COPD: Journal of Chronic Obstructive Pulmonary Disease最新文献

Background: Despite limited breakthroughs in COPD pharmacotherapy, recent trials have shown promising results for biologics in COPD patients. However, robust evidence synthesis in this area is currently lacking.

Methods: We conducted a systematic review of MEDLINE, EMBASE, and Cochrane CENTRAL from inception to July 17, 2024, to identify randomized trials of biologic medications in patients with COPD. We performed a random effects frequentist network meta-analysis and present the results using relative risk (RR) and 95% confidence intervals (CI). We used the GRADE framework to rate the certainty of the evidence. Outcomes of interest included exacerbations, change in FEV1, change in quality of life, and serious adverse events.

Results: Dupilumab reduced exacerbations as compared to placebo (RR 0.68 [95% CI 0.59 to 0.79]) (high certainty). Benralizumab (RR 0.89 [95% CI 0.78 to 1]), itepekimab (RR 0.81 [95% CI 0.61 to 1.07]) and tezepelumab (RR 0.83 [95% CI 0.61 to 1.12]) may reduce exacerbations as compared to placebo (all low certainty). Dupilumab probably reduced exacerbations more than mepolizumab (RR 0.74 [95% CI 0.62 to 0.89]) (moderate certainty). Dupilumab may reduce exacerbations more than tezepelumab (RR 0.82 [95% CI 1.14]) (low certainty). For all patients, no treatment improved FEV1 above the pre-specified minimal clinically important difference (MCID) of 0.1 L. Dupilumab probably has no meaningful effect on FEV1 compared to placebo (MD 0.07 [95% CI 0.02 to 0.13]) (moderate certainty). However, in the subgroup of patients with blood eosinophils ≥300/mcL, both tezepelumab (MD 0.15 [95% CI 0.05 to 0.26]) and dupilumab (MD 0.13 [95% CI 0.06 to 0.19]) probably improved FEV1 above the MCID.

Conclusion: Dupilumab is effective at improving patient-relevant outcomes in COPD with higher eosinophil levels. Other biological therapies, including tezepelumab, have no important effect on patient-relevant outcomes.

Chronic obstructive pulmonary disease (COPD) is characterized by restricted airflow that leads to significant respiratory difficulties. This progressive disease often results in diminished pulmonary function and the onset of additional respiratory conditions. Autophagy, a critical cellular homeostasis mechanism, plays a significant role in the exacerbation of COPD. In this study, we utilized various bioinformatics tools to identify autophagy-related genes activated by smoking in individuals with COPD. Furthermore, we explored the immune landscape of COPD through these genes, analyzing cell communication patterns using scRNA-seq data. This analysis focused on key pathways between epithelial cells and other cellular subpopulations with different autophagy scores, essential for understanding the initiation and progression of COPD.

Objective: To analyze the status of research on treating chronic obstructive pulmonary disease (COPD) combined with respiratory failure internationally to reveal its development trends through visualization methods and to provide a reference and suggestions for future research directions.

Methods: Literature on the treatment of COPD combined with respiratory failure published from the year of inception of the Web of Science database to December 31, 2023, was searched. CiteSpace 6.2.R7 software was used to visualize and analyze the published articles. A bibliometric analysis of the publications, keyword co-occurrence analysis, keyword clustering analysis, and keyword emergence analysis were performed to draw a correlation map and analyze the results.

Results: A total of 369 articles were analyzed. An overall increasing trend was observed in the number of publications. The network of researchers was relatively dense, and a core team was clearly observed. The researchers' affiliations were mainly European universities and hospitals, and close cooperation between institutions was observed. The keyword analysis obtained high-frequency keywords such as "noninvasive ventilation", "mechanical ventilation", and "positive pressure ventilation". The keyword clustering analysis revealed 10 clusters, and the keyword emergence analysis yielded 20 keywords.

Conclusions: The focus of attention internationally has been on respiratory failure classification and types of ventilation support, such as high-flow oxygenation and noninvasive positive pressure ventilation. Future directions should include clinical research on high-flow oxygen administration to improve patient prognosis and the application of extracorporeal carbon dioxide removal technology to enhance patients' quality of life.

Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis) are associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, their role in the pathogenesis of COPD is unknown. We retrospectively analysed the clinical data of patients with AECOPD (modified British Medical Research Council scale score, Global Initiative for Chronic Obstructive Lung Disease [GOLD] classification, pre-admission antibiotic and inhalant usage, sputum culture and epidemic influenza virus antigen test) for association with admission frequency. Among 169 eligible patients, pathogens were and were not detected in 64 and 105, respectively. The GOLD classification grade was higher in the non-detection group with a prior antimicrobial administration rate of 21.9% than in the detection group. H. influenzae and M. catarrhalis, each identified in 24.6% of the total number of detected pathogens, were the most common infectious bacteria. The GOLD classification grade was higher in the re-hospitalisation group than in the one-time hospitalisation group (p < 0.01). Regarding type of pathogen, M. catarrhalis infection (n = 16) was more common in the re-hospitalisation group. History of M. catarrhalis, H. influenzae infection and GOLD grade ≥ III were risk factors for re-hospitalisation, with odds ratios of 92.7 (95% confidence interval [CI]: 3.68-2340.0, p < 0.01), 20.1 (CI: 1.48-274.0, p < 0.05) and 9.83 (CI: 2.33-41.4, p < 0.01), respectively. These bacterial infections and severe airway limitation were associated with increased AECOPD frequency. Routine microbial monitoring may be useful for AECOPD prevention, reducing medical burden and improving prognosis.

Background: The prevalence of combinations of comorbidities and their associations with inpatient service utilization and readmission among patients with chronic obstructive pulmonary disease (COPD) have not been extensively examined. To address this gap in knowledge, an observational prospective study was conducted using retrospective data.

Aims: To identify patterns of comorbidities linked to length of hospital stay, daily expenses, and one-year readmission.

Methods: The 30 most common comorbidities were identified in patients with secondary diagnoses using the association rule mining (ARM) method. Regression models were used to examine the relationships between combinations of comorbidities and service utilization, with adjustments for covariates.

Results: The five most prevalent comorbidities were pulmonary heart disease (40.99%), ischemic heart disease (38.97%), heart failure (36.77%), hypertension (34.11%), and respiratory disorders (19.12%). Most combinations of comorbidities identified by ARM showed significant associations with an extended length of stay (>13 days), increased daily expenses (>930 CNY), and reduced readmission rates. Among these combinations, glycoprotein metabolism disorder had the strongest association with prolonged length of stay (adjusted odds ratio [aOR]): 1.89, 95% confidence interval [CI]: 1.82-1.95). Conversely, the combination of other brain diseases and respiratory failure was linked to higher daily expenses (aOR: 11.34, 95% CI: 10.58-12.15), and the presence of pulmonary heart disease was associated with elevated one-year readmission rates (aOR: 1.41, 95% CI: 1.37-1.46).

Conclusion: Common combinations of comorbidities among inpatients with COPD were identified from an extensive collection of discharge medical records. Furthermore, the associations between comorbidities, inpatient service usage, and readmission rates were determined.

Objective: To investigate the effects of cigarette smoke (CS) on Serine/Threonine Kinase 11 (STK11) and to determine STK11's role in CS-induced airway epithelial cell cytotoxicity.Methods: STK11 expression levels in the lung tissues of smokers with or without COPD and mice exposed to CS or room air (RA) were determined by immunoblotting and RT-PCR. BEAS-2Bs-human bronchial airway epithelial cells were exposed to CS extract (CSE), and the changes in STK11 expression levels were determined by immunoblotting and RT-PCR. BEAS-2B cells were transfected with STK11-specific siRNA or STK11 expression plasmid, and the effects of CSE on airway epithelial cell cytotoxicity were measured. To determine the specific STK11 degradation-proteolytic pathway, BEAS-2Bs were treated with cycloheximide alone or combined with MG132 or leupeptin. Finally, to identify the F-box protein mediating the STK11 degradation, a screening assay was performed using transfection with a panel of FBXL E3 ligase subunits.Results: STK11 protein levels were significantly decreased in the lung tissues of smokers with COPD relative to smokers without COPD. STK11 protein levels were also significantly decreased in mouse lung tissues exposed to CS compared to RA. Exposure to CSE shortened the STK11 mRNA and protein half-life to 4 h in BEAS-2B cells. STK11 protein overexpression attenuated the CSE-induced cytotoxicity; in contrast, its knockdown augmented CSE-induced cytotoxicity. FBXL19 mediates CSE-induced STK11 protein degradation via the ubiquitin-proteasome pathway in cultured BEAS-2B cells. FBXL19 overexpression led to accelerated STK11 ubiquitination and degradation in a dose-dependent manner.Conclusions: Our results suggest that CSE enhances the degradation of STK11 protein in airway epithelial cells via the FBXL19-mediated ubiquitin-proteasomal pathway, leading to augmented cell death.HIGHLIGHTSLung tissues of COPD-smokers exhibited a decreased STK11 RNA and protein expression.STK11 overexpression attenuates CS-induced airway epithelial cell cytotoxicity.STK11 depletion augments CS-induced airway epithelial cell cytotoxicity.CS diminishes STK11 via FBXL19-mediated ubiquitin-proteasome degradation.

