International Journal Of Chronic Obstructive Pulmonary Disease[JOURNAL]
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200 papers
Causal Relationship Between Methotrexate and Chronic Obstructive Pulmonary Disease: A Study Based on Network Toxicology and Mendelian Randomization.
Xiang YX, Zou FS, Shi MF … +1 more , Xu Q
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42328420 · Full text
INTRODUCTION: Previous studies have shown that methotrexate (MTX) may have potential effects on chronic obstructive pulmonary disease (COPD), but the specific causal relationship remains unclear. OBJECTIVE: This research...
INTRODUCTION: Previous studies have shown that methotrexate (MTX) may have potential effects on chronic obstructive pulmonary disease (COPD), but the specific causal relationship remains unclear. OBJECTIVE: This research intends to investigate whether a potential causal association exists between MTX usage and the risk of developing COPD. METHODS: To systematically explore the potential association between MTX and the occurrence of COPD, this study adopted a multi-dimensional research strategy: on the one hand, the network toxicology method was used to predict the relevant action targets and metabolic pathways of MTX; on the other hand, the Mendelian randomization (MR) analysis method was applied to conduct research at the macro-epidemiological level. RESULTS: Network toxicology analysis showed that MTX can affect the onset of COPD through multiple pathways and metabolic routes, and has strong binding energy with proteins encoded by , and . Meanwhile, MR analysis showed a significant positive correlation between MTX and COPD. CONCLUSION: This study suggests that there is a certain association between the use of MTX and the increased risk of COPD, providing new ideas for subsequent in - depth research.
Risk Factors and Prediction of Chronic Obstructive Pulmonary Disease After Pulmonary Tuberculosis: A Prospective Cohort Study.
Ye X, Le S, Han S … +3 more , Zhang Z, Li Q, Gao F
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42328419 · Full text
BACKGROUND: Pulmonary tuberculosis (PTB) is increasingly recognized as a major precursor of chronic obstructive pulmonary disease (COPD). However, validated tools to predict the risk of COPD following PTB cure remain lim...
BACKGROUND: Pulmonary tuberculosis (PTB) is increasingly recognized as a major precursor of chronic obstructive pulmonary disease (COPD). However, validated tools to predict the risk of COPD following PTB cure remain limited. Early identification of individuals at high risk is essential to facilitate targeted follow-up and preventive interventions. METHODS: This prospective cohort study was conducted at Hunan Chest Hospital. Adults with newly diagnosed PTB who completed standard anti-tuberculosis treatment were enrolled between January and June 2023 and followed until June 2025. Follow-up assessments were performed monthly during the first 3 months, quarterly from months 6 to 12, and every 6 months thereafter, with standardized evaluation of respiratory symptoms and lung function. Incident COPD was defined as a post-bronchodilator FEV/FVC ratio <0.70. Candidate predictors spanning demographic, clinical, inflammatory, and immunological domains were initially screened using random forest ranking and least absolute shrinkage and selection operator regression, followed by multivariable logistic regression. A prediction model was developed and internally validated using bootstrap resampling. Calibration was assessed using calibration plots with 1000 bootstrap iterations, and clinical utility was evaluated by decision curve analysis. RESULTS: During follow-up, 83 of 324 participants (25.6%) developed COPD. Older age (≥65 years), active smoking, cavitary PTB, invasive fungal disease, dyspnea, an elevated systemic immune-inflammation index (SII), and a reduced CD4⁺/CD8⁺ T-cell ratio were independently associated with COPD development. A prediction model incorporating these seven variables demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.806 (95% CI: 0.751-0.861), and satisfactory calibration. Internal validation yielded a bootstrap-corrected concordance index of 0.787, indicating favorable clinical utility across a broad range of decision thresholds. CONCLUSION: More than one-quarter of patients developed COPD after PTB cure, highlighting the substantial burden of post-tuberculosis respiratory sequelae. The proposed prediction model enables individualized risk stratification and may support early surveillance and targeted preventive strategies, extending post-TB care beyond microbiological cure to long-term respiratory outcomes.
Diaphragmatic Thickening Fraction and Excursion: Different Clinical Values in Non-Critically Ill Patients with AECOPD - An Exploratory Study.
Yang X, Zhu L, Ren R
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42317523 · Full text
PURPOSE: Diaphragm dysfunction is a key mechanism of respiratory failure during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Diaphragmatic thickening fraction (DTF) and excursion (DE) are commonl...
