International Journal Of Chronic Obstructive Pulmonary Disease[JOURNAL]
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200 papers
Equivalent of Carbon Dioxide at the Anaerobic Threshold Predicts Acute Exacerbations in Patients with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.
Li Y, Li X, Lin F … +9 more , Hu X, Liu S, Qiu M, Zhang J, Zhao R, Nie S, Xu B, Yan F, Yu G
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42239674 · Full text
PURPOSE: To investigate the predictive value of the equivalent of carbon dioxide at the anaerobic threshold (EqCO@AT) for acute exacerbations (AE) in patients with chronic obstructive pulmonary disease (COPD). PATIENTS A...
PURPOSE: To investigate the predictive value of the equivalent of carbon dioxide at the anaerobic threshold (EqCO@AT) for acute exacerbations (AE) in patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: This retrospective cohort study included 79 patients with COPD who underwent baseline pulmonary function testing and cardiopulmonary exercise testing (CPET). EqCO@AT = 30 was used only as an empirical threshold for descriptive stratification, rather than as an outcome-derived cutoff. Patients were also classified into non-AE and AE groups according to annualized exacerbation frequency. Baseline characteristics, pulmonary function, and CPET parameters were compared between groups. Logistic regression was used to evaluate the association between EqCO@AT and AE risk. Predictive performance was assessed using receiver operating characteristic curves, calibration analysis, decision curve analysis, Kaplan-Meier analysis, and a simplified nomogram. RESULTS: Of the 79 patients, 16 were classified into the low EqCO@AT group and 63 into the high EqCO@AT group. Patients with higher EqCO@AT were older, had lower BMI, greater smoking exposure, lower FEV% predicted and DLCO% predicted, reduced exercise capacity, and higher ventilatory inefficiency parameters. Compared with the non-AE group, the AE group had worse lung function, lower exercise capacity, and higher VE/VCO slope and EqCO@AT. EqCO@AT was associated with AE risk in univariable analysis (OR 1.122, 95% CI 1.027-1.226, P = 0.011) and remained significant after adjustment for age, BMI, and FEV% predicted (OR 1.269, 95% CI 1.110-1.450, P < 0.001). The AUC of EqCO@AT alone was 0.739, whereas the combined model achieved an AUC of 0.850. Kaplan-Meier analysis showed significantly lower AE-free survival in the high EqCO@AT group (log-rank P = 0.002). The simplified nomogram provided an individualized visual tool for AE risk estimation. CONCLUSION: Elevated EqCO@AT is associated with impaired ventilatory efficiency, reduced exercise capacity, and increased AE risk in COPD. A model incorporating EqCO@AT, age, BMI, and FEV% predicted showed good predictive performance and may support individualized AE risk stratification. These findings suggest that CPET-derived ventilatory efficiency parameters may provide clinically useful information beyond conventional pulmonary function assessment, although validation in larger multicenter prospective cohorts is still required.
Exploring COPD Participants' Experiences in a Comprehensive Telewellness Program within a Mixed-Disability Cohort: A Qualitative Study.
Arora P, Bhatt SP, Rimmer JH
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42239673 · Full text
BACKGROUND: Telehealth pulmonary rehabilitation (PR) has expanded access to rehabilitation services for individuals with Chronic Obstructive Pulmonary Disease (COPD); however, participation and adherence remain variable....
BACKGROUND: Telehealth pulmonary rehabilitation (PR) has expanded access to rehabilitation services for individuals with Chronic Obstructive Pulmonary Disease (COPD); however, participation and adherence remain variable. COPD management emphasizes patient-centered approaches that address heterogeneity of this condition. Although telehealth PR has improved access to care, there is a need to better understand how broader telewellness programs can support patient-centered care and improve patient engagement. OBJECTIVE: This study aimed to explore how individuals with COPD perceive changes in their physical and psychological health after participation in a generic, group-based telewellness (MENTOR: mindfulness, exercise and nutrition to optimize resilience) program. It further examined how personal and contextual factors influence engagement by identifying barriers and facilitators across five domains (built environment and community context, service delivery, instructional strategies, equipment and technology use, and policy factors) as per Guidelines, Recommendations, and Adaptations Including Disability (GRAIDs) framework. Additionally, we explored the recommendations for enhancing telewellness models for individuals with COPD. METHODS: In-depth semi-structured interviews were conducted with participants (n=15) who completed the program. Transcripts were analyzed using Braun and Clarke's six-step thematic analysis. RESULTS: Twelve primary themes were identified. Participants reported improvements in motivation, confidence in physical activity, emotional regulation, and nutrition awareness. The group-based format reduced isolation and fostered peer support. Program engagement was influenced by symptom burden, comorbidities, home environment, social support, and digital literacy. Participants valued supportive instructors, multimodal instructions (verbal, visual, written summaries, live demonstrations), adaptive exercise program, a user-friendly telehealth platform, and program's holistic nature. Participants emphasized the need for tailored nutrition guidance, technical training for telehealth platform and equipment use, and long-term access to program resources. CONCLUSION: A generic, 8-week telewellness program designed for individuals with mobility limitations was acceptable and beneficial for individuals with COPD.
Analysis of Current Status and Influencing Factors of Inhaler Treatment Adherence Among COPD Patients.
Jin Z, Ba B, Zhang W … +2 more , Yang Z, Wang X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42232872 · Full text
PURPOSE: To investigate the current status of inhaler treatment adherence and analyze its influencing factors among patients with chronic obstructive pulmonary disease (COPD) based on the clinical treatment data of a ter...
