European Respiratory Review最新文献

{"title":"Cellular senescence in adult pulmonary hypertension: current state and future challenges.","authors":"Sarah-Eve Lemay, Yukimitsu Kuwabara, Sébastien Bonnet, François Potus, Steeve Provencher, Serge Adnot, Olivier Boucherat","doi":"10.1183/16000617.0030-2025","DOIUrl":"10.1183/16000617.0030-2025","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.","authors":"Thomas Lacoste-Palasset, Benoit Aguado, Julien Grynblat, Florence Coulet, Marc Humbert, Fabrice Antigny, David Montani, Grégoire Ruffenach","doi":"10.1183/16000617.0081-2025","DOIUrl":"10.1183/16000617.0081-2025","url":null,"abstract":"<p><p>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 <i>SOX17</i> (SRY-box transcription factor 17) associated with PAH onset. <i>SOX17</i>, 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 <i>SOX17</i> 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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-decade prevalence of delirium in pneumonia, risk factors and associated mortality: a systematic review and meta-analysis.","authors":"Erika L Juarez-Martinez, Aida Araia, Dillan Prasad, Shreya Dhar, Khizar Nandoliya, Ian G Sherrington, Catherine Zhao, Annie Wescott, Chiagozie I Pickens, Richard G Wunderink, Eyal Y Kimchi","doi":"10.1183/16000617.0111-2025","DOIUrl":"10.1183/16000617.0111-2025","url":null,"abstract":"<p><strong>Background: </strong>Delirium can occur in patients with pneumonia, but its prevalence is inconsistent across studies. Unreliable estimates and uncertainty regarding the significance of patient-specific <i>versus</i> 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<i>=</i>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).</p><p><strong>Interpretation: </strong>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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Air pollution and alveolar health.","authors":"Carmelo Sofia, James G H Parkin, Joseph A Bell, Lareb S N Dean, Liam J Edgeway, Lucy Sayer, Natasha H C Easton, Donna E Davies, Ben G Marshall, Stephen T Holgate, Luca Richeldi, Mark G Jones, Matthew Loxham","doi":"10.1183/16000617.0280-2024","DOIUrl":"10.1183/16000617.0280-2024","url":null,"abstract":"<p><p>Exposure to air pollution has been associated with up to 9 million premature deaths per year worldwide, with the respiratory system a key site for its effects. Air pollution exposure is a well-established risk factor for the development and exacerbation of airways diseases and lung cancer, however relatively little is known regarding the risks associated with air pollution interacting with areas of gas exchange - the alveoli and pulmonary interstitium. In recent years, evidence has emerged identifying a role in the development and progression of sub-clinical interstitial lung abnormalities as well as progression and risk of exacerbation of fibrotic interstitial lung diseases. This review outlines the epidemiologic evidence that air pollution perturbs alveolar health. It considers the different components of ambient air pollution, how penetration to the alveoli is determined by particle size and whether the response to alveolar exposure may be modulated by personal susceptibility factors. We discuss potential acute and chronic pathogenic mechanisms of injury upon the pulmonary interstitium and how these may contribute to the development and/or progression of interstitial processes. Finally, we explore current knowledge gaps and the potential for air pollution interventions in vulnerable individuals to support alveolar homeostasis and so prevent disease development and/or progression.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging technologies in experimental pulmonary fibrosis research: essential tool for enhanced translational relevance.","authors":"Flore Belmans, Irma Mahmutovic Persson, Sam Bayat, James Eaden, Wim Vos, Joseph Jacob, Rachel C Chambers, Greetje Vande Velde","doi":"10.1183/16000617.0012-2025","DOIUrl":"10.1183/16000617.0012-2025","url":null,"abstract":"<p><p>Pulmonary fibrosis remains a devastating and often fatal condition due to the lack of effective treatments that halt disease progression. Rodent models of pulmonary fibrosis are crucial to identify candidate targets and novel therapeutic agents. However, the attrition rate of novel drug candidates in clinical trials remains