PURPOSE: Diaphragm dysfunction is a key mechanism of respiratory failure during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Diaphragmatic thickening fraction (DTF) and excursion (DE) are commonly used ultrasound parameters, but their clinical value in non-critically ill AECOPD patients remains unclear. This study aimed to investigate the association of early DTF and DE with subsequent noninvasive ventilation (NIV) requirement and treatment response. PATIENTS AND METHODS: This retrospective observational study enrolled AECOPD patients admitted between December 2025 and January 2026. DTF and DE were measured within 24 hours of admission and before NIV initiation. Primary outcomes were NIV requirement within 48 hours, and among NIV recipients, the difference in ultrasound parameters between treatment responders and non-responders. Multivariable logistic regression assessed whether DTF provided incremental information beyond traditional clinical predictors. RESULTS: Of 123 included patients, 56 received NIV. DTF was significantly higher in the NIV group than in the non-NIV group (=0.033), while DE did not differ. After adjusting for traditional clinical indicators, DTF was no longer significant (=0.121). Among NIV-treated patients, DE was significantly higher in responders than in non-responders (=0.015), while DTF did not differ. CONCLUSION: In non-critically ill AECOPD patients, elevated DTF is associated with NIV requirement but does not provide independent predictive information beyond traditional clinical indicators. DE is associated with NIV treatment response and may reflect diaphragmatic contractile reserve. These exploratory findings, including subgroup analyses and threshold estimates, require prospective validation before clinical application. The two parameters have distinct clinical values, and their interpretation should consider disease stage.
A Maltese Study in Determining the Presence of Chronic Obstructive Pulmonary Disease in Metabolic Syndrome.
Gauci J, Gauci Pullicino S, Caruana E … +6 more , Petroni Magri V, Formosa MM, Fenech AG, Fava S, Montefort S, Fsadni P
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42312315 · Full text
INTRODUCTION: Both Chronic Obstructive Pulmonary Disease (COPD) and Metabolic Syndrome (MetS) are pro-inflammatory states, and while the diagnosis of MetS in COPD has been extensively studied, the diagnosis of COPD in Me...
INTRODUCTION: Both Chronic Obstructive Pulmonary Disease (COPD) and Metabolic Syndrome (MetS) are pro-inflammatory states, and while the diagnosis of MetS in COPD has been extensively studied, the diagnosis of COPD in MetS is poorly studied. The study focuses on determining the presence of COPD in persons living with diabetes and MetS in Malta, and aims to identify differences in biomarkers between MetS subjects with and without COPD. MATERIALS AND METHODS: Diabetic MetS subjects at Malta's main general hospital were assessed through St George's Respiratory Questionnaire for COPD (SGRQ-C), modified Medical Research Council scale (mMRC), COPD Assessment Test (CAT), Centre for Epidemiological Studies Depression scale (CES-D), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale, Spirometry, Six Minute Walk Test (6MWT), BODE index (composed of Body Mass Index, Obstruction, Dyspnoea, Exercise capacity) and routine blood tests. They were divided into three groups: the main study group consisted of MetS subjects with COPD, one control group consisted of MetS subjects with a smoking history but not COPD, and the other control group consisted of diabetic MetS subjects with no smoking history. RESULTS: A total of 67 MetS subjects were included. Those with COPD had significantly worse outcomes in SGRQ-C scores, mMRC, CAT, spirometry, BODE, CES-D and FACIT Fatigue scale than smokers without COPD and non-smokers. 25-hydroxy-vitamin D levels were significantly lower in MetS subjects with COPD compared to smokers without COPD (=0.030) and non-smokers (=0.043). C-reactive protein (=0.036), triglycerides (=0.023) and total cholesterol (=0.039) were significantly higher in MetS subjects with COPD compared to smokers without COPD. DISCUSSION: Screening for depression and fatigue in subjects with COPD and MetS is recommended. Low vitamin D, high CRP, high triglyceride and high total cholesterol levels are correlated with a COPD diagnosis within the local MetS population, and monitoring these parameters would enable timely management.
Diagnostic Value of Bilateral Pectoralis Major Total Cross-Sectional Area in Patients with AECOPD Complicated by Malnutrition.
Lu Q, Wang L, Pei D … +3 more , Jiang X, Liu L, Yue L
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42312314 · Full text
INTRODUCTION: Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often suffer from malnutrition, and traditional assessment methods struggle to fully capture muscle loss. The value of tot...
INTRODUCTION: Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often suffer from malnutrition, and traditional assessment methods struggle to fully capture muscle loss. The value of total pectoralis major area (tPMA) measured by CT remains to be determined. This study aimed to investigate the relationship between tPMA and malnutrition in patients with AECOPD and its diagnostic value. METHODS: A total of 123 patients with AECOPD were enrolled (35 in the malnutrition group and 88 in the non-malnutrition group). Clinical and imaging parameters were compared between the two groups. Logistic regression analysis was used to assess the independent association between tPMA and malnutrition, and ROC curves were employed to evaluate its diagnostic performance when used alone or in combination with albumin (ALB) or total protein (TP). Spearman correlation analysis was used to examine the relationship between tPMA and other nutritional and disease severity indicators. RESULTS: tPMA levels were significantly lower in the malnourished group than in the non-malnourished group (P < 0.01). tPMA was a protective factor against malnutrition in patients with AECOPD (OR = 0.998, P < 0.001); this association remained statistically significant after adjusting for confounding factors (P < 0.05). The AUC of tPMA for the standalone diagnosis of malnutrition was 0.770; when combined with ALB or TP, the AUC increased to 0.901 and 0.916, respectively (P < 0.05). tPMA was positively correlated with nutritional indicators and negatively correlated with the NRS2002 and CAT (P < 0.05). DISCUSSION: tPMA is an independent associated factor against malnutrition in patients with AECOPD; when combined with ALB or TP, it significantly improves diagnostic performance and can serve as an objective adjunctive assessment indicator.
