International Journal of Chronic Obstructive Pulmonary Disease最新文献

Purpose: Airway disease is the main pathological basis of chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are unknown. Bone morphogenetic protein-7 (BMP7) is a multi-functional growth factor that belongs to the transforming growth factor superfamily, which affects the regulation of proliferation, differentiation, and apoptosis. Previous research has shown that BMP7 is highly expressed in the airway epithelia of patients with COPD, but its role in airway disease has not been fully elucidated.

Methods: A lung tissue cohort and a sputum cohort were included in the study. BMP7 expression in the airway epithelium and the BMP7 level in sputum supernatants were detected. Human primary bronchial epithelial cells (HPBECs) were isolated by bronchoscopy from healthy individuals. The functional consequences of adding recombinant human BMP7 or BMP7 overexpression to HPBECs were explored.

Results: BMP7 expression in bronchial epithelial cells of patients with COPD was significantly higher than that in smoking and nonsmoking controls. The expression of BMP7 in the bronchial epithelia of patients with COPD was negatively correlated with the airway counts measured by quantitative computed tomography, positively correlated with airway wall thickness, and negatively correlated with FEV1. The BMP7 level in the induced sputum of patients with COPD was higher than that in controls, and was related to the levels of interleukin-6 (IL-6), IL-8, and IL-1β. The addition of rhBMP7 (100 ng/mL) inhibited the proliferation of HPBECs and promoted squamous metaplasia and inhibit ciliated cell differentiation in human bronchial epithelial cells. BMP7 overexpression promotes apoptosis in human bronchial epithelial cells, through regulating MKK7/JNK2 signaling pathway and activating the caspase-3 pathway.

Conclusion: High expression of BMP7 in the bronchial epithelia may play a crucial role in airway disease of COPD through inhibiting proliferation and promoting abnormal differentiation and excessive apoptosis of human bronchial epithelial cells.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammation. The peripheral blood (neutrophil + monocyte)/lymphocyte ratio (NMLR) can predict the clinical outcomes of several inflammatory diseases. However, its prognostic value in COPD remains unknown.

Methods: This retrospective study included 870 patients with COPD due to acute exacerbation, and the 5-year all-cause mortality of these patients was recorded. The Kaplan-Meier method was used to compare the mortality risk of these patients according to their NMLR value. Multivariable COX hazard regression and restricted cubic spline model were used to assess the relationship between the NMLR and 5-year all-cause mortality of patients with COPD.

Results: The NMLR values of non-surviving patients with COPD were significantly increased compared to the survivors [3.88 (2.53-7.17) vs 2.95 (2.08-4.89), P=0.000]. The area under the NMLR receiver operating characteristic curve for predicting the 5-year all-cause mortality of COPD patients was 0.63. Kaplan-Meier survival curves showed that the 5-year all-cause mortality of COPD patients was significantly increased when the admission peripheral blood NMLR was ≥ 5.90 (27.3% vs 12.4%, P=0.000). The COX regression model showed that NMLR was an independent predictor of 5-year all-cause mortality in COPD patients (hazard ratio=1.84, 95% confidence interval: 1.28-2.64, P=0.001). Moreover, the restricted cubic spline model showed a non-linear relationship between NMLR and COPD death risk (P_non-linear < 0.05).

Conclusion: The admission peripheral blood NMLR is a significant predictor of 5-year all-cause mortality in patients with COPD, and high NMLR values may indicate a poor clinical prognosis.

Background: Bone marrow mesenchymal stem cell (BMSC) therapy is a novel approach for treating COPD. However, the difficulty in engraftment and easy clearance of BMSCs in vivo has hindered their clinical application. Hence, exploring effective methods to improve the engraftment and differentiation rates of BMSCs in vivo is urgent.

Methods: We constructed BMSCs overexpressing Wnt3a by lentivirus infection and transplanted them into a COPD rat model. The damage level of COPD rat lung tissue was assessed by pathology analysis and inflammatory cytokines analysis. The engraftment of BMSC was detected by immunofluorescence staining. Statistical analysis was performed using GraphPad Prism 7.

Results: We found that Wnt3a significantly enhanced the engraftment rate of BMSCs in the lungs of rats and further increased their differentiation rate into type II alveolar epithelial cells. We also assessed the expression of inflammatory factors in the lung tissues of COPD rats and discovered that Wnt3a reduced the levels of the inflammatory factors IL-6 and IL-1β while increasing the level of the anti-inflammatory factor IL-10. Our study demonstrates that Wnt3a can improve the engraftment and differentiation rates of BMSCs in the host and further alleviate COPD symptoms by regulating the secretion of inflammatory factors.

