furthermore, the different phyla of respiratory prokaryotic microbiota are associated with innate immunity, metabolism, and inflammation factors related to COPD. CONCLUSION: This review summarizes evidence on dynamic changes in the airway prokaryotic microbiome during COPD progression. It highlights the dual role of these microbial changes as biomarkers of disease progression and modifiable targets for personalized care. Observed patterns-such as reduced abundance in stable disease and the dominance of , and during acute exacerbations-provide a basis for stratifying patients and designing individualized treatment plans. Microbiome analysis may aid in early identification of high-risk patients for preventive strategies, guide pathogen-specific antimicrobial or immunomodulatory therapy, and allow treatment response to be monitored through microbial shifts. By linking distinct microbial profiles to host immune and inflammatory pathways, this approach supports the development of tailored interventions to restore microbial balance. These strategies could improve clinical outcomes and advance precision medicine in COPD management.
Genetic Architecture of Comorbidity Between Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: Exploring Shared Mechanisms and Potential Therapeutic Targets.
Chen S, Li X, Xie R
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859020 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs), including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF), are major global health burdens. The shared...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs), including hypertension (HTN), coronary heart disease (CHD), and heart failure (HF), are major global health burdens. The shared genetic mechanisms underlying the high comorbidity between COPD and CVDs remain unclear. METHODS: We integrated large-scale GWAS summary statistics for COPD and three major CVDs (HTN, CHD, HF). Several analytic approaches were applied, including linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), multi-marker analysis of genomic annotation (MAGMA), pleiotropic analysis under composite null hypothesis (PLACO), and summary-data-based Mendelian randomization (SMR). These methods were used to evaluate genetic correlations, identify shared risk loci, and prioritize potential therapeutic targets. RESULTS: LDSC and HDL analyses revealed significant positive genetic correlations between COPD and the three CVDs (rg = 0.23-0.38, P < 0.05). MAGMA enrichment analysis identified 277 unique pleiotropic genes enriched in pathways such as Notch signaling and nicotinic acetylcholine receptor signaling. Tissue-specific analyses indicated that shared genetic signals were enriched not only in the lung and heart but also in neuroendocrine-related tissues such as the cerebellum and pituitary, suggesting the involvement of a potential "lung-heart-brain" multi-organ axis. PLACO identified 94 pleiotropic SNPs, with consistent colocalization signals at 15q25.1 (CHRNA3/5, IREB2) and 4q22 (SOX7). SMR analysis further prioritized 626 candidate genes, including ZNF652, XRCC3, SLC22A5, and SOX7, which may serve as potential therapeutic targets. CONCLUSION: This study provides genetic evidence for shared mechanisms linking COPD with HTN, CHD, and HF. It highlights the roles of neurotransmitter receptors, iron metabolism, vascular development, and energy metabolism in COPD-CVD comorbidity. These findings offer insights into precision prevention and therapeutic strategies targeting COPD-CVD comorbidity.
Impact of Emphysema on Therapeutic Efficacy and Immune-Related Pneumonitis Risk in NSCLC Patients Receiving ICIs: A Meta-Analysis of Improved Survival but Increased Toxicity.
Li W, Liu S, Yu X … +2 more , Lan W, Liu X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859019 · Full text
PURPOSE: To identify the impact of CT-defined emphysema on efficacy and immune checkpoint inhibitor-related pneumonitis (ICIP) risk among non-small cell lung cancer (NSCLC) patients who receive ICIs. METHODS: PubMed, EMB...
PURPOSE: To identify the impact of CT-defined emphysema on efficacy and immune checkpoint inhibitor-related pneumonitis (ICIP) risk among non-small cell lung cancer (NSCLC) patients who receive ICIs. METHODS: PubMed, EMBASE, Web of Science and CNKI databases were searched up to January 8, 2025. Primary outcome was the therapeutic efficacy including the progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR) and disease control rate (DCR). Second outcome was the ICIP. The hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) were combined. RESULTS: Nine studies with 1076 cases were included. Pooled results demonstrated that the presence of emphysema was significantly associated with improved PFS (HR = 0.43, 95% CI: 0.28-0.67, P < 0.001), OS (HR = 0.43, 95% CI: 0.25-0.75, P = 0.003), PR (OR = 2.10, 95% CI: 1.18-3.75, P = 0.012), PD (OR = 0.60, 95% CI: 0.43-0.83, P = 0.002) and DCR (OR = 1.48, 95% CI: 1.14-1.94, P = 0.004). However, emphysema was associated with increased incidence of ICIP (OR = 1.32, 95% CI: 1.15-1.53, P < 0.001). CONCLUSION: Based on available evidence, CT-defined emphysema indicates better therapeutic efficacy with longer PFS and OS, but increased risk of ICIP among NSCLC patients receiving ICIs. These findings suggest emphysema may guide personalized immunotherapy decisions in NSCLC.