Association Between Sleep Disorders and Adverse Cardiovascular Outcomes in Patients with Chronic Obstructive Pulmonary Disease: Insights from the UK Biobank.
An X, Chen Y, Wang Y … +6 more , Zhu W, Li F, Shen J, Zhang C, Wu Y, Yu R
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42306044 · Full text
BACKGROUND AND OBJECTIVE: A potential association between sleep disturbances and adverse cardiovascular prognoses has been proposed in patients with chronic obstructive pulmonary disease (COPD), although high-quality con...
BACKGROUND AND OBJECTIVE: A potential association between sleep disturbances and adverse cardiovascular prognoses has been proposed in patients with chronic obstructive pulmonary disease (COPD), although high-quality confirmatory evidence remains limited. Sleep disturbances may contribute to increased cardiovascular risk through multiple biological pathways, including chronic intermittent hypoxia, systemic inflammation, and metabolic dysregulation. This study aimed to examine the association between sleep disturbances and adverse cardiovascular events in patients with COPD. MATERIALS AND METHODS: A prospective cohort study of 21423 UK Biobank participants with COPD. We set the research subjects as non-sleep disorder group and sleep disorder group. Outcomes included stroke, heart failure (HF), atrial fibrillation (AF), angina pectoris, and myocardial infarction (MI). Cox proportional hazards models were applied with adjustment for sociodemographic and lifestyle factors to evaluate the association between sleep disorders and subsequent cardiovascular outcomes. RESULTS: In this manuscript, compared with COPD patients in the non-sleep disorder group, sleep disorder group had a 79% higher risk of HF (HR = 1.79, 95% CI: 1.57-2.03). Moreover, sleep disorder had a 49% higher HR for AF (HR = 1.49, 95% CI: 1.32-1.68) and a 44% higher HR for angina development (HR = 1.44, 95% CI: 1.23-1.68). The risk of MI was also increased by 0.24-fold in the sleep disorder group (HR = 1.24, 95% CI: 1.01-1.54). Furthermore, male sex, older age, previous cardiovascular medication use, smoking, and obesity were significantly associated with elevated cardiovascular risk among COPD patients with sleep disorders. CONCLUSION: Sleep disorders are associated with an increased risk of adverse cardiovascular outcomes in COPD patients. These findings suggest that identification and appropriate management of sleep disorders could potentially contribute to improved cardiovascular risk profiles in this population.
Identification of Th17 Cell-Associated Biomarkers and Their Potential Regulatory Mechanisms in Chronic Obstructive Pulmonary Disease Through Integrated Bioinformatics Analysis and Machine Learning.
Li Q, Xue D, Yu J … +3 more , Yang M, Zhang Y, Obuli R
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42306043 · Full text
PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and chronic airway inflammation. Th17 cell-related immune pathways may contribute to COPD-associated immune dysregul...
PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and chronic airway inflammation. Th17 cell-related immune pathways may contribute to COPD-associated immune dysregulation, but their molecular associations remain incompletely understood. This study aimed to preliminarily explore Th17 cell-associated biomarkers and their potential regulatory networks in COPD. METHODS: Transcriptomic profiles from COPD and control samples were analyzed to identify differentially expressed genes (DEGs). Th17 cell-related DEGs were obtained by intersecting DEGs with Th17-related genes. Random forest and Boruta algorithms were used for biomarker screening, followed by expression validation in training and validation cohorts and RT-qPCR verification. A nomogram model was constructed, and chromosome localization, immune infiltration, gene set enrichment analysis (GSEA), regulatory network analysis, and drug prediction were performed. RESULTS: A total of 3811 DEGs were identified, including 1408 upregulated and 2403 downregulated genes; 16 overlapped with Th17-related genes. AUC was 1.000, with a 95% confidence interval of 1.000-1.000. Machine learning and validation analyses indicated that TGFBR2 and IKBKB may serve as COPD-associated biomarkers, with both genes showing significant downregulation in COPD samples and RT-qPCR validation (p < 0.05). Immune infiltration analysis indicated significant differences in 11 immune cell types between COPD and control groups. TGFBR2 and IKBKB were negatively correlated with Th17 cell infiltration (TGFBR2: cor = -0.502, p < 0.05; IKBKB: cor = -0.466, p < 0.05). IKBKB was also negatively correlated with macrophages (cor = -0.725, p < 0.001), while TGFBR2 was negatively correlated with natural killer T cells (cor = -0.635, p < 0.001). GSEA suggested 78 enriched pathways, including 42 related to TGFBR2 and 36 related to IKBKB. Drug prediction suggested 92 potential agents. CONCLUSION: This preliminary, hypothesis-generating study suggests that TGFBR2 and IKBKB may be associated with Th17-related immune alterations in COPD and may provide candidate markers for further mechanistic and therapeutic validation.
