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To investigate the anti-inflammatory and therapeutic effects of Ginkgo biloba extract (GBE) on chronic obstructive pulmonary disease (COPD), and to elucidate the underlying molecular mechanism by which GBE modulates the p38 mitogen-activated protein kinase (MAPK) signaling pathway and maintains the balance of T helper 1 (Th1)/T helper 2 (Th2) cells, thereby alleviating pulmonary inflammation, alveolar destruction and airway remodeling in COPD. Rats were randomly assigned to one of six groups: a blank group, a COPD model group, a high-dose GBE group (14 mg/kg/day), a medium-dose GBE group (7 mg/kg/day), a low-- dose GBE group (3.5 mg/kg/day), and a p38 MAPK inhibitor group, with 15 rats in each group. Except for the blank group, COPD models were established in the other groups using cigarette smoke (CS) inhalation combined with intratracheal lipopolysaccharide (LPS) instillation. Following the establishment of the models, the respective treatments were administered to each group. After the drug interventions, histological examination using HE staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, quantitative real-time polymerase chain reaction (PCR), and Western blot analysis were performed to explore the underlying mechanisms. Different doses of GBE and the p38 MAPK inhibitor alleviated alveolar destruction and airway remodeling in COPD rats, reducing inflammatory infiltration around alveoli and bronchi. Compared with the COPD model group, all GBE dose groups and the p38 MAPK inhibitor group inhibited p38 MAPK signaling and the activation of upstream regulatory factors (TLR3, MKK3, MKK6) (p<0.05), reduced CD4+ T cell differentiation toward Th1 (p<0.05), suppressed secretion of inflammatory cytokines interferon-γ (IFN-γ) and interleukin-2 (IL-2) (p<0.05), and mitigated immune-inflammatory damage to alveoli and bronchi. The core pathological issues of COPD include immune-inflammatory imbalance, destruction of alveolar structure, and airway remodeling. This study indicates that GBE can act simultaneously on these three core aspects. This research links GBE with the p38 MAPK signaling pathway and the regulation of Th1/Th2 balance. It improves airway remodeling by regulating the p38 MAPK pathway and corrects immune-inflammatory disorders by maintaining the Th1/Th2 balance, providing clear molecular mechanism support for the action of GBE, rather than merely remaining at the level of phenomenon observation. GBE alleviates COPD immune-inflammatory responses, prevents alveolar destruction, and attenuates airway remodeling by regulating the p38 MAPK signaling pathway to maintain Th1/Th2 balance, thereby exerting therapeutic effects on COPD.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease marked by persistent airway limitation. Airway epithelial injury is pivotal in the onset and progression of COPD. Fibroblast growth factor 7 (FGF7) has been reported to promote alveolar epithelial regeneration following lung injury. Nonetheless, how FGF7 protects epithelial cells against cigarette smoke (CS)-induced airway injury remained unclear. FGF7 levels were analyzed in human lung tissues (n=32; 17 COPD and 15 control subjects) and serum samples (n=71; 51 COPD and 20 control subjects) using immunohistochemistry, RT-qPCR, Western blot, and ELISA. In a COPD rat model subjected to CS exposure for 12 weeks, the impact of intratracheal administration of AAV-FGF7 or AAV-shFGF7 on lung function was assessed by lung ventilation and histology, expression levels of cytokines, and other signaling molecules. In the CSE-injured 16HBE cell model, recombinant FGF7 was applied with or without SB202190 (a p38 inhibitor), LY294002 (a PI3K inhibitor), or AG1478 (an EGFR inhibitor) to evaluate cell viability, migratory capacity, cytokine production, and activation of corresponding signaling pathways. COPD patients demonstrated an increased level of FGF7 in lung tissues, while serum FGF7 levels decreased. In the rat model, CS exposure led to heightened airway inflammation, collagen deposition, and elevated cytokine levels in bronchoalveolar lavage fluid (BALF). Transfection of AAV-FGF7 resulted in improvements in MVb/PIFb/EF50, a reduction in inflammation and peribronchial fibrosis, and decreased levels of IL-1β, IL-6, TNF-α, TGF-β1, and ET-1 in BALF. Correspondingly, AAV-shFGF7 aggravated these pathological effects. FGF7 was found to enhance the phosphorylation of ADAM17 and EGFR, as well as ERK1/2, p38, and AKT, whereas knockdown of FGF7 inhibited the activation of these signaling pathways. In 16HBE cells, FGF7 was observed to restore cell viability and migration, suppress cytokine release, and activate ADAM17, EGFR, and ERK1/2, and these effects were diminished by the blockade of p38, PI3K, or EGFR. FGF7 is specifically upregulated in the lung tissues of COPD patients. It mitigates CS-induced airway epithelial damage and inflammation through the ADAM17-dependent EGFR-ERK1/2 axis, p38, and PI3K/AKT pathways. FGF7 therefore emerges as a promising therapeutic target for interventions aimed at preventing airway remodeling in COPD.
