European Respiratory Review最新文献

Extracellular vesicles (EVs) are small, membrane-bound particles released by cells into the extracellular space. Once considered as cellular waste disposal organelles, EVs are now recognised as functional cellular components because they carry a variety of cargo biomolecules, including nucleic acids, proteins and lipids. EVs are constitutively released under homeostatic conditions, but their numbers increase and their cargo composition is altered under nonhomeostatic conditions, such as exposure to environmental pollutants, viral infections or disease states. Therefore, EVs are being actively explored as noninvasive biomarkers for many diseases, including lung diseases. In addition, EVs are key mediators of intercellular communication through the transfer of their cargo biomolecules from EV-releasing donor cells to recipient (target) cells through membrane fusion, endocytosis or receptor-ligand interactions. This intercellular communication between the cells positions EVs as novel drug delivery vectors because of their low immunogenicity, high biocompatibility and unique cargo compositions. While EV-based drugs have not yet been approved by regulatory authorities, numerous clinical trials are evaluating their use either as therapeutics or as delivery systems. In this review, we discuss EVs, with particular emphasis on recent advances in identifying reliable and sensitive biomarkers for lung diseases, and on their emerging role as targeted drug delivery systems.

Background: Respiratory syncytial virus (RSV) infection has been associated with an increased risk of cardiac events. This systematic review aims to synthesise the evidence on the absolute and relative risks of cardiac events in adults with RSV disease.

Methods: We searched Embase, PubMed and grey literature sources for studies published between 1 January 2000 and 6 March 2024, reporting on cardiac events in adults with RSV disease. Study quality was assessed using a validated checklist. Absolute and relative risks of cardiac events following RSV disease were summarised and pooled estimates using random effects meta-analysis were calculated.

Results: Of 3887 publications, 28 met the inclusion criteria. Among hospitalised patients with RSV disease (25 studies), the pooled estimates showed that 19.2% (95% CI 15.1-24.2) experienced any cardiac event (including specific and unspecific events and combinations of cardiac events), 15.7% (95% CI 14.8-16.5%) heart failure (HF) and 5.4% (95% CI 3.1-9.5%) acute coronary syndrome (ACS). Cardiac event-related mortality ranged from 1.1 to 9.8%. Compared to influenza patients, those with RSV disease had a risk ratio of 1.2 (95% CI 1.1-1.4) for any cardiac event, 1.3 (95% CI 1.1-1.6) for HF and 1.2 (95% CI 0.9-1.5) for ACS.

Conclusion: RSV disease poses significant risks beyond respiratory illness, including cardiac events, among older adult patients. RSV was associated with a higher risk of HF compared to influenza. Further research is needed to more precisely define the risk period of cardiac events following RSV disease.

Background: Progressive systemic sclerosis-related interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in systemic sclerosis (Ssc). Yet, there remains no consensus definition of interstitial lung disease (ILD) progression or risk stratification tool to aid in identifying for whom and when therapeutic intervention is warranted or which patients should be included in clinical trials because they are especially at risk of progressive disease.

Objective: We aimed to determine from the literature which variables were consistently associated with SSc-ILD and, more importantly, which have been demonstrated to be predictors of progression.

Methods: We used two electronic databases, EMBASE and PubMed, to perform a scoping literature review of published articles on SSc-ILD, with a primary focus on ILD progression. Any variables reported to be associated with or predictive of ILD progression were recorded.

Results: Of the 1327 citations identified, 56 full-text articles were included in this scoping review. Most studies assessed the association of baseline variables with ILD progression and were not true assessments of the predictive value of these variables. In fact, analysis of the literature revealed a lack of a clear consensus definition for ILD progression. As such, there is a paucity of variables that can predict with confidence which patients will show ILD progression. Only one variable, the serological biomarker KL-6, was found to be consistently predictive of progression.

Conclusions: Significant knowledge gaps remain in our ability to predict individuals at risk of progressive SSc-ILD. Given the significant morbidity and mortality associated with progressive ILD, identifying these patients and their successful enrolment in clinical therapeutic trials is of the upmost importance.