PURPOSE: To investigate the current status of inhaler treatment adherence and analyze its influencing factors among patients with chronic obstructive pulmonary disease (COPD) based on the clinical treatment data of a tertiary grade A hospital. PATIENTS AND METHODS: A retrospective study design was adopted. COPD patients who received inhaler treatment at The First Affiliated Hospital of Shihezi University from July to December 2023 were enrolled. Their medical visit records, prescription data within 18 months after enrollment, and medical insurance reimbursement records were collected. Medication adherence was evaluated using proportion of days' supply covered (PDC) calculated from prescription and reimbursement records, not by direct measurement of actual inhaler, and patients were divided into three groups. The relationships between adherence and patients' basic characteristics, disease-related factors, and inhaler usage were analyzed. RESULTS: A total of 706 patients were included in the study. Overall, patient adherence was poor as assessed by PDC, mean PDC of 43.67% ± 32.44%. Among them, 18.42% of patients had high adherence and 60.48% had low adherence. Male patients and those with a smoking history had higher adherence. The inhaler treatment adherence of COPD patients increased with the aggravation of the disease (Gamma = 0.267, p = 0.024), the prolongation of disease duration (r = 0.155, p < 0.01), and the increase in the number of acute exacerbations (p < 0.01). Patients using fluticasone furoate/vilanterol/umeclidinium bromide inhalation powder had higher overall adherence than those using budesonide/formoterol fumarate inhalation powder. CONCLUSION: Among patients with COPD at our hospital, adherence to inhaled therapy as measured by PDC is generally low. Lower PDC was observed in newly diagnosed patients and those without a history of acute exacerbations. In clinical practice, greater emphasis should be placed on medication education and long-term management for these patients.
Laryngeal Responses During Non-Invasive Ventilation in Stable Chronic Obstructive Pulmonary Disease: An Observational Study.
Brekka AK, Solli PV, Indrekvam S … +9 more , Engeset MS, Røksund OD, Lehmann S, Clemm HH, Halvorsen T, Heimdal JH, Murphy PB, Vollsæter M, Andersen TM
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42232871 · Full text
PURPOSE: Long-term non-invasive ventilation (NIV) is an established therapy for hypercapnic chronic obstructive pulmonary disease (COPD); however, many patients remain challenging to ventilate effectively. We hypothesize...
PURPOSE: Long-term non-invasive ventilation (NIV) is an established therapy for hypercapnic chronic obstructive pulmonary disease (COPD); however, many patients remain challenging to ventilate effectively. We hypothesized that NIV-induced laryngeal obstruction (NIV-ILO), observed during laryngoscopy, may contribute to reduced ventilatory effectiveness, and that this obstruction can be identified using laryngeal ultrasound (US). PATIENTS AND METHODS: This exploratory cross-sectional study included 15 participants with stable COPD receiving long-term NIV. Laryngeal responses were assessed using transnasal flexible laryngoscopy (TFL) and US. Assessments began during spontaneous breathing, followed by NIV at each participant's prescribed settings. Inspiratory positive airway pressure (IPAP) was increased in 2 cmHO increments to the device's maximum. Laryngeal responses were assessed in real time and reassessed retrospectively from video recordings. The participants rated discomfort using a numeric rating scale (0-10). RESULTS: Fifteen participants (40% female) were included. The prescribed IPAP ranged from 7 to 30 cmHO, with NIV-ILO observed in 5 of 15 participants at a median of 22.0 cmHO. During subsequent pressure increments, additional 6 of 15 developed NIV-ILO at a median (range) IPAP of 20.5 cmHO (16.0-30.0), yielding 11 participants (73.3%) developing NIV-ILO within the pressure range of their device. US was assessable in 11 participants, with the structures of interest visualized during 54 of 63 pressure increments. The two methods demonstrated complete concordance for all assessable findings. CONCLUSION: NIV-ILO was common in patients with COPD using long-term NIV, occurring within the pressure range typically applied to achieve effective ventilation. US can serve as a less invasive diagnostic alternative to TFL.
Dipeptidyl Peptidase-4 Inhibitor Use and Risk of Major Adverse Cardiovascular Events in Patients with COPD and Diabetes: A Nationwide Retrospective Cohort Study.
Ho CH, Shao YC, Wu YC … +1 more , Liao KM
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42232870 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder frequently followed by cardiovascular disease and diabetes mellitus (DM) that may increase the risk of major adverse cardiovasc...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder frequently followed by cardiovascular disease and diabetes mellitus (DM) that may increase the risk of major adverse cardiovascular events (MACE). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely used antidiabetic agents with potential anti-inflammatory and cardiovascular protective effects beyond glycemic control. This study investigated the association between DPP-4i use and the risk of MACE in patients with COPD and comorbid DM. METHODS: This nationwide retrospective cohort study used data from Taiwan's National Health Insurance Research Database between 2016 and 2021. Patients aged ≥40 years with at least one hospitalization for COPD and a diagnosis of DM were included. DPP-4i users were identified by prescription records (ATC code A10BH*), and non-users were defined as patients receiving other antidiabetic agents without DPP-4i. The primary outcome was MACE, defined as a composite of cardiovascular death, myocardial infarction, and stroke. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) of MACE with 95% confidence intervals (CIs), adjusting for demographic characteristics, comorbidities, and overall disease burden. RESULTS: A total of 24,215 patients with COPD and DM were included, of whom 5737 (23.7%) were DPP-4i users and 18,478 (76.3%) were non-users. During follow-up, DPP-4i users had a significantly lower incidence of MACE compared with non-users (17.88% vs 26.34%, p < 0.0001). Non-DPP-4i use was associated with a higher risk of MACE (adjusted HR: 1.56; 95% CI: 1.46-1.67; p < 0.0001) compared with DPP-4i use. The association of DPP-4i was consistent across sex, age groups, and patients with prior myocardial infarction, stroke, or hypertension. CONCLUSION: In this nationwide retrospective cohort study, DPP-4i use was associated with a lower risk of MACE among patients with COPD and comorbid DM. These findings suggest that DPP-4i may provide cardiovascular benefits beyond glycemic control in this high-risk population. However, given the observational design, causal relationships cannot be established, and the findings should be interpreted with caution due to potential residual confounding and selection bias. Further randomized controlled trials are warranted to confirm findings.