The relationship between increased right ventricular (RV) afterload (moderate-to-high suspicion of pulmonary hypertension indicated by echocardiography) and the prognosis of patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not yet well understood. This prospective cohort study was conducted in 11 hospitals from 2017 to 2020, involving patients hospitalized with AECOPD. Echocardiography was performed within 48 hours of admission. Patients were classified into two groups: those with increased RV afterload (n=237) and those with normal RV afterload (n=415). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis to evaluate the impact of RV afterload on patient outcomes. Kaplan-Meier survival curves were employed to assess the association between RV afterload and 3-year all-cause mortality. Kaplan-Meier survival curves demonstrated that the 3-year all-cause mortality rates were 22.8% in AECOPD patients with increased RV afterload and 9.5% in those with normal RV afterload. Cox regression analysis indicated that increased RV afterload is an independent predictor of poor prognosis in hospitalized AECOPD patients, significantly increasing the risk of 3-year all-cause mortality (HR=2.172, 95% CI: 1.384-3.411; P<0.001). Additionally, elevated brain natriuretic peptide (BNP) or n-terminal pro-brain natriuretic peptide (NT-proBNP) (HR=2.694, 95% CI: 1.724-4.209; P<0.001), and lower body mass index (BMI) (HR=0.880, 95% CI: 0.833-0.930; P<0.001) were independent risk factors for mortality. Increased RV afterload is associated with a significant increase in the risk of 3-year all-cause mortality in patients hospitalized with AECOPD, posing a 2.2-fold higher risk compared to those with normal RV afterload. It also stands as an independent risk factor for mortality. Elevated BNP or NT-proBNP levels and reduced BMI are additional independent risk factors of mortality. Early detection of these three risk factors could play a role in stratifying high-risk patients, guiding clinical decision-making, and improving patient outcomes in AECOPD. In this study, we focused on individuals hospitalized for AECOPD. We investigated the association between moderate-to-high suspicion of pulmonary hypertension on echocardiography and their prognosis. Our results can help identify those at high risk of mortality. Echocardiography is a noninvasive and widely available tool, yet its validation in large real-world cohorts remains limited. Moreover, many people are hospitalized for AECOPD, and our findings apply to the much larger population seen in primary care and routine clinical practice.
Acute exacerbations of COPD (AECOPD) significantly impair patients' quality of life and contribute to higher healthcare burdens and mortality. Recent evidence suggests a potential link between dysphagia and AECOPD. This meta-analysis aims to quantitatively evaluate the impact of dysphagia on the risk of AECOPD. A comprehensive systematic search was conducted across multiple databases, including PubMed, SinoMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and the Cochrane Library, to identify cohort studies reporting on the association between dysphagia and AECOPD. The search covered all publications from the inception of each database up to 31 May 2025. Two researchers independently performed literature screening, data extraction and quality assessment. Meta-analysis was performed using RevMan 5.4 and Stata 15.0, with pooled risk ratios calculated employing the Mantel-Haenszel method under a random effects model. Seven studies involving 669 patients were included in the analysis. Meta-analysis showed that dysphagia significantly increased both the risk of AECOPD (rate ratio 2.37 (95% CI 1.75-3.20); p<0.00001) and the annual number of annual exacerbations (mean difference 1.13 (95% CI 0.88-1.38); p<0.00001). The Egger test indicated publication bias (p=0.022); after trim-and-fill adjustment, the revised rate ratio was 1.85 (95% CI 1.35-2.53). Sensitivity analyses confirmed the robustness of these results. Subgroup analyses according to publication year, country, age, study design, lung function, dysphagia assessment methods, definition of a frequent exacerbator and study quality did not significantly change the results. This systematic review and meta-analysis shows a significant association between dysphagia and increased risk of AECOPD. The findings highlight the importance to add swallowing function screening to standard COPD management. Future research should explore underlying mechanisms and potential confounders further.
