European Respiratory Review最新文献

Mechanical ventilation is a life-saving method for those critically ill patients with acute or chronic respiratory failure without assistance. However, even short-term mechanical ventilation can lead to alterations in the fibrous structure and reduced contraction force of the diaphragm, which is defined as ventilator-induced diaphragmatic dysfunction (VIDD). This condition is associated with various risks of adverse clinical outcomes. Research on mechanical ventilation-related respiratory mechanics helps us to understand the macroscopic myotrauma mechanisms of VIDD. Ongoing clinical trials into comprehensive management strategies for lung- and diaphragm-protective ventilation are continually refining respiratory therapy protocols in clinical practice. Although the cellular and molecular mechanisms are not fully defined, pathways involving mitochondrial oxidative stress have been identified as key contributors to disease progression, leading to both accelerated proteolysis and depressed protein synthesis. Additionally, research on the ubiquitin-proteasome pathway, lysosomal autophagy, calpain, caspase-3 and dysfunction of the ryanodine receptor-1 pathway is enhancing our understanding of the downstream mechanisms involved. Promising interventions based on these findings have yielded hopeful results in animal models for preventing VIDD. This review summarises the epidemiology and pathophysiological mechanisms of VIDD and advances in potential treatment and prevention.

Background: Positive airway pressure (PAP) including noninvasive ventilation or continuous PAP are standard of care in chronic hypercapnic respiratory failure (CHRF). PAP is applied during sleep so its impact on sleep quality and daytime sleepiness is relevant. This systematic review and meta-analysis investigated the effects of PAP for CHRF on sleep quality.

Methods: Relevant studies were identified by a PubMed/Embase search up to October 2024. Eligible studies included PAP initiation and evaluation of sleep quality/sleepiness. Evaluated outcomes were sleep efficiency, Pittsburgh Sleep Quality Index (PSQI), Severe Respiratory Insufficiency sleep subscale (SRI-AS) and Epworth Sleepiness Scale (ESS).

Results: 58 studies were included (n=2511; mean age 59.1 years, 57% male) and the indication for PAP was obesity hypoventilation syndrome (n=1073), neuromuscular disease (NMD) (n=649), COPD (n=428) or other/mixed aetiologies (n=361). Overall improvements were +5.87% (95% CI 2.64-9.09) for sleep efficiency, -2.51 (95% CI -3.22--1.80) for PSQI, +10.75 (95% CI 6.11-15.40) for SRI-AS score and -4.96 (95% CI -5.96--3.97) for ESS score. Adherence to PAP was the only factor significantly associated with sleep efficiency improvement. ESS and PSQI improved to a greater extent in people with a higher body mass index, younger age and hypercapnia correction during PAP. ESS improvement was associated with sleep efficiency improvement. PSQI improved to a greater extent in females and those with NMD.

Conclusion: PAP initiation was associated with clinically relevant objective and subjective sleep quality improvements. Given the health benefits of good sleep, the effect of sleep quality improvements during PAP on prognosis should be investigated.

The human respiratory tract virome is an underexplored component of the microbiome that includes eukaryotic viruses, bacteriophages and archaeal viruses. The respiratory virome represents a dynamic and heterogeneous ecosystem, shaped by host, environmental and microbial factors. Advances in metagenomic sequencing have expanded our understanding of virome composition, dynamics and potential roles in health and disease. Despite increasing interest, virome research remains fragmented and often secondary to bacteriome studies. Challenges in study design, genomic characterisation and interpretation limit consistent conclusions. This review summarises current knowledge of the respiratory virome in health and across acute and chronic respiratory diseases, including acute respiratory infection, asthma, COPD, cystic fibrosis and bronchiectasis. While each condition is distinct, they share features of airway inflammation and immune dysregulation where the virome may act as a modifier or marker. Across these syndromes, emerging evidence highlights the consistent detection of respiratory viruses including potential commensals, such as Anelloviridae, and the often-overlooked role of bacteriophages. We also discuss the concept of viral dark matter, where large proportions of sequence data remain unclassified, potentially representing novel viral taxa. Technical and conceptual challenges are evaluated, alongside recent methodological innovations such as meta-transcriptomics and viral enrichment protocols. We outline how standardised, multi-omic and longitudinal approaches are urgently needed to clarify the virome's functional role, interactions with immunity and microbial communities and its utility as a biomarker or therapeutic target.

