International Journal of Chronic Obstructive Pulmonary Disease最新文献

Purpose: This study aimed to establish the prevalence of pulmonary embolism (PE) in chronic obstructive pulmonary disease (COPD) patients with secondary polycythemia (SP) and explore the risk factors for PE in COPD patients with SP.

Patients and methods: We analyzed the prevalence of PE among COPD patients with SP who were hospitalized at Qinghai Provincial People's Hospital between January 2015 and December 2020. From January 2021 to January 2024, we enrolled patients into three groups (COPD+SP+PE, COPD+SP, and control) and performed laboratory measurements, biomarkers, echocardiography, and pulmonary function tests. Patients in the COPD+SP group received clinical treatment, and biomarkers were measured again seven days after treatment.

Results: The prevalence of PE in patients with COPD SP was 5.21%. We found that COPD+SP+PE group had significantly higher levels of erythrocyte distribution width (RDW), platelet volume distribution width (PDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte to large platelet ratio (MLPR), 5-hydroxytryptamine (5-HT), activated protein C (APC), urokinase-type plasminogen activator (u-PA), thrombomodulin (TM), interleukin-38 (IL-38), tissue factor (TF), and fractalkine (FKN) in contrast to COPD+SP group. Biomarkers, such as FKN, β-thromboglobulin (β-TG), APC, u-PA, TM, TF, and IL-38, were risk factors for COPD patients with SP who are complicated by PE. Clinical treatment significantly reduced the levels of β-TG, IL-38, APC, endothelin-1 (ET-1), u-PA, FKN, TM, 5-HT, and neutrophil extracellular traps (NETs) in patients with COPD+SP.

Conclusion: PE incidence was significantly higher in patients with COPD and SP. In COPD patients with SP, routine joint detection of blood and cardiac markers, blood gas analysis, and pulmonary function tests can help to identify patients with PE. APC, u-PA, TF, FKN, TM, and IL-38 are risk factors for PE in patients with COPD and SP, and clinical treatment can effectively reduce this risk.

Objective: To explore the predictive value of cellular inflammatory factors and T cell subsets for disease recurrence and prognosis in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD).

Methods: Serum samples were collected from the two groups to detect and compare the levels of inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], T cell subsets (CD4+, CD8+), and clinical related indicators. Pearson correlation analysis was used to analyze the correlation between inflammatory cytokines, T cell subsets, and clinical indicators. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of serum inflammatory factors and T cell subsets for acute exacerbations of COPD.

Results: The observation group had higher levels of IL-1β, IL-6, TNF-α, and CD8+, and lower CD4+ levels (P<0.05). The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) was lower, while procalcitonin (PCT) and white blood cell count (WBC) were higher (P<0.05). Correlation analysis showed positive correlations between IL-1β, IL-6, TNF-α, and CD8+, and negative correlations with CD4+ and FEV1/FVC (P<0.05). After 6 months, 15 out of 73 patients had acute recurrences, with higher IL-1β, IL-6, TNF-α, and CD8+ levels (P<0.05). Binary logistic regression identified IL-1β, IL-6, TNF-α, and CD8+ as significant predictors of exacerbations, while CD4+ was protective. ROC analysis showed that combined biomarkers had the highest predictive efficiency (AUC = 0.907).

Conclusion: This study is the first to integrate multiple serum inflammatory factors and T cell subsets into a comprehensive predictive model for acute recurrence of COPD within six months (AUC = 0.907), offering a more accurate prediction than traditional methods. The findings underscore the value of these biomarkers in clinical follow-up and highlight their independent predictive power, providing new insights into the interaction between immune markers and clinical indicators in COPD exacerbations.

Mucus clearance is crucial for airway protection, and its dysfunction leads to chronic obstructive pulmonary disease (COPD) characterized by mucus hypersecretion (MHS) and impaired clearance. MUC5AC and MUC5B mucin proteins are key components of airway mucus, with MUC5AC being particularly responsive to environmental stimuli, making it a potential COPD biomarker. N-acetylcysteine (NAC) is a mucolytic agent with known effects on mucus viscosity and clearance, but its precise mechanisms in COPD remain unclear. This systematic review evaluated the impact of NAC on MHS in the airways, reporting significant inhibitory effects on MUC5AC and MUC5B gene and protein expression, as well as a reduction in the number of goblet cells. NAC has demonstrated efficacy in vitro and in animal models of MHS, including COPD models, but data on human bronchial tissue are lacking. This systematic review suggests that NAC acts as a mucolytic and a mucoregulator, directly inhibiting mucus secretion and goblet cell hyperplasia. Given the critical role of MHS in COPD progression, exacerbations, and mortality, these findings highlight the potential of NAC as a targeted therapy for hypersecretion COPD phenotypes. However, further studies are needed to confirm the results of this systematic review, even in human bronchial tissue, to provide translatable evidence in clinical settings. Understanding the intimate mechanism of NAC versus MHS regulation may pave the way for more effective treatments targeting airway mucus dysfunction in COPD, ultimately improving patient outcomes and reducing morbidity and mortality associated with chronic mucus hypersecretion.