Chronic obstructive pulmonary disease (COPD) represents a major global health burden, largely attributable to tobacco exposure, including emerging patterns such as early initiation and dual use with electronic cigarettes. Early detection through spirometry in primary care remains suboptimal, potentially limiting timely identification of early disease stages, including Pre-COPD and Preserved Ratio Impaired Spirometry (PRISm). This study aimed to assess whether the implementation of a structured, spirometry-based COPD clinic within primary care networks (Aggregazioni Funzionali Territoriali, AFTs) may be associated with improved diagnostic appropriateness, more consistent therapeutic management, and more efficient use of healthcare resources. We conducted a retrospective observational analysis of routinely collected clinical data from approximately 30,000 patients across three AFTs in the Campania Region (Italy), each including about 10,000 individuals. One AFT was equipped with a dedicated respiratory clinic providing in-house spirometry performed by trained personnel, while the other two followed standard care pathways without structured respiratory services. Key variables included spirometry utilization, diagnostic confirmation of COPD, patterns of care, and selected indicators of healthcare use. In the two standard AFTs, COPD diagnoses were not supported by spirometric confirmation in approximately 65% and 70% of cases, respectively. In contrast, the AFT with a dedicated clinic showed a substantially higher use of spirometry (approximately 80% vs. 30-35%), predominantly performed within the primary care setting. This organizational model was associated with improved alignment between diagnosis and objective testing, and with indicators suggestive of better therapeutic adherence and more appropriate use of secondary care services. The integration of structured, spirometry-enabled respiratory services within primary care networks may contribute to more appropriate COPD diagnosis and management. While the availability of spirometry alone is insufficient, organizational models that incorporate trained personnel, standardized procedures, and coordinated care pathways could represent a potentially effective approach to addressing under- and misdiagnosis in COPD.
Dysphagia is a common yet often overlooked complication in Chronic Obstructive Pulmonary Disease (COPD) patients, who are prone due to abnormal breathing patterns, impaired airway protection, and generalized frailty. This not only predisposes them to aspiration pneumonia but also serves as a key trigger for acute exacerbations of COPD, substantially increasing the risk of adverse outcomes. Early identification of dysphagia is essential for improving prognosis in COPD. However, research on early detection is limited, particularly regarding machine learning prediction. This study aimed to develop and validate a machine learning based risk assessment model for dysphagia in COPD and deploy it as a user-friendly web-based clinical tool to assist clinicians in risk identification and early intervention. Retrospective medical records from 710 COPD patients admitted between February 2025 and January 2026 were analyzed. Swallowing function was assessed using the Water-Swallowing Test. Univariate and multivariate logistic regression identified independent risk factors, which were used to develop and compare eight machine learning models. Model performance was evaluated using ROC, calibration, and decision curves with Bootstrap internal validation. Key variables were interpreted via Shapley Additive Explanations, and the final model was deployed online. Dysphagia prevalence was 29.3%. Multivariate regression identified five key risk factors: disease duration, BMI, history of tracheal intubation, muscle strength, and the modified Medical Research Council (mMRC) score for dyspnea severity. Among eight machine learning models, the XGBoost model showed the best performance in the training set (AUC 0.921, 95% CI 0.901-0.940) and demonstrated good calibration and highest clinical net benefit. The model was deployed online (https://dysphagiamodel.shinyapps.io/COPD-DP/). We developed and validated an online machine learning-based dysphagia risk assessment tool for COPD, demonstrating discrimination, calibration, and clinical utility for risk stratification and clinical decision-making.
