ObjectiveBlood eosinophil (EOS) guides corticosteroid therapy in stable chronic obstructive pulmonary disease (COPD), but its prognostic value in COPD exacerbation (ECOPD) remains controversial. This study characterized clinical features and assessed the impact of EOS levels on clinical outcomes in hospitalized ECOPD patients.MethodsWe retrospectively reviewed hospitalized patients with ECOPD between 2018 and 2023. Patients were categorized according to percentage of peripheral blood eosinophil: the eosinophilic group (EOS ≥ 2%) and the non-EOS group (EOS < 2%). The primary outcome was in-hospital mortality, while the secondary outcomes included ICU admission, mechanical ventilation, and length of hospital stay.ResultsAmong 511 patients (EOS group, n = 139; non-EOS group, n = 372), the EOS group had lower levels of inflammatory markers (C-reactive protein and procalcitonin) and a lower detection rate of Gram-negative bacilli, especially Acinetobacter baumannii. The EOS group exhibited significantly lower rates of ICU admission (25.18% vs. 50.27%; P < 0.001) and in-hospital mortality (1.44% vs. 6.72%; p = 0.018). In the multivariable analyses, EOS% ≥ 2% remained associated with lower odds of in-hospital mortality after adjustment for age and heart failure (adjusted OR, 0.225; 95% CI, 0.052–0.971; p = 0.046) and with lower odds of ICU admission after adjustment for age, sex, and heart failure (adjusted OR, 0.357; 95% CI, 0.229–0.556; p < 0.001).ConclusionAmong hospitalized patients with ECOPD, elevated peripheral blood eosinophils were associated with favorable clinical outcomes, especially a reduced risk of ICU admission, as well as a lower systemic inflammation burden.

Background:The beneficial effects of omega-3 fatty acids for patients with chronic obstructive pulmonary disease (COPD) had been observed, including attenuating lung function decline and reducing their respiratory symptom burdens. However, the impact of omega-3 fatty acids on COPD exacerbation-related outcomes remains unclear. This study aimed to evaluate whether reduced serum omega-3 fatty acid levels are associated with a higher risk of future hospital readmission due to COPD exacerbation (ECOPD). Methods:This retrospective cohort study included 88 patients hospitalized for ECOPD between April 2017 and March 2018. Clinical data were collected, and serum omega-3 fatty acid levels were analyzed using liquid chromatography-mass spectrometry (LC-MS). All patients were followed up for a median period of 53.5 months and categorized into two groups based on whether they experienced ECOPD-related readmission during the follow-up period. The clinical characteristics and serum levels of omega-3 fatty acid levels, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), between the two groups were compared. Additionally, patients were categorized into low and high DHA groups based on the median DHA level, and the association between DHA level and ECOPD-related readmission rate was analyzed using a Cox regression model. Result:Patients who experienced ECOPD-related readmission during the follow-up period (n = 36) had lower serum levels of DHA than those who did not experience readmission. The serum levels of EPA did not significantly differ between groups. Kaplan-Meier curve showed that patients in the low-DHA group exhibited a significantly higher ECOPD-related readmission rate compared to those in the high-DHA group (log-rank p = 0.023). Multivariable Cox regression analysis identified low DHA level as an independent risk factor for ECOPD-related readmission. A nomogram based on DHA levels demonstrated good predictive performance. Conclusion:A low DHA level serves as an independent risk factor for ECOPD-related readmission, suggesting DHA may have a potential protective effect to reduce the risk of exacerbation in patients with COPD.