Conclusion: Constructing BMSCs overexpressing Wnt3a could serve as a new strategy for stem cell therapy in COPD.

Background: In preliminary research and literature review, we identified a potential link between chronic obstructive pulmonary disease (COPD) and lipid metabolism. Therefore, this study employed Mendelian randomization (MR) analysis to investigate the potential causal connection between blood lipids and COPD.

Materials and methods: A genome-wide association study (GWAS) on COPD was conducted, encompassing a total of 112,583 European participants from the MRC-IEU. Additionally, extensive UK Biobank data pertaining to blood lipid profiles within European cohorts included measurements for low-density lipoprotein cholesterol (LDL-C) with 440,546 individuals, high-density lipoprotein cholesterol (HDL-C) with 403,943 individuals, triglycerides (TG) with 441,016 individuals, total cholesterol (TC) with 187,365 individuals, apolipoprotein A-I (apoA-I) with 393,193 individuals, and apolipoprotein B (apoB) with 439,214 individuals. Then, MR analyses were performed for lipids and COPD, respectively. The primary analytical technique employed was the inverse-variance weighted (IVW) approach, which included a 95% confidence interval (CI) to calculate the odds ratio (OR). Additionally, a sensitivity analysis was conducted to assess the dependability of the MR analysis outcomes.

Results: MR analysis was primarily based on IVW, unveiled a causal link between COPD and LDL-C (OR=0.994, 95% CI (0.989, 0.999), P=0.019), TG (OR=1.005, 95% CI (1.002, 1.009), P=0.006), and apoA-I (OR=0.995, 95% CI (0.992, 0.999), P=0.008), in addition, no causal link was found with HDL-C, TC, apoB. Sensitivity analysis demonstrated the robustness of these causal relationships. However, through multivariate MR(MVMR) and multiple testing correction, LDL-C and TG had no causal effect on the outcome. ApoA-I remained a protective factor for the risk of COPD (OR=0.994, 95% CI (0.990-0.999), P=0.008).

Conclusion: Through MR analysis, this study offers evidence of a causal link between apoA-I with COPD. This further substantiates the potential role of lipid metabolism in COPD, and has significant clinical implications for the prevention and management of COPD.

Objective: There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with coronary heart disease (CHD). In this study, we provide valuable insights in the field by examining the evolution of the relationship between COPD and CHD over the past 20 years.

Methods: A comprehensive computer search was conducted in the Web of Science (WOS) core dataset, covering literature on COPD combined with CHD from January 1, 2005, to August 20, 2024. Visual analyses were performed using VOSviewer, CiteSpace, and Bibliometrix to assess countries, institutions, the centrality of institutional intermediaries, authorship patterns, including co-cited authors and references, and keywords; Excel (version 2021) software was utilized for generating relevant descriptive analysis tables.

Results: A total of 2420 publications sourced from WOS were included in this study. Since 2005, there has been a continuous increase in the literature about COPD combined with CHD; polynomial fitting yielded an R² value of 0.7758. The volume of literature in this domain is projected to continue growing steadily. The United States emerged as the leading country by publication count; Lin Cheng-li ranked first among authors, while China Medical University topped institutional contributions. Notably, Sin dd, Mannino dm, and Helvaci Mr were identified as the top three authors based on citation frequency. The Journal of Vascular Surgery recorded the highest number of publications, whereas The Lancet was recognized as the most influential among the top ten co-cited journals. The most frequently cited reference pertains to systemic inflammation's role in increasing cardiovascular risk among patients with COPD. Through keyword clustering analysis, we categorized all keywords into three distinct groups: management strategies for COPD and CHD; diseases associated with both conditions; and epidemiological characteristics concerning their burden-current hotspots include multimorbidity factors such as hypertension and obesity alongside outcomes like diagnosis during COVID-19 pandemic implications within societal contexts are highlighted here too.

Conclusion: Presently focused research on COPD coupled with CHD primarily revolves around five key areas: pathogenesis exploration, early diagnostic techniques, COVID-19 infection, dynamics intervention, methodologies, and treatment protocol development efforts. To improve the early detection rate of COPD complicated with CHD, the main development direction in the future is to extract computed tomography (CT) features using imaging omics and establish an early prediction model. The results of this study will provide new ideas and directions for subsequent related research.

