European Respiratory Review最新文献

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.

The management of asthma exacerbations is well established, including inhaled short-acting β₂-agonist administration, systemic corticosteroid therapy and supplemental oxygen. Severe asthma exacerbations (SAEs) nonresponsive to medical and O₂ therapy may require mechanical ventilation via endotracheal intubation (ETI), evaluation and admission to the intensive care unit (ICU). However, up to 35% of intubated and ventilated patients die due to conventional mechanical ventilation (CMV)-related life-threatening complications (i.e. barotrauma, circulatory collapse, cardiac arrhythmias, acute coronary syndrome, atelectasis and pneumonia). Among noninvasive respiratory therapies, the effectiveness of noninvasive ventilation (NIV) in preventing clinical deterioration and CMV in the earlier phases of SAE remains controversial. Limited tolerance to mechanical ventilation represents a drawback that can compromise treatment success. The high-flow nasal cannula (HFNC) is a widely applied respiratory supportive tool for the management of several patterns and types of acute respiratory failure, with patient acceptance being a key point favouring its application. Despite a potential pathophysiological rationale, clinical data on the feasibility and effectiveness of HFNC in SAEs are lacking. We conducted this concise narrative review to summarise the physiological and clinical benefits of HFNC compared to conventional oxygen therapy (COT) in adult patients with SAEs, focusing on outcomes such as dyspnoea, comfort, lung gas exchange, facilitation of inhaled therapy, hospitalisations, ETI and ICU admission. According to available data, there is no evidence of either superiority or inferiority of HFNC versus COT in SAEs. Further larger randomised control trials are required to define the role of HFNC in asthmatic attacks.

In COPD, acute exacerbations (AECOPD) are major contributors to morbidity and mortality, emphasising the need for effective stratification of individuals at high risk. Quantitative computed tomography (qCT) refers to the extraction of numerical data from CT images to objectively characterise anatomical and functional features, and it has been increasingly investigated in COPD assessment. We systematically reviewed the literature to evaluate the use of qCT for the diagnosis and prognosis of AECOPD. Of 362 screened records, 18 studies were included in this review. No studies were identified that used qCT features to diagnose AECOPD in CT scans made at the point of exacerbation. 11 studies reported qCT features identified in CT scans performed in stable COPD that are associated with frequent AECOPD and seven studies developed and tested models integrating CT features for the prediction of AECOPD. Across these studies, greater emphysema extent, thicker bronchial walls and increased air trapping were associated with higher exacerbation risk. However, current evidence is limited by heterogeneity in study design and lack of prospective validation. This review highlights the potential of quantitative CT analysis, which may be further enhanced by the integration of automated software, to support the development of imaging biomarkers for AECOPD. Future research is needed to refine qCT features for diagnosing AECOPD and establish CT-based tools that can predict AECOPD.

COPD is a heterogeneous, progressive inflammatory airway disease, with patients presenting with a wide variety of symptoms, comorbid conditions and underlying pathophysiology. Smoking is a major contributing factor to disease burden, alongside other environmental and patient-related risk factors. Airway inflammation is consistently present in COPD and is implicated in disease pathogenesis and progression. The airway epithelium functions as an active physiochemical barrier, protecting the lungs from pathogens and airborne environmental triggers, and as an immune organ that coordinates immunological activity in response to pollutant, bacterial, viral or allergen exposure. Inhalation of cigarette smoke and other airborne triggers can damage bronchial epithelial cells, leading to exaggerated inflammatory responses and airway remodelling. Airway inflammation in COPD, including neutrophilic and eosinophilic phenotypes, is mediated by the epithelium and epithelial cell-derived cytokines. Improving our understanding of epithelial-related inflammation in COPD is essential for the identification of novel biomarkers, stratification of patients, development of targeted therapeutics and creation of personalised treatment strategies. Here, we review the current understanding of the role of the airway epithelium in COPD pathogenesis, providing an overview of the pathological changes to the epithelium and the role of the epithelial-derived cytokines in driving different inflammatory phenotypes. We then consider biomarkers related to epithelial function in COPD and discuss how the epithelium might be targeted by novel COPD therapies.

A large proportion of patients (40-60%) with severe asthma present with persistent airway obstruction (PAO). Patients with severe eosinophilic asthma (SEA) and PAO appear to be an underrepresented group in clinical guidance, despite being associated with considerable healthcare and economic burden. High levels of eosinophils drive airway inflammation, obstruction and hyperresponsiveness, which are key characteristics of SEA and can increase the risk of PAO and subsequent irreversible worsening of lung function. Available clinical and real-world data must examine the effectiveness of biologic treatment targeting SEA in PAO to identify any data gaps that might help further define such patients and optimise their management. However, clinical trials of SEA frequently exclude the enrolment of patients with PAO. Eosinophils are activated and recruited to airways in response to different cytokines, particularly interleukin-5 (IL-5), produced via a complex molecular and cellular cascade. A few studies evaluating the effectiveness of benralizumab and mepolizumab were able to identify cohorts of patients with SEA and PAO who had a significant response to these IL-5/Rα-targeted biologics. PAO in patients with SEA represents a distinct clinical entity, one which could be referred to as "persistent eosinophilic airway obstruction". Patients with persistent eosinophilic airway obstruction are likely to be responsive to targeted biologic treatment, although additional clinical studies and real-world data are needed to further assess treatment efficacy and safety in this population and provide guidance to clinical practice.

Background: Barriers to delivery of pulmonary rehabilitation are not evenly distributed across people with chronic lung disease. The aim of this systematic review was to evaluate equity in pulmonary rehabilitation delivery and outcomes, in relation to the social determinants of health.

Methods: A systematic search of four online databases was undertaken. Two reviewers independently screened studies and extracted data. Social determinants of health were categorised according to the PROGRESS-Plus framework, and mapped to the Health Equity Implementation Framework. We reported the impact of PROGRESS-Plus factors on pulmonary rehabilitation access, uptake and completion, and outcomes of health-related quality of life and exercise capacity.

Results: 32 studies from 13 countries were included. Place of residence (rurality, travel distance) was consistently associated with poor access and uptake. Uptake was lower for Black people than White people (OR 0.87, 95% CI 0.81-0.95; two studies, n=1 128 623) and in those of low socioeconomic status (OR 0.63, 95% CI 0.55-0.73; two studies, n=1 134 811). Men were more likely to complete than women (OR 1.13, 95% CI 1.06-1.20; eight studies, n=20 509). People who were working were less likely to complete (OR 0.70, 95% CI 0.47-1.04; three studies, n=3292). There was no impact of PROGRESS-Plus features on improvements in health-related quality of life or exercise capacity with pulmonary rehabilitation.

Conclusions: There are inequities in delivery of pulmonary rehabilitation. Targeted efforts to improve pulmonary rehabilitation delivery in disadvantaged groups are required, to ensure that all people with chronic lung disease are able to realise its benefits.