The inhaled dose of air pollution (IDoAP) is an air pollution exposure quantification method that accounts for individuals' amount of inspired air (i.e. minute ventilation), and thus for the physical activity practised by individuals. We aimed to summarise the existing literature and identify research gaps on the health effects of IDoAP.We included original peer-reviewed research in PubMed, Scopus, SPORTDiscus, Embase and Cochrane prior to November 2024 and appraised bias following Cochrane and ROBINS-E tools. Title, abstract and full-text screening, data extraction and bias appraisal were completed in duplicate.Of 1888 screened studies, 25 studies were included, mostly focusing on healthy adults (21 out of 25 studies), overlooking susceptible populations such as pregnant individuals or those with pre-existing disease. Studies focused primarily on IDoAP of O₃ (IDoAP-O₃) (14 out of 25 studies) and particulate matter <2.5 µm in aerodynamic diameter (IDoAP-PM_2.5) (13 out of 25 studies), with an exposure duration of up to 24 h. Lung function was the most studied outcome (19 out of 25 studies). Acute exposure to IDoAP-O₃ was associated with reduced lung function: increasing IDoAP-O₃ by 150 μg·m^-3 led to a decrease in forced expiratory volume in 1 s (FEV₁) of 0.27 L. This was driven by O₃ concentration, while increases in minute ventilation did not affect FEV₁ A number of research gaps were identified. These comprised research on susceptible and vulnerable populations, including residents of low-to-middle-income regions, and people with extreme occupational exposures; air pollutants other than O₃ and PM_2.5; and outcomes besides respiratory markers. Alternative statistical approaches are also required, such as multi-exposure models.Our findings support initiatives to generate low-pollution public corridors to keep IDoAP levels as low as possible to maximise health benefits from physical activity.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by dysregulated inflammation, immune imbalance and impaired alveolar repair. Despite advances in supportive care, effective targeted therapies remain limited. Palmitoylation, a reversible lipid-based post-translational modification, has recently emerged as a regulatory mechanism in ARDS pathogenesis. Acting in a context-dependent manner, palmitoylation affects key processes, including immune activation, programmed cell death and epithelial remodelling. Accumulating evidence suggests that palmitoylation may exert dual roles in ARDS: it can promote inflammation and immune evasion in the early phase, while contributing to resolution and tissue repair during later stages. This review summarises current findings regarding the spatial and temporal regulation of palmitoylation in immune and structural cells involved in ARDS, including its effects on inflammasome activation, epithelial-immune interactions and fibrotic progression. Therapeutic approaches under investigation include selective inhibition of palmitoyltransferases (zinc finger aspartate-histidine-histidine-cysteine motif-containing-type palmitoyltransferase family), modulation of depalmitoylation enzymes and substrate-targeted strategies. Several preclinical studies support the feasibility of targeting palmitoylation to reduce lung injury and improve immune regulation. Overall, palmitoylation represents a potential regulatory node in ARDS pathophysiology. Further research is required to clarify its cell-specific functions and to assess the translational potential of palmitoylation-based interventions.