Background:Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular disease and chronic kidney disease, but with conflicting estimates. We aimed to quantify the association of COPD and incident cardiovascular diseases, chronic kidney disease and death. Methods:In this systematic review and meta-analysis, we searched MEDLINE and Embase for case-control studies reporting associations between COPD and cardiovascular diseases, chronic kidney disease and death from database inception until 15 April 2026. Two reviewers independently extracted study characteristics and reported risk ratios of incident outcomes associated with COPD, specifically: atrial fibrillation and flutter, ventricular fibrillation and tachycardia, myocardial infarction, ischaemic stroke, heart failure, peripheral arterial disease, chronic kidney disease, cardiovascular mortality and all-cause mortality. Pooled estimates were obtained using random-effects models with restricted maximum likelihood estimation as substantial heterogeneity was anticipated. Ten sensitivity analyses stratifying studies by design, follow-up duration, region, clinical context, sample size, publication date, COPD ascertainment, leave-one-out, ratio adjustment and risk of bias, subgroup analyses by age and risk group were undertaken, and subsequent univariate and multivariate meta regression was performed. Study quality was assessed using the risk of bias in non-randomised follow-up studies of exposure effects (ROBINS-E) tool, and certainty of evidence was assessed using Grading of Assessment, Evaluation, Development and Evaluation (GRADE) criteria. Risk of publication bias was assessed using funnel plots and Egger's regression. This review was registered on PROSPERO (CRD42025639084). Findings:Of 140 case-control studies including 30,144,481 patients (3,062,712 with COPD) with median follow -up duration of 3.0 years (IQR 1.0-5.2), COPD was associated with increased risk of heart failure (risk ratio [RR] 2.33, 95% CI 1.78-3.06), ventricular tachycardia (2.05, 1.27-3.31), peripheral arterial disease (1.99, 1.49-2.65), heart failure hospitalisation (1.78, 1.28-2.47), chronic kidney disease (1.65, 1.25-2.16), all-cause mortality (1.55, 1.42-1.70), cardiovascular mortality (1.55, 1.33-1.82), myocardial infarction (1.47, 1.28-1.68), ischaemic stroke (1.38, 1.18-1.62), and atrial fibrillation (1.38, 1.19-1.61) when compared to those without COPD. Despite substantial heterogeneity for all outcomes, associations between COPD and outcomes were broadly consistent across sensitivity analyses. Interpretation:COPD is associated with an increased risk for a range of incident cardiovascular diseases, chronic kidney disease and mortality. The impact of current and novel treatments on a broader range of cardiovascular and kidney outcomes in patients with COPD requires prospective randomised assessment. Funding:The British Heart Foundation.

Purpose:Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation, largely driven by airway remodeling. Epithelial-mesenchymal transition (EMT) is a key mechanism underlying this process. Laminin subunit gamma-2 (LAMC2) is implicated in fibrosis and EMT, but its role in COPD-associated airway remodeling remains unclear. Methods:Differential expression analysis was performed using airway epithelial cell datasets from COPD patients and TGF-β1-induced EMT models. Findings were validated in COPD patient lung tissues, smoke-exposed mice, and in vitro experiments. In vivo, chronic smoke-exposed mice were pre-treated intratracheally with adeno-associated virus (AAV)-shLAMC2. Functional assays involved siRNA knockdown or plasmid overexpression of LAMC2 in bronchial epithelial cells. RNA sequencing and pathway analyses were conducted to explore underlying mechanisms. Results:LAMC2 was significantly upregulated in COPD patient and murine airway epithelia. AAV-shLAMC2 administration alleviated airway remodeling and restored epithelial E-cadherin while reducing mesenchymal markers (N-cadherin, fibronectin), indicating attenuation of EMT. In vitro, LAMC2 was upregulated in TGF-β1-stimulated epithelial cells, and its modulation significantly influenced EMT progression. Transcriptomic analysis suggested that AKT signaling as a potential downstream of LAMC2, supported by functional assays. Conclusion:LAMC2 is upregulated in COPD airway epithelium and promotes airway remodeling by regulating EMT, potentially through AKT signaling. These findings suggest that targeting LAMC2 may represent a potential strategy for mitigating COPD-associated airway remodeling.

Aspergillus spp are common airborne fungi, and the commonest fungal pathogen of human lungs. In patients with chronic obstructive pulmonary disease (COPD), the usual defences against disease are impaired to various degrees, leading to persistent airway infection, especially with bronchiectasis; allergy (or sensitisation) and probable additional airways resistance; and chronic pulmonary aspergillosis or invasive aspergillosis. Recurrent COPD exacerbations are more common in those with Aspergillus found in the airways, opening up an unassessed therapeutic opportunity to reduce hospital admissions and deaths. External factors worsening the effect of this negative interaction include damp and/or mould in homes, higher air pollution indices. and respiratory viral infections that abrogate key immune defences. Corticosteroid therapy, both systemic and oral, further impairs airway and lung defences. Both local and general immune responses are affected. Aspergillus infection in patients with COPD is markedly under-recognised, primarily because the sensitivity of culture of Aspergillus from sputum is poor, bronchoscopy can be harmful in patients with chronic respiratory impariment, induced sputum is only used in research studies, and the role of serum Aspergillus IgG and antigen testing is not appreciated. In hospitalised patients and those at higher risk, high-volume fungal culture and PCR for Aspergillus on sputum would enable many more diagnoses. With approximately 60 million patients with COPD hospitalised with exacerbations globally, and high mortality rates in both invasive and chronic pulmonary aspergillosis in those with COPD, many opportunities for prevention, earlier diagnosis, and therapeutic interventions are untested. Reducing corticosteroid exposure in patients with COPD could greatly reduce the impact of Aspergillus in patients with COPD.