The Relationship Between Gas Transfer Measurements, Lung Volumes, and Spirometric Indices in Alpha-1 Antitrypsin Deficiency and Non-AATD COPD: A Systematic Review.
Alshahrani M, Alshehri A, Sapey E … +1 more , Stockley RA
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42232869 · Full text
BACKGROUND: Alpha-1 Antitrypsin Deficiency (AATD) is associated with persistent airflow limitation with a predominant emphysema phenotype. While spirometry is the gold standard for diagnosis and staging of airflow obstru...
BACKGROUND: Alpha-1 Antitrypsin Deficiency (AATD) is associated with persistent airflow limitation with a predominant emphysema phenotype. While spirometry is the gold standard for diagnosis and staging of airflow obstruction, gas transfer is more specific for alveolar damage and may support early diagnosis. We performed a systematic review of the published evidence to support measurements of gas transfer in AATD, with comparison to non-AATD Chronic Obstructive Pulmonary Disease (COPD). METHODS: The systematic review was conducted using standardised methodology (protocol registration number: CRD42024516788). Electronic databases were searched and randomised controlled trials, observational studies, and case series of >10 participants with AATD which compared gas transfer tests with spirometry were included. Non-AATD COPD studies were included only where they contained a separate AATD comparative cohort. Risk of bias was assessed using Newcastle-Ottawa Scale. The primary outcome was the relationship between gas transfer and airflow obstruction. Additional outcomes included gas transfer measurements with other lung function measures, respiratory symptom scores, exacerbation frequency, mortality, and imaging markers of emphysema. RESULTS: Twenty-two studies were included. Gas transfer impairment was common in patients with AATD and generally associated with worse airflow obstruction. Gas transfer impairment related strongly with imaging markers of emphysema and was consistently associated with worse health-related quality of life (HRQL), greater exacerbation frequency, and increased mortality, most strongly in AATD, but also in non-AATD COPD patients. In several studies, impaired gas transfer was present with normal spirometry and studies of never smokers identified through screening suggested that impairments in gas transfer were an early marker of disease. However, all studies highlighted the heterogeneity of lung function decline and presentation in AATD, which could only be partially explained by antitrypsin genotype. CONCLUSION: Gas transfer measurements provide valuable, early information in assessing physiological impairment and risk of poor outcomes in both AATD and non-AATD COPD.
Genetic and Epigenetic Association of Lung Function and Chronic Obstructive Pulmonary Disease-Related Phenotypes in the Korean Genome and Epidemiology Study: A Scoping Review.
Kang SY, Roh S, Gim JA
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42226760 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is influenced by environmental exposure and genetic susceptibility. Although large-scale genetic studies have identified loci associated with COPD and lung functio...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is influenced by environmental exposure and genetic susceptibility. Although large-scale genetic studies have identified loci associated with COPD and lung function, most evidence has come from populations of European ancestry, and data from Asian populations remain limited. OBJECTIVE: This scoping review aimed to summarize KoGES-based studies on genetic and epigenetic associations with COPD and COPD-related lung function phenotypes. METHODS: PubMed, Scopus, Web of Science, KoreaMed, RISS, KISS, and DBpia were searched from inception to April 27, 2026. Original studies using KoGES data to investigate genetic or epigenetic associations with COPD, airflow limitation, lung function traits, or longitudinal lung function decline were included. The review followed the Arksey and O'Malley framework and PRISMA-ScR guidance. RESULTS: Of 20 unique records identified for final assessment, one conference abstract/preliminary report corresponding to a subsequently published full-length article was removed before screening. The remaining 19 records were screened, and 12 studies met the eligibility criteria. Most KoGES-based studies focused on spirometric traits, including FEV1, FEV1/FVC, and longitudinal lung function decline, rather than clinically defined COPD. Major approaches included genome-wide association studies (GWAS), exome array analysis, gene-environment interaction, polygenic/genetic risk score (PRS/GRS) analysis, epigenome-wide association studies (EWAS), and heritability analysis. Recurrent signals involved FAM13A and the 6p21/AGER region. Recent studies increasingly addressed longitudinal phenotypes, including rapid FEV1 decline and annual lung function decline. CONCLUSION: KoGES-based studies provide population-specific evidence on genetic and epigenetic associations with COPD-related lung function phenotypes in Koreans. However, evidence for clinically defined COPD, externally validated risk prediction, and integrative multi-omics remains limited. Future studies should distinguish spirometric traits, longitudinal decline, and clinically defined COPD while validating KoGES findings in larger Asian and multi-ethnic populations.