Prognostic Value of the ROX Index for Mortality in Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study Using the MIMIC-IV Database.
Liu K, Fu Z, Luo D … +2 more , Xiao H, Wu Q
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859018 · Full text
OBJECTIVE: While the ROX index has been extensively studied in acute hypoxemic respiratory failure, its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to...
OBJECTIVE: While the ROX index has been extensively studied in acute hypoxemic respiratory failure, its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the association between the ROX index and mortality in critically ill COPD patients. METHODS: We conducted a retrospective cohort study of 2,176 critically ill COPD patients admitted to the intensive care unit (ICU) using the MIMIC-IV database, a publicly available repository of critically ill patients admitted to intensive care units. The ROX index was categorized into quartiles. The association between the ROX index and all-cause mortality was analyzed using restricted cubic splines (RCS) and multivariable Cox proportional hazards models. Subgroup analyses were performed to validate the robustness of the findings. RESULTS: RCS analysis revealed a nonlinear, L-shaped association between the ROX index and mortality, with an inflection point at 9.72. Below this threshold, each unit increase in the ROX index was associated with a significant 16% reduction in 28-day mortality (HR: 0.84, 95% CI: 0.78-0.90, P<0.001). Above 9.72, no significant association was observed (HR: 1.01, 95% CI: 0.96-1.07, P = 0.628). Compared to the lowest quartile (Q1), patients in Q2 (HR=0.75, 95% CI: 0.59-0.96, P=0.021), Q3 (HR=0.60, 95% CI: 0.46-0.77, P<0.001), and Q4 (HR=0.58, 95% CI: 0.45-0.75, P<0.001) had progressively lower 28-day mortality risks; Similar trends were observed for 3-month and 1-year mortality. The association remained statistically significant across all predefined subgroups (all P<0.05). CONCLUSION: The ROX index is a practical bedside tool for risk stratification in critically ill COPD patients. Its predictive value follows a threshold-dependent pattern, with values below approximately 9.72 independently associated with increased mortality. This makes it particularly useful for the early identification of high-risk patients in the ICU.
Innovative Applications and Challenges of Artificial Intelligence in the Whole-Course Management of Chronic Obstructive Pulmonary Disease.
Chen S, Xing S, Zhang G … +1 more , Qiu F
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859017 · Full text
OBJECTIVE: To systematically map how artificial intelligence (AI) can transform whole-course chronic obstructive pulmonary disease (COPD) management across prevention, diagnosis, treatment and rehabilitation within a 4P...
OBJECTIVE: To systematically map how artificial intelligence (AI) can transform whole-course chronic obstructive pulmonary disease (COPD) management across prevention, diagnosis, treatment and rehabilitation within a 4P (Predictive, Preventive, Personalized, Participatory) medicine framework, and to identify actionable strategies for overcoming current barriers. METHODS: A systematic search of PubMed, Web of Science and Embase was performed for articles published between January 2021 and June 2025. This review was conducted following the PRISMA guidelines. Forty empirical studies and reviews that applied AI/ML to COPD prevention, early detection, personalised therapy, exacerbation prediction or pulmonary rehabilitation were critically appraised. Data were extracted on technical foundations, data modalities, algorithms, validation metrics and implementation outcomes. RESULTS: AI models integrating multimodal data (imaging, wearables, environmental exposures, genomics) achieved AUC ≥ 0.80 for predicting acute exacerbations up to seven days in advance, were associated with a reduction in emergency visits of up to 98% and a lowering of readmission rates by 25-48%. Screening tools using chest X-ray, CT or smartphone sensors attained ≥90% accuracy for early COPD detection in primary-care settings. Personalised treatment optimisation was linked to a 53% lowering of exacerbation risk in best-responding subgroups. Home-based AI rehabilitation platforms increased adherence by >30% without additional equipment. Key implementation challenges include data heterogeneity, limited explainability, digital divide among older adults and unclear regulatory frameworks. CONCLUSION: AI is poised to operationalise 4P COPD care, delivering substantial clinical and economic benefits. Future success depends on cross-centre data standards, explainable-AI toolchains, federated learning and inclusive reimbursement policies.
