Chronic Obstructive Pulmonary Diseases-Journal of the Copd Foundation最新文献

Background: The association between 25-hydroxyvitamin D (25(OH)D) levels and chronic obstructive pulmonary disease (COPD) remains unclear. The study aims to investigate the association between 25(OH)D concentrations and the incidence and survival of COPD in the U.K. Biobank cohort.

Methods: We conducted a cross-sectional analysis using U.K. Biobank data from 328,855 participants with complete 25-Hydroxyvitamin D (25(OH)D). This analysis examined the association between 25(OH)D levels and COPD prevalence via logistic regression. Additionally, we prospectively followed a cohort of 327,871 individuals without baseline COPD. We assessed the risk of incident COPD and survival outcomes in this cohort using multivariable-adjusted Cox proportional hazards models. Kaplan-Meier estimates were used to generate survival curves.

Results: The prevalence of COPD was significantly higher in individuals with 25(OH)D deficiency compared to those with a normal level, as evidenced by an adjusted odds ratio (95% confidence interval [CI]) of 1.266(1.206–1.330) for COPD. During the median follow-up period of 15 years (interquartile range: 14–16 years), the overall COPD incidence was 262.3 per 10,000 person years, with higher rates among those with 25(OH)D deficiency (345.2 per 10,000 person years) compared to normal levels (232.6 per 10,000 person years) (p<0.001). In fully adjusted models, 25(OH)D deficiency was significantly associated with increased COPD incidence (hazard ratio [HR] 1.874, 95% CI 1.659 to 2.117) and mortality (HR 1.598, 95% CI 1.406–1.816). Subgroup analyses revealed stronger associations with COPD incidence among men, current smokers, and individuals not taking vitamin D supplements, as well as an increased COPD mortality risk among patients with depression (p for interaction <0.05).

Conclusions: Our study suggests that 25(OH)D deficiency is associated with COPD incidence and survival, providing a basis for preventive strategies and interventions.

The article "Metabolic Dysfunction-Associated Fatty Liver Disease in Chronic Obstructive Pulmonary Disease Patients: Insights From Vietnam" published in the July 2025 issue of Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation ( JCOPDF) is significantly similar and in some sections, identical, to an article published in the January 2025 issue of the Vietnam Medical Journal. In December of 2024, Dr. Doan Le Minh Hanh, on behalf of all the above listed authors, claimed during the submission process to the JCOPDF that the manuscript had not been published or submitted elsewhere by answering this question affirmatively: "Confirm that the manuscript has been submitted solely to this journal and is not published, in press, or submitted elsewhere." In October 2025, Dr. Hanh notified the JCOPDF of the duplicate publication. As a result of this notification, we retract this article from the literature.

Introduction: In South America, the rise in chronic respiratory diseases and weight-related issues due to the ongoing epidemiological transition has prompted research into their interrelationship.

Methods: We sought to assess the association between body mass index (BMI) and bronchodilator responsiveness (BDR) among adults in Peru, Chile, Uruguay, and Argentina, using population-based data from 2 cohort studies. We defined BDR as a ≥12% and ≥200mL increase in either forced expiratory volume in 1 second (FEV₁) or forced vital capacity (FVC) after administration of a short-acting bronchodilator. The analysis also distinguished between FEV₁- and FVC-specific BDR. We used logistic regression adjusted for confounders to evaluate associations with BMI.

Results: Among 7160 participants (55.2% men, mean age 57.3 years), 23.7% had a BMI <25kg/m² and 35.5% had a BMI ≥30 kg/m². Overall, 9.5% met the criteria for BDR; with 7.8% showing FEV₁-specific and 4.9% FVC-specific responses. Compared to a BMI of 20-24.9kg/m², a BMI ≥30kg/m² was associated with higher odds of FVC-specific BDR (adjusted odds ratio = 1.47, 95% confidence interval 1.08-2.03), whereas a BMI <20kg/m² was associated with FEV₁-specific BDR among participants with asthma (6.61, 1.23-35.6) and chronic bronchitis (4.71, 1.28-15.9), and with higher odds of any BDR in those with chronic bronchitis (3.90, 1.19-11.9).