Psychological-Symptom Mismatch Phenotypes and Their Clinical Implications in Patients with Chronic Obstructive Pulmonary Disease.
Cai Y, Ren X, Wang K … +1 more , Cheng H
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42306042 · Full text
PURPOSE: Psychological distress in Chronic obstructive pulmonary disease (COPD) patients often does not correspond to symptom severity. The clinical significance of psychological-symptom mismatch phenotypes is unclear. T...
PURPOSE: Psychological distress in Chronic obstructive pulmonary disease (COPD) patients often does not correspond to symptom severity. The clinical significance of psychological-symptom mismatch phenotypes is unclear. To identify psychological-symptom mismatch phenotypes in COPD and examine their associations with clinical outcomes. PATIENTS AND METHODS: A cross-sectional study was conducted in 306 COPD patients from a tertiary hospital in Shandong, China. Latent profile analysis was applied to standardized measures of anxiety, depression, lung function, symptom severity, and dyspnea to identify phenotypes. Multivariable linear and negative binomial regressions assessed associations with clinical outcomes. RESULTS: Four phenotypes were identified: psychological-dominant mismatch (22%), low (47%), moderate (26%), and high psychological-symptom burden (5%). The mismatch phenotype was characterized by disproportionately elevated psychological burden relative to symptom burden and was associated with the poorest quality of life. In adjusted analyses, patients in the low, moderate, and high burden phenotypes had better quality of life than those in the mismatch phenotype (all P <0.001). Patients in the low and moderate burden phenotypes had fewer hospitalizations in the preceding year (incidence rate ratios, 0.592 [95% CI, 0.355-0.989] and 0.233 [95% CI, 0.141-0.386], respectively), whereas no significant difference was observed for the high burden phenotype. Differences in self-management and coping were limited, while patterns of health locus of control varied across phenotypes. CONCLUSION: Psychological-symptom mismatch appears to be a common and clinically relevant pattern in COPD. Patients with a psychological-dominant mismatch phenotype exhibited poorer quality of life and a higher likelihood of hospitalization. These findings highlight the potential importance of incorporating psychological assessment into routine COPD care and suggest that phenotype-informed approaches may help identify patients with differing clinical needs.
A Real-World Evaluation of Therapeutic Inertia in Patients with Severe Uncontrolled Chronic Obstructive Pulmonary Disease.
Calle Rubio M, Soler-Cataluña JJ, Almagro P … +3 more , Huerta A, González-Segura D, Cosío BG
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42299310 · Full text
BACKGROUND: Therapeutic inertia (TI) defined as failure to escalate or initiate adequate therapy when treatment goals are not met, contributes to poor outcome in patients with chronic obstructive pulmonary disease (COPD)...
BACKGROUND: Therapeutic inertia (TI) defined as failure to escalate or initiate adequate therapy when treatment goals are not met, contributes to poor outcome in patients with chronic obstructive pulmonary disease (COPD). This real-world study aimed to investigate TI and the discrepancy between disease control assessed by physicians' perception and objective methods. METHODS: This was a post hoc analysis of data of 4801 patients with severe COPD (FEV < 50% predicted) included in an observational cross-sectional multicenter nationwide study conducted in Spain. Controlled vs. uncontrolled disease was considered according to COPD assessment test (CAT) score ≤ or > 16 and absence or presence of at least one exacerbation in the past 3 months. A 5-point Likert scale (very poor/poor; satisfactory/good/very good) was used to assess COPD control perceived by physicians and patients' satisfaction with treatment. RESULTS: Uncontrolled COPD was present in 3479 of 4801 patients (72.5%) and controlled COPD in 1322 (27.5%). Among patients with uncontrolled COPD, no treatment adjustments were made in 1519, with a rate of TI of 43.7%. In the multivariate analysis, former smokers, lower exacerbations history, white sputum, lower degree of dyspnea, higher adherence to inhaled therapy, use of dual/triple inhaled medications, absence of SABA use, secondary healthcare level, and patient's satisfaction with treatment were significantly associated with TI. Physicians perceived controlled disease in 2373 patients with uncontrolled COPD, with a discordance rate of 68.2%. Among patients with controlled COPD, the discordant rate was 6.3%. The most influential variables associated with controlled COPD rated by physicians were patients' satisfaction with treatment, no exacerbations in the past year, triple therapy, and ex-smoking status. CONCLUSION: The high rate of TI and the gap between actual COPD control and physicians' perceptions, highlights the urgent need to systematize and standardize the follow-up of patients with severe COPD in daily practice.
Critical Biological Functions and Clinical Implications of Epigenetic-Related Candidate Biomarkers in Chronic Obstructive Pulmonary Disease: Integrated Machine Learning Screening and Basic Experimental Validation.