Chronic Obstructive Pulmonary Disease (COPD) is associated with diaphragm dysfunction and reduced functional capacity. Altered deep core muscle function, particularly of deep abdominal muscles may further compromise postural stability and functional performance. However, objective clinical assessment of deep core muscle activation across COPD severity remains underexplored. To explore potential associations between deep core muscle function using a pressure biofeedback unit (PBU) and Pulmonary Function parameters (PFT) across Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages in individuals with COPD. In this cross-sectional exploratory study, 84 individuals with COPD were assessed. Pulmonary function (FEV1, FVC and FEV1/FVC) was measured using spirometry. Deep core muscle function was evaluated using a Pressure Biofeedback Unit (PBU) during the Abdominal Drawing-In Maneuver (ADIM) in prone position. Associations between PBU measures and pulmonary function parameters were examined using Spearman's correlation including exploratory analysis across GOLD stages. Deep core muscle function demonstrated statistically significant negative correlations with pulmonary function parameters, including FEV1/FVC (ρ = -0.55; p < 0.001), FEV1 (ρ = -0.72; p < 0.001) and FVC (ρ = -0.59; p < 0.001). Mean PBU pressure values progressively increased across GOLD stages (Kruskal-Wallis H (3) = 50.053; p < 0.001; Ɛ2 = 0.59). Stage-wise exploratory analyses demonstrated variable correlations across GOLD stages, however findings should be interpreted cautiously due to small subgroup sample sizes. Deep core muscle function assessed via pressure biofeedback demonstrated exploratory association with pulmonary function and varied across COPD severity categories. Participants with greater airflow limitation generally exhibited poorer deep abdominal muscle activation. These findings indicate a possible association between COPD severity and altered deep core muscle activation patterns. However, due to the exploratory cross-sectional design and methodological limitations, the findings should be considered hypothesis-generating rather than confirmatory. Longitudinal and interventional studies are required to further investigate these associations. The data for the present study were collected as part of a PhD thesis and the study was registered with the Clinical Trials Registry of India (CTRI/2022/12/048039).
Chronic obstructive pulmonary disease (COPD) leads to persistent and irreversible airflow limitation due to lung tissue inflammation. Pyroptosis is closely involved in the pathogenesis of COPD and participates in the release of inflammatory factors. IL-17RA is a key receptor for IL-17A; however, the impact of IL-17RA on pyroptosis requires further investigation. This study elucidates the promoting effect of IL-17RA on the progression of COPD by constructing IL-17RA alveolar type II (AT2) epithelial cell-specific knockout animal models and knockdown models of IL-17RA in AT2 epithelial cells. The process of cellular pyroptosis was observed through transmission electron microscopy. Molecular biology techniques and functional experiments were conducted both in vivo and in vitro to validate the activation of canonical and non-canonical pyroptosis pathways by IL-17RA. Our research findings indicate that the specific knockout of IL-17RA significantly alleviates damage to alveolar epithelial cells in a mouse model exposed to cigarette smoke, thereby delaying the progression of COPD in these mice. In this model, the absence of IL-17RA inhibits pyroptosis in cells and reduces the expression of proteins associated with pyroptosis. In the AT2 cell lines line, the knockdown of IL-17RA significantly suppresses the CSE-induced NLRP3/Caspase1/GSDMD and NFκB/GSDME pathways, thereby mitigating the occurrence of pyroptosis. In the AT2 cell lines line, IL-17A binds to IL-17RA, triggering the NLRP3/Caspase1/GSDMD pathway without activating the NFκB/GSDME pathway. Our research emphasizes that IL-17RA promotes pyroptosis by activating the NLRP3/Caspase1/GSDMD and NFκB/GSDME pathways, and is involved in the progression of COPD, providing a promising target for the prevention and intervention of COPD in clinical settings.