Conclusion: There was a differential relationship between BMI and types of BDR: higher BMI was associated with FVC-specific responsiveness, whereas lower BMI was linked to FEV₁-specific BDR in individuals with asthma and chronic bronchitis and to overall BDR in those with chronic bronchitis.

Background: Chronic obstructive pulmonary disease (COPD) is classified by its clinical phenotypes-chronic bronchitis and emphysema. A computed tomography (CT)-based mucus plug score (MPS) was recently identified as a biomarker to a subgroup of COPD patients with increased airway mucus plugs. While not necessarily linked to more pronounced symptoms or structural lung changes, mucus plugs are associated with increased mortality. Interestingly, a higher MPS seems to be associated with a lower body mass index (BMI), likewise associated with increased mortality. This study aims to characterize patients with advanced emphysema presenting for lung volume reduction therapy with a special focus on mucus plug occurrence.

Material and methods: This retrospective, monocentric study assessed MPS in advanced COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] stages 3 or 4) and emphysema patients evaluated for lung volume reduction therapy at Charité-Universitätsmedizin Berlin. CT scans were analyzed for mucus plugging, and clinical data were obtained from the emphysema registry.

Results: A total of 127 CT scans were assessed for MPS. About 50% had no mucus plugs (score = 0), 25% had an intermediate burden (score 1-2), and 25% had a high burden (score ≥3). A higher MPS correlated with a lower BMI, more pronounced emphysema, and worse lung function, including forced expiratory volume in 1 second, vital capacity, and diffusing capacity of carbon monoxide. Residual volume, partial pressure of carbon dioxide, the 6-minute walk test, and quality-of-life parameters were unaffected. Multivariate regression analysis found a strong association between mucus plugs and BMI, showing that a decrease in BMI was associated with a higher mucus burden (p<0.001; coefficient of -1.584).

Interpretation: This study supports an association between high MPS and BMI in a vulnerable subgroup of advanced COPD patients. Further research is needed to understand the pathophysiology and consequences of mucus plugs, aiming for individualized risk assessments and treatment strategies.

Eosinophilic chronic obstructive pulmonary disease (COPD) is a distinct subtype with clinical and biological differences from noneosinophilic COPD and asthma. Fractional exhaled nitric oxide (FeNO) is an established marker of type 2 airway inflammation in asthma, but its utility in eosinophilic COPD is less well understood. We analyzed baseline data from 176 participants in the Air Purification for Eosinophilic COPD Study, a randomized controlled trial of former smokers with eosinophilic COPD. At enrollment, FeNO and blood eosinophil counts were measured, and participants reported asthma history and severe COPD exacerbations requiring hospitalization in the prior year. Each 50cells/μL higher eosinophil count was associated with a 3.2% increase in FeNO (95% confidence interval [CI]: 0.3-6.1%). Asthma history was associated with a 29.1% higher FeNO (95% CI: 5.2-58.5%). Elevated FeNO, defined as ≥25 or ≥50 parts per billion, was linked to greater odds of an asthma diagnosis and a recent severe exacerbation, although CIs included the null. These findings suggest that FeNO may serve as a practical, noninvasive biomarker of type 2 inflammation in eosinophilic COPD and could help identify patients at higher risk of severe exacerbation.

Background: Pulmonary diffusing capacity for nitric oxide (DLNO) remains underutilized despite potential advantages over pulmonary diffusing capacity for carbon monoxide (DLCO). We evaluated whether DLNO better detects emphysema than DLCO, spirometry, or lung volumes in smokers.

Methods: We performed an individual participant data meta-analysis of adult smokers (14-43 pack years) with and without computed tomography-defined emphysema using a standardized 10 ± 2-second breath-hold time double diffusion protocol. Variables were converted to z-scores. Prespecified models contrasted DLCO- versus DLNO-based approaches. Model selection used the Bayesian information criterion (BIC) and leave-one-out information criterion; discrimination used area under the receiver operating characteristic (AUROC) curve and Matthews correlation coefficient (MCC) with repeated cross-validation.