Pulmonary hypertension (PH) is a life-threatening disease increasingly being diagnosed in the elderly population, marked by vascular injury, excessive vasoconstriction and progressive remodelling of the pulmonary arteries (PAs). These lead to sustained elevation of PA pressure and subsequent development of right ventricular failure. Despite the beneficial effects on disease progression and quality of life, current treatments do not cure PH, highlighting the need for a deeper understanding of the underlying mechanisms. Recently, cellular senescence has gained much attention as a stress response programme with substantial and somewhat controversial implications for both functional and structural changes within the pulmonary vasculature. Herein, we provide updated insights into the complex role and duelling good and bad effects of senescent cells in the development and progression of PH and discuss the novel therapeutic avenues that this connection opens. Finally, we identify challenges and unmet needs in understanding the two-faced nature of cellular senescence in PH and leveraging senescence therapeutically.

Pulmonary arterial hypertension (PAH) is a severe disease characterised by progressive remodelling and loss of pulmonary microvessels, driven by endothelial cell dysfunction, smooth muscle cell abnormalities, inflammation and immune system dysregulation. Recent research advancements have uncovered pathogenic rare loss-of-function variants of SOX17 (SRY-box transcription factor 17) associated with PAH onset. SOX17, a member of the Sry-related high-mobility group box gene family, encodes a crucial transcription factor in embryogenesis, implicated in the formation and maintenance of endoderm, formation of the heart and vascular tree, and haematopoiesis and stem cell formation, with a strong relationship with hypoxia-inducible factors. Consistent with SOX17's pleiotropic embryogenic role, PAH patients carrying SOX17 variants present a particular phenotype associated with congenital heart diseases, younger age, as well as thoracic and extrathoracic vascular anomalies. Genetic and fundamental evidence suggest that SOX17 deficiency is a common occurrence in other forms of PAH. SOX17 deficiency appears to be central in PAH pathophysiology, playing a core role in endothelial dysfunction, intercellular crosstalk and endothelial-to-mesenchymal transition, with differential expression in males and females. Taken together, these data suggest its role as key element of the "multiple hits" theory of PAH, both as a first and second hit and support the notion that therapies aimed at restoring or enhancing its expression may offer promising therapeutic potential for all PAH patients. In this review, we integrate the latest knowledge on SOX17 function in embryogenesis and the PAH pathogenesis to provide an in-depth perspective on SOX17 function in cardiovascular and pulmonary physiology.

Background: Delirium can occur in patients with pneumonia, but its prevalence is inconsistent across studies. Unreliable estimates and uncertainty regarding the significance of patient-specific versus microbiological risk factors hinder delirium management and prognosis. Here, we provide robust estimates of delirium prevalence in patients with pneumonia, associated risk factors and association with mortality.

Methods: We searched five databases (Medline, Cochrane Library, Embase, PsycINFO and Scopus), from inception to 6 August 2024. We included studies in adults hospitalised with pneumonia reporting delirium, encephalopathy or altered mental status. Two investigators extracted data and assessed risk of bias. Summary rates were calculated using random-effects models. We performed prespecified analyses for diagnostic methods, microbiologic factors, clinical factors and mortality, with sensitivity analysis among studies at low risk of bias. The review protocol was registered with PROSPERO: CRD42023385571.

Results: Delirium prevalence across 126 studies was 22% (95% CI 18-26%) and higher in studies at low risk of bias (40%, 95% CI 24%-58%; n=11). Standardised assessments yielded higher rates than symptom- or International Classification of Diseases code-based assessments (p<0.05). Surprisingly, delirium rates did not differ by microbiological aetiology (p=0.63), including COVID-19, nor by pneumonia origin (p=0.14). Predisposing factors included older age and neurologic and systemic comorbidities. Delirium was associated with increased mortality (odds ratio 4.3, 95% CI 3.24-5.76; p<0.001), without change over five decades (p=0.32).

Interpretation: Delirium is highly prevalent and enduring in pneumonia, with nearly double the estimated prevalence when standardised diagnostic methods for both pneumonia and delirium are used. Our results emphasise patient- and care-related factors over microbiological causes, including COVID-19. Delirium's entrenched association with mortality, even considering covariates, reinforces the need to manage delirium as a convergent syndrome in pneumonia.