OBJECTIVES:This observational, multicenter, prospective, single-arm study (NCT04536402) aimed to describe the safety profile and clinical outcomes of Budesonide/Glycopyrrolate/Formoterol Fumarate metered dose inhaler (BGF MDI) for Chinese patients with COPD in clinical practice. METHODS:COPD patients who had been prescribed and had planned to take at least one inhalation of BGF MDI were followed-up for 12 weeks at 4-week intervals. The primary endpoints were incidences of adverse events (AEs) and serious adverse events (SAEs). Secondary endpoints included changes from baseline in COPD Assessment Test (CAT) score and St George's Respiratory Questionnaire (SGRQ) score and patient global impression of change (PGIC) scale at week 4. Patients were also stratified into subgroups according to the asthma history, exacerbation history, and baseline treatment and assessed. RESULTS:Of the enrolled 3,317 patients, 2,137 completed and 1,180 discontinued the study. No unexpected safety signals were observed; most AEs were mild (13.2%) or moderate (7.2%). SAEs occurred in 4.9% of patients. BGF MDI was associated with decreased CAT and SGRQ total scores (mean [SD] changes from baseline: -6.7 [7.27], -14.5 [18.19]) and increased FEV1 (189 mL, n = 241) at week 12. Similar trend of improvement was also observed in the subgroups. At week 4, 84.8% rated overall PGIC status as "improved," and 87.6% were satisfied with the MDI device. CONCLUSION:In real-world practice, BGF MDI demonstrated good tolerability consistent with previous RCTs, and associated with a trend toward improvement in patients' symptoms, quality of life, and lung function, regardless of asthma history, exacerbation history, or baseline treatment. TRIAL REGISTRATION:NCT04536402 (ClinicalTrials.gov), registered on 28 August 2020.

Asthma is a complex and chronic inflammatory airway disease associated with the abnormal activation of immune cells. T-cell senescence is linked to immune dysfunction and persistent inflammation, but the relationship between asthma and T-cell senescence remains unexplored. This study reveals significantly higher percentages of cluster of differentiation 4-positive (CD4+) senescent T cells (Tsens) in asthma patients than in healthy controls, while CD8+ Tsen percentages do not appear to increase. CD4+ Tsen percentages in both the blood and sputum are positively correlated with fractional exhaled nitric oxide (FeNO) values, eosinophil abundance, and T helper type 2 (Th2) cell abundance in the blood. The clinical manifestations of asthma were recreated in a house dust mite (HDM)-induced mouse model. In HDM-exposed mice, CD4+ Tsen percentages were also elevated in the lungs. To counteract T-cell senescence, therapeutic interventions, including interleukin-4 (IL-4) antibodies and dexamethasone, were administered to the mice. IL-4 neutralization reduced CD4+ Tsen percentages and inhibited p38 mitogen-activated protein kinase (MAPK) activation. Adoptive transfer of CD4+ Tsens did not induce spontaneous asthma in phosphate-buffered saline (PBS)-treated mice but exacerbated type 2 inflammation in HDM-treated mice. Our study revealed a significant increase in CD4+ Tsen (CD57+CD28-) abundance in asthma patients and suggested that type 2 inflammation drives CD4+ T-cell senescence in asthma. Furthermore, adoptive transfer of CD4+ Tsens appears to exacerbate type 2 inflammation.