Xie J, Huang L, Chen X … +1 more , Wang X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42292533 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the primary cause of deaths related to respiratory diseases. Epigenetic modifications are crucial in the development of mammals, and any disruption to epigeneti...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the primary cause of deaths related to respiratory diseases. Epigenetic modifications are crucial in the development of mammals, and any disruption to epigenetic regulation may result in disease. METHODS: We performed differential expression analysis on the GSE19407, GSE11784 and GSE20257 datasets from the Gene Expression Omnibus (GEO) dataset and obtained differentially expressed epigenetic-related genes (DE-ERGs) in COPD. Three machine learning techniques were used to screen the candidate epigenetic-related biomarkers in DE-ERGs, thereby further enhancing the robustness of the analysis framework. Immune infiltration analysis was performed on biomarkers. RESULTS: A total of 5 biomarkers (, and ) were screened utilizing three machine learning algorithms. Immune infiltration analysis showed that the was positively correlated with activated CD4 T cells and memory B cells and negatively correlated with CD56dim. In quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation, the expression levels of 5 biomarkers were notably higher in COPD than in normal samples. CONCLUSION: In summary, we identified 5 epigenetic-related candidate biomarkers that might be involved in COPD progression by bioinformatics techniques, which still require further experimental validation.
Global Economic and Social Burden of Chronic Obstructive Pulmonary Disease: A Systematic Review (2020-2024).
Gutiérrez-Villegas C, Herrero-Montes M, Fernández Cacho LM … +4 more , Amado-Diago CA, Perales-García V, Aceros Lora AM, Paz-Zulueta M
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42292532 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and imposes a substantial economic and social burden on healthcare systems and society. OBJECTIVE: To analy...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and imposes a substantial economic and social burden on healthcare systems and society. OBJECTIVE: To analyse recent evidence (2020-2024) on the economic and social burden of COPD, including direct, indirect, and intangible costs. METHODS: A systematic review was conducted to synthesise recent evidence on the economic and social burden of COPD published between January 2020 and December 2024. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science. Original studies reporting direct healthcare costs, direct non-healthcare costs, indirect costs or intangible costs related to health-related quality of life (HRQoL) were included. RESULTS: Thirty studies from 15 countries were included. Direct healthcare costs represent the main component of expenditure, largely driven by hospitalisations and exacerbations. Annual costs ranged from €3500 to €10,000 per patient in Europe and from US$10,000 to US$17,000 in the United States. Although absolute costs were lower in Asia, the relative financial burden on patients was considerable. Direct non-healthcare costs, including out-of-pocket expenses and long-term care, were particularly relevant in severe disease. Indirect costs related to productivity losses and unemployment were substantial and, in some middle-income countries, exceeded healthcare costs. Intangible costs included anxiety, depression, caregiver distress, impaired quality of life, and perceived financial toxicity, with high overall prevalence. CONCLUSION: COPD creates a considerable economic and social burden. Although direct costs are predominant, indirect, and intangible costs are decisive, particularly in contexts with lower healthcare coverage. Clinical factors (severity, exacerbations, and comorbidities) and socio-economic factors (educational level, income, and employment) explain much of the variability. A holistic approach that addresses health, social, and emotional dimensions is required for a more equitable and sustainable management.
Sociodemographic Determinants of Hospitalized Exacerbations in Exposure-Defined COPD Phenotypes: A Nationwide Prospective Cohort Study in China.
Zheng Z, Tang X, Li W … +13 more , Niu H, Dong F, Yan J, Shi M, Cui Y, Huang T, Han Z, Peng Y, Su R, Wang C, Russell REK, Yang T, Huang K
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42281812 · Full text
PURPOSE: Chronic obstructive pulmonary disease (COPD) a major cause of morbidity, hospitalization, and healthcare burden worldwide and is increasingly recognized as a heterogeneous syndrome with diverse environmental and...
PURPOSE: Chronic obstructive pulmonary disease (COPD) a major cause of morbidity, hospitalization, and healthcare burden worldwide and is increasingly recognized as a heterogeneous syndrome with diverse environmental and socioeconomic determinants. We aimed to identify phenotype-specific determinants of hospitalized exacerbations and annual total length of hospital stay (LHS) in smoking and non-smoking COPD. PATIENTS AND METHODS: We analyzed 3,913 COPD patients from a nationwide multicenter prospective cohort in China, stratified by smoking status. Hospitalized exacerbations at baseline and during one-year follow-up, as well as LHS, were assessed. Multivariable logistic regression and ordinal logistic regression models were used to estimate adjusted odds ratios (ORs) for hospitalized exacerbations and annual total LHS within each subgroup. RESULTS: Among 3,913 participants, 1,709 (43.7%) had non-smoking COPD and 2,204 (56.3%) had smoking-related COPD. During follow-up, 28.0% of non-smokers and 29.9% of smokers experienced hospitalized exacerbations. Rural residence, larger household size, and prior hospitalizations in the preceding year were consistently associated with hospitalized exacerbations and longer annual total LHS in both groups. Biomass exposure was independently associated with hospitalized exacerbations among non-smoking patients but not among smokers after full adjustment. Low body mass index (BMI) was associated with increased risk in non-smoking COPD. Findings were consistent across baseline and prospective analyses, as well as binary and ordinal outcome models. CONCLUSION: In China, rural residence, larger household size, and prior exacerbation history were common determinants of hospitalized exacerbations and longer annual total LHS in patients with COPD, while biomass exposure and low BMI exerted stronger effects in non-smoking COPD.
