International Journal of Chronic Obstructive Pulmonary Disease最新文献

Introduction: Nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of oxidative stress responses, is downregulated in patients with GOLD stage III-IV chronic obstructive pulmonary disease (COPD). However, the mechanisms underlying the epigenetic regulation of Nrf2 in COPD remain poorly understood.

Methods: Protein levels of Nrf2, heme oxygenase-1 (HO-1), ten-eleven translocation methylcytosine dioxygenase 1 (TET1), and DNA methyltransferase 1 (DNMT1) were assessed by Western blotting in peripheral lung tissue and primary bronchial epithelial cells obtained from patients with COPD, never-smokers (control-NS), and smokers without COPD (control-S). CSE-treated human bronchial epithelial (HBE) cells were used as an in vitro model. Nrf2 promoter methylation was evaluated using bisulfite sequencing. Apoptosis of HBE cells was measured by flow cytometry. Chromatin immunoprecipitation (ChIP) was performed to assess the binding of TET1 to the Nrf2 promoter. Malondialdehyde (MDA) and superoxide dismutase (SOD) activity assays were used to quantify oxidative stress and antioxidant capacity.

Results: Nrf2 and HO-1 expression was significantly reduced in both lung tissue and primary epithelial cells from patients with COPD. In vitro, CSE exposure increased Nrf2 promoter methylation in HBE cells. Overexpression of Nrf2 mitigated oxidative stress, increased SOD activity, and reduced apoptosis in response to CSE. TET1 expression was decreased in COPD lungs, and TET1 was shown to bind the Nrf2 promoter and enhance its transcription. TET1 overexpression reduced oxidative damage and apoptosis via Nrf2 upregulation.

Conclusion: Reduced Nrf2 expression in COPD may result from promoter hypermethylation. TET1 directly binds and demethylates the Nrf2 promoter, restoring its expression and attenuating CSE-induced HBE cells apoptosis. These findings identify a potential epigenetic mechanism contributing to COPD pathogenesis and suggest TET1 as a novel therapeutic target.

Background: Chronic obstructive pulmonary disease (COPD) involves progressive lung function decline, with hypoxia playing a key pathogenic role. However, systematic investigations focusing on hypoxia-related genes (HRGs) in COPD remain limited.

Methods: We applied machine learning to identify HRG-associated diagnostic biomarkers and evaluated their performance via Receiver Operating Characteristic (ROC) analysis. Mendelian randomization (MR) was conducted to assess causal relationships between candidate genes and COPD. A nomogram model was constructed to evaluate clinical utility, and a ceRNA network was developed using ENCORI database.

Results: Six HRG-based diagnostic biomarkers were identified, including SLC2A1, which demonstrated strong diagnostic value (AUC > 0.8). MR analysis revealed a significant causal effect of SLC2A1 expression on COPD risk (OR = 1.32, 95% CI: 1.02-1.71, P < 0.05). Functional evidence suggests SLC2A1 promotes hypoxia-induced metabolic reprogramming in airway epithelial cells. The constructed nomogram showed good clinical applicability. ceRNA analysis highlighted MALAT1, NEAT1, and XIST as potential upstream regulators.

Conclusion: Our findings identify SLC2A1 as a causal and diagnostically relevant gene in COPD, offering novel insight into hypoxia-driven disease mechanisms and supporting future personalized therapeutic strategies.

Purpose: Older adults with chronic obstructive pulmonary disease (COPD) have a higher risk of falls than their peers without COPD. Home-based exercise programs can improve balance and strength and reduce falls in older adults and could be an option for older adults with COPD who access virtual care. We pilot tested a 6-month home-based balance and strength exercise program with virtual care support aimed at improving strength and balance in people with COPD aged 50 years and over.

Patients and methods: Adults aged 50 years and over with COPD who access a virtual care service were invited to participate in an exercise program designed to improve balance and strength and reduce fall risk.