Development and Interpretable Machine Learning-Based Prediction of Cardiovascular Disease Risk in Chinese COPD Patients: An Analysis of the CHARLS Database.
Yuan Y, Zhu J, Zhao X … +9 more , Huang Q, Li J, Wang Y, Liu W, Chen M, Li D, Wu B, Li W, Wu D
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42220548 · Full text
BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) experience a significant decline in their quality of life owing to cardiovascular disease (CVD). This study aimed to develop a predictive framewor...
BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) experience a significant decline in their quality of life owing to cardiovascular disease (CVD). This study aimed to develop a predictive framework for evaluating CVD risk in patients with COPD. PATIENTS AND METHODS: Data from 1070 COPD patients participating in the 2015 China Health and Retirement Longitudinal Study (CHARLS) were analyzed. To ensure robust feature selection, Least Absolute Shrinkage and Selection Operator (LASSO) regression and the Boruta algorithm were utilized. Subsequently, the predictive performance of six distinct Machine learning (ML) models (Logistic Regression, Random Forest, Support Vector Machine (SVM), Gradient Boosting Machine, XGBoost, and Multi-Layer Perceptron) was comprehensively compared. The Synthetic Minority Oversampling Technique-Nominal Continuous (SMOTE-NC) was applied to the training set to combat class imbalance. An interpretable risk assessment tool was developed using SHapley Additive exPlanations (SHAP). RESULTS: 305 participants (28.50%) had CVD. Seven variables were used to build the six models. The SVM model showed comparatively better performance than the others, with a training Area Under the Receiver Operating Characteristic curve (AUROC) of 0.819 (95% Confidence Interval (CI) 0.793-0.844), accuracy of 74.42%, sensitivity of 75.56%, precision of 74.18%, specificity of 73.26%, and F1 score of 74.86%. In the test set, the AUROC was 0.719 (95% CI, 0.670-0.760), with an accuracy of 68.63%, sensitivity of 64.20%, precision of 66.53%, specificity of 64.96%, and F1 score of 69.36%. CONCLUSION: This study identified seven key predictors-sex, body weight, hypertension, dyslipidemia, disability, self-rated health, and vision status-that are significantly associated with cardiovascular risk in Chinese patients with COPD. Among the six machine-learning algorithms evaluated, the SVM model demonstrated the most robust performance; however, its predictive capacity remains moderate, reflecting the inherent limitations of cross-sectional survey data and the reliance on self-reported diagnoses. Future prospective studies and rigorous external validation in independent cohorts are essential to refine these predictors and translate this machine-learning approach into reliable clinical decision-support systems for the personalized management of COPD patients.
Revisiting Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Insights from Applying the Rome Proposal in a North American Academic Hospital.
Saint-Pierre MD, Neder JA
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42220547 · Full text
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are traditionally classified by healthcare utilization, a framework that may not reflect physiologic severity. The 2021 Rome Proposal intr...
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are traditionally classified by healthcare utilization, a framework that may not reflect physiologic severity. The 2021 Rome Proposal introduced objective criteria for grading AECOPD, but North American data, including emergency department (ED)-treated patients, are limited. RESEARCH QUESTIONS: To determine the distribution of AECOPD severity using the Rome Proposal in a North American hospital cohort, characterize patients with mild events, and assess whether Rome-based grading predicts short-term readmissions among ED-treated patients. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study of 481 patients treated for AECOPD in a large tertiary hospital in Ontario, Canada, between January 2022 and September 2024. Events were reclassified as mild, moderate, or severe as per the Rome Proposal criteria (modified Medical Research Council score ≥2 substituted for dyspnea visual analog scale). Clinical characteristics and 1- and 3-month hospital representation were analyzed. RESULTS: Overall, 49% of events were severe, 22% moderate, and 29% mild. Among hospitalized patients, 69% met criteria for severe AECOPD, whereas most ED-only events were mild (65%). Compared with moderate/severe events, mild events were associated with younger age, less home supplemental oxygen use, and higher mean forced expiratory volume in the first second. Among ED-treated patients, moderate/severe events were associated with significantly higher 3-month representation for AECOPD (31% versus 16%; mean 0.48 versus 0.18 visits per patient). INTERPRETATION: Application of the Rome Proposal criteria substantially reclassified AECOPD severity and demonstrated meaningful clinical and prognostic discrimination, particularly in ED-treated patients.
Gender Divergence in COPD Phenotypes and Narrowing Urban-Rural Diagnostic Gaps: A Surveillance Study in Chongqing, China, 2020-2024.
Tan Q, Gao Y, Lv X … +3 more , Jiao Y, Lian J, Ding X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42220546 · Full text
PURPOSE: To analyze epidemiological trends of COPD, chronic bronchitis, and emphysema in Chongqing, China (2020-2024), and assess spirometry-confirmed diagnosis rates. PATIENTS AND METHODS: Data were obtained from the Ch...