Identification and Functional Characterization of COPD Molecular Subtypes Based on Oxeiptosis-Related Genes via WGCNA and Machine Learning.
Chen W, Zhao J, Sun Z … +3 more , Zhou X, Zhang X, Yan Z
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42273328 · Full text
BACKGROUND: This study establishes the first molecular stratification framework for chronic obstructive pulmonary disease (COPD) based on oxeiptosis biology, exploring how this reactive oxygen species (ROS)-induced cell...
BACKGROUND: This study establishes the first molecular stratification framework for chronic obstructive pulmonary disease (COPD) based on oxeiptosis biology, exploring how this reactive oxygen species (ROS)-induced cell death pathway shapes disease heterogeneity. The precise role of oxeiptosis in COPD pathogenesis remains poorly understood. METHODS: Transcriptomic profiles from two independent cohorts, GSE47460 (220 COPD cases and 108 controls) and GSE76925 (111 COPD cases and 40 controls), were systematically evaluated using a fully in silico computational pipeline. Oxeiptosis-related differentially expressed genes (ORDEGs) were identified through correlation and differential expression analyses, prioritized using machine learning, and then applied for unsupervised clustering. Subtypes were externally validated and functionally characterized through pathway enrichment and network analysis. RESULTS: The support vector machine (SVM) model prioritized four of the seven ORDEGs for further analysis. Two reproducible subtypes were identified: C1, characterized by diminished ORDEGs activity and significantly worse pulmonary function (FEV% predicted: C1 vs. C2, 44% vs 59%, < 0.05), and C2, marked by heightened activity and less severe dysfunction. Weighted gene coexpression network analysis (WGCNA) revealed a black module associated with subtype classification, enriched in cytokine signaling and extracellular matrix remodeling pathways. A predictive model was constructed to investigate clinical applicability. CONCLUSION: This computational discovery framework introduces an oxeiptosis-specific molecular taxonomy of COPD. The results underscore oxidative stress and the interaction between immune regulation and matrix remodeling as pivotal elements linked to disease heterogeneity, presenting potential pathways for precise diagnosis and treatment.
COPD Patients with a High Exacerbation Risk: Baseline Data Analysis of a National Chinese Prospective Multi-Center Study of Quality Improvement Project.
Yang K, Chen D, Wang Y … +9 more , Wang F, Wang L, Wang J, Yu T, Hou H, Liu W, Huang P, Yang H, Chen R
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42266895 · Full text
PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) with a history of frequent exacerbations have a high disease burden and poor progression, demanding optimized management. This study aimed to evaluate t...
PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) with a history of frequent exacerbations have a high disease burden and poor progression, demanding optimized management. This study aimed to evaluate the real-world clinical situation, adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations, and the associated factors. PATIENTS AND METHODS: We conducted a cross-sectional analysis of baseline data from the national multi-center Quality Improvement Program, which enrolled 1055 COPD patients with a high exacerbation risk from 40 hospitals across five geographic regions in China (NCT05638646). Patient characteristics, disease burden, management patterns and the associated factors were analyzed. RESULTS: The study population had a mean age of 66.2 years, and 85.6% were male. Most patients had substantial disease burden, with 43.3% classified as GOLD stages 3-4 and 93.6% categorized into GOLD group E. In previous 12 months, 39.0% and 67.2% of these patients experienced at least one moderate or severe exacerbation, respectively. Overall, 75.1% received maintenance therapy using long-acting bronchodilators, but only 17.7% were receiving maintenance therapy consistent with the GOLD recommendations for initial treatment. Among patients receiving inhaled therapy, 70.9% initiated maintenance therapy within one month after diagnosis, whereas the self-reported good compliance was only 47.3%. Despite most patients received inhalation technique checks and education, only 61.9% can use the inhalation device appropriately, as evaluated by research team. Hospital level, hospital region, availability of blood eosinophil counts, and disease severity were significantly associated with the management patterns. CONCLUSION: COPD patients with a high exacerbation risk in China had a substantial disease burden and important gaps between real-world management patterns and GOLD recommendations. These findings suggest opportunities to improve guideline implementation, particularly in secondary and county-based hospitals. Future studies should evaluate whether targeted quality improvement interventions can improve patient outcomes. TRIAL REGISTRATION NUMBER: NCT05638646.
Safety and Feasibility of an Asynchronous AI-Integrated Tele-Pulmonary Rehabilitation Application Among Patients with COPD.