Results: Thirteen people enrolled in the pilot program (mean age 72 ± SD 7 years, 9 females). Six participants (46%) reported having one or more falls in the 12-months prior to the study. A mixed model for repeated measures and Bonferroni correction for post hoc pairwise comparisons showed significant improvement in the Short Physical Performance Battery (SPPB) score between baseline and 6-months, effect size of 2.01; 95% CI [0.45-3.58], and between 3-months and 6-months, effect size of 1.65; 95% CI [0.48 to 2.81]. The alternate step test improved by more than 3 seconds between baseline and 3-months, effect size of -3.30; 95% CI [-5.94 to -0.66] and improved by 4 seconds between baseline and 6-months, effect size of -4.01; 95% CI [-7.42 to -0.61]. There was no significant difference in fear of falling between between baseline, 3 months or 6 months. The program had a high level of acceptability, with all participants intending to continue to do the exercises and 10/12 (83%) participants stating that they would recommend the program to other people with COPD. The program was feasible to implement, with 12/13 participants remaining in the program and attending exercise sessions.

Conclusion: On average, participants completed the exercises twice per week rather than the recommended 3 times per week. Despite this, the home-based exercise program improved strength and balance, as measured by the SPPB. The program was acceptable to participants and feasible to implement and has the potential to reduce the risk of falls in older people with COPD.

Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of coronary artery disease (CAD). However, the role of emphysema, which represents an important structural subtype of COPD, in the development of CAD remains insufficiently clarified. This study aimed to evaluate whether quantitatively assessed emphysema on high-resolution computed tomography (HRCT) independently predicts CAD in COPD patients.

Methods: This retrospective cohort study included 392 COPD patients with no prior history of CAD between 2015 and 2020. All participants underwent HRCT for automated emphysema quantification using 3D Slicer software. Emphysema extent was quantified as the percentage of low attenuation areas (LAA%) below -950 Hounsfield units, with severe emphysema defined as LAA% >16.95%. Logistic regression and restricted cubic spline (RCS) analysis were employed to assess the relationship between emphysema index and CAD, including subgroup and interaction analyses. The ability of the emphysema index to predict CAD was evaluated using receiver operating characteristic (ROC) curves.

Results: Severe emphysema was independently associated with a higher risk of CAD in COPD patients (OR = 2.08, 95% CI: 1.30-3.34; p = 0.002). This association remained robust even after adjusting for confounders (adjusted OR= 2.28, p = 0.005). RCS analysis indicates that the risk of CAD increases with the rise of the emphysema (p for nonlinearity =0.031). The area under the ROC curve for the predictive model was 0.81 (95% CI 0.77, 0.86). Additionally, patients with severe emphysema exhibited significantly more complex coronary lesions, reflected by higher SYNTAX scores (median 10.00 vs 16.29; p = 0.013).

Conclusion: Quantitative HRCT-based emphysema independently predicts CAD in COPD and demonstrates additive risk with traditional cardiovascular factors. Integrating emphysema quantification with clinical risk assessment improves CAD risk stratification in COPD patients.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with limited response to standard anti-inflammatory therapies. Biologics targeting specific inflammatory pathways have emerged as potential treatments, but their efficacy remains variable across distinct COPD endotypes.

Objective: To systematically evaluate the efficacy and trial quality of biologics tested in COPD patients using a multicriteria decision analysis (MCDA) approach, with attention to type 2 (T2) and non-T2 inflammatory targets.

Methods: We assessed 20 trials encompassing 12 biologics and 9294 patients with COPD. Each trial was scored (0-3 per domain, total 12 points) across four domains: exacerbation reduction, lung function improvement, biomarker stratification, and trial design quality.

Results: Dupilumab (anti-IL-4Rα) demonstrated the most robust efficacy in eosinophilic COPD, with consistent reductions in exacerbation rates and improvements in FEV₁, supported by high trial quality. Mepolizumab and benralizumab (anti-IL-5/IL-5R) showed moderate efficacy in biomarker-enriched populations. Anti-alarmins, specifically tozorakimab (anti-IL-33), itepekimab (anti-IL-33/IL-1RL1), astegolimab (anti-ST2), and tezepelumab (anti-TSLP), showed mixed results, with modest lung function gains but largely non-significant effects on exacerbation rates. Agents targeting non-T2 pathways, including infliximab (anti-TNF-α), canakinumab (anti-IL-1β), MEDI8968 (anti-IL-1R1), CNTO6785 (anti-IL-17A), and ABX-IL8 (anti-IL-8), consistently failed to demonstrate clinical efficacy, often due to small sample sizes, early-phase design, and lack of biomarker stratification.