BACKGROUND:Emphysema, a major component of chronic obstructive pulmonary disease (COPD) characterized by progressive alveolar destruction, lacks effective medical therapies. Hepatocyte growth factor (HGF) possesses potent regenerative functions, but its therapeutic potential remains unrealized due to challenges in achieving targeted delivery and sustained lung expression. METHODS:We first assessed associations between HGF expression and emphysema severity using human datasets, lung tissue, and both elastase-induced and cigarette-smoke-induced murine models. We repurposed a clinical-stage SM102 lipid nanoparticles (LNPs) platform to deliver human HGF mRNA in murine models, evaluating therapeutic efficacy via i.t. instillation in the elastase model. After optimizing nebulization, we assessed efficacy in the cigarette-smoke model. We investigated underlying mechanisms via single-cell RNA sequencing (scRNA-seq), which we validated in patient-derived lung organoids. RESULTS:HGF expression displayed a biphasic pattern across the emphysema spectrum, with upregulation in milder disease states and marked reduction in advanced emphysema. i.t. delivery of HGF mRNA LNPs restored lung function and attenuated alveolar destruction in the elastase model. Nebulized delivery achieved efficient pulmonary distribution and demonstrated comparable therapeutic efficacy in the cigarette-smoke model, including improved lung function, reduced inflammation, and decreased apoptosis. scRNA-seq analysis detected enhanced alveolar type II (AT2) cell proliferation and differentiation in the elastase model and human organoids. CONCLUSION:This study provides proof-of-concept evidence for a therapeutic strategy for emphysema. Using a clinical-stage LNPs platform, we demonstrate that HGF mRNA therapy is effective via both direct instillation and optimized nebulization, prompting structural and functional recovery by activating endogenous repair pathways in AT2 cells.

Purpose:The rising incidence of Pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus (HIV) infection, coupled with high mortality rates, highlights growing challenges in disease management. However, mortality risk factors in non-HIV PJP remain incompletely defined, particularly in large cohorts. Thus, we aimed to explore the clinical characteristics and mortality risk factors in these patients. Patients and Methods:This study included non-HIV patients with PJP who were hospitalized at Peking University Third Hospital between January 2014 and May 2023. We collected relevant clinical data and performed logistic regression analysis to identify mortality risk factors. Results:This study included 207 participants (127 male and 80 female) with a median age of 57 (interquartile range: 45-68) years. The 90-day all-cause mortality rate was 15%. Renal transplant recipients accounted for the highest proportion of patients with underlying diseases (34.8%), followed by those with immune-mediated inflammatory diseases (23.7%). In multivariate logistic regression analysis, the percentage of neutrophils in bronchoalveolar lavage fluid (BALF) and a ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg were independently associated with 90-day mortality. A neutrophil percentage ≥41.5% in BALF effectively identified patients at high risk of death. Conclusion:In non-HIV patients with PJP, the percentage of neutrophils in BALF and PaO2/FiO2 ratio were strong predictors of adverse outcomes. These markers may help clinicians identify high-risk patients and initiate early intensive care intervention.

Objective:Post tuberculosis lung disease (PTLD) manifests in various forms, including tuberculosis-associated chronic obstructive pulmonary disease (TB-COPD), yet the clinical features of PTLD remain undercharacterized. This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB. Methods:Patients with active pulmonary TB were enrolled in this study and were followed during treatment, at treatment completion and five years post-treatment. Assessments included lung function and chest CT, analyzing longitudinal trends and airflow obstruction risk factors. Results:Among 53 patients (mean age 36.9 ± 13.9 years; 64.2% male), 7 patients (13.2%) exhibited airflow obstruction. At the 5-year follow-up, the mean FEV 1/FVC declined significantly (76.27% ± 12.04% vs. 80.23% ± 11.02%, P < 0.001) and 9 patients (17.0%) exhibited airflow obstruction. Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT, aligning with TB-COPD phenotype. Notably, four young-to-middle-aged patients (< 60 years old) had persistent obstruction over the five years. Conclusion:The initial test revealed that 13.2% of patients presented with airflow obstruction. By the 5-year follow-up, this proportion had increased to 17.0%, with most cases demonstrating imaging findings aligning with TB-COPD, even among younger, non-smoking individuals. These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.

