COPD: Journal of Chronic Obstructive Pulmonary Disease最新文献

This randomized controlled trial evaluated the effectiveness of two home-based, stand-alone inspiratory muscle training (IMT) modalities - inspiratory flow-resistive loading with biofeedback (IRFL) and mechanical threshold loading (MTL) - compared to a sham MTL group for improving inspiratory muscle performance and functional exercise capacity in COPD patients. Thirty-six COPD patients trained at home for 8 weeks under remote monitoring. Primary outcomes included inspiratory muscle performance assessed via the Test of Incremental Respiratory Endurance (TIRE), functional exercise capacity, lung function, and other COPD-related measures. Both the TIRE IRFL and MTL groups showed significant improvements in inspiratory muscle strength compared to the sham MTL group (p < 0.05). Additionally, the IRFL with biofeedback group demonstrated significant gains in inspiratory muscle work capacity and 6MWT distance compared to both the MTL and sham groups (p < 0.05). No adverse events were reported, and adherence to training protocols was high across all groups. This study supports home-based IMT as a feasible, effective stand-alone intervention for COPD patients, particularly for those who face barriers in accessing traditional pulmonary rehabilitation programs. TIRE IFRL showed superior benefits in enhancing inspiratory muscle function and overall functional exercise capacity compared to fixed-load IMT.

Purpose: Cigarette smoke activates lung inflammation and destruction and the development of COPD. Among various factors influenced by lung inflammation, adiponectin produced by lung epithelial cells is thought to play a significant role in regulating inflammation and maintaining tissue integrity. This study aims to examine adiponectin expression in a mouse model of cigarette smoke extract (CSE)-induced emphysema and explore the effects of adiponectin on cell survival and cytokine gene expression in CSE-induced lung epithelial cell damage.

Methods: CSE was prepared by passing cigarette smoke through a glass tube containing solvent. PBS or CSE was intraperitoneally administered to C57BL/6 mice. Inflammatory cells, cytokines, adiponectin expression in lung, bronchoalveolar lavage fluid (BALF) and adipose tissue were assessed. CSE and adiponectin were administered to A549 cells to determine cell viability and cytokine gene expression.

Results: Intraperitoneal CSE injection significantly increased the mean alveolar linear intercept by 23.11%. CSE significantly increased total cells, macrophages, neutrophils, eosinophils, TNFα, IL-1β levels in BALF. CSE enhanced lung adiponectin protein expression. Treatment of A549 cells with CSE reduced cell survival and adiponectin gene expression. Furthermore, adiponectin treatment enhanced MCP-1 and IL-8 gene expression in A549 cells post-CSE exposure.

Conclusion: Intraperitoneal CSE treatment induced lung inflammation, airspace enlargement, and increased adiponectin expression in mice. CSE-exposed A549 cells showed reduced cell viability, upregulated proinflammatory genes, downregulated adiponectin genes. Adiponectin treatment further intensified these genes expressions, aligning with in vivo findings. Elevated adiponectin expression in alveolar epithelial cells suggests its potential role in the development of COPD by enhancing lung inflammation.

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.

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.

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.

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.

The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR^-ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR^-ILC3s. The study involved both in vivo and in vitro experiments. In the former, the frequencies of lung NCR^-ILC3s and NKp46^-IL-17A⁺ ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1β quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46^-IL-17A⁺ ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45⁺Lin^-CD127⁺ ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45⁺Lin^-CD127⁺ ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR^-ILC3s and NKp46^-IL-17A⁺ ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46^-IL-17A⁺ ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR^-ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR^-ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.

Background: Patients with chronic obstructive pulmonary disease (COPD) often do not seek care until they experience an exacerbation. Improving self-management for these patients may increase health-related quality of life and reduce hospitalizations. Patients are willing to use wearable technology for real-time data reporting and perceive mobile technology as potentially helpful in COPD management, but there are many barriers to the uptake of these technologies.

Objective: We aimed to understand patients' experiences using a wearable and mobile app and identify areas for improvement.

Methods: We conducted semi-structured interviews as part of a larger prospective cohort study wherein patients used a wearable and app for 6 months. We asked which features patients found accessible, acceptable and useful.

Results: We completed 26 interviews. We summarized our research findings into four main themes: (1) information, support and reassurance, (2) barriers to adoption, (3) impact on communication with health care providers, and (4) opportunities for improvement. Most patients found the feedback received through the app to be reassuring and useful. Some patients experienced technical difficulties with the app and found the wearable to be uncomfortable.

Conclusions: Patients found a wearable device and mobile application to be acceptable and useful for the management of COPD. We identified barriers to adoption and opportunities for improvement to the design of our app. Further research is needed to understand what people with COPD and their healthcare providers want and will use in a mobile app and wearable for COPD management.