Conclusion: Biologics targeting T2 inflammation offer therapeutic promise in eosinophilic COPD when guided by biomarkers. Conversely, current biologics directed at non-T2 and alarmin pathways yield limited or inconsistent benefits, emphasizing the need for improved phenotyping and targeted intervention strategies in non-eosinophilic COPD.

Chronic Obstructive Pulmonary Disease (COPD) is a prevalent chronic respiratory disorder characterized by airway inflammation and irreversible airflow limitation. Its marked heterogeneity and complexity pose significant challenges to traditional clinical assessments in terms of prognostic prediction and personalized management. In recent years, the exploration of biomarkers has opened new avenues for the precise evaluation of COPD, particularly through multi-biomarker prediction models and integrative multimodal data strategies, which have substantially improved the accuracy and reliability of prognostic assessments. This review summarizes the key biomarkers associated with COPD prognosis, systematically discusses the practical applications and future potential of combined predictive models and multimodal data integration, and evaluates their translational value in clinical practice. As a narrative review, this study aims to provide a scientific foundation for the precision management of patients with COPD.

Purpose: This study aims to identify predictors of long-term survival in patients with chronic obstructive pulmonary disease (COPD) undergoing anatomical resections for non-small cell lung cancer (NSCLC), with focus on COPD severity, to improve perioperative risk stratification and patient care.

Patients and methods: This retrospective study included all patients with NSCLC and COPD undergoing anatomical resections at the Lung Tumor Center Munich between 2011 and 2020. COPD severity was classified by Global Initiative for Obstructive Lung Disease criteria: Group 1 (mild/moderate obstruction, COPD I-II) and Group 2 (severe obstruction, COPD III-IV). The relationship between COPD severity and perioperative parameters was analyzed using Kaplan-Meier and Cox proportional hazard model.

Results: Of 1663 NSCLC patients undergoing anatomical resections, 476 (28.6%) patients with COPD I-IV (40.5% female, median age 67.28 [60.57; 73.27] years) were included. No significant differences were observed between groups in demographics, topography, TNM classification, histology of the primary tumor, and surgical approach. Group 2 experienced more frequently prolonged mechanical ventilation >2 days (p=0.016), air leaks >5 days (p = 0.020), and arrhythmias (p=0.012). Median overall survival (OS) was reduced in Group 2 (43.73 [30.14; 57.33] vs 85.30 [67.46; 103.14] months, p=0.001). Independent predictors of reduced OS included COPD III-IV (p<0.0001), pT_3-4 (p=0.007), pN_1-2 (p<0.0001), preoperative CRP >0.6 mg/dL (p=0.014) and VO₂max <17 mL/min/kg (p=0.040). These predictors increased the risk of death by 1.6 [1.27-1.90], 1.3 [1.06-1.48], 2.1 [1.49-3.03], 1.6 [1.09-2.20] and 1. [1.02-2.00] fold, respectively.

Conclusion: COPD severity independently predicts perioperative morbidity and long-term survival in operable NSCLC patients. Comprehensive assessment of COPD severity can help in identifying high-risk patients and optimizing perioperative care.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Previous studies have explored the relationship between different dietary patterns, systemic inflammation index (SII)and the risk of COPD. However, the joint effects and interactions between SII and HEI-2015 in COPD have not been fully investigated. This study aimed to explore the relationships between COPD and SII and HEI-2015.

Methods: Data from the National Health and Nutrition Examination Surveys (NHANES) were utilized.Univariate and multivariate logistic regression analyzed the associations between SII and HEI-2015 with COPD. Restricted cubic spline (RCS) model analyzed the relationship between SII and HEI-2015 and COPD.Use the area enclosed under the ROC curve (AUC) to represent its predicted value. Interaction indices and subgroup analyses were performed. The Kaplan-Meier curve was used to evaluate the impact on mortality of COPD patients.