ABSTRACT Dysregulated chronic inflammation underlies a spectrum of severe asthma phenotypes, among which neutrophilic asthma (NA) represents a treatment‐recalcitrant endotype characterized by Th17‐driven airway inflammation and steroid resistance. Although lipid mediators are known to play dual roles in promoting and resolving inflammation, the lipid species governing the Th17‐neutrophil axis in NA remain unknown. Here, through integrated lipidomic profiling of clinical samples (exhaled breath condensate, plasma, sputum) from an NA cohort and a murine model of Th17‐driven airway inflammation, a deficiency in very‐long‐chain ceramides, notably Cer24:1, was identified. This reduction correlated with disease severity and neutrophilic inflammation. In vivo, Cer24:1 supplementation alleviated airway hyperresponsiveness and neutrophilic infiltration, while Smpd1 knockout mice—with impaired ceramide generation—displayed exacerbated Th17 pathology. Using structure‐guided molecular docking, surface plasmon resonance, and functional assays, Cer24:1 was shown to directly target the prostaglandin E2 receptor EP2 on CD4+ T cells. This interaction suppressed JAK2–STAT3 signaling and RORγt‐driven Th17 differentiation. Notably, PGE2 competitively reversed Cer24:1's protective effects, further supporting EP2‐dependent modulation. Our results reveal Cer24:1 as an endogenous pro‐resolving lipid that constrains neutrophilic inflammation via direct modulation of the EP2–STAT3 axis in Th17 cells, providing a new metabolic checkpoint and potential therapeutic strategy for severe neutrophilic asthma.

Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterised by airway obstruction. Aspergillus fumigatus sensitisation represents a distinct, clinically relevant endotype in COPD. In recent years, studies have shown that sensitised patients experience more frequent respiratory symptoms, exacerbations and a poorer prognosis, while the coexistence of allergic bronchopulmonary aspergillosis (ABPA) further increases morbidity and mortality. Recognising Aspergillus sensitisation (AS) as a potential treatable trait in COPD could provide new insights into disease heterogeneity and offer opportunities for personalised management. This review summarises the prevalence and clinical associations of AS among COPD patients.

Background:History of exacerbations is a predictor of future exacerbations in COPD but there are also predictors that are independent of exacerbation history. However, it is unclear whether their relative contribution is consistent across different degrees of airflow limitation. Methods:This analysis used data from COMPASS, a prospective study in COPD. Baseline demographics, clinical history, spirometry and patient-reported outcomes were collected. Multivariable models were created to predict moderate or severe exacerbations in the 18 months after baseline. Covariates included forced expiratory volume in 1 s (FEV1) % predicted, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, modified Medical Research Council (mMRC) and COPD Assessment Test (CAT) scores, and exacerbation history. Goodness of fit was tested using C-statistics. Results:At baseline there were 1696 patients; 89.6% males, 46.9% current smokers, mean±sd age of 65.4±7.5 years, post-bronchodilator FEV1 66.6±20.1% predicted and 0.5±1.0 moderate/severe exacerbations in the prior year. Over 18 months, 17.8% of patients had ≥1 moderate/severe exacerbation. The best fit model identified six independent variables, C-statistic 0.739. Subgroup analysis into GOLD grades I, II and III+IV combined showed different predictor patterns. In grade I, history of moderate exacerbations was the strongest predictor, together with chronic bronchitis and gastro-oesophageal reflux. In grades III+IV, only history of severe exacerbations and mMRC score were significant. Grade II showed an intermediate picture in which severe exacerbations, chronic bronchitis and gastro-oesophageal reflux were all significant. Conclusions:There are multiple predictors of COPD exacerbations, which differ between GOLD grades. Future predictive models for exacerbation risk should take this into account.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease with limited therapeutic options. Mesenchymal stromal cells (MSCs) have shown promise in preclinical models of lung fibrosis. Methods We conducted an open-label, multicenter, dose-escalation phase I trial (NCT06230822) to assess the safety and preliminary efficacy of intravenous human umbilical cord-derived MSCs (UC-MSCs; VUM02) in patients with IPF. Nine patients were enrolled in three dose cohorts (0.5, 1.0, and 2.0 × 10⁸ cells per infusion, three infusions every 3 days) following a “3 + 3” design. Results No dose-limiting toxicities occurred. Seventy-four adverse events were recorded, most grade 1–2; only 13 events in four patients were considered possibly or probably related to UC-MSCs. Six serious adverse events occurred in five patients, all deemed unrelated to the investigational product. In the high-dose cohort, forced vital capacity (FVC) showed a numerical increase of 57 mL (+ 2.36%) at week 24 compared with baseline. Carbon monoxide diffusion capacity (DLCO % predicted) increased by 7.39% in the low-dose cohort at week 24. Exploratory immunological and plasma proteomic analyses suggested immunomodulatory effects and identified ribosomal protein S23 (RPS23) as a candidate biomarker that consistently decreased after treatment. Conclusions Multiple intravenous infusions of UC-MSCs up to 2 × 10⁸ cells were well tolerated in patients with IPF. Preliminary efficacy signals, particularly the numerical FVC improvement in the high-dose group, warrant further investigation in larger controlled trials. Trial registration: ClinicalTrials.gov NCT06230822.