Despite recent advances, the underlying mechanisms of the development and progression of many chronic respiratory diseases remain to be elucidated. Factors such as heterogeneity and complexity of human diseases and difficulty interpreting large datasets hinder research into chronic respiratory diseases. Omics assesses the changes in specific biological entities, such as mRNA expression, epigenetics/epigenomics, genomics, proteomics, metagenomics and metabolomics, and provides valuable insights into the roles of these processes in chronic respiratory diseases. High-throughput omics at bulk, single-cell and spatial levels empower the exploration of disease-related changes through untargeted data-driven statistical methods. Multi-omics is the exploration and integration of multiple biological processes, which compared to a single-omics, can provide a substantially greater and more holistic overview of the pathogenic mechanisms that underpin complex diseases. Multi-omics analysis can comprehensively characterise the mechanisms that drive chronic respiratory diseases, capturing unique biological signatures and cellular interactions at different omics levels. Use of these methods has begun to identify key factors and biomarkers in chronic respiratory diseases. Here, we review current omics approaches and highlight recent advances in respiratory research achieved using multi-omics and integrative methods. Our review provides a valuable resource for researchers and clinicians in this area.

Background: Multiple biologics targeting type 2 inflammation have been evaluated for the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) separately.

Objective: To evaluate the efficacy and safety of biologics in patients with comorbid asthma and CRSwNP.

Methods: A systematic review of randomised controlled trials (RCTs) from Medline, Embase, Web of Science and Scopus (up to 31 October 2025) was conducted. Random-effects meta-analysis assessed efficacy and safety outcomes.

Results: 16 studies involving 3598 patients were included in the meta-analysis. Overall, biologics reduced asthma exacerbations by 73% (rate ratio 0.27, 95% CI 0.21-0.34), increased forced expiratory volume in 1 s by 0.21 L (95% CI 0.11-0.30), improved asthma control questionnaire score by -0.70 points (95% CI -0.83--0.56) and asthma quality of life questionnaire score by 0.71 points (95% CI 0.49-0.93). Regarding sino-nasal outcomes, the sino-nasal outcome test 22 (SNOT-22) score was reduced by 15.15 points (95% CI -19.64--10.66), the nasal polyp score by 1.39 points (95% CI -1.88--0.89), the Lund-Mackay computed tomography score by 6.64 points (95% CI -8.88--4.40) and the nasal congestion/obstruction score by 0.84 points (95% CI -1.13--0.54). Heterogeneity across biologic classes varied by outcome, ranging from low to substantial. Overall, biologics exhibited a favourable safety profile.

Conclusions: Biologics significantly reduced asthma exacerbations, improved lung function, asthma control and quality of life, and alleviated sino-nasal outcomes in patients with comorbid asthma and CRSwNP, with an acceptable safety profile.

Introduction: Intrapleural enzyme therapy (IET) with fibrinolytics and deoxyribonuclease (DNase) is increasingly being added to standard care (SC) for the treatment of pleural infection.

Methods: A systematic literature search of the PubMed and Embase databases was conducted from January 2010 to December 2022 to identify studies reporting treatment response, safety or mortality of IET or SC in pleural infection.

Results: 19 studies were included. 12 evaluated treatment response with IET, with a pooled hospital length of stay (LOS) of 12.9 (95% CI 10.4-15.4) days and an average surgery requirement of 11.5% (95% CI 7.2-18.0). In SC, six studies assessed treatment response, with a pooled hospital LOS of 22.7 (95% CI 17.9-27.4) days and a surgery requirement of 23.4% (95% CI 8.3-50.5). The pooled incidence of significant bleeding in the IET group, assessed in 11 studies, was 3.7% (95% CI 2.9-4.5). In-hospital mortality rates were 3.7% (95% CI 1.5-9.1) for IET and 13.7% (95% CI 5.6-29.9) for SC.

Conclusions: IET demonstrated a favourable treatment response and lower mortality rate compared to SC, with an acceptable safety profile.