PURPOSE: To analyze epidemiological trends of COPD, chronic bronchitis, and emphysema in Chongqing, China (2020-2024), and assess spirometry-confirmed diagnosis rates. PATIENTS AND METHODS: Data were obtained from the Chongqing Chronic Disease Surveillance System (CCDSS), including 975,421 incident cases and 1,244,978 prevalent cases among residents aged ≥15 years, and 239,086 deaths from all age groups. Age‑standardized rates were calculated using the 2000 Chinese census population. Type 1 (spirometry‑confirmed) COPD diagnosis rate was analyzed by urban-rural residence. RESULTS: Age-standardized prevalence per 100,000 increased for COPD (732.06 to 1,424.54), emphysema (182.51 to 536.71), and chronic bronchitis (309.48 to 1,021.75). COPD and emphysema were male-predominant; chronic bronchitis became female-predominant after 2023. Rural burden was consistently higher. Type 1 diagnosis rate rose sharply from 6.96% (2022) to 26.04% (2024), with urban-rural gap narrowing to 0.77 percentage points. CONCLUSION: The rising prevalence mainly reflects improved case ascertainment. Female‑predominant chronic bronchitis highlights the need for sex‑specific public health strategies. The rapid increase in spirometry‑confirmed diagnosis and near‑elimination of urban-rural disparity demonstrate a successful model for diagnostic standardization in primary care.
and Polymorphisms Modulate COPD Susceptibility in a High-Altitude Population: A Case-Control Study.
Lin L, Zhang Y, Fu X … +5 more , Zhang Y, Wang Y, Yang Z, Ma X, Wang X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42206079 · Full text
BACKGROUND: The onset and progression of Chronic Obstructive Pulmonary Disease (COPD) are influenced by both environmental and genetic factors. Persistent hypoxia at high altitudes is a major environmental stressor. Unde...
BACKGROUND: The onset and progression of Chronic Obstructive Pulmonary Disease (COPD) are influenced by both environmental and genetic factors. Persistent hypoxia at high altitudes is a major environmental stressor. Under hypoxic conditions, is stably expressed and activates its downstream target gene ; however, the underlying mechanisms remain unclear. METHODS: We conducted a case-control study in Gansu Province: to evaluate the association between gene polymorphisms (rs4953354, rs6743991, rs7589861, rs13419896) and susceptibility to COPD in high-altitude populations, we enrolled 517 patients and 580 controls (no significant differences in ethnic distribution, no stratification was performed); To evaluate the association of gene polymorphisms (rs10434, rs2010963, rs3025020, rs833070) in Tibetan and Han populations, we enrolled 397 patients (148 Tibetans, 249 Han) and 807 controls (251 Tibetans, 556 Han). RESULTS: For , rs4953354 A>G was associated with a decreased risk of COPD (AG vs. AA: OR = 0.680, 95% CI = 0.523-0.885; AG+GG vs. AA: OR = 0.708, 95% CI = 0.551-0.910). For , in Han population, rs2010963 C>G (CG vs. CC: OR = 1.619, 95% CI = 1.070-2.449; GG vs. CC: OR = 1.751, 95% CI = 1.119-2.740; CG+GG vs. CC: OR = 1.670, 95% CI = 1.133-2.462) and rs3025020 C>T (TT vs. CC: OR = 2.290, 95% CI = 1.321-3.971; TT vs. CT+CC: OR = 2.151, 95% CI = 1.276-3.626) were associated with an increased risk of COPD. Conversely, in the Tibetan population, rs3025020 C>T was associated with a decreased risk of COPD (CT vs. CC: OR = 0.530, 95% CI = 0.329-0.853; CT+TT vs. CC: OR = 0.571, 95% CI = 0.365-0.893). No significant associations were observed for other loci. CONCLUSION: This study reveals that and gene polymorphisms are associated with susceptibility to COPD in populations residing at high altitudes.
Smoking-Attributable Burden of Chronic Obstructive Pulmonary Disease from 1990 to 2021: Temporal Trends and Evidence from the Global Burden of Disease Study.
Ma T, Yue X, Rong S … +5 more , Sun R, Wang J, Zheng X, Chen X, Sun R
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42206078 · Full text
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide, with smoking being the primary contributor. This study aims to assess the temporal and spatial trends in th...
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide, with smoking being the primary contributor. This study aims to assess the temporal and spatial trends in the burden of smoking-attributable COPD from 1990 to 2021 and project future trajectories, providing insights for COPD prevention strategies. METHODS: The data were sourced from the Global Burden of Disease (GBD) 2021 database, incorporating estimates and uncertainty intervals () for deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) of smoking-attributable COPD across 204 countries and regions worldwide. Estimated annual percentage change (EAPC), frontier analysis, decomposition analysis, and Bayesian age-period-cohort (BAPC) modeling were used to evaluate temporal trends, development-related gaps, drivers of change, and future burden. RESULTS: From 1990 to 2021, global smoking-attributable COPD showed a divergence between rising absolute burden and declining ASRs. Deaths increased from 10,538 (95% : 8,724-12,339) hundred to 13,350 (95% : 10,533-15,966) hundred, and DALYs rose from 23,601 (95% : 19,648-27,495) thousand to 27,795 (95% : 22,234-32,884) thousand, whereas ASRs declined across most regions. The steepest declines in ASRs were observed in High-middle SDI regions, whereas Middle and Low-middle SDI regions carried the greatest absolute burden in 2021. Males consistently bore a higher burden than females. DALYs increased with age, peaking at 70-74 years. Ageing and population growth were the main contributors to the rise in DALYs, while epidemiological changes had a negative effect. By 2040, global ASMR and ASDR are projected to decline to 11.62 and 240.32 per 100,000 population, respectively. CONCLUSION: Despite global progress in reducing the ASRs of smoking-related COPD, the absolute burden continues to rise. Further progress may require sustained tobacco control, earlier detection, and improved long-term COPD care, especially in settings where demographic pressures offset epidemiological gains.
