European Respiratory Review最新文献

Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterised by progressive accumulation of surfactant-derived lipoproteinaceous material within alveoli, impairing gas exchange and causing respiratory insufficiency. Despite therapeutic advances such as whole lung lavage, substantial heterogeneity persists in outcome selection and reporting across studies, limiting comparability and evidence synthesis.

Objective: To systematically map and categorise outcomes and outcome measures reported in studies of PAP treatments and establish a foundation for developing a standardised core outcome set (COS).

Methods: A scoping review was conducted across four databases and two clinical trial registries (May 2024, updated May 2025). Eligible studies included those reporting treatment outcomes in patients of any age with PAP. Outcomes and measures were extracted and categorised using the Core Outcome Measures in Effectiveness Trials taxonomy.

Results: From 8475 screened records, 62 studies met the inclusion criteria, encompassing 31 distinct outcomes and 92 corresponding outcome measures. Physiological parameters dominated reporting, including arterial oxygenation (n=55, 89%; such as arterial oxygen tension and alveolar-arterial oxygen gradient) and lung function indices (n=53, 85%; such as diffusing capacity of the lung for carbon monoxide and forced vital capacity) were most frequently assessed. In contrast, patient-centred outcomes such as quality of life were reported in only 10 (16%) studies, while adverse events were relatively well-reported (n=41, 66%).

Conclusions: The reporting of outcomes and outcome measures in PAP studies is highly variable. There is an urgent need for a COS tailored to PAP that focuses on physiological outcomes, adverse events and patient-reported outcomes.

Tuberculosis (TB) primarily manifests as pulmonary TB (PTB), but extrapulmonary TB (EPTB) remains a major clinical challenge. Distinct diagnostic and therapeutic difficulties arise from differences in immune responses, pathogen behaviour and host susceptibility. However, the factors driving disease localisation are still incompletely understood. We conducted a comprehensive narrative review of studies examining differences between PTB and EPTB in terms of epidemiology, mycobacterial factors, genetic and epigenetic determinants, host immune responses, transcriptomic profiles, cytokine and chemokine patterns, and immunophenotypes. EPTB is more common among females, children, older adults and immunocompromised individuals with deficient granuloma formation. This review is intended to provide deeper insight for clinicians and researchers and provides an accessible synthesis of current basic science findings together with their relevance for clinical practice. Certain Mycobacterium tuberculosis lineages, notably lineage 1, and specific virulence factors are associated with extrapulmonary dissemination. While genetic polymorphisms influence TB localisation, no studies specifically addressing epigenetic predisposition to EPTB were identified. PTB typically is characterised by T-helper 1-driven immunity, high bacillary loads and robust macrophage activation, whereas EPTB involves compartmentalised immune responses, reduced cytotoxicity and broader cytokine variability. Transcriptomic analyses reveal site-specific gene expression differences and emerging diagnostic blood-based biomarkers show promise but require further validation. Cytokine profiles and immunophenotyping suggest greater immune exhaustion and regulatory T-cell activity in EPTB. We outline practical implications for diagnosis and management and highlight constraints in resource-limited settings and emphasise access and implementation considerations. Integrating these clinical and mechanistic insights can guide more timely recognition and tailored care.

Background: Ultrafine particles (≤100 nm diameter) may have a higher toxicity than larger particles but are still not regulated nor part of routine air pollution monitoring. So far, health effects of long-term exposure to ambient ultrafine particles are not well understood, owing to a lack of exposure data and epidemiological studies.

Methods: We conducted a systematic review and meta-analysis on the health effects of long-term exposure to ultrafine particles, including studies published until December 2024. A meta-analysis was conducted for outcomes with at least four available effect estimates. Confidence in the body of evidence was evaluated using the Office of Health Assessment and Translation method.

Results: We identified 85 studies investigating various mortality, morbidity and subclinical outcomes. In meta-analyses of single-pollutant models, we found positive associations with natural mortality (hazard ratio 1.06, 95% CI 1.04-1.08) and C-reactive protein (10.14% increase (95% CI -0.51-21.99%) per 10 000 pt·cm^-3 increase in long-term exposure to ultrafine particles, with low and inadequate levels of evidence, respectively. The remaining studies revealed overall limited evidence for adverse effects on a wide range of outcomes. Less than half of the studies adjusted for co-pollutants.

Conclusion: The evidence base on long-term health effects of ultrafine particles has increased substantially in the past decade, while the overall evidence for independent effects of long-term ultrafine particle exposure remains inadequate to low. More studies are needed to draw firm conclusions about the independent adverse effects of long-term ultrafine particles on various health end-points, with a special focus on the influence of co-pollutant adjustment.

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.