Background: The platelet to high-density lipoprotein cholesterol ratio (PHR) is a novel biomarker for inflammation and hypercoagulability. This study aimed to explore the potential association between PHR and prevalence of chronic obstructive pulmonary disease (COPD).

Methods: Participants aged between 40 and 85 years from the 1999-2018 US National Health and Nutrition Examination Survey with COPD were included. Multivariable logistic regression and restricted cubic spline analysis were applied to evaluate the associations between PHR and COPD. Propensity score matching (PSM) was performed to reduce the impact of potential confounding factors.

Results: A total of 25751 participants, including 753 with COPD, at a mean age of 57.19 years and 47.83% men, were included. The multivariable-adjusted model showed that the odds ratio (OR) and 95% confidence interval (CI) for PHR to predict COPD was 1.002 (1.001-1.003). Compared with the lowest quartile, the ORs and 95% CIs for the Q2, Q3, and Q4 PHR quartile were 1.162 (0.874-1.546), 1.225 (0.924-1.625), and 1.510 (1.102-2.069), respectively (P for trend = 0.012). Restricted cubic spline analysis demonstrated a linear association between PHR and COPD prevalence both before and after PSM. Significant association between PHR and COPD prevalence was observed only in participants without hypertension. Receiver-operating characteristic curves showed significantly higher area under the curve for distinguishing COPD from non-COPD by PHR than platelet count and high-density lipoprotein cholesterol.

Conclusion: PHR is significantly associated with COPD prevalence in US adults aged 40 to 85 years without hypertension, supporting the effectiveness of PHR as a potential biomarker for COPD.

Background: The prevalence of chronic obstructive pulmonary disease (COPD) in patients with ischemic heart disease (IHD) remains uncertain, and its association with adverse outcomes is frequently overlooked. This study aimed to estimate the prevalence of COPD, and its impact on pharmacological treatment, and clinical outcomes in patients with IHD.

Methods: A systematic literature search was conducted in Web of Science, Embase, and PubMed until November 20, 2023. All studies that reported the prevalence of COPD in IHD patients were included, and a random-effects model was employed to calculate the pooled prevalence. Data on cardiovascular risk factors/comorbidities, beta-blockers (BBs) prescription, acute phase outcomes [in-hospital mortality, major adverse cardiovascular events (MACE), acute heart failure (AHF), and cardiogenic shock], and long-term mortality were compared according to COPD status.

Results: A total of 82 eligible studies that reported the prevalence of COPD in 18 million IHD patients were included. The pooled prevalence of COPD was 12.0% [95% confidence intervals (CI): 9.9%-14.1%] in patients with IHD. In subgroup analysis, the prevalence of COPD was highest in North America (15.3%), followed by Europe (10.0%), and Asia (8.8%). In addition, COPD was associated with a higher burden of cardiovascular risk factors/comorbidities, but lower BBs prescription [odds ratio (OR) 0.50, 95% CI 0.38-0.66]. Moreover, COPD was linked to an increased risk of in-hospital mortality (OR 1.47, 95% CI 1.37-1.58), MACE (OR 1.81, 95% CI 1.44-2.27), AHF (OR 2.14, 95% CI 1.86-2.46), cardiogenic shock (OR 1.30, 95% CI 1.01-1.68), as well as long-term mortality (OR 1.99, 95% CI 1.80-2.20).

Conclusion: This meta-analysis demonstrated that COPD is prevalent in IHD, involving 12.0% of IHD patients, and is linked to a lower prescription of BBs, an increased burden of comorbidities, and worse acute phase outcomes and long-term mortality.

