International Journal of Chronic Obstructive Pulmonary Disease最新文献

Background: Hyperkalemia increases mortality in various patient populations. The risk of hyperkalemia in COPD patients is poorly recognized. Hyperkalemia may increase cardiovascular mortality during and soon after COPD exacerbations.

Patients and methods: A cohort based on two clinical trials comprising 7968 patients with moderate-to-very severe COPD was analysed retrospectively for associations between hyperkalemia and common comorbidities such as chronic kidney disease, diabetes mellitus (DM), or renin-angiotensin-aldosterone system inhibitor use.

Results: Overall, 6.4% of 7968 patients had hyperkalemia (5.3% Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2, 6.8% GOLD 3, and 8.0% GOLD 4). COPD severity was associated with significantly higher hyperkalemia risk in GOLD 3 (odds ratio [OR]=1.28, 95% CI 1.04-1.58) and GOLD 4 (OR=1.64, 95% CI 1.19-2.22) versus GOLD 2 patients. Hyperkalemia cases increased with decreasing renal function. Patients with moderate-to-severe renal impairment had >2-fold increased hyperkalemia risk versus those with normal renal function (OR=2.29, 95% CI 1.71-3.04). DM was associated with increased hyperkalemia risk (OR=1.28, 95% CI 1.02-1.59). Angiotensin-converting-enzyme inhibitor (ACEi) use increased hyperkalemia risk (OR=1.25, 95% CI 1.02-1.53). Unexpectedly, the association between hyperkalemia and renin-angiotensin-aldosterone system inhibitor use was statistically significant only in the normal renal function group (OR=1.63, 95% CI 1.13-2.34).

Conclusion: Hyperkalemia risk is higher in severe and very severe COPD patients than patients with moderate COPD. Hyperkalemia was also associated with decreasing kidney function, DM, and ACEi use. Serum potassium levels should be monitored regularly in patients with COPD, particularly those with GOLD-3 and 4.

Purpose: The management of the coexistence of chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) remains unclear due to a lack of evidence. This study aimed to find the effect of beta-blockers and renin-angiotensin-aldosterone system inhibitors (RAASi) in this special population.

Patients and methods: We designed an observational real-world study that included 2016 AF patients from 20 hospitals across the country. The diagnosis of COPD was extracted from case report forms and confirmed by specialists. The study endpoint was all-cause mortality. Kaplan-Meier curves and Log rank test were used to analyse the prognosis of different treatments. Several multivariable Cox regression models were performed to identify the independent prognostic value of the medications.

Results: Approximately 30% of patients were prescribed beta-blockers or RAASi. Survival curves showed that beta-blockers did not affect all-cause mortality in AF patients with COPD (P=0.130). Patients with RAASi had a better prognosis than those without (P=0.011). After multivariable Cox regression analysis adjusting for demographics, other comorbidities and treatments, beta-blockers and angiotensin II receptor blockers (ARB) did not independently affect the endpoint. Angiotensin converting enzyme inhibitors (ACEI) remained a protective factor for overall survival in AF patients with COPD (model 1: HR=0.45, 95% CI 0.21-0.98, P=0.045; model 2: HR=0.41, 95% CI 0.18-0.93, P=0.034; model 3: HR=0.38, 95% CI 0.16-0.89, P=0.026).

Conclusion: Beta-blockers did not affect overall survival in patients with AF and COPD, whereas ACEI may be protective.

Background: This systematic review aims to comprehensively assess the current application of discrete event simulation (DES) models in managing chronic obstructive pulmonary disease (COPD). By synthesizing and analyzing multiple studies, we incorporate the latest evidence, evaluate research quality, identify gaps, and provide recommendations for the future application of DES in COPD management.

Methods: We systematically searched six electronic databases including PubMed, Web of Science, Embase, Cochrane, Econlit, and China National Knowledge Infrastructure (CNKI) for articles published up to August 22, 2024. Reference lists of the included articles were also manually checked. Depending on the study type, we assessed quality using either the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist or the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Practice Guidelines.

Results: Out of the 273 records identified, nine studies met the inclusion criteria. All of these studies focused on health economic evaluations using DES in COPD management, and were conducted in high-income countries. The studies were divided into three groups based on the modeling systems they used: cost-effectiveness analyses of different pharmacological treatments (n=3), economic evaluations of case detection strategies (n=3), and assessments of various interventions on COPD healthcare services (n=3). All studies reported model validation methods (n=9); however, only two studies performed subgroup analysis.