high. This review suggests complementing traditional methods used to evaluate antifibrotic therapies in rodent models, such as histopathological and biochemical markers, and lung function tests, with innovative imaging technologies. These imaging techniques could improve the predictive power and translatability of animal studies in human clinical trials. Notably, previous studies in mice and other rodents have observed compensatory lung enlargement in response to lung injury, questioning whether the conventional view of pulmonary fibrosis as a restrictive disease applies to rodents. By adding longitudinal image-based biomarkers, we aim to better unravel the complexity of lung responses and facilitate more effective drug development for pulmonary fibrosis, ultimately improving patient outcomes.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ambient air pollution exposure, mediating biomarkers and risk of COPD: a cohort study and meta-analysis.","authors":"Tinggui Wang, Mengdan Liang, Xiaoying Ye, Xiaoxiao Huang, Hanbing Chen, Xiongkun He, Mengying Xie, Xiaowei Xie, Xiannuan Jiang, Zhehui Chen, Baosong Xie, Yiming Zeng, Xiaoxu Xie","doi":"10.1183/16000617.0055-2025","DOIUrl":"10.1183/16000617.0055-2025","url":null,"abstract":"<p><strong>Background: </strong>Limited evidence exists on air pollution's systemic impact on lung function and mediating biomarkers. This study comprehensively evaluated associations between air pollution, COPD and lung function, while exploring biomarker mediation.</p><p><strong>Methods: </strong>A prospective analysis of 451 566 UK Biobank participants was conducted. Land use regression models estimated exposure to particulate matter (PM) ≤2.5 μm (PM_2.5), PM ≤10 μm (PM₁₀), PM with diameters between 2.5 and 10 μm, reflectance measured on PM_2.5 filters and transformed into absorbance (PM_{2.5 absorbance}), nitrogen dioxide (NO₂) and nitrogen oxides (NOx). Linear and Cox regression assessed pollution effects on forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), FEV₁:FVC ratio, peak expiratory flow (PEF) and COPD incidence. A meta-analysis synthesised results with prior cohorts (PROSPERO: CRD42023411304). Mediation analysis evaluated biomarkers.</p><p><strong>Results: </strong>Elevated PM_2.5, PM_{2.5 absorbance}, NO_x and NO₂ correlated with reduced lung function (measured as FEV₁, FVC, FEV₁:FVC ratio and PEF) and higher COPD risk (hazard ratio: 1.08-1.15). Race-stratified analyses revealed interactions, with White populations showing greater COPD susceptibility. Meta-analysis confirmed air pollution-COPD links. Mediation analyses implicated plasma lipid metabolites, inflammatory cell counts and cytokines as mechanistic intermediaries.</p><p><strong>Conclusion: </strong>Air pollution associates with lung function decline and elevated COPD risk, with White populations disproportionately affected. Lipid, inflammatory and haematological biomarkers mediate this relationship. Findings underscore the urgency of air pollution control to mitigate respiratory harm and inform targeted preventive and therapeutic strategies.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Risk of malignant transformation and infections in congenital lung malformations in adults: a systematic review.","authors":"Louis W J Dossche, Lieke S Kamphuis, Sara J Baart, Hanneke IJsselstijn, J Marco Schnater","doi":"10.1183/16000617.0141-2025","DOIUrl":"10.1183/16000617.0141-2025","url":null,"abstract":"","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of home-based <i>versus</i> centre-based exercise programmes for pulmonary hypertension: a systematic review with meta-analysis.","authors":"Indyanara C Ribeiro, Sofia M Sieczkowska, Renata Jashchenko, Daniela Jara, Denielli da Silva Gonçalves Bos, Rogério De Souza, Celso R F Carvalho, Kátia De Angelis, Marcelle Paula-Ribeiro","doi":"10.1183/16000617.0102-2025","DOIUrl":"10.1183/16000617.0102-2025","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary hypertension is a pathophysiological disorder with poor prognosis. Exercise intolerance and lower physical activity levels are common features of pulmonary hypertension and affect patients' quality of life. Exercise training effectively improves clinical outcomes in this population, but access to rehabilitation centres is often limited. A home-based exercise training component could be an accessible and cost-effective alternative, but the efficacy and safety of this approach in pulmonary hypertension remain unclear.