Preventing acute exacerbations in COPD (AECOPDs) is key in striving for disease stability. To investigate the differential impact of risk factors across AECOPD phenotypes, we identified baseline health determinants and comorbidities associated with transitions from non-exacerbator (NE) to persistent frequent-exacerbator (FE) and reversion. Patients ≥45 years with ≥3 months treatment for obstructive airway diseases or hospital-labelled COPD without (concomitant) asthma were identified in Belgian nationwide data between January 2017-February 2018. Factors associated with disease worsening (transitioning from NE to persistent FE), reversion (from FE to stable NE) or transition to death were investigated using multinomial logistic regression. Among 183 762 patients (mean age 68.6 years, 48.0% female), 11.5% (21 072) never experienced AECOPDs and 11.6% (21 375) exacerbated frequently in each of three consecutive years. Among 56 933 NE at baseline (31.0%), 4.1% transitioned to persistent FE, whereas among 80 502 FE (43.8%), 7.3% reversed to stable NE. Transitions from NE towards persistent FE were associated with having lung cancer (adjusted odds ratio (aOR) 3.67, 95% CI 2.33-5.78), being an ever-smoker (aOR 2.09, 95% CI 1.94-2.43) or having neuropsychiatric or musculoskeletal comorbidity. Overuse of short-acting bronchodilators (aOR 0.57, 95% CI 0.46-0.49), ever-smoking or having overuse of maintenance therapy were factors most strongly associated with lower odds of reversion. Cardiovascular comorbidities were significantly associated with increased mortality odds, but not with disease worsening. The results of this cohort study support addressing smoking and inhaler overuse to promote reversion to stable NE, while managing lung cancer and neuropsychiatric or musculoskeletal comorbidities to reduce worsening.
While human genetics implicate the interleukin-6 (IL6) signaling pathway as a potential therapeutic target in chronic obstructive pulmonary disease (COPD), its functional role in pulmonary macrophages remains paradoxical given its established role in promoting cholesterol efflux. Here, integrating single-cell transcriptomics of human COPD lungs with mechanistic studies, we resolve this paradox by identifying a pathogenic rewiring of the IL6/STAT3 pathway. We discovered a disease-enriched macrophage subpopulation exhibiting co-activation of IL6/STAT3 signaling, cholesterol biosynthesis, and inflammatory pathways. In a murine COPD model, chronic cigarette smoke (CS) exposure recapitulated this immunometabolic phenotype. We defined a linear pathway wherein CS-induced IL6 activates STAT3, which directly transactivates the sterol regulatory element-binding protein 2 (SREBP2) to drive de novo cholesterol synthesis. This SREBP2-dependent cholesterol accumulation was essential for NLRP3 inflammasome activation and pro-inflammatory cytokine release. In vitro, pharmacological inhibition of STAT3 or SREBP2, as well as IL6 silencing, disrupted this cascade, suppressing cholesterol-driven inflammation. Critically, in vivo macrophage-specific Il6 knockdown attenuated pulmonary inflammation, cholesterol accumulation, and emphysema development by disrupting the entire IL6/STAT3/SREBP2 axis. Thus, we define the IL6/STAT3/SREBP2 axis as a core immunometabolic driver of COPD pathogenesis, which directly couples CS exposure to sustained macrophage inflammation via pathological cholesterol synthesis, thereby providing a mechanistic basis for targeting this druggable pathway.
Airway-occluding mucus plugs (MPs)-as identified on CT scans-are frequent in patients with chronic obstructive pulmonary disease (COPD). Prior studies have shown that body mass index (BMI) tends to be lower among individuals with MPs. To further investigate this relationship, we assessed whether BMI is associated with MPs in two large, multicentre cohorts of tobacco-exposed participants with and without COPD. In multivariable models, lower BMI was associated with an increased prevalence of MPs in COPD and non-COPD groups. Future studies are warranted to elucidate the mechanisms underlying this association.