Results: After harmonization and quality control, 408 participants (85 emphysema, 323 controls) were analyzed. The lowest BIC (164.6) occurred for the 3-predictor model with total lung capacity (TLC), forced expiratory volume in 1 second (FEV₁), and DLNO z-scores, with an 88% probability of being superior to the next-lowest BIC model (168.5). Discrimination (AUROC 0.97, 95% confidence interval [CI] 0.95-0.98) and classification (MCC 0.80, 95% CI 0.69-0.89) were high. Hierarchical partitioning showed unique contributions from FEV₁ z-scores (R²=0.35) > DLNO z-scores (R²=0.21) > TLC z-scores (R²=0.11), totaling McFadden's R²=0.663. Adding DLCO z-scores increased the total R² trivially (by 0.003) and contributed largely shared information with DLNO (variance inflation factors ≤ 4.5). Category-free reclassification and Youden-threshold analyses showed small but favorable gains; the case-control risk gap improved by up to ~5% when adding DLNO to a DLCO-based model.

Interpretation: When predicting the likelihood of emphysema in smokers, a parsimonious z-score model comprising TLC, FEV₁, and DLNO z-scores provides excellent performance and stable rank superiority.

Background: Patients with airflow limitation according to the fixed ratio but not the lower limit of normal (FR+LLN-) have a poorer respiratory prognosis and higher mortality than the normal fixed ratio. However, whether tiotropium treatment improves respiratory health outcomes in patients with FR+LLN- remains unclear.

Methods: This was a secondary analysis of the 24-month Tiotropium in Early Chronic Obstructive Pulmonary Disease Patients in China (Tie-COPD) study, a multicenter, randomized, double-blind clinical trial comparing tiotropium with placebo for mild-to-moderate COPD. FR+LLN- was defined as a postbronchodilator forced expiratory volume in 1 second (FEV₁) to forced vital capacity ratio of <0.70 but ≥ the lower limit of normal. The primary endpoint was the between-group difference in the change from baseline to 24 months in prebronchodilator FEV₁. Key secondary endpoints included the between-group difference in the annual decline in prebronchodilator FEV₁ and exacerbations.

Results: In the Tie-COPD study, 92 patients (12%) had FR+LLN-. Tiotropium resulted in a significantly higher prebronchodilator FEV₁ at 24 months (adjusted difference 191mL; 95% confidence interval [CI] 99, 283), with a least-squares mean change from baseline of 47mL (95% CI -13, 108) versus -140mL (95% CI -215, -64) with placebo. The annual decline in the prebronchodilator FEV₁ was 24mL/year with tiotropium and 89mL/year with placebo (adjusted difference 60mL/year; 95% CI 2, 118) from 30 days through 24 months. Tiotropium reduced total exacerbations compared with placebo (relative risk=0.50; 95% CI 0.27, 0.94).

Conclusion: This study demonstrated tiotropium treatment improved lung function, ameliorated lung function decline, and reduced exacerbations compared with placebo in patients with FR+LLN-, providing evidence-based medicine support for the treatment in this population.

Background: Some studies suggest that statins could reduce the risk of chronic obstructive pulmonary disease (COPD), but it is unclear if this effect is related to their lipid-lowering properties. The causal link between serum lipid levels and COPD risk remains uncertain. This study aims to clarify this potential causal relationship and evaluate the impact of lipid-lowering drug target genes on COPD.

Methods: Mendelian randomization (MR) was used to investigate causal associations between lipid levels, lipid-lowering drug target genes, and COPD risk. Data were obtained from publicly available genome-wide association study databases. The inverse variance weighted method was the primary statistical approach for evaluating causal effects, complemented by various sensitivity analyses.