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of studies retrieved from six international databases. The studies evaluated home-based exercise interventions in patients with pulmonary hypertension, including both stand-alone and hybrid setups, and assessed safety, efficacy (exercise capacity, cardiorespiratory outcomes and functional class) and adherence.</p><p><strong>Results: </strong>We included 19 studies. Compared with inactive controls, home-based exercise training improved the 6-min walk distance (mean difference (MD) 54.85 m, p<0.01), peak oxygen uptake (standardised MD 0.83 mL·kg^-1·min^-1, p<0.01), ventilatory efficiency (MD -3.93, p<0.01) and quality of life scores. Improvements in clinical outcomes were comparable between home-based and centre-based interventions. No clinical worsening or exercise training-related severe adverse events were reported; however, most studies did not report health-related self-monitoring strategies at home. The level of adherence was generally high, and the drop-out rates were comparable between home-based and centre-based interventions.</p><p><strong>Conclusion: </strong>Home-based exercise interventions appear to be viable alternatives to centre-based programmes for patients with pulmonary hypertension, showing comparable improvements in clinical outcomes. However, limited reporting on self-monitoring may affect the overall safety assessment. Further research is needed to determine the optimal implementation of these interventions.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Comment on: Risk of malignant transformation and infections in congenital lung malformations in adults: a systematic review.","authors":"Federica Pederiva, Paolo Dalena, Noemi Pasqua, Ilia Bresesti, Valeria Testa, Salvatore Zirpoli, Valerio Gentilino","doi":"10.1183/16000617.0166-2025","DOIUrl":"10.1183/16000617.0166-2025","url":null,"abstract":"","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right-sided heart failure in acute respiratory distress syndrome.","authors":"Athiththan Yogeswaran, Nils C Kremer, Patrick Janetzko, Simon Schäfer, Zvonimir A Rako, István Vadász, Matthias Hecker, Khodr Tello","doi":"10.1183/16000617.0060-2025","DOIUrl":"https://doi.org/10.1183/16000617.0060-2025","url":null,"abstract":"<p><p>Right-sided heart dysfunction (RHD) has emerged as a critical yet often underappreciated aspect of acute respiratory distress syndrome (ARDS). This review describes the role of RHD in ARDS, providing an updated overview of its pathophysiology, diagnosis and potential treatments. Several mechanisms contribute to increased right ventricular (RV) afterload in ARDS, including hypoxic vasoconstriction, hypercapnia, acidosis, <i>in situ</i> thrombosis and an imbalance between pulmonary vasoconstrictors and vasodilators. Mechanical ventilation, a cornerstone in ARDS management, can worsen haemodynamic instability due to impaired lung compliance. Systemic implications of RHD include renal dysfunction due to impaired organ perfusion and venous congestion. Volume overload further exacerbates RV strain, setting off a vicious cycle of deteriorating RV function, interventricular septal bowing, reduced left ventricular preload and ultimately circulatory failure. The diagnosis and management of RHD in ARDS require an integrated approach that combines invasive haemodynamic monitoring, imaging techniques and noninvasive assessments. Specific treatment options targeting RHD in ARDS remain limited. Titration of positive end-expiratory pressure plays a critical role in mitigating RHD. Prone positioning has shown inconsistent effects on RV function which require further investigation. Inhaled pulmonary vasodilators, such as nitric oxide and prostacyclins, are commonly used to modulate pulmonary vascular tone in ARDS. Small studies suggest that levosimendan and commonly used vasoactive drugs such as norepinephrine, epinephrine, vasopressin and milrinone may improve RV function in ARDS. However, no pharmacologic treatment is specifically approved for ARDS-associated RHD. Large-scale clinical trials are necessary to identify the most effective treatment strategies for specific patient populations.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}