Background: The existence of an association between physical activity (PA) and asthma and chronic obstructive pulmonary disease (COPD) has been confirmed in observational studies. Therefore, it is necessary to reveal whether there is a risk-effect relationship between physical activity and asthma and COPD through Mendelian randomization (MR) analysis.

Materials and methods: Univariate Mendelian randomization (UVMR) analyses were performed to examine the associations between moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA), accelerometer-assessed physical activity (AA), and strenuous exercise or other exercise (SSOE) with asthma and COPD. The methods of analysis were dominated by Inverse Variance-Weighted (IVW), Weighted median (WM), and MR-Egger methods. In addition, multivariate Mendelian randomization (MVMR) analyses were performed to correct the effects of four types of physical activity on asthma and COPD. Finally, potential mediating effect relationships were identified through mediation analyses.

Results: The results of Univariate Mendelian randomization analysis showed that SSOE could reduce the risk of asthma and COPD(asthma: OR=0.15,95% CI=0.04-0.58, P=0.006; COPD: OR=0.05, 95% CI=0.01-0.33, P=0.002). The results of the Multivariate Mendelian randomization analysis showed that SSOE was still able to reduce the risk of asthma and COPD after adjusting for the effects of different types of physical activity(asthma: 95% CI=-2.77--0.31, P=0.014; COPD: 95% CI=-4.00--0.50, P=0.012). Mediation analyses showed that frailty intervened in the causal relationship between physical activity and asthma and chronic obstructive pulmonary disease.

Conclusion: SSOE is a protective factor for asthma and COPD in the European population, while frailty plays a mediating role.

Purpose: Several lung function endpoints are utilized in clinical trials of inhaled bronchodilators for chronic obstructive pulmonary disease (COPD). Trough forced expiratory volume in 1 second (FEV₁) is a commonly reported endpoint in COPD trials and can be complemented by area under the FEV₁ vs time curve (FEV₁ AUC), which provides information on duration and consistency of bronchodilation over a dosing interval. Revefenacin, a once-daily bronchodilator, significantly improved lung function in patients with COPD when measured by trough FEV₁ in two replicate Phase 3 trials. Here, we report an FEV₁ AUC substudy using data from these trials.

Patients and methods: This post hoc analysis examined substudy data from 12-week replicate Phase 3 trials (NCT02459080/NCT02512510); patients with moderate to very severe COPD were randomized 1:1 to revefenacin 175 μg or placebo once daily. The substudy patients had FEV₁ AUC_0-2h assessed on Day 1, and those who continued to Day 84 also underwent 24-hour serial spirometry postdose where FEV₁ AUC_0-2h, AUC_0-12h, AUC_12-24h, and AUC_0-24h were evaluated.

Results: Fifty and 47 patients who received revefenacin and placebo underwent 24-hour serial spirometry; most baseline characteristics were aligned between groups. At Day 84 postdose, revefenacin demonstrated sustained improvements in bronchodilation over 24 hours; differences in least squares mean vs placebo were 282, 220, 205, and 212 mL for FEV₁ AUC_0-2h, AUC_0-12h, AUC_12-24h, and AUC_0-24h (all P <0.001), respectively.

Conclusion: This substudy analysis supplements previous findings that revefenacin provides sustained bronchodilation over 24 hours. Assessing additional complementary COPD clinical trial endpoints can help clinicians make treatment decisions.

Purpose: Race-based correction is widely utilized in clinical practice, but may contribute to overestimation of lung function, underdiagnoses in minority groups, and exclusion of minority groups from research trials. The aim of this systematic review is to examine the usage of race-based correction in pulmonary function testing (PFT) within chronic obstructive lung disease (COPD) research and its impact on the exclusion of minority groups from research trials.

Methods: We systematically searched Medline from 2010 to 2022 to identify randomized controlled trials (RCTs) that examine inhaler therapy for COPD. Article screening, critical appraisal, and data extraction were completed in duplicate by independent reviewers. Data regarding study design, inclusion criteria, demographics, and race-based correction were extracted and synthesized narratively.

Results: Of the 774 screened articles, we included 21 RCTs in the review, which were multinational trials involving 70696 study participants. All studies had an inclusion criteria of an FEV₁ cutoff of 50% to 80%. Racial minorities remained underrepresented in the trials, with the proportion of black participants ranging from <1% to 4.7%. Four studies directly mentioned race-based correction, while the remainder of the studies did not provide any explicit details. After obtaining additional information by contacting authors and reviewing the citations, 15 were estimated to utilize race-based correction.