Results: MR analysis demonstrated a causal relationship between low-density lipoprotein cholesterol (LDL-C) and a reduced risk of COPD (odds ratio [OR]=0.90, 95% confidence interval [CI]=0.85-0.95, P=1.50×10⁻⁴). Causal relationships were also identified for 2 lipid-lowering drug target genes, HMGCR (OR=0.63, 95%CI=0.54-0.75, P=4.92×10⁻⁸) and PCSK9 (OR=0.87, 95%CI=0.80-0.95, P=0.001), with a reduced COPD risk. Although MR analysis indicated a potential causal relationship between LPL (OR=0.86, 95%CI=0.79-0.94, P=6.37×10⁻⁴) and reduced COPD risk, colocalization analysis did not support this finding. No associations were observed between other lipid traits, lipid-lowering drug target genes, and COPD.

Conclusion: This study genetically identified causal relationships between serum LDL-C levels, the 2 coding genes HMGCR and PCSK9, and a reduced risk of COPD. These findings suggest that the protective effect of statins on COPD may occur independently of their lipid-lowering function. Further clinical validation is needed to confirm this hypothesis.

Background: The incidence of infections caused by nontuberculous mycobacteria (NTM) are steadily increasing worldwide, and the most common site of infection is the lung. Clinical characteristics of individuals with NTM pulmonary disease (NTM-PD) demonstrate pronounced geographical heterogeneity. In the United States, NTM-PD has an affinity for postmenopausal White females, many of whom are never-smokers, whereas in Asia, NTM-PD is more common in males with post-tuberculosis lung disease. While these geographical differences are known on the global scale, it remains unclear whether radiographic sex-associated differences in NTM-PD are present within the U.S. cohort.

Objective/method: In this single center, cross-sectional retrospective study of our patient registry, we sought to assess this knowledge gap by comparing radiographic and clinical features of individuals with NTM-PD by sex.

Results: We observed a significant preponderance of cavitary disease in men, while women commonly presented with bilateral apical fibrosis, increased nodules and tree-in-bud patterns in the lower lobes, and an increased risk of refractory disease and concomitant co-infection.

Conclusion: Results from this study demonstrate several sex-associated differences in the radiographic phenotype of NTM-PD and may be the result of differences in pre-existing risk factors that contribute to the development of NTM-PD. Future studies will be required to better assess the broad applicability of these findings to centers from other geographic regions where the underlying etiology of disease may vary.

Objectives: This meta-analysis assessed the effects of aerobic exercise on the function, prognosis, quality of life, and psychological outcome of patients with chronic obstructive pulmonary disease (COPD).

Methods: The Cochrane Library, Scopus, PubMed, and Web of Science were searched from the inception to June 20, 2025, to identify eligible studies. A random-effects model was employed for meta-analysis.

Results: Twenty randomized controlled trials with 1003 participants were included. The risk of bias was high in most studies, particularly because blinding was not feasible. For most outcomes, we observed high heterogeneity among studies. The meta-analysis indicated that compared to the control group, patients with COPD undergoing exercise training had a significantly increased 6MWT (WMD 42.44 m), FEV1 (WMD 0.08 L), FEV1/FVC (WMD 5.42%), and SpO2 (WMD 1.56%), which suggests that aerobic exercise can improve the functional capacity and respiratory reserve of patients with COPD. On the other hand, the results revealed that compared to the control group, aerobic exercise markedly decreased the SGRQ symptom score (SMD -1.13), SGRQ total score (SMD -1.44), mMRC score for dyspnea (SMD -0.81), and HADS-anxiety score (SMD -1.17), but its effect on the HADS-depression score (SMD -0.25) did not meet the threshold of statistical significance. Subgroup analysis unveiled that aerobic exercise can offer greater benefits in the long term, and those with FEV1 and FEV1/FVC of more than 50% can benefit more from aerobic exercise.

Conclusion: Aerobic exercise may improve the functional capacity, symptoms, respiratory reserve, quality of life, and psychological outcomes of patients with COPD.