Conclusion: This review highlights the current use of DES in COPD management and suggests avenues for future research and resource allocation to enhance the effectiveness of COPD interventions.

Background: Among critically ill patients, chronic obstructive pulmonary disease (COPD) is an independent risk factor for death. Recently, biomarkers such as neutrophil-lymphocyte ratio (NLR) and albumin (ALB) have been used to predict the prognosis in patients with COPD. However, the association between NLR/ALB and all-cause mortality in critically ill COPD patients remains unclear. This study aims to explore the association between the NLR/ALB and prognosis in critically ill patients with COPD.

Methods: Data was sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Primary outcome was 28-day all-cause mortality, with secondary outcomes being in-hospital and 90-day all-cause mortality. The area under the receiver operating characteristic curve (AUROC) was calculated to compare prognostic accuracy of NLR, NLR/ALB, PLR, SII and MLR variables. After identifying the most predictive factor, KM survival curves, Cox models and subgroup analyses were used to examine NLR/ALB's relationship with mortality in critically ill COPD patients. Additionally, patients with COPD from the National Health and Nutrition Examination Survey data (1999-2018) was used with Cox regression to investigate NLR/ALB's correlation with all-cause mortality in COPD patients.

Results: 1916 critically ill COPD patients from MIMIC IV, divided into quartiles by NLR/ALB levels: Q1 (NLR/ALB<1.108), Q2 (2.095>NLR/ALB≥1.108), Q3 (4.221>NLR/ALB≥2.095), Q4 (NLR/ALB≥4.221). In multivariate Cox regression, Q4 vs Q1: 28-day mortality HR=2.27 (95% CI: 1.63-3.16); 90-day mortality HR=2.06 (95% CI: 1.56-2.71); in-hospital mortality HR=1.93 (95% CI: 1.35-2.77); P<0.001. Subgroup analyses showed that the correlation between NLR/ALB and 28-day mortality was stable Additionally, we recruited 2,003 COPD patients from the NHANES that found NLR/ALB also correlated with all-cause mortality in COPD (In multivariate Cox regression: Q4 vs Q1 hR=1.92 (95% CI: 1.45-2.55, P<0.001)).

Conclusion: Elevated NLR/ALB levels are associated with increased all-cause mortality in critically ill patients with COPD.

Objective: To evaluate the efficacy and safety of a novel percutaneous volume reduction technique combining erythromycin sclerotherapy with bronchoscopic occlusion for giant emphysematous bulla (GEB) patients unsuitable for surgery.

Methods: This retrospective study analyzed 70 patients with GEB who underwent a novel percutaneous volume reduction technique. Outcomes including St. George's Respiratory Questionnaire (SGRQ), 6-minute walk test (6MWT), modified Medical Research Council (mMRC) score, pulmonary function, and blood gas analysis were assessed before the procedure, at discharge, and 6 months post-procedure. The primary endpoint was improvement in mMRC grade. Related complications were also recorded.

Results: The average GEB size of 70 patients was 14.91±2.68cm (10-21cm). The mMRC grade improved in 43 patients, and the efficacy of volume reduction was 61.4%. The forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), residual volume (RV), total lung capacity (TLC), PaO₂/FIO₂, PaCO₂, 6MWT, total SGRQ, mMRC grades before discharge showed significant improvement compared to those before the procedure. FEV₁, FVC, 6MWT, total SGRQ score, and PaO₂/FIO₂ continued to improve at 6 months after the procedure compared to those before discharge. There was significant correlation between mediastinal displacement and postoperative efficacy of GEB volume reduction (OR=3.609, 95% CI: 1.263-10.316, p=0.017). In addition, the major postoperative complications included pneumothorax (36 cases, 51%) and pleural effusion (44 cases, 63%). Most of the symptoms were mild and improved after symptomatic treatment for the involved patients. There were no deaths during the perioperative period.

Conclusion: The novel percutaneous bulla volume reduction technique represents a safe and effective non-surgical alternative for patients with inoperable GEB, demonstrating sustained therapeutic benefits lasting at least six months. The procedure appears particularly beneficial for patients with mediastinal displacement. However, the study has limitations, including its retrospective design and lack of long-term efficacy data, which may affect the generalizability of the findings.