Data on COPD patients who experience multiple intensive care unit (ICU) admissions for severe acute exacerbations (AECOPD) are scarce. We aimed to describe and compare patients' characteristics by recurrent admission status and to identify factors associated with recurrent ICU-level exacerbations. We conducted a single-centre, retrospective cohort study including all patients admitted to our ICU between 2015 and 2022 for a severe AECOPD. Patients with more than one ICU admission during the study period were classified as "recurrent exacerbator" phenotype. Multivariable regression and competing-risk models were used. We included 328 patients who had a total of 445 admissions. Seventy-two (22.0%) patients had multiple ICU admissions. Compared with non-recurrent patients, recurrent exacerbators were younger (median 67 vs 70 years, p=0.037), had a lower prevalence of impaired Performance Status (13.9% vs 25.8%, p=0.035), and had higher blood eosinophil counts (0.06 vs 0.04 G/L, p=0.025). One-year mortality was similar between groups (18.1% vs 18.4%, p=0.95). In multivariate model, factors independently associated with recurrent severe exacerbation were long-term oxygen therapy (HR = 1.79, p=0.045) and initial blood eosinophil count (HR per +0.1 G/L = 1.10, p<0.001). A Performance Status ≥3 was inversely associated with recurrence (HR per point = 0.41, p=0.030). Patients with recurrent ICU admission for severe COPD exacerbations were younger and had higher blood eosinophil counts than those with a single admission. These findings may suggest that phenotyping-including blood eosinophils-could help stratify the risk of recurrent severe exacerbations and personalised treatment.
Mucus plugs have been previously recognized as an important pathological feature in asthma and COPD, but their clinical role in these diseases has not been explored in-depth until recently. Mucus plug formation is driven by mucus hyperconcentration, changes in mucus viscoelastic properties, impaired clearance, and mucociliary collapse. Scoring systems, such as the bronchopulmonary segment mucus plug score, have been used to associate greater mucus plug burden with poor clinical outcomes. Additional scoring methods obtained through quantitative image processing are currently under development. Mucus plug burden has been associated with greater exacerbations and spirometric decline in both asthma and COPD, as well as greater mortality in COPD. Recently, mucus plug burden has been used as an endpoint in clinical trials to evaluate the effectiveness of biologic therapies in asthma; multiple biologic therapies demonstrated decreases in mucus plug burden and associated improvements in spirometry with treatment. Together, this data suggests mucus plugs may be a treatable trait in asthma and COPD. Mucus plug burden has current clinical, phenotypic, and predictive utility and shows promise as a future biomarker. Increased incorporation into clinical trials, expanded evidence of treatment effect, and standardization of methodology and imaging protocols will be needed. CT-detection of mucus plug burden is ready for greater incorporation into both research outcomes and clinical care.
IntroductionEffective airway clearance is crucial in COPD management, and oscillatory positive expiratory pressure (OPEP) devices are a potential adjunct therapy for this. However, their clinical efficacy remains uncertain due to limited trial data.AimTo update our previous (2020) systematic review investigating the use of OPEP devices to augment sputum clearance in COPD.MethodsRandomised Clinical Trails s evaluating OPEP devices in COPD were identified from PubMed, CINAHL, Medline, Cochrane, and Embase (2020-2024). Outcomes included lung function, exercise capacity, exacerbations, and health-related quality of life (HRQoL), with pooled estimates calculated using random-effects models.ResultsTwelve trials (741 participants) were included. OPEP devices significantly reduced exacerbations (Odds Ratio: 0.39) and improved exercise capacity (+49 m at 6MWD). Small improvements were observed in FVC%, while HRQoL changes were not statistically significant. Accumulating evidence suggests benefits for sputum clearance and reduced antibiotic use. Devices were generally well accepted and safe.ConclusionOPEP devices appear to be safe and may reduce exacerbations, improve functional exercise capacity, and support sputum clearance in COPD.
Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation. Despite the availability of comprehensive, evidence-based guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), utilization of these recommendations remains limited in clinical practice. COPD contributes substantially to global morbidity, mortality, and economic burden and is projected by the World Health Organization to become the third leading cause of death worldwide by 2030. Early recognition and diagnosis, adherence to guideline-based pharmacologic management, smoking cessation, vaccination, and pulmonary rehabilitation are mainstay strategies to slow disease progression and prevent exacerbations. Understanding the pathophysiology and systemic complications is essential for improving outcomes and enhancing quality of life in patients with COPD.