Genetically Predicted Use of Common Analgesics and Risk of Chronic Obstructive Pulmonary Disease: A Bidirectional Mendelian Randomization Study.
Chen G, You W
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42199875 · Full text
BACKGROUND: Observational studies suggest a link between common analgesic use and chronic obstructive pulmonary disease (COPD), but causality is unclear. This study aimed to investigate the bidirectional causal relations...
BACKGROUND: Observational studies suggest a link between common analgesic use and chronic obstructive pulmonary disease (COPD), but causality is unclear. This study aimed to investigate the bidirectional causal relationship between the genetically predicted use of paracetamol, aspirin, and ibuprofen, and COPD risk using a two-sample Mendelian randomization (MR) approach. METHODS: We performed a bidirectional MR study using summary statistics from large-scale genome-wide association studies (GWAS). Genetic instruments for paracetamol, aspirin, and ibuprofen use were from the UK Biobank (N=457,547). COPD summary statistics were from the FinnGen consortium (24,138 cases, 409,070 controls). The primary analysis used the inverse-variance weighted (IVW) method. We conducted extensive sensitivity analyses (MR-Egger, weighted median, weighted mode, MR-PRESSO) to assess pleiotropy and heterogeneity. RESULTS: Genetically predicted paracetamol use was significantly associated with an increased risk of COPD (IVW OR: 6.00, 95% CI: 2.43-14.82, P < 0.001). Conversely, genetically predicted aspirin use was associated with a decreased risk of COPD (IVW OR: 0.19, 95% CI: 0.05-0.71, P = 0.014). Genetically predicted ibuprofen use showed no significant association with COPD risk (IVW OR: 0.47, 95% CI: 0.06-3.82, P = 0.483). In the reverse analysis, genetic liability to COPD was not causally associated with the use of any of the three analgesics (P > 0.05). Sensitivity analyses supported the robustness of these findings, showing no significant directional pleiotropy or heterogeneity for the primary results. CONCLUSION: This MR study provides genetic evidence supporting a causal relationship between paracetamol use and an increased risk of COPD, and between aspirin use and a decreased risk. These findings suggest that the choice of analgesic may have important implications for COPD risk, warranting further clinical investigation.
Genetic and Molecular Interconnections Between Chronic Obstructive Pulmonary Disease and Osteoporosis: Insights from Single-Cell and Mendelian Randomization Analyses.
Xue C, Liu P, Zhao S … +5 more , Wei A, Huang L, Li L, Xu H, Zhao D
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42180802 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and osteoporosis are common comorbid conditions, both of which impose a significant health burden. This research employs single-cell data and Mendelian randomizati...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and osteoporosis are common comorbid conditions, both of which impose a significant health burden. This research employs single-cell data and Mendelian randomization analysis to pinpoint genes associated with both conditions and investigate their possible mechanistic links. METHODS: Single-cell datasets pertaining to chronic obstructive pulmonary disease and osteoporosis were subjected to analysis to identify DEGs. Mendelian Randomization analysis was employed to prioritize key causal genes. Subsequent functional profiling encompassed the reconstruction of gene regulatory networks, evaluation of Chemical-disease associations, annotation of specific cell types, and development of pseudo-time trajectory models, along with immune cell infiltration analysis, molecular docking, and molecular dynamics simulations. RESULTS: Single-cell analysis found 2,623 genes linked to chronic obstructive pulmonary disease and 2,454 to osteoporosis, with 161 genes upregulated and 106 downregulated in both. Mendelian randomization analysis identified PADI4 and TUBB2A as key regulators. The MAPK signaling pathway was a critical shared pathway. Molecular docking and molecular dynamics simulations revealed strong binding potential between BPA, TCDD, estradiol and the target proteins. NK cells were identified as a key cell type in COPD, and monocytes in osteoporosis. Pseudo-time analysis revealed distinct developmental trajectories for NK and monocyte subpopulations. CONCLUSION: This study identifies PADI4 and TUBB2A as potential genetic links between COPD and osteoporosis, and highlights BPA, TCDD, and estradiol as potential chemical factors, providing insights into their shared molecular mechanisms.
COPD-Lung Cancer Comorbidity: Mechanistic Insights and Precision Oncology Implications.
He Y, Liu B, Li W … +2 more , Zhou X, Tao H
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42180801 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and lung cancer frequently coexist, constituting a clinically consequential comorbidity with major implications for precision medicine. MECHANISTIC INSIGHTS: Beyon...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and lung cancer frequently coexist, constituting a clinically consequential comorbidity with major implications for precision medicine. MECHANISTIC INSIGHTS: Beyond shared environmental exposures such as tobacco smoke and air pollution, COPD has emerged as an independent driver of pulmonary carcinogenesis, mediated through persistent inflammation, genomic instability, epigenetic remodeling, and microbiome-immune dysregulation. Patients with COPD-associated lung cancer exhibit distinct molecular hallmarks, including reduced EGFR mutation frequency, enrichment of LRP1B truncations, and elevated tumor mutational burden, which collectively reprogram tumor immunogenicity and therapeutic responsiveness, favoring immune checkpoint blockade over targeted EGFR-directed therapy. DIAGNOSTIC AND PREVENTIVE STRATEGIES: Recent advances integrating low-dose CT (LDCT) with spirometry, liquid biomarkers (eg, S100A12, TLR4), and AI-enhanced radiomic algorithms have substantially improved early detection capabilities. In parallel, microbiome-derived signatures provide novel tools for risk stratification and treatment personalization. THERAPEUTIC IMPLICATIONS: Preventive and therapeutic strategies, including statin therapy, inhaled corticosteroids, preoperative pulmonary optimization, and microbiome modulation, are emerging as promising approaches to intercept the COPD-lung cancer continuum and improve clinical outcomes. CONCLUSION: This review synthesizes current evidence spanning epidemiology, molecular pathogenesis, diagnostic innovations, and comorbidity-tailored interventions, culminating in a "comorbidity-centered precision management" framework. By bridging mechanistic discoveries with clinical implementation, this paradigm may contribute to reducing COPD-lung cancer mortality and could support the advancement of the global precision oncology agenda.