Purpose: Globally, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the leading cause of hospitalization and mortality in COPD patients. The estimated plasma volume status (ePVS) is an indicator of fluid status that has been proven to correlate with the prognosis of intensive care unit (ICU) patients. Our study aims to explore the association of ePVS and in-hospital mortality in AECPD patients admitted in the ICU.

Methods: Data of this retrospective cohort study were extracted from the electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Outcome was the in-hospital mortality in AECOPD patients. The formulas, Duarte formula and Kaplan-Hakim (KH) formula, were used to assess ePVS. The weighted univariable and multivariable Cox regression models were utilized to explore the association of Duarte-ePVS and KH-ePVS and in-hospital mortality in AECOPD patients, with hazard ratios (HRs) and 95% confidence intervals (CIs). Kaplan-Meier survival analysis was used to pool the in-hospital mortality for different KH-ePVS levels. Restricted cubic splines curve analysis was used to assess the linear correlation of KH-ePVS and in-hospital mortality in AECOPD patients. These associations were further explored in different subgroups.

Results: In total, 2,773 AECOPD patients were included, of whom, 219 (7.90%) died within 6.24 (4.01-9.26) days. After adjusted confounding factors, we found AECOPD patients with high KH-ePVS level were associated with high risk of in-hospital mortality (HR=1.53, 95% CI: 1.05-2.24). No significant association was found between Duarte-ePVS and in-hospital mortality (P>0.05). The Kaplan-Meier analysis also suggested consistent association between KH-ePVS and in-hospital mortality in AECOPD patients. Subgroup analysis also suggested the association of KH-ePVS and in-hospital mortality in AECOPD patients remained robust.

Conclusion: Elevated KH-ePVS levels are associated with the high in-hospital mortality among AECOPD patients. As a simple and convenient indicator, KH-ePVS is expected to become a prognostic predictor for predicting in-hospital mortality in severe AECOPD patients.

Purpose: To explore the role of the miR-146a-5p-mediated regulation of the EGFR/MEK/ERK pathway in the effect of effective-component compatibility of Bufei Yishen Formula III (ECC-BYF III) on ameliorating mucus hypersecretion by bronchial epithelial cells (BEAS-2B cells).

Methods: BEAS-2B cells exposed to cigarette smoke extract (CSE) were used to establish a mucus hypersecretion model of BEAS-2B cells. The optimal intervention concentration of ECC-BYF III was screened by CCK-8, qRT-PCR and ELISA, the effects of ECC-BYF III on MUC5AC, MUC5B, IL-4, IL-8, TNF-α, IL-1α, miR-146a-5p and EGFR/MEK/ERK pathway expression were assessed. Furthermore, dual luciferase reporter gene was used to verify the relationship between miR-146a-5p and EGFR/MEK/ERK, and to observe the effect of down-regulating miR-146a-5p on ECC-BYF III ameliorating mucus hypersecretion and EGFR/MEK/ERK pathway.

Results: ECC-BYF III reduced the expression of MUC5AC and MUC5B, decreased the mRNA expression of IL-1α, IL-8 and TNF-α, increased the mRNA expression of IL-4, and decreased the protein expression of TNF-α. Moreover, ECC-BYF III ameliorated CSE induced mucus hypersecretion in BEAS-2B cells through EGFR/MEK/ERK pathway. Finally, our results indicated that ECC-BYF III ameliorated the model by targeting miR-146a-5p and downregulating the EGFR/MEK/ERK pathway.

Conclusion: ECC-BYF III can ameliorate CSE induced mucus hypersecretion by BEAS-2B cells and reduce the inflammatory response. The underlying mechanism may be related to the regulation of miR-146a-5p and the EGFR/MEK/ERK pathway. ECC-BYF III can inhibit activation of the EGFR/MEK/ERK pathway by upregulating the expression of miR-146a-5p, thereby ameliorating mucus hypersecretion by BEAS-2B cells.

Purpose: The miR-125a-5p has been reported influence the development of lung cancer, however, the link between it and chronic obstructive pulmonary disease (COPD) is still not well understood. Hence, this study was designed to investigate the molecular pathway by which miR-125a-5p related biomarkers were involved in COPD.

Patients and methods: The differentially expressed genes (DEGs) and module genes related to COPD in GSE100153 were screened out by differential analysis and weighted gene co-expression network analysis, respectively. Then, the target genes of miR-125a-5p obtained from miRWalk database were intersected with DEGs and module genes, followed by identification of biomarkers through SVM-RFE algorithms. Moreover, the gene set enrichment analysis, immune infiltration analysis, construction of regulatory network, single-cell analysis and Mendelian randomization (MR) analysis were performed. At last, the expression levels of the biomarkers were further validated in GSE100153 and GSE146560 as well as in qRT-PCR.