Influenza A virus (IAV) infections continue to represent a significant global health concern, both in terms of severe individual cases of acute respiratory distress syndrome (ARDS) and the potential for the emergence of pandemics. Despite decades of research, therapeutic options remain limited and the pathogenesis of severe disease is not yet fully understood. One critical yet underappreciated aspect is how IAV reprogrammes the ribosomal landscape of the host to facilitate viral replication and evade immune responses. Ribosomes take centre stage during infection, as both the immune response and viral propagation depend on the protein synthesis machinery. Recent studies have shown that the ribosome is not a static structure but can undergo dynamic changes in composition and function (ribosomal heterogeneity), which may influence the balance between viral propagation and host defence. Additionally, cancer research has remarkably demonstrated the feasibility of targeting the ribosome therapeutically. In this review, we summarise emerging evidence on how IAV hijacks the ribosomal landscape, including ribosomal biogenesis, ribosomal proteins, translation factors and associated signalling pathways, and how these changes may shape the course of infection, immune response and lung injury. Drawing parallels with cancer biology, we explore whether components of this reprogrammed landscape could serve as therapeutic targets in severe IAV infection and ARDS. By connecting molecular mechanisms with clinical relevance, we aim to highlight a novel perspective on host-virus interaction that could open avenues for future treatment strategies.

Acute and chronic lung rejection are major barriers to the long-term survival of lung transplant recipients. Current spirometry-based monitoring of allograft function is limited by the low sensitivity in detecting distal airway abnormalities where allograft rejection evolves. Emerging evidence from haematopoietic stem cell transplant patients with chronic pulmonary graft-versus-host disease suggests that respiratory oscillometry may offer improved sensitivity in identifying small airway obstruction at earlier stages. In this scoping review, we explore the utility of oscillometry in monitoring lung transplant allograft function. We identify eight studies reporting the analysis of 1282 bilateral and 36 single lung transplant (SLT) recipients conducted between 2016 and 2024. While the limited number of studies precludes definitive conclusions, the review findings highlight some compelling and promising data. Oscillometry may be more sensitive in detecting acute rejection, tracking graft injury and monitoring rejection treatment than spirometry. Additionally, oscillometry demonstrated the potential to independently identify and distinguish different chronic lung allograft dysfunction (CLAD) phenotypes at onset, providing a risk assessment for subsequent CLAD development. Oscillometry parameters also correlated well with spirometry in both healthy lung allografts and advanced CLAD cases, suggesting that oscillometry may complement or even substitute for spirometry in situations where spirometry is not feasible. This review underscores the potential of respiratory oscillometry as a valuable tool in post-lung transplant monitoring. Future large-scale, multicentre, prospective studies are needed to further validate its clinical utility, especially in combination with spirometry and other noninvasive modalities, to enhance the early detection and management of allograft rejection.

Despite the enormous global burden associated with chronic obstructive pulmonary disease (COPD), its precise underlying mechanisms remain incompletely understood. A key feature of COPD is persistent, nonresolving inflammation, traditionally attributed to an exaggerated immune response, oxidative stress, protease-antiprotease imbalances and increased cell death. While excessive cell death in COPD is well described, emerging evidence highlights defects in the subsequent clearance process, known as efferocytosis. Effective removal of dead cells is essential to prevent further inflammation in order to maintain tissue homeostasis. In this article, we critically review the literature and highlight the significant impairment of efferocytosis in COPD, as alveolar macrophages from COPD patients show a reduced capacity to engulf apoptotic airway epithelial cells. This impairment appears to be irreversible once COPD has developed, even after smoking cessation. This raises the possibility that impaired efferocytosis may represent an additional pathogenetic mechanism in COPD. We further discuss recent literature on how dysregulation in each of the consecutive steps of efferocytosis, namely the "find-me", "eat-me", uptake and degradation phases, can contribute to COPD pathogenesis. Finally, we propose future directions for both basic and clinical research in COPD and highlight novel therapeutic opportunities aimed at targeting the underlying disease mechanisms, rather than merely addressing symptoms.