Efficacy of Nebulized Pentoxifylline in a Mouse Model of Emphysema Induced by Cigarette Smoke and Aerosolized Lipopolysaccharide.
Hu Z, Yu Y, Peng T … +5 more , Niu R, Li Z, Wang W, Zheng X, Zhang J
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859016 · Full text
OBJECTIVE: To investigate the impact of pentoxifylline dosage on lung pathological changes and inflammation triggered by the combined exposure to cigarette smoke and aerosolized lipopolysaccharides. METHODS: Female C57BL...
OBJECTIVE: To investigate the impact of pentoxifylline dosage on lung pathological changes and inflammation triggered by the combined exposure to cigarette smoke and aerosolized lipopolysaccharides. METHODS: Female C57BL/6 mice were subjected to either cigarette smoke (CS) plus lipopolysaccharide (LPS) exposure or sham smoke (SCS) exposure for a duration of 10 weeks. Starting from the 9th week, the mice were randomly assigned to distinct intervention groups, where they received nebulized treatments of pentoxifylline (at varying doses), theophylline, or budesonide suspension for 2 weeks. A co-solvent control group was also included. At the end of the 10th week, the mice were euthanized. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the expression levels of tumor necrosis factor-α (TNF-α), keratinocyte chemoattractant/C-X-C motif chemokine ligand 1 (KC/CXCL1, the murine functional homolog), and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF). After tissue homogenization, ELISA was also used to measure the expression of matrix metalloproteinase-12 (MMP-12) and the level of histone deacetylase 2 (HDAC2). Hematoxylin and eosin (H&E) staining was performed on lung tissue sections to determine the alveolar mean linear intercept (Lm) and alveolar destruction index (ADI). Additionally, Wright-Giemsa staining was utilized for the classification and quantification of cells in BALF. RESULTS: Chronic exposure to CS+LPS resulted in a significant exacerbation of pulmonary inflammation, which was characterized by elevated levels of TNF-α, KC/CXCL1, IL-1β, and MMP-12 (CS+LPS group vs SCS group, all p<0.05). Moreover, a notable reduction in HDAC2 level was observed, accompanied by significant increases in Lm and ADI (all p<0.05). The total cell count in BALF was also significantly higher in the CS+LPS group (p<0.05). Budesonide treatment led to a significant reduction in the levels of inflammatory cytokines and MMP-12; however, it had no significant effect on HDAC2 level. Both pentoxifylline (PTX) at different doses and theophylline (THEO) effectively decreased the expression of inflammatory markers and increased HDAC2 level (p<0.05). Notably, none of the treatments resulted in a significant improvement in Lm, whereas ADI was significantly reduced following treatment. Although THEO induced a reduction in TNF-α levels, this change did not reach statistical significance. CONCLUSION: Nebulized pentoxifylline and theophylline can alleviate lung inflammation induced by CS and LPS exposure, as evidenced by the decreased expression of TNF-α, KC/CXCL1, IL-1β, and MMP-12, and the restoration of HDAC2 level (which was reduced by CS+LPS exposure). In contrast, budesonide alone was capable of reducing inflammation but failed to exert an impact on HDAC2 level. A numerical trend indicated that pentoxifylline at a concentration of 22.0 mg/mL might exhibit greater efficacy; however, no statistically significant differences were observed among the various PTX doses tested. Further research is required to identify the optimal concentration of pentoxifylline for this application.
Epigenetic Mechanisms Linking Chronic Obstructive Pulmonary Disease and Atrial Fibrillation: A Multi-Omics Mendelian Randomization Study.