Results: A total of 10 genes were acquired by intersecting the 126 DEGs, the 3989 module genes, and 2329 target genes, of which PITHD1, CNTNAP2 and GUCD1 were identified as biomarkers. Enrichment analysis showed their roles in various cellular functions. In addition, significant associations were identified between 9 distinct cells and biomarkers. Subsequently, 5 TFs and 63 therapeutic agents were predicted as biomarkers. Moreover, GUCD1 and PITHD1 were significantly different between case and control in T cells and Alveolar cells. In COPD, GUCD1 and PITHD1 were significantly down-regulated in GSE100153 and GSE146560 datasets and confirmed by qRT-PCR.

Conclusion: In our study, PITHD1, CNTNAP2, and GUCD1 were recognized as biomarkers related to miR-125a-5p-related genes in COPD, providing new references for treatment of COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with high morbidity and mortality worldwide. Observational studies have shown correlations between common extrapulmonary comorbidities and COPD, but the existence of correlations does not necessarily prove a causal association. Therefore, causal relationships between diseases need to be explored by means of causal inference methods.

Materials and methods: Genetic correlation and two-sample Mendelian randomization (MR) analysis were explored to assess the causal relationship between exposures and outcomes with the genome-wide association studies (GWAS) dataset. Different sensitivity analyses were conducted to verify the robustness and consistency of results.

Results: The linkage disequilibrium score regression showed that cardiovascular disease (CVD), hypertension (HTN) and type 2 diabetes mellitus (T2DM) were significantly genetically associated with COPD. T2DM and HTN were found to have a positive causal effect on COPD. The odds ratio (OR) of T2DM on COPD was 1.111 (95% CI, 1.063-1.160; P<0.0001) and that of HTN on COPD was 1.125 (95% CI, 1.084-1.167; P < 0.0001). Similar results were verified by different MR methods. Furthermore, COPD had a positive causal effect on T2DM (OR 1.152 (95% CI, 1.064-1.246; P=0.0005)).

Conclusion: Our findings provided evidence for the causal association between HTN, T2DM and COPD, which would render new insights into the pathogenesis, prevention and intervention for COPD.

Purpose: Following the relatively recent introduction of single-inhaler triple therapies in Japan, this study compared the effectiveness of switching from multiple-inhaler triple therapy (MITT) to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) by investigating COPD exacerbations and adherence among patients with chronic obstructive pulmonary disease (COPD) in Japan.

Methods: This retrospective, pre-post cohort study using the Medical Data Vision Co. Ltd database identified patients with ≥1 inpatient diagnosis and/or ≥2 outpatient diagnoses of COPD at age ≥40 years prior to the index date (first/earliest date of single-inhaler FF/UMEC/VI initiation from May 1, 2019-February 28, 2022, following a switch from MITT). The proportion of patients with ≥1 overall (moderate-to-severe), moderate, or severe COPD exacerbation and rate of exacerbations were assessed at 6 months pre- and post-index. Medication adherence (proportion of days covered [PDC]) was also assessed.

Results: In total, 2365 patients were included, with a mean (standard deviation) age of 75.3 (9.7) years, and 77.1% were male. In the 6 months post-switch from MITT to FF/UMEC/VI, there was a statistically significant decrease in the proportion of patients who experienced ≥1 overall (11.2% to 8.8%; p=0.0014) and severe exacerbation (4.6% to 3.2%; p=0.0069). There was a similar proportion of patients who experienced ≥1 moderate exacerbation pre- and post-switch (6.9% to 6.2%; p=0.2394). Rates of overall (rate ratio [RR]: 0.86, 95% confidence interval [CI]: 0.74-1.00; p=0.0528) and moderate exacerbations (RR: 0.95, 95% CI: 0.79-1.13; p=0.5796) were numerically lower post-switch. There was a significant reduction in severe exacerbations post-switch (RR: 0.68, 95% CI: 0.51-0.90; p=0.0084). Mean PDC was significantly higher in the 6 months post- versus pre-switch (0.83 versus 0.80; p<0.0001).

Conclusion: Patients who switched from MITT to FF/UMEC/VI had reduced exacerbations and improved adherence. These results may help inform healthcare providers on the optimum management strategy for patients with COPD in Japan.