Gene Polymorphisms and Their Association with COPD in Tibetan and Han Populations from Gansu, China.
Gao R, Zhang M, Zhang Y … +5 more , Wang Y, Yang Z, Lin A, Wu Y, Wang X
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42180800 · Full text
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is influenced by both genetic and environmental factors, with chronic hypoxia playing a pivotal role in its pathogenesis. Peroxisome proliferator-activated recepto...
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is influenced by both genetic and environmental factors, with chronic hypoxia playing a pivotal role in its pathogenesis. Peroxisome proliferator-activated receptor alpha (PPARA), a core regulator of the hypoxia pathway, exhibits genetic differentiation in high-altitude populations. This study aimed to investigate the association between PPARA gene polymorphisms and COPD susceptibility in Tibetan and Han populations in Gansu Province. METHODS: A case-control study design was employed. A total of 1276 participants (399 Tibetans and 877 Han Chinese) were recruited from Gansu province. Using Haploview software, four tag SNPs of the gene (rs135538, rs135539, rs135549, rs4253758) were selected. Genotyping was performed using the iMLDR (Improved Multiple Ligase Detection Reaction) multiplex SNP genotyping technique. RESULTS: In the Tibetan population, the rs135539A>C polymorphism under a dominant model was associated with an increased risk of COPD (CC+CA vs. AA: = 1.779, 95% CI: 1.080-2.903, =0.024). In the Han population, rs135549T>C under a dominant model was associated with a reduced COPD risk (CC+CT vs. TT: = 0.719, 95% CI: 0.547-0.944, = 0.017). The rs4253758T>C SNP exhibited a dual effect in Han Chinese: under an additive model, both TC ( = 1.722, 95% CI: 1.504-2.813, = 0.030) and CC ( = 1.778, 95% CI: 1.083-2.922, = 0.023) genotypes increased risk compared to the TT genotype. However, under a recessive model, the CC genotype was protective compared to TT+TC ( = 0.572, 95% CI: 0.356-0.918, = 0.021). No significant associations were found for other SNPs. CONCLUSION: gene polymorphisms are associated with COPD susceptibility in a population-specific manner among Tibetan and Han populations in Gansu. The rs135539A>C variant increases COPD risk in Tibetans, whereas rs135549T>C and rs4253758T>C exert protective and dual effects, respectively, in the Han population.
Longitudinal Spirometric Trajectory from Normal Lung Function to PRISm and COPD in a Population-Based Korean Cohort.
Kang SY, Roh S, Yeo IH … +3 more , Ko YK, Oh JY, Gim JA
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42180799 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) develops through heterogeneous lung-function trajectories, but the longitudinal role of preserved ratio impaired spirometry (PRISm) in progression toward COPD rema...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) develops through heterogeneous lung-function trajectories, but the longitudinal role of preserved ratio impaired spirometry (PRISm) in progression toward COPD remains unclear. OBJECTIVE: We aimed to characterize long-term spirometric trajectories and transitions from normal spirometry to PRISm or COPD in a population-based cohort. PATIENTS AND METHODS: We analyzed data from the Ansan-Ansung cohort of the Korean Genome and Epidemiology Study. Among medication-free participants with normal baseline spirometry who had classifiable spirometry across seven examinations over approximately 12 years, longitudinal trajectories of forced expiratory volume in 1 second (FEV, % predicted) and the FEV/FVC ratio were evaluated. Participants were classified into normal maintenance, PRISm, or COPD trajectory groups using a clinically interpretable, rule-based approach. Because post-bronchodilator measurements were not available across all examinations, COPD was operationally defined using pre-bronchodilator spirometry as FEV/FVC < 0.70. RESULTS: Lung-function decline followed heterogeneous trajectories rather than a single linear pathway. Among 1,753 participants, 1,658 (94.6%) remained normal, 21 (1.2%) developed PRISm, and 74 (4.2%) progressed to COPD. Most individuals who developed COPD did so without a preceding sustained PRISm phase. In descriptive baseline comparisons, the COPD trajectory showed greater smoking exposure, higher blood pressure, and more pronounced central adiposity, whereas PRISm was more closely associated with wheeze-related respiratory symptoms and lower baseline lung function. In multivariable logistic regression, older age and current smoking were the strongest independent predictors of progression to COPD. CONCLUSION: Progression toward COPD in the general population is heterogeneous, and PRISm is not an obligatory precursor to COPD. Longitudinal spirometric assessment may provide clinically relevant insights beyond single time-point classification in the general population.
Small Airway Disease in Pre-COPD and Early COPD: Insights Into the Pulmonary "Silent Zone".
Li J, Liu L, Tang J … +3 more , He C, Pu G, Sun J
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42164058 · Full text
Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a life-course disorder with origins rooted in early-life insults. However, the current diagnostic reliance on the FEV1/FVC < 0.7 threshold often...
Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a life-course disorder with origins rooted in early-life insults. However, the current diagnostic reliance on the FEV1/FVC < 0.7 threshold often fails to capture the early phases of disease evolution, particularly within the pulmonary "Silent Zone." This narrative review examines small airway disease (SAD) in pre-COPD and early COPD by integrating physiological, structural, molecular, and diagnostic evidence. Findings from imaging and pathology studies indicate that terminal bronchiole loss, mucus plugging, alveolar attachment disruption, and vascular remodeling may occur before overt spirometric obstruction develops. We also summarize candidate molecular mechanisms that may contribute to early remodeling, including ATP5B-related epithelial signaling, STAT3/PINK1-Parkin-associated mitophagy, endothelial-to-mesenchymal transition, and inflammaging, while emphasizing that many of these pathways remain preliminary and require further validation. To bridge the diagnostic gap, we review multimodal approaches including FEV3-based indices, impulse oscillometry, parametric response mapping, CT-visible airway counts, and computational fluid dynamics. We further discuss clinical phenotypes such as PRISm and non-obstructive chronic bronchitis, as well as the contribution of non-tobacco environmental exposures. Overall, this review highlights how a Silent Zone-centered framework may improve early risk stratification and inform future studies aimed at disease modification before irreversible airflow obstruction develops.
From Weight Loss to Standardized Sarcopenia Assessment: A Multi-Database Bibliometric Study of COPD with Sarcopenia (2005-2025).
Fang H, Zhao Y, Wang J … +1 more , Wu H
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42158234 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) often coexists with sarcopenia, contributing to poorer exercise tolerance, quality of life, and prognosis. Although interest in this topic has increased, a compreh...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) often coexists with sarcopenia, contributing to poorer exercise tolerance, quality of life, and prognosis. Although interest in this topic has increased, a comprehensive bibliometric overview is still lacking. METHODS: English-language articles and reviews on COPD complicated with sarcopenia published between 2005 and 2025 were retrieved from the Web of Science Core Collection and Scopus. After screening and deduplication, bibliometric and visualisation analyses were conducted using bibliometrix/biblioshiny, VOSviewer, and CiteSpace to evaluate publication trends, major contributors, collaboration networks, co-citation patterns, and keyword evolution. RESULTS: A total of 922 publications from 421 journals were included. Output increased markedly over time, especially after 2018, peaking in 2025. The United States and China were the main contributors and major collaboration hubs, while several European countries showed strong international collaboration and high citation impact. Core journals included International Journal of Chronic Obstructive Pulmonary Disease, Journal of Cachexia, Sarcopenia and Muscle, and Clinical Nutrition. Co-citation analysis showed that the knowledge base was mainly supported by studies on COPD systemic effects and body composition, together with consensus documents on sarcopenia definition and grading. Research hotspots evolved from early work on weight loss, malnutrition, and muscle wasting to functional assessment and clinical outcomes, and more recently to interventions such as nutrition support, resistance training, and pulmonary rehabilitation, alongside emerging mechanistic themes including inflammation, oxidative stress, and metabolic abnormalities. CONCLUSION: Research on COPD complicated with sarcopenia has shifted from descriptive phenotypes to standardised assessment, functional outcomes, and clinical management. Future studies should strengthen multicentre longitudinal designs and multidisciplinary collaboration to better integrate mechanisms with clinical assessment and intervention.
Impact of Nutritional Status and Sarcopenia on Acute Exacerbation Risk in Stable Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.
Pan H, Wang M, Chen X … +1 more , Wang Y
Int J Chron Obstruct Pulmon Dis · 2026 · PMID 42158233 · Full text
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) drive disease progression and mortality. This study aims to investigate whether nutritional risk and sarcopenia independently predict (AEC...
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) drive disease progression and mortality. This study aims to investigate whether nutritional risk and sarcopenia independently predict (AECOPD) in patients with stable COPD. METHODS: In this single-center retrospective cohort study, 264 hospitalized patients with stable COPD were followed for 12 months. Nutritional risk was assessed using the Nutritional Risk Screening 2002. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Appendicular skeletal muscle index (ASMI), handgrip strength, gait speed, and five-repetition sit-to-stand (5STS) time were measured. Independent predictors of AECOPD were identified using multivariable logistic regression. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: During follow-up, 102 patients (38.6%) developed AECOPD. Patients with AECOPD exhibited higher rates of sarcopenia (64.71% vs. 32.72%, < 0.001) and nutritional risk (64.71% vs. 39.51%, < 0.001), alongside lower ASMI, reduced handgrip strength, slower gait speed, and prolonged 5STS time (all < 0.01). After adjustment for age, sex, smoking history, forced expiratory volume in 1 second (FEV)% predicted, and prior AECOPD, and comorbidity burden, both sarcopenia (OR 6.265, 95% CI 3.008-13.049) and nutritional risk (OR 3.016, 95% CI 1.571-5.793) remained independent predictors. ASMI demonstrated a protective association (OR 0.266, 95% CI 0.177-0.399), while TNF-α was positively associated with AECOPD risk (OR 1.175, 95% CI 1.044-1.322). The ASMI-based model achieved the highest discrimination (AUC 0.893). CONCLUSION: Sarcopenia and nutritional risk independently increase AECOPD risk in stable COPD. Incorporating muscle mass parameters into risk stratification may improve predictive accuracy.
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