Background:Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and a major cause of mortality and morbidity in China. Global studies have revealed a subgroup of patients who had COPD symptoms and frequent exacerbations while receiving triple inhaled therapy. This study aimed to describe the clinical characteristics and disease burden of this patient population in China. Methods:This cross-sectional, real-world study drew data from the Adelphi COPD Disease Specific Programme (DSP)™ from July to November 2022 in China. Adult patients with a diagnosis of COPD and receiving triple therapy at survey date were included; among them, patients who had frequent productive cough and sputum, a history of smoking, ≥2 moderate or ≥1 severe exacerbation(s) in the prior 12 months and were receiving triple therapy were identified as the symptomatic SET cohort; all other patients were categorized as the triple therapy cohort. Disease-related characteristics and perceptions of disease control were described for both cohorts. Results:Of the 135 patients receiving triple therapy, 39 (28.9%) were categorized into the symptomatic SET cohort and 96 (71.1%) into the triple therapy cohort. In the triple therapy and symptomatic SET cohorts, mean (SD) age was 65.9 (9.0) and 69.2 (8.7), respectively; mean (SD) number of exacerbations during the last 12 months was 1.3 (1.4) and 2.3 (1.3), respectively; mean (SD) CAT score was 21.0 (8.3) and 25.7 (7.1), respectively. According to physicians' perception, around 70% of patients in the symptomatic SET cohort had, at the minimum, somewhat controlled COPD (completely controlled: 2.6%; well controlled: 28.2%; somewhat controlled: 38.5%). Satisfactory COPD control was achieved in 33.3% and 38.5% of patients in the symptomatic SET cohort as perceived by physicians and patients, respectively. Conclusion:Substantial disease burden and large unmet needs existed among patients with symptomatic and exacerbating COPD while receiving triple inhaled therapy in clinical settings in China. Novel therapeutic options and improved guideline-directed disease management are needed.

Over 400 million people have chronic obstructive pulmonary disease (COPD), with exacerbations representing a major health burden. Although the overall incidence of invasive pulmonary aspergillosis (IPA) in patients with COPD with hospitalised exacerbation is only 1 to 4%, certain factors substantially increase this frequency. Risk factors compromising defences against Aspergillus spp in COPD patients include systemic or high-dose inhaled corticosteroids, comorbidities including bronchiectasis, diabetes, and cardiovascular disease, and prolonged courses of antibiotics. An international group of experts met to develop criteria for diagnosing IPA based on existing literature and consensus in non-ventilated COPD patients. The preliminary diagnostic recommendations were further evaluated by additional experts using the Delphi methodology. A hospitalized exacerbation of COPD with two or more of the above clinical risk factors should prompt 1) a CT scan of the chest, 2) sending a respiratory sample (sputum, induced sputum or bronchoscopy sample) for direct microscopy for fungi, high volume fungal culture and preferably Aspergillus PCR, and if a bronchoscopy sample is obtained then also Aspergillus antigen (galactomannan), 3) a serum sample for galactomannan and Aspergillus IgG. The combination of a high-risk COPD patient, with compatible imaging abnormalities and any two positive tests (two samples or different tests on the same respiratory sample) for Aspergillus is sufficient to establish the diagnosis of IPA with enough confidence to initiate antifungal therapy and/or enroll the patient in a clinical or epidemiological study of IPA in COPD. Additional studies are required to augment performance data for most assays in COPD and validate the proposed diagnostic criteria.

