Laura Houweling, Iris Rots, Lizan D Bloemsma, Robert van Vorstenbosch, Simone Del Motto, Roel C H Vermeulen, Anke H Maitland-Van der Zee, Korneliusz Golebski, George S Downward
{"title":"Impact of air pollution on COVID-19 severity: a systematic review of underlying biological mechanisms.","authors":"Laura Houweling, Iris Rots, Lizan D Bloemsma, Robert van Vorstenbosch, Simone Del Motto, Roel C H Vermeulen, Anke H Maitland-Van der Zee, Korneliusz Golebski, George S Downward","doi":"10.1183/16000617.0070-2025","DOIUrl":"10.1183/16000617.0070-2025","url":null,"abstract":"<p><strong>Background: </strong>Our recent systematic review highlighted key associations between ambient air pollution (AAP) exposure and COVID-19 severity. This systematic review aims to summarise toxicological studies on the biological mechanisms underlying these associations.</p><p><strong>Methods: </strong>On 17 July 2025, PubMed, Embase, Scopus and Web of Science were searched for <i>in vitro</i>, <i>in vivo</i> and <i>in silico</i> studies that examined the biological mechanisms of AAP exposure on COVID-19 health outcomes. Two independent reviewers engaged in the selection and data extraction process. The methodological quality of the included studies was assessed with the Toxicological Data Reliability Assessment Tool. The Integrated Network and Dynamical Reasoning Assembler (INDRA) was used to provide visual biomechanistic summaries of the included studies by creating knowledge graphs of the described mechanisms.</p><p><strong>Results: </strong>A total of 18 studies were included in this review. Findings consistently indicated that AAP exposure can worsen COVID-19 severity through two key mechanisms 1) increased expression of viral entry factors (<i>e.g.</i> angiotensin-converting enzyme 2 and transmembrane serine protease 2), facilitating infection, and 2) immune dysregulation, resulting in increased inflammation and oxidative stress. These key mechanisms were also identified in the INDRA networks. While studies commonly focused on particulate matter (n=15), similar effects were seen with ultrafine particles and ozone.</p><p><strong>Conclusion: </strong>These findings highlight the impact of AAP exposure on COVID-19 health outcomes on the molecular level. The findings of this review illustrate the urgent need for air quality improvements to help shape public health strategies to reduce and prevent future health impacts caused by AAP exposure.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 178","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250197","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}
Ivo Neto Silva, Claire Bennett, José Alberto Duarte, Karim Bendjelid
{"title":"Ultrasound innovations in diaphragm assessment: an integrative review of expanding clinical applications.","authors":"Ivo Neto Silva, Claire Bennett, José Alberto Duarte, Karim Bendjelid","doi":"10.1183/16000617.0089-2025","DOIUrl":"10.1183/16000617.0089-2025","url":null,"abstract":"<p><strong>Introduction: </strong>Diaphragm dysfunction is prevalent across various patient populations, requiring precise structural and functional assessment. Ultrasound, being bedside-accessible and radiation-free, has gained relevance for evaluating the diaphragm and other respiratory muscle. Recent advancements have introduced novel techniques that have expanding its assessment scope. This review aims to identify emerging ultrasound methods for quantitative diaphragm assessment in adults, emphasising reliability and clinical relevance.</p><p><strong>Methods: </strong>A systematic literature search was conducted using keywords related to the diaphragm, ultrasound techniques and innovation. We included original studies on adult participants using innovative ultrasound methods extending beyond conventional assessments. Studies lacking original data, case reports, animal studies and studies on automated analysis techniques were excluded. Screening and data extraction followed a structured process, with one researcher extracting data and a second verifying accuracy. Results were categorised by reliability and by physiological and clinical outcomes.</p><p><strong>Results: </strong>Of 1411 records screened, 288 full-text articles were reviewed, and 36 studies met inclusion criteria, with four additional studies identified <i>via</i> reference analysis. These studies, published between 2013 and 2024, explored seven innovative techniques: the area method, contrast-enhanced ultrasound, echogenicity/echodensity, excursion of the zone of apposition, shear wave/strain elastography, speckle tracking and pulsed-wave tissue Doppler imaging. Studies focused on both healthy subjects and critically ill, surgical and COPD patients.</p><p><strong>Conclusions: </strong>Recent ultrasound advancements enhance diaphragm assessment by evaluating muscle quality, functional mechanical properties and blood flow. These innovative methods also provide alternatives when conventional approaches are limited. Further research is essential to refine protocols, validate clinical applications and standardise assessments for broader implementation.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 178","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250226","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}
Jordi Almirall, Ramón Boixeda, Mari C de la Torre, Marcial Cariqueo, Antoni Torres