Zhang M, Li T, Tan L … +3 more , Yu J, Yao Q, Chen L
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859015 · Full text
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) frequently co-occur, yet the underlying molecular mechanisms remain unclear. We assessed whether genetic liability to CO...
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) frequently co-occur, yet the underlying molecular mechanisms remain unclear. We assessed whether genetic liability to COPD increases AF risk and mapped epigenetic mediators using multi-omics data. METHODS: We integrated genome-wide association data for COPD and AF with epigenome-wide DNA methylation profiles and gene expression datasets. Summary-data-based Mendelian randomization served as the primary approach to link disease-associated variants with methylation, gene expression, and AF, complemented by two-sample Mendelian randomization, colocalization, and checks for pleiotropy. We prioritized COPD-related CpG sites and genes, examined functional context using protein-protein interaction networks and pathway enrichment, and nominated candidate therapeutics with drug-prediction algorithms followed by molecular docking. Analyses were conducted primarily in cohorts of European ancestry. RESULTS: Genetic liability to COPD was associated with a higher risk of AF (odds ratio [OR] = 1.156, 95% confidence interval [CI] 1.025-1.304; p = 0.018). We identified 109 COPD-related CpG sites associated with AF risk. Cross-omics triangulation highlighted seven candidate genes, with FES showing consistent evidence across genomic, epigenetic, and transcriptomic layers. Functional analyses indicated enrichment in immune signaling and signal transduction pathways. Docking analyses suggested favorable binding between predicted drugs and their targets. CONCLUSION: These findings support a pathway by which COPD may influence AF risk through epigenetic regulation and prioritize CpG sites, genes, and potentially druggable targets for further study. Because the underlying datasets are predominantly from individuals of European ancestry, replication in more diverse populations is needed to assess generalizability.
Effectiveness of Benralizumab in Reducing Asthma and COPD Exacerbations in Patients with Severe Asthma and Concomitant COPD: Real-World Evidence from the ZEPHYR-5 Study.
Adrish M, DeMartino JK, Carstens D … +4 more , Jackson M, Wilson K, Schinkel J, Tkacz J
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 41859014 · Full text
PURPOSE: This real-world evidence study sought to evaluate the effectiveness of benralizumab on reducing both asthma and COPD exacerbations among patients with a diagnosis of asthma and concomitant COPD. PATIENTS AND MET...
PURPOSE: This real-world evidence study sought to evaluate the effectiveness of benralizumab on reducing both asthma and COPD exacerbations among patients with a diagnosis of asthma and concomitant COPD. PATIENTS AND METHODS: This study was a non-interventional, single-arm, retrospective database analysis of the MORE Registry and the 100% Medicare Fee-for-Service (FFS) claims databases from 2017-2022. Inclusion criteria were as follows: 1) prescription claim for benralizumab and ≥1 refill within 90 days (earliest claim=index date), 2) 12 months of database enrollment preceding (baseline) and following (follow-up) the index date, 3) medical claims with diagnoses of asthma and COPD during the baseline period, and 4) presence of ≥2 asthma exacerbations during the baseline period. Percent change in the annual rates of both asthma and COPD exacerbations were assessed from the baseline to follow-up, with paired t-tests used to examine statistically significant differences. Subgroup analyses were also conducted among the subset of patients with blood eosinophil levels, and by payer type. RESULTS: A total of 2894 patients with asthma and concomitant COPD were included. Following initiation of benralizumab, the mean (SD) number of total asthma exacerbations decreased by 39.2% (from 4.0 (2.2) to 2.4 (2.4) exacerbations/year; < 0.001), while COPD exacerbations decreased by 45.6% (from 3.6 (2.5) to 1.9 (2.2) exacerbations/year; p < 0.001). The proportion of patients receiving systemic corticosteroids decreased by 11.4% from 100% to 88.6% ( < 0.001). Subgroup analyses revealed that patients with the highest eosinophil levels (≥ 300 eosinophils/µL) experienced the greatest reductions in asthma exacerbations (42.7%) and COPD exacerbations (50.8%; all < 0.001). CONCLUSION: This study provides real-world evidence supporting the effectiveness of benralizumab in reducing both asthma and COPD exacerbations and decreasing reliance on corticosteroids, particularly among those with elevated eosinophil levels.
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