Freund O, Urtreger N, Cohn-Schwartz D … +3 more , Barel N, Yacoby Halevi I, Bar-Shai A
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42266894 · Full text
PURPOSE: Pulmonary rehabilitation (PR) is an effective intervention for patients with chronic obstructive pulmonary disease (COPD), yet its utilization remains very limited. Tele-pulmonary rehabilitation (TPR) may improv...
PURPOSE: Pulmonary rehabilitation (PR) is an effective intervention for patients with chronic obstructive pulmonary disease (COPD), yet its utilization remains very limited. Tele-pulmonary rehabilitation (TPR) may improve access, but the safety and feasibility of asynchronous, app-based programs remain insufficiently studied, especially for patients with severe disease. PATIENTS AND METHODS: This is a retrospective study of patients with COPD who participated in an asynchronous AI-supported TPR program using the ActiveLungs© mobile application between 2022 and 2025. Patients were included if they had spirometry-validated COPD and completed ≥10 training sessions in the application. Safety, feasibility, and adherence with the app trainings were evaluated. RESULTS: A total of 124 patients were included (median age 74 years, 54% female, median FEV1 50%predicted), of whom 55% used long-term oxygen therapy. During the study period, 17,399 trainings and 61,706 exercise sessions were completed. No serious adverse events were reported. Self-reported respiratory worsening occurred in 23% of patients and was associated only with chronic oxygen use (HR 2.68, 95% CI 1.08-6.65, p=0.033). Median (IQR) program use was 129 days (65-433), with trainings performed in 49% (31-64) of the days, and 79% completing more than 24 trainings. All four exercise sessions (2 aerobic and 2 resistance) were completed in 82% of the trainings. CONCLUSION: An asynchronous, AI-integrated TPR mobile application demonstrated a favorable safety profile and good patient engagement, even in patients with severe COPD. Prospective studies are warranted to evaluate its effectiveness on clinical outcomes.
Emphysema Phenotype and 1‑Year Readmission Risk After Acute Exacerbation of COPD: A Real-World Study Using Propensity Score-Based Methods.
Fu C, Wu Y, Huang A … +2 more , Chen G, Hu Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42266893 · Full text
BACKGROUND: The association between emphysema phenotype and readmission risk after acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains unclear. This real‑world study evaluated this association wi...
BACKGROUND: The association between emphysema phenotype and readmission risk after acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains unclear. This real‑world study evaluated this association with rigorous confounding control. METHODS: This retrospective cohort study included patients hospitalized for AECOPD (2023). Emphysema was diagnosed by chest CT. The outcome was 1‑year acute exacerbation‑related readmission. Propensity score matching (PSM), multiple-weighting methods, doubly robust analysis, Schoenfeld residuals test, Kaplan‑Meier curves, and subgroup analyses were used. RESULTS: Among 875 patients, PSM yielded 171 matched pairs. Emphysema was associated with higher readmission risk in adjusted analysis (HR=1.64, 95% CI:1.17-2.32, p=0.005), and after PSM (HR=1.81, 95% CI:1.22-2.68, p=0.003). Results were consistent across all weighting methods. The Schoenfeld test satisfied the proportional hazards assumption. Kaplan‑Meier curves showed significantly lower readmission‑free survival in the emphysema group. Subgroup analyses revealed a stronger association in patients not using inhaled corticosteroids. CONCLUSION: Emphysema was associated with a higher risk of 1‑year readmission after AECOPD. The emphysema phenotype may aid risk stratification and guide individualized therapy, though these findings should be interpreted cautiously.
Type 2 Diabetes Mellitus and Chronic Obstructive Pulmonary Disease - from Pathophysiology to Effective Management Overview.
Prisacaru V, Covantsev S, Ceasovschih A … +4 more , Sivapalan P, Tural S, Corlateanu A, Deleanu OC
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42261400 · Full text
Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) are two chronic conditions with significant global impact and high incidence, frequently occurring as comorbidities. This article analyzes...
Type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) are two chronic conditions with significant global impact and high incidence, frequently occurring as comorbidities. This article analyzes the particularities of pathophysiological, genetic, and epigenetic interactions, as well as the therapeutic implications in patients with both conditions. Additionally, the clinical management of these patients is investigated in correlation with updated international guidelines, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 and the American Diabetes Association (ADA) 2026. The importance of rigorous monitoring, personalized treatment, and the use of modern therapies with proven benefits-including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists-is highlighted. The conclusion emphasizes the necessity of an integrated, multidisciplinary approach aimed at preventing complications, reducing cardiovascular risk, and improving the quality of life in comorbid patients.
A Single Cell Atlas of the COPD Lung Identifies Inflammatory Reprogramming in Fibroblasts.