Results: This study included 10,898 participants.After adjusting,logistic regression analysis showed that higher SII (OR=1.03, 95% CI: 1.01-1.05) were associated with an increased risk of COPD, while higher HEI-2015 (OR=0.97, 95% CI: 0.96-0.99) reduced the risk.The RCS model observed a non-linear relationship between SII and HEI-2015 and COPD risk. Additionally, ROC showed a more significant advantage in predicting COPD prevalence (AUC=0.68). Interaction analysis indicated that SII and HEI-2015 might be independent influencing factors for COPD risk. Kaplan-Meier survival curves showed a lower all-cause mortality rate among in the group with high SII and low HEI-2015 (p < 0.0001).

Conclusion: The results of this study indicate that a higher SII level and a lower HEI-2015 are associated with COPD risk. COPD patients with higher SII levels combined with lower HEI - 2015 levels have a higher all-cause death risk.

Purpose: The ASTER study described the management of chronic obstructive pulmonary disease (COPD) by general practitioners (GPs) in Italy, focusing on the treatment patterns and clinical outcomes of patients over 6 months.

Patients and methods: This multicenter prospective cohort study included patients aged 40-80 years with spirometry-confirmed COPD, post-bronchodilator FEV₁ ≥50% of predicted value, and ≤1 exacerbation in the previous year. Eligible patients had a COPD assessment test (CAT) score of ≥10 and, according to the prescription limits for GPs before Note 99, they could have been treated in the last 3 months before enrollment exclusively with a short or long acting bronchodilator or an corticosteroid/long-acting beta₂-agonist ICS/LABA. Patients were evaluated at enrollment, 3 months, and 6 months, with data collected on treatment, exacerbations, patient-reported outcomes (CAT and mMRC scores), and lung function.

Results: Overall, 385 patients were enrolled, and 344 (89.4%) met the study criteria, of which 332 (96.5%) completed the study. The cohort included patients with mild to moderate COPD, predominantly males (61.9%), and current/former smokers (91%). At baseline, ongoing treatments included LAMA (20.9%), ICS/LABA (13.7%), and LABA (2.9%). However, 62.5% of patients were not treated. By 6 months, only 10.2% of patients were not receiving any treatment and 55.4% were treated with a LABA/LAMA combination. FEV1 showed a mean increase of 140 mL, mMRC ≥ 2 decreased from 54.9% to 23.5%, CAT exhibited a 3.6 point mean decrease, and only 13 patients (3.9%) experienced mild/moderate exacerbations in the last 6 months.

Conclusion: ASTER study highlights the effectiveness of COPD treatment by GPs in Italy. Early detection and proactive management, along with a regular treatment prescription was associated with improved lung function, dyspnea, quality of life, and a reduction in the incidence of exacerbations. Empowering GPs with diagnostic and therapeutic responsibilities, improves care and outcomes of COPD.

Purpose: Chronic obstructive pulmonary disease (COPD) is associated with frailty and leads to poor outcomes. The relationship between COPD and cardiovascular events is well established. However, the impact of frailty on cardiovascular events in COPD patients remains unknown. We aimed to evaluate the long-term association between frailty, assessed using the hospital frailty risk score (HFRS), and major adverse cardiovascular events (MACE) in COPD patients.

Patients and methods: We recruited Japanese patients with COPD between 2013 and 2023 from Sado-Himawari Net, a regional electronic health record system in Sado City, Niigata Prefecture, Japan. MACE were defined as a composite of acute coronary syndrome, heart failure, and stroke. We classified the participants into four frailty categories according to HFRS: no-frailty with HFRS=0, low with HFRS >0 and <5, intermediate with HFRS ≥5 and <15, and high with HFRS ≥15. We used a Cox regression model adjusted for age, sex, inhaled treatments, and comorbidities to evaluate the hazard ratio (HR) for MACE.

Results: We recruited 1527 patients with COPD. In multivariable analysis, COPD was associated with MACE as follows: no-frailty versus low HFRS (HR, 1.47 [95% confidence interval, 1.01-2.14], p<0.05), intermediate HFRS (HR 2.00 [1.34-2.97], p<0.001), and high HFRS (HR 2.62 [1.50-4.59], p<0.001). Similar relationships were observed even after adjusting for the severity of airflow limitation and COPD exacerbation.

Conclusion: Frailty was independently associated with MACE in COPD patients during the 10-year follow-up period. Frailty assessment supports the identification of patients with COPD at risk of MACE.