Lung hyperinflation in COPD adversely affects cardiac function and may influence autonomic nervous system activity. The onset of cardiac improvement with dual bronchodilator therapy remains uncertain. In this randomised, placebo-controlled, investigator-blinded, mechanistic, single-dose crossover trial with an open-label 2-week extension we assessed tiotropium/olodaterol (T/O) effects on cardiopulmonary function and muscle sympathetic nerve activity (MSNA) in hyperinflated COPD patients. 32 participants received saline (placebo) and T/O (5 µg/5 µg) in a crossover design, followed by 14 days of open-label T/O. The primary end-point was change in left ventricular end-diastolic volume index (LV-EDVi) measured by magnetic resonance imaging (MRI). Secondary assessments included pulmonary function tests, MSNA measurements and advanced lung imaging including 129Xe-MRI. Single-dose T/O significantly increased LV-EDVi relative to placebo (3.25 mL·m-2; 95% CI 0.95 to 5.56), driven partly by a decrease under placebo. Compared with baseline, T/O's acute LV-EDVi gain was minimal, yet it reached significance at 14 days (4.70 mL·m-2; 95% CI 1.75 to 7.65). Pulmonary parameters, in contrast, showed immediate improvement, with a marked reduction in residual volume (-0.67 L; 95% CI -0.82 to -0.51) after a single dose. MSNA demonstrated a nonsignificant numerical rise post single-dose T/O. No serious adverse events occurred. T/O rapidly improves pulmonary function in hyperinflated COPD patients, but significant cardiac benefits seem to require sustained therapy. These results underscore the importance of continued dual bronchodilator therapy to achieve cardiovascular improvements. The nonsignificant rise in MSNA after a single dose suggests minimal immediate effect on sympathetic activity; further studies are necessary to evaluate long-term autonomic outcomes.
Real-world evidence concerning the cardiovascular (CV) risk of umeclidinium (UMEC) monotherapy or UMEC/vilanterol (VI) is scarce. This real-world study investigated CV risk in new users of UMEC or UMEC/VI versus new users of tiotropium (TIO) in patients with chronic obstructive pulmonary disease (COPD). This prospective, observational, multinational, cohort study enrolled patients ≥18 years with COPD who initiated UMEC, UMEC/VI or TIO between 2 February 2016 and 31 January 2023. Noninferiority (95% confidence interval upper bound <2.0) of UMEC and UMEC/VI to TIO was compared for the time-to-first event (hazard ratio (HR) over 24 months) of a composite CV end-point of myocardial infarction, stroke, heart failure or sudden cardiac death. Stabilised inverse probability of treatment weighting adjusted for differences in baseline covariate balance between groups. Incidence rates for the composite CV end-point were calculated. In total, 6606 patients were enrolled; 6165 were included in the analysis. Both UMEC (n=1246) and UMEC/VI (n=2448) were noninferior to TIO (n=2471) for the risk of the composite CV end-point (adjusted HR (95% CI): UMEC versus TIO: 1.254 (0.830-1.896); UMEC/VI versus TIO: 1.352 (0.952-1.922)). Unadjusted composite CV incidence rates were low across cohorts (incidence rate (95% CI) per 100 person-years: UMEC: 1.157 (0.814-1.594); UMEC/VI: 1.287 (1.034-1.584); TIO: 0.924 (0.716-1.174)). Both UMEC and UMEC/VI were noninferior to TIO for composite CV risk, suggesting that physicians may consider escalating patients to dual bronchodilator therapy if COPD symptoms are not effectively managed with monotherapy.