Introduction: Potential associations between Chronic Obstructive Pulmonary Disease (COPD) and osteoporosis have been studied, but areas of uncertainty remain.

Objective: This scoping review aimed to identify the published evidence on the epidemiological relationships between COPD and osteoporosis.

Methods: Experimental and observational evidence evaluating relationships between COPD and osteoporosis on epidemiology, clinical manifestations, risk factors (RFs), therapeutic management and quality of life (QoL) was searched on PubMed and Embase (until May 2023). The studies were categorized according to their objectives and characteristics. Data were analyzed using descriptive statistics.

Results: Ninety-nine studies were selected, namely 33 (33%) reporting epidemiologic measures, 11 (11%) clinical manifestations, 74 (75%) RFs (45 ones, of which body mass index [BMI; n = 22 studies], corticosteroids' use [n = 20], and COPD severity [n = 15] were the most studied), 7 (7%) therapeutic management, and 3 (3%) QoL. Twenty-seven (27.6%) studies evaluated ≥2 domains. Most studies followed a cross-sectional design (n = 37; 37.4%). Eighty-nine studies (90%) assessed patients with COPD at baseline and studied its relationship with osteoporosis.

Conclusion: There are well-established features linking COPD and osteoporosis, including shared RFs, such as smoking, elderly, physical inactivity, or low BMI. Others deserve clarification, including the impact of COPD severity, or the use of inhaled corticosteroids on the incidence of osteoporosis and fractures, as well as the value of performing routine imaging tests, or prescribing anti-resorptive medications in COPD to prevent osteoporotic-related outcomes. QoL studies are also lacking. Investigating such issues is needed to propose clinical guidelines for managing osteoporosis in patients with COPD.

Exertional dyspnea, a key complaint of patients with chronic obstructive pulmonary disease (COPD), ultimately reflects an increased inspiratory neural drive to breathe. In non-hypoxemic patients with largely preserved lung mechanics - as those in the initial stages of the disease - the heightened inspiratory neural drive is strongly associated with an exaggerated ventilatory response to metabolic demand. Several lines of evidence indicate that the so-called excess ventilation (high ventilation-CO₂ output relationship) primarily reflects poor gas exchange efficiency, namely increased physiological dead space. Pulmonary function tests estimating the extension of the wasted ventilation and selected cardiopulmonary exercise testing variables can, therefore, shed unique light on the genesis of patients' out-of-proportion dyspnea. After a succinct overview of the basis of gas exchange efficiency in health and inefficiency in COPD, we discuss how wasted ventilation translates into exertional dyspnea in individual patients. We then outline what is currently known about the structural basis of wasted ventilation in "minor/trivial" COPD vis-à-vis the contribution of emphysema versus a potential impairment in lung perfusion across non-emphysematous lung. After summarizing some unanswered questions on the field, we propose that functional imaging be amalgamated with pulmonary function tests beyond spirometry to improve our understanding of this deeply neglected cause of exertional dyspnea. Advances in the field will depend on our ability to develop robust platforms for deeply phenotyping (structurally and functionally), the dyspneic patients showing unordinary high wasted ventilation despite relatively preserved FEV₁.