Background: Both Aspergillus fumigatus sensitization and mucus plugs are associated with poor clinical outcomes in COPD. However, little is known about the association between Aspergillus hypersensitivity and mucus plugging in patients with COPD.

Methods: We retrospectively enrolled COPD patients who had visited Peking University Third Hospital and received measurement of the Aspergillus Fumigatus specific IgE (Af sIgE) from Oct 1, 2018 to Sep 30, 2023. The clinical, laboratory, and chest CT features were analyzed, with mucus plugging evaluation using the bronchopulmonary segment-based scoring system. Comparison was performed between COPD patients with and without Aspergillus hypersensitivity (AH).

Results: Among the 378 COPD patients with measurement of Af sIgE, 29 (7.7%) were classified as having AH (Af sIgE>0.35KU/L). By propensity score matching (1:2), 58 patients without AH were included for comparison. Patients with AH had lower FEV1%pred (P=0.008) and FEV1/FVC (%) (P=0.023), and were more likely to have a blood eosinophil count exceeding 300/µL and higher white blood cell and neutrophil counts. The prevalence of luminal plugging on chest CT in subjects with AH was 58.6%, compared to 31.0% in those without AH (P=0.013). Multivariate regression analyses showed that Af sIgE more than 0.70 KU/L and blood neutrophil count were associated with mucus plugging.

Conclusion: In patients with COPD, Aspergillus sensitization was associated with lower lung function and mucus plugging on chest CT.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, airflow limitation, reduced health-related quality of life (HRQL), and exercise intolerance. Pulmonary rehabilitation (PR) is essential for COPD management, but outcomes may be influenced by individual physiological factors. Cardiopulmonary exercise testing (CPET) measures oxygen pulse (O2P), an indicator of stroke volume, yet the impact of baseline O2P on PR effectiveness remains unclear.

Methods: This retrospective study included 97 participants with COPD who had received PR, of whom 48 were classified as Group 1 (normal O2P) and 49 as Group 2 (low O2P). PR involved 12 weeks of hospital-based endurance training on a bike, performed twice a week. Participants were assessed before and after PR using spirometry, respiratory muscle strength measurements, CPET, and HRQL evaluation with the St. George's Respiratory Questionnaire (SGRQ).

Results: PR significantly improved exercise capacity (peak work rate and oxygen consumption), dyspnea score, and all domains of the SGRQ, maximum expiratory pressure, ventilatory equivalent, respiratory rate, and mean blood pressure at rest in both groups (p < 0.05). However, improvements in O2P, maximal inspiratory pressure, and tidal volume at rest were observed only in Group 2 but not in Group 1.

Conclusion: PR improves exercise capacity, HRQL and specific respiratory function in participants with COPD, regardless of baseline O2P levels. Individuals with lower baseline O2P experience more benefits from PR, including a significant increase in O2P.

Objective: This study sought to examine the potential relationship between Hemoglobin/Red Cell Distribution Width Ratio (HRR) and the all-cause mortality risk in critically ill patients with chronic obstructive pulmonary disease (COPD).

Patients and methods: In a retrospective analysis of the MIMIC-IV database, patients were divided into two groups based on a specific HRR threshold. Propensity score matching (PSM) was employed to address covariate imbalances. Logistic regression models was used to examine the association between HRR and mortality. A restricted cubic spline (RCS) model was employed to visualize the association between HRR and mortality. Receiver Operating Characteristic (ROC) curves were utilized to assess the predictive capability of HRR, and Decision Curve Analysis (DCA) was conducted for clinical evaluation. Furthermore, subgroup analyses were performed to explore potential variations within specific cohorts.

Results: A comprehensive analysis identified a total of 1,061 patients. The threshold value established for HRR is 5.395 g/L/%. Following the application of PSM, the matched cohort comprised 544 patients. Both the original and matched cohorts exhibited higher rates of all-cause mortality and extended hospital stays among individuals with low HRRs. Logistic regression analyses demonstrated that HRR is an independent risk factor of mortality. The RCS analysis demonstrated a significant linear relationship between HRR and mortality. The ROC curves yielded values of 0.58 for the original cohort and 0.60 for the matched cohort. DCA analysis indicated that HRR is clinically valuable. Subgroup analyses further validated the robustness of these core findings.

Conclusion: A lower HRR is positively associated with all-cause mortality in critically ill patients with COPD.