Chronic obstructive pulmonary disease (COPD) is associated with right ventricular (RV) dysfunction and subclinical myocardial injury. The effects of dual bronchodilation on RV function and cardiac injury biomarkers remain limited. To evaluate 12-week changes in pulmonary function, RV function, and serum troponin-I in newly-diagnosed COPD patients receiving tiotropium/olodaterol as routine clinical care and to assess differences in RV function and troponin-I between COPD and non-COPD controls with comparable cardiovascular diseases (CVDs). Prospective real-world observational study. Treatment-naïve patients with moderate-to-severe COPD were assessed at baseline and after 12 weeks of treatment. Evaluations included spirometry, plethysmography, two-dimensional and speckle-tracking transthoracic echocardiography, cardiac magnetic resonance imaging (MRI), and troponin-I. Baseline RV measurements and troponin-I were compared between COPD (n = 47) and controls (n = 23). COPD patients had lower RV fractional area change and RV free-wall strain (FWS) than controls (p < 0.001 and p = 0.018, respectively). Troponin-I was above the limit of detection in 93.6% of COPD and in 56.5% of controls (p < 0.001). COPD treatment increased forced expiratory volume in 1 second (FEV1) and forced vital capacity while reducing residual volume-to-total lung capacity (TLC) and functional residual capacity (FRC)-to-TLC (p < 0.05). RV global longitudinal strain (GLS) improved from 21.7 ± 2.6% to 23.0 ± 2.8%, and RV-FWS from 24.2 ± 3.3% to 26.1 ± 3.6% (both p < 0.05) in echocardiography (n = 29). ΔRV-GLS correlated positively with ΔFEV1 and inversely with ΔFRC/TLC (p < 0.05). In the moderate COPD subgroup, RV-GLS in MRI changed from 22.6 ± 6.1% to 25.5 ± 7.5% (p = 0.037), and troponin-I decreased from 1.23 pg/mL (IQR 1.03-1.56) to 1.09 pg/mL (IQR 0.95-1.20; p = 0.049). COPD affects RV function and troponin-I regardless of concomitant CVDs. Initiation of dual bronchodilation is associated with beneficial effects on RV strain and troponin-I in patients with COPD. Because of the small sample size, these findings should be interpreted cautiously and confirmed in larger studies. ClinicalTrials.gov; ID NCT06072690; https://clinicaltrials.gov/study/NCT06072690.
Although increasingly recognized, loneliness in COPD remains poorly understood. This review aims to inform rehabilitation practice and guide future research. The review was guided by the following questions: What are the key characteristics of emotional, social, and existential loneliness as described by individuals living with COPD? What constitutes COPD-related loneliness as experienced by these individuals? This scoping review is informed by the Joanna Briggs Institute guidance. A systematic search was conducted in seven databases. Studies were screened following a stepwise approach. Data was extracted to identify key characteristics of loneliness and to develop analytical themes of COPD-related loneliness. Seventeen publications were included. First, key characteristics of emotional, social, and existential loneliness were identified. Next, four analytical themes describing COPD-related loneliness were developed: (1) the condition reduces social contacts and interactions, (2) being housebound, (3) it is a lonely battle, and (4) feeling like a second-class person living in a parallel world. COPD-related loneliness is a complex and evolving experience. Current rehabilitation programs insufficiently address emotional and existential dimensions of loneliness. Rehabilitation must explicitly target COPD-related loneliness as a central component of care, supported by tailored assessment tools and interventions that capture its condition-specific features. Individuals living with chronic obstructive pulmonary disease (COPD) experience profound social, emotional, and existential loneliness, which significantly impacts their rehabilitation outcomes.Understanding and acknowledging the key characteristics of loneliness when living with COPD is essential to strengthen rehabilitation strategies and tailor interventions.Effective interventions require the involvement of healthcare professionals to identify, acknowledge, and address COPD-related loneliness within rehabilitation and care pathways.Active engagement of family members and close social networks is essential to support social connection and reduce loneliness among people living with COPD.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by persistent airflow limitation and chronic respiratory symptoms. COPD is the second leading cause of death in India and the third leading cause of death worldwide. Osteoporosis, a significant and often overlooked comorbidity of COPD, presents a major challenge. The disease itself, combined with multiple risk factors, including the use of inhaled corticosteroids-a cornerstone of COPD treatment-contributes to a decline in bone mineral density (BMD). This cross-sectional study investigates the prevalence of osteopenia and osteoporosis among COPD patients at a tertiary care center in South India, with a particular focus on the impact of inhaled and systemic corticosteroids on BMD and other associated risk factors. One hundred COPD patients were assessed for their BMD. Our findings reveal a strikingly high prevalence (88%) of reduced BMD among COPD patients, with 69% diagnosed with osteoporosis and 19% with osteopenia. Most COPD patients are middle-aged smokers and frequently use steroid-containing inhalers, which contribute to decreased BMD and an increased risk of fractures. The study highlights a significant association between osteoporosis and factors such as smoking history, COPD severity (GOLD classification), and cumulative steroid exposure. These results highlight the urgent need for proactive, regular screening and early intervention to assess bone health in COPD care.