{"title":"Factors driving outcome variability in aspiration and community-acquired pneumonia: a meta-analysis.","authors":"Jordi Almirall, Ramón Boixeda, Mari C de la Torre, Marcial Cariqueo, Antoni Torres","doi":"10.1183/16000617.0037-2025","DOIUrl":"10.1183/16000617.0037-2025","url":null,"abstract":"<p><strong>Background: </strong>Aspiration community-acquired pneumonia (ACAP) is common among older adults and is associated with worse outcomes than nonaspiration community-acquired pneumonia (CAP). Understanding these differences is essential for improving patient care.</p><p><strong>Objectives: </strong>To determine the prevalence of ACAP among pneumonia patients and compare clinical outcomes, including hospital length of stay, intensive care unit (ICU) admissions and mortality rates, between patients with ACAP and those with CAP.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted following MOOSE (Meta-Analysis of Observational Studies in Epidemiology) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Literature searches in PubMed, Embase and Google Scholar from January 1995 to January 2024 identified studies involving adults diagnosed with CAP or ACAP. Data extraction and quality assessment were performed independently by two reviewers. Random-effects meta-analysis and meta-regression analyses were conducted to identify sources of heterogeneity.</p><p><strong>Results: </strong>49 samples from 44 studies were included, encompassing 1 277 615 older adults (mean age 80.2 years). The pooled prevalence of ACAP was 25% (95% CI 19-31) and higher in studies with a mean age of 70 years or older at 32% (95% CI 25-39). Compared to CAP patients, those with ACAP had significantly longer hospital stays (mean difference 4.92 days, 95% CI 4.71-5.14), increased ICU admissions (risk ratio 2.33, 95% CI 1.77-3.07), higher in-hospital mortality (risk ratio 2.14, 95% CI 1.73-2.65), higher 30-day mortality (risk ratio 2.56, 95% CI 2.12-3.1), higher 1-year mortality (risk ratio 1.96, 95% CI 1.44-2.66) and greater recurrence rates (risk ratio 1.75, 95% CI 1.44-2.66). Meta-regression identified publication year, patient age, study design, nursing home residency and compliance with therapeutic guidelines as significant moderators explaining heterogeneity.</p><p><strong>Conclusions: </strong>Patients with ACAP experience significantly worse clinical outcomes than those with CAP. These findings highlight the importance of early identification and management of aspiration risks, adherence to therapeutic guidelines and the need for standardised diagnostic criteria to improve outcomes in this vulnerable population.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 178","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250104","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":"Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.","authors":"Wei Fu, Lili Guan, Qi Liu, Zhefan Xie, Junting You, Rongchang Chen","doi":"10.1183/16000617.0069-2025","DOIUrl":"10.1183/16000617.0069-2025","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 178","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250261","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}
Pierre Tankéré, Léa Razakamanantsoa, Charles Khouri, Maxime Patout, Emeric Stauffer, Sebastien Baillieul, Thierry Petitjean, Jean Louis Pépin, Laure Peter Derex, Renaud Tamisier
{"title":"Impact of positive airway pressure for chronic hypercapnic respiratory failure on sleep quality: a systematic review and meta-analysis.","authors":"Pierre Tankéré, Léa Razakamanantsoa, Charles Khouri, Maxime Patout, Emeric Stauffer, Sebastien Baillieul, Thierry Petitjean, Jean Louis Pépin, Laure Peter Derex, Renaud Tamisier","doi":"10.1183/16000617.0090-2025","DOIUrl":"10.1183/16000617.0090-2025","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174437","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}
Martha Purcell, Jodie Ackland, Karl J Staples, Anna Freeman, Tom M A Wilkinson
{"title":"The respiratory tract virome: unravelling the role of viral dark matter in respiratory health and disease.","authors":"Martha Purcell, Jodie Ackland, Karl J Staples, Anna Freeman, Tom M A Wilkinson","doi":"10.1183/16000617.0284-2024","DOIUrl":"10.1183/16000617.0284-2024","url":null,"abstract":"<p><p>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 <i>Anelloviridae</i>, 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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174393","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}
Alícia Josa-Culleré, Aslihan Cakmak-Onal, Elena Gimeno-Santos, Victoria Alcaraz-Serrano, Joren Buekers, Laura Delgado-Ortiz, Alicia Marin, Diego A Rodríguez-Chiaradia, Judith Garcia-Aymerich, Ioar Rivas, Sarah Koch
{"title":"Effects of the inhaled dose of air pollution on health: a systematic review.","authors":"Alícia Josa-Culleré, Aslihan Cakmak-Onal, Elena Gimeno-Santos, Victoria Alcaraz-Serrano, Joren Buekers, Laura Delgado-Ortiz, Alicia Marin, Diego A Rodríguez-Chiaradia, Judith Garcia-Aymerich, Ioar Rivas, Sarah Koch","doi":"10.1183/16000617.0042-2025","DOIUrl":"10.1183/16000617.0042-2025","url":null,"abstract":"<p><p>The inhaled dose of air pollution (IDoAP) is an air pollution exposure quantification method that accounts for individuals' amount of inspired air (<i>i.e.</i> 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 O<sub>3</sub> (IDoAP-O<sub>3</sub>) (14 out of 25 studies) and particulate matter <2.5 µm in aerodynamic diameter (IDoAP-PM<sub>2.5</sub>) (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-O<sub>3</sub> was associated with reduced lung function: increasing IDoAP-O<sub>3</sub> by 150 μg·m<sup>-3</sup> led to a decrease in forced expiratory volume in 1 s (FEV<sub>1</sub>) of 0.27 L. This was driven by O<sub>3</sub> concentration, while increases in minute ventilation did not affect FEV<sub>1</sub> 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 O<sub>3</sub> and PM<sub>2.5</sub>; 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.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"34 177","pages":""},"PeriodicalIF":10.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174435","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":"Context-dependent roles of palmitoylation in acute respiratory distress syndrome: integrating inflammation, cell death and repair.","authors":"Qimin Ma, Yusong Wang, Feng Zhu","doi":"10.1183/16000617.0086-2025","DOIUrl":"10.1183/16000617.0086-2025","url":null,"abstract":"<p><p>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.</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/PMC12441815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080108","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}