Dong L, Chen H, Li F … +5 more , Wang H, Zhou H, Cao L, Ye Y, Sun Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42261399 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation, structural remodeling, and irreversible airflow limitation, but the cellular mechanisms that sustain chronic inflammat...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation, structural remodeling, and irreversible airflow limitation, but the cellular mechanisms that sustain chronic inflammatory remodeling remain poorly understood. METHODS: We integrated newly generated single cell transcriptomic data with publicly available datasets, comprising 6 healthy controls and 10 patients with COPD. Gene expression programs, intercellular communication, pseudotime trajectories, and transcription factor regulatory networks were assessed to define fibroblast associated changes in COPD lung tissue. RESULTS: Fibroblasts exhibited the strongest outgoing signaling activity among lung parenchymal cells and showed the greatest increase in outgoing signaling in COPD. Across multiple fibroblast subpopulations, fibroblasts from COPD lungs acquired a shared proinflammatory and immunoregulatory state associated with inflammatory activation, tissue injury, and fibrotic remodeling. This state was characterized by increased expression of inflammatory mediators and enhanced potential to promote immune cell recruitment and activation. Regulatory analyses further suggested that this inflammatory program was accompanied by extensive remodeling of transcription factor networks in fibroblasts. CONCLUSION: These findings identify fibroblasts as key immunoregulatory cells in COPD lung tissue and suggest that fibroblast associated inflammatory programs may contribute to the maintenance of chronic inflammatory remodeling. Fibroblast centered inflammatory pathways may represent potential targets for future mechanistic and translational studies.
Referral to and Engagement with Pulmonary Rehabilitation: A Review and Strategic Behavioural Analysis of Factors Influencing Behaviour and Intervention Opportunities.
Moore AP, Reardon I, Ramkissoon O … +10 more , Early F, Payerne E, Ashford PA, Holmes S, Kelly MP, Singh SJ, Habib GMM, Fuld J, Lorencatto F, UPTURN Team
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42253401 · Full text
BACKGROUND: Despite strong evidence of benefit, in the UK only 40% of eligible patients are referred to Pulmonary Rehabilitation (PR) and there are poor levels of uptake and completion globally. Understanding how current...
BACKGROUND: Despite strong evidence of benefit, in the UK only 40% of eligible patients are referred to Pulmonary Rehabilitation (PR) and there are poor levels of uptake and completion globally. Understanding how current interventions address reported barriers to PR referral and engagement can help understand intervention effectiveness and highlight opportunities for future policy and intervention. METHODS: Two systematic reviews were conducted: 1) Review of studies reporting barriers/enablers to PR delivery and engagement behaviours, with extracted barriers/enablers inductively synthesized into themes and coded to the domains of the Theoretical Domains Framework (TDF). 2) Review of existing interventions to improve PR uptake/engagement, specifying component Behaviour Change Techniques (BCTs) using established taxonomies. Interventions were categorised for promise according to evidence of change in behaviour for one or more outcomes. Findings from both reviews were triangulated using the Theories and Techniques tool (TaTT), to assess the extent to which components in current interventions targeted key barriers/enablers. RESULTS: Sixty-three studies were included in the analysis. Barriers and enablers to PR mainly fell under the TDF domains ; and . There are opportunities to further support referral by considering interventions targeted at memory and decision making and by streamlining referral processes. For patient engagement with PR, the highly represented TDF domains were ; and . Fifty-four percent of referral interventions and 15% of engagement interventions were considered very promising. BCTs in promising interventions targeting patient engagement included provision of social support and guidance on planning and goal setting. Opportunities for improving engagement include consideration of the emotional burden associated with COPD and attending PR. CONCLUSION: These findings can inform development of new, or refinement of existing, interventions targeting PR for people with COPD.
The Role of Microbiota Homeostasis in the Progression and Treatment of Chronic Obstructive Pulmonary Disease.
He T, Cairang Z, Xu Y … +3 more , Shangguan Y, Wang B, Song Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42244886 · Full text
Chronic obstructive pulmonary disease (COPD) is a heterogeneous chronic respiratory disorder characterized by persistent airflow obstruction. Its high morbidity and mortality have posed a substantial public health burden...
Chronic obstructive pulmonary disease (COPD) is a heterogeneous chronic respiratory disorder characterized by persistent airflow obstruction. Its high morbidity and mortality have posed a substantial public health burden, with current symptomatic treatments exhibiting inadequate control and potential adverse effects. With advances in microecological research techniques, the critical role of microbial homeostasis in the oral cavity, lungs, and gut in respiratory health has become increasingly prominent, and microbial dysbiosis is closely associated with progression and therapeutic outcomes of COPD. This review summarizes the compositional alterations of oral, lung, and gut microbiota in COPD patients, analyzes the interactions of the oral-lung axis and gut-lung axis, and delineates three mechanisms through which microbial dysbiosis promotes COPD progression: pathogenic bacterial migration, abnormal metabolite production and immune dysregulation. Additionally, this review summarizes Western and traditional Chinese medicine interventions targeting microbiota homeostasis, including antibiotics, microecological preparations, and herbal medicines, which have shown potential in improving COPD clinical outcomes. This review aims to provide a theoretical reference for the clinical diagnosis and management of COPD.
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