Conclusion: Race-based correction may be frequently utilized in major COPD RCTs, but there remains inconsistent reporting regarding the usage of race-based correction. This may contribute to the exclusion of racialized populations from research trials as there remains significant underrepresentation of racialized populations from research.

Background: Epidemiologic studies have shown that patients with acute exacerbation of COPD (AECOPD) suffer from morbidity and mortality from venous thromboembolism (VTE) and poor diagnosis. Von Willebrand factor (vWF) and plasminogen activator inhibitor type-1 (PAI-1) are frequently investigated in COPD as crucial parameters for coagulation and fibrinolysis. Nevertheless, the role of vWF and PAI-1 in AECOPD needs further exploration.

Objective: We sought to evaluate the hypercoagulability in AECOPD and investigate the association of plasma vWF and PAI-1 with occurrence and exacerbation risk of AECOPD patients.

Methods: Fifty-seven AECOPD patients and 34 control subjects were enrolled in our study. The concentrations of plasma vWF and PAI-1 antigens were measured by ELISA kit. Independent samples t-test or Wilcoxon rank sum test was applied for group comparison. Spearman correlation analysis, subject work curve (ROC) analysis, and Logistic regression were used to evaluate the role of the plasma vWF and PAI-1 in AECOPD.

Results: We observed increased vWF (770.15 ± 325.52 vs 327.62 ± 210.97 ng/mL, P < 0.001) and PAI-1 (0.47 vs 0.17 ng/mL, P < 0.001) levels in AECOPD patients compared with control subjects. Both vWF and PAI-1 are closely related to COPD (vWF: AUC = 0.8741, P < 0.001; PAI-1: AUC = 0.8222, P < 0.001). Moreover, elevated vWF could be an independent risk factor for COPD (OR = 1.01, 95% CI: 1.00-1.01, P = 0.01). We also discovered higher plasma levels of vWF and PAI-1 in the COPD "E" group in contract to "AB" group (vWF: 966.29 ± 251.18 vs 552.21 ± 253.28, P < 0.0001; PAI-1: 1.02 vs 0.38, P = 0.003). And vWF levels increased with increasing COPD exacerbation risk, moreover, plasma vWF positively related with patients' CAT scores and SGRQ scores. In addition, plasma vWF and PAI-1 correlated with each other in total participants and AECOPD subgroup analysis.

Conclusion: This study demonstrated that AECOPD patients have a prothrombotic state, as demonstrated by vWF and PAI-1 levels in plasma compared with those in control subjects, and the prothrombotic state increases with increasing COPD exacerbation risk.

Introduction: Exacerbations of chronic obstructive pulmonary disease (COPD) are risk factors for severe cardiovascular (CV) events, with the risk remaining significantly elevated long after the symptomatic phase of the exacerbation. The pathophysiology underpinning the relationship between acute events of both COPD and CV diseases has been understudied. Our objectives were to review the mechanisms by which COPD exacerbations increase the risk of CV events and understand the temporality of this risk.

Methods: A pragmatic and targeted literature review was conducted with a focus on identifying recent, high-impact papers up to June 2023, guided by insights from subject matter experts including pulmonologists and cardiologists.

Results: A substantial number of inter-related mechanisms underpin the spiral of anatomical and functional deterioration of lung and heart affecting COPD patients during stable state. In turn, an exacerbation of COPD may trigger a CV event, during and beyond the symptomatic phase, due to ventilation/perfusion mismatch, oxygen supply-demand imbalance, oxidative stress, systemic inflammation, hypercoagulable state, dynamic hyperinflation, pulmonary hypertension, and sympathetic activation. However, no study was identified that explored the mechanisms by which an exacerbation confers a sustained risk of CV event.

Conclusion: While our review identified multiple dynamic and interacting pathophysiological mechanisms during and after an exacerbation of COPD that contribute to increasing the risk of a wide range of cardiac events, little is known regarding the precise long-term mechanisms after acute exacerbation to explain the persistent increased CV event risk beyond the symptomatic phase. The temporal changes in static and dynamic substrates need further characterization to better understand the different risk factors and risk periods for a CV event following the onset of an exacerbation. Moreover, guideline-directed cardiopulmonary therapies should be implemented at every opportunity; preventing exacerbations and intensively treating traditional CV risk factors should be a focus in COPD management.