Background: Chronic obstructive pulmonary disease is associated with excess cardiovascular morbidity, but the circulating molecular signatures linking chronic obstructive pulmonary disease-related systemic biology with cardiovascular prognosis remain incompletely characterised. Methods: We analysed UK Biobank participants with baseline spirometry, Olink plasma proteomic profiling, and linked health records. Proteins associated with chronic obstructive pulmonary disease were identified using proteome-wide logistic regression. Among participants with chronic obstructive pulmonary disease, these proteins were evaluated for associations with incident cardiovascular and mortality outcomes using Cox models. Pathway enrichment, mediation-consistent analyses, and elastic-net prognostic modelling were performed. Findings: Among 36,728 participants, 6089 had chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease was associated with higher risks of major adverse cardiovascular events, heart failure, atrial fibrillation, and stroke after multivariable adjustment. Proteome-wide analyses identified 1409 chronic obstructive pulmonary disease-associated proteins. Among participants with chronic obstructive pulmonary disease, recurrent prognostic proteins included cardiopulmonary stress, inflammatory, tissue-remodelling, and vascular markers. Protein-enhanced models improved prediction of major adverse cardiovascular events, heart failure, and atrial fibrillation beyond clinical predictors. Interpretation: Chronic obstructive pulmonary disease is characterised by systemic proteomic perturbations that are linked to cardiovascular prognosis. These proteins may help prioritise biological pathways and candidate markers for cardiovascular risk stratification in chronic obstructive pulmonary disease, pending external validation.

Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularly atherosclerotic CVD, remain poorly understood. Extracellular vesicles (EVs), as key mediators of inter-organ communication, may participate in this pathological connection. This study aims to determine whether EVs derived from airway epithelial cells (AECs) of individuals with COPD contribute to endothelial dysfunction and atherosclerosis. EVs were isolated from primary airway epithelial cells of COPD patients and matched controls. Their effects on endothelial cell function were assessed in vitro by evaluating inflammation, apoptosis, and monocyte adhesion. ApoE-/- mice were intravenously injected with these EVs to examine their impact on atherosclerotic lesion development. Differentially expressed microRNAs were identified, and the regulatory relationship between miR-141-3p and PDCD4 was validated through molecular assays. Additionally, miR-141-3p supplementation was performed to determine its therapeutic potential in mitigating endothelial injury and atherosclerosis. COPD AECs-derived EVs markedly increased endothelial inflammation, apoptosis, and monocyte adhesion compared with control EVs. In ApoE-/- mice, COPD-derived EVs accelerated the formation of atherosclerotic plaques. Mechanistic analyses revealed that miR-141-3p was significantly downregulated in COPD EVs and directly targeted the 3’ untranslated region of PDCD4 to regulate its transcription, leading to dysregulation of PDCD4/NF-κB signaling in endothelial cells. Restoration of miR-141-3p levels in COPD-derived EVs alleviated endothelial injury and reduced atherosclerotic lesion progression both in vitro and in vivo. This study identifies a previously unrecognized mechanism by which COPD AECs-derived EVs may promote atherosclerotic CVD via miR-141-3p–mediated regulation of PDCD4 and subsequent activation of NF-κB signaling. These findings highlight miR-141-3p as a promising therapeutic target to reduce vascular complications in COPD.

Existing knowledge regarding the involvement of lncRNA OIP5-AS1 in lung adenocarcinoma (LUAD) development is still incomplete and requires further investigation. Our research aimed to reveal the function of OIP5-AS1 in LUAD. We evaluated the level of OIP5-AS1 and its association with clinicopathological factors in LUAD. The research examined the potential implications of targeting OIP5-AS1 in mitigating the invasive properties of lung cancer cells. A nude mouse xenograft model was utilised to examine tumour growth. We used bioinformatics data and a dual-luciferase reporter assay to study the interactions between OIP5-AS1 and hsa-miR-29b-3p. OIP5-AS1 was significantly overexpressed in LUAD, with a higher level correlating with adverse clinicopathological features. Knockdown of OIP5-AS1 resulted in notable decreases in LUAD cell growth, movement, and aggressive behaviour, accompanied by a decrease in tumour size in vivo. Furthermore, OIP5-AS1 was confirmed to act as a molecular sponge for hsa-miR-29b-3p. The elevated expression of hsa-miR-29b-3p intensified the inhibitory outcomes of OIP5-AS1 knockdown on LUAD cell properties. ZIC5 was experimentally determined to be a direct molecular target of hs-miR-29b-3p, emphasising its integral position in the regulatory interaction. This study reveals a new regulatory route involving OIP5-AS1, hsa-miR-29b-3p and ZIC5 in LUAD pathogenesis. Given its oncogenic traits, OIP5-AS1 presents a promising predictive biomarker and therapeutic target for optimising lung cancer treatment.