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

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.

Background: Chronic obstructive pulmonary disease (COPD) phenotyping is an approach for developing tailored therapies. The eosinophilic phenotype is associated with exacerbation risk and response to specific treatments. This study evaluates the relationship between sputum and blood eosinophilia, hypothesizing that sputum eosinophil percentage (SpE%) better reflects disease severity and exacerbation risk than blood eosinophil counts (BEC).

Methods: This was a single-center, prospective observational cohort with 107 participants aged 40-80 with clinically diagnosed COPD. Participants completed spirometry, a 6-minute walk test, and questionnaires, and blood and sputum samples were provided at baseline and 3 months. BEC and SpE% were measured via routine complete blood counts and flow cytometric analyses (fluorescence-activated cell sorting [FACS]). Eosinophilic phenotype thresholds were defined as BEC≥300 cells/μL and SpE%≥2%, and associations with clinical characteristics and outcomes were investigated.

Results: Adequate sputum specimens were obtained less frequently than blood (60.7% versus 98%). SpE% showed poor repeatability (interclass coefficient 0.36) and poor correlation with FACS (Spearman's 𝜌=0.008, p=0.58). Conversely, BEC showed higher repeatability (𝜌=0.67, p<0.01) and better correlation with FACS (𝜌=0.74, p<0.01). More participants were classified as eosinophilic COPD by sputum (33.3%) than by blood (19.6%). BEC values were poorly correlated with SpE% (𝜌=0.13, P=0.39), and sputum and blood-based diagnostic criteria showed poor agreement (64.5%, Cohen's 𝜅 0.10). High SpE%, but not high BEC, was associated with lower forced expiratory volume in 1 second percentage predicted.

Conclusions: In stable COPD patients, BEC and SpE% did not correlate well, and blood- and sputum-based diagnostic criteria identified different individuals. Defining eosinophilic COPD requires a better understanding of the bio-compartment sampled, testing methods, and cut-off values used.

Background: Chronic obstructive pulmonary disease (COPD) remains underdiagnosed and undertreated. Because screening asymptomatic individuals for COPD is not recommended, several case-finding tools have been explored. The COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) questionnaire and peak expiratory flow (PEF) rate (CAPTURE tool) have been tested in the primary care setting, with disappointing results. We hypothesized that these tools could yield better results in a computed tomography lung screening (CTLS) program, where individuals have a history of cigarette smoking and higher prevalence of COPD.

Methods: We recruited 67 patients referred to a CTLS program at a single institution. Participants completed the CAPTURE and COPD Assessment Test (CAT) questionnaires. Spirometric testing was completed with a portable device and low-dose chest computed tomography (CT) was performed according to a standard protocol.

Results: The group's mean age was 66 ±7 years, 43% were male, with a 37 pack-year smoking history. Eighteen (27%) had COPD (forced expiratory volume in 1 second of 60 ±22% predicted) and a higher CAT score (12 [interquartile range (IQR) 6-15]) compared to the nonobstructed group (CAT=7 [IQR 3-10]), p<0.02. Combining the CAPTURE questionnaire with PEF generated the best COPD diagnostic criteria (sensitivity=0.82, specificity=0.73, area under the receiver operating curve [AUROC]=0.784), followed by combining the CAPTURE questionnaire and emphysema presence (sensitivity=0.73, specificity=0.71, AUROC=0.779). The CAPTURE questionnaire alone had a sensitivity=0.766, specificity=0.616, and AUROC=0.669.

Conclusions: The CAPTURE tool is an effective method to find COPD cases in lung cancer screenings. A CT diagnosis of emphysema can substitute peak flow in this population.

Background: Pulmonary function tests may predict future outcomes; however, they are not often performed in middle-aged individuals at risk for future airway obstruction. We examined whether smokers with low lung function (LLF) have an increased risk of developing health problems and mortality over time.

Methods: Current and ever smokers (n=830) from the Lovelace Cohort aged 40-60 years without baseline airway obstruction and with at least 2 spirometry measurements over 18 months were included. Participants were divided into high lung function (HLF) and LLF function tertiles based on forced expiratory volume in 1 second percentage predicted (FEV₁%pred). Lung function, health status, and comorbidities were compared at baseline and over 17 years; mortality at 17 years was also assessed. From these participants, 61 HLF (baseline FEV1%pred >99%) and 26 LLF (baseline FEV1%pred <88%) were examined at 17 years follow-up using logistic regression.

Results: Baseline demographic and clinical characteristics were generally similar between the LLF and HLF tertiles, except for age, sex, body mass index, and lung function. In the overall cohort (LLF, n=277; HLF, n=277), survival of the HLF versus LLF cohort showed a hazard ratio of 0.49 (p=0.02). At the 17-year follow-up, LLF was associated with increased prevalence of wheeze, cardiovascular diseases, chronic lung diseases, diabetes, and worse health status.

Conclusions: Smokers with LLF without airflow obstruction exhibited reduced survival and an increased risk for development of chronic morbidities. Thus, spirometry may be used to identify at-risk individuals, allowing for early preventative interventions that can improve long-term health outcomes. Take home message: Among ever smokers without airflow obstruction, LLF is associated with increased mortality and poor health status. Spirometry may identify at-risk patients, enabling early emphasis on interventions with the potential to improve long-term health outcomes.