European Respiratory Review最新文献

{"title":"The dipeptidyl peptidase 1 inhibition landscape in bronchiectasis and its future direction.","authors":"James D Chalmers, Raksha Jain, Anne E O'Donnell, Marcus A Mall, Patrick A Flume","doi":"10.1183/16000617.0213-2026","DOIUrl":"10.1183/16000617.0213-2026","url":null,"abstract":"<p><p>Bronchiectasis (BE) is a heterogeneous lung disease characterised by chronic neutrophilic inflammation. A \"vicious vortex\" develops through the interactions between neutrophilic inflammation, infection and impaired mucociliary clearance, leading to progressive structural lung damage and worsening lung function. As part of this neutrophilic inflammation, neutrophil serine proteases (NSPs) overwhelm their natural inhibitors, with high NSP levels being associated with pulmonary exacerbations in people with BE. NSPs, activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation in the bone marrow, are released from neutrophils at sites of inflammation. Pharmacological inhibition of DPP1 is a compelling approach to reduce neutrophilic inflammation in BE. Three DPP1 inhibitors have had favourable results in clinical studies for BE, namely brensocatib, florensocatib and verducatib, with recent approval of brensocatib, a first-in-class DPP1 inhibitor, in the US and Europe, providing a promising treatment option for people with BE. Many questions about DPP1 inhibition remain, including long-term efficacy and safety, and efficacy in people with cystic fibrosis, primary COPD and immunodeficiencies, who were generally excluded from prior large studies. Despite the availability of cystic fibrosis transmembrane conductance regulator modulator therapy, many people with cystic fibrosis continue to have pulmonary exacerbations. The inclusion of a broad population with a range of aetiologies is key in the development of DPP1 inhibitors to support access to treatment for all those who could benefit. This review explores the current DPP1 inhibition landscape, discussing the clinical studies to date for these three novel DPP1 inhibitors and the evolution of DPP1 studies in BE.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 182","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127121","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":"Inflammasomes in respiratory diseases: from disease pathogenesis to drug development and use of multi-omics.","authors":"Rebecca Shipley, Matthew B O'Rourke, Sobia Idrees, Annalicia Vaughan, Keshav Raj Paudel, Ashleigh M Philp, Ridhima Wadhwa, Vivek Dharwal, Elinor Hortle, Jaesung P Choi, Diana Quan, Gang Liu, Rosa Faner, Alen Faiz, Philip M Hansbro, Matt D Johansen","doi":"10.1183/16000617.0205-2026","DOIUrl":"10.1183/16000617.0205-2026","url":null,"abstract":"<p><p>Inflammasomes are pivotal for the initiation and control of host inflammatory responses. This is particularly important in the respiratory system due to its direct exposure to noxious environmental and infectious stimuli, which can cause local inflammation, tissue damage and impaired function. Inflammasomes are activated by a variety of processes that result in a loss of cellular homeostasis, leading to the oligomerisation of specific innate immune sensors. Inflammasome complex formation then results in a form of programmed cell death known as pyroptosis and release of cleaved active pro-inflammatory cytokines, interleukin (IL)-1β and IL-18, and the subsequent inflammatory cascade. While acute inflammasome activation can be protective in controlling infection, chronic inflammasome activation is detrimental and can lead to irreversible changes in the lung micro-environment such as chronic inflammation, emphysema, lung fibrosis and impaired gas exchange and lung function. In this review, we describe the role of inflammasomes in the pathogenesis of acute and chronic respiratory diseases, highlight currently available preclinical and clinically available therapies that regulate or inhibit inflammasome activation, and outline the use of multi-omics to identify novel inflammasome biomarkers and therapeutics.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 182","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127100","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":"Manual compared to automated closed-loop oxygen control strategies in hospitalised adults: a systematic review and meta-analysis.","authors":"Louis Kirton, Rowan Biggs, Neakiry Kivi, Francesca Lynch, Tanira Kingi, Ross Sayers, Jenny Sparks, Allie Eathorne, Mark Weatherall, Richard Beasley","doi":"10.1183/16000617.0167-2026","DOIUrl":"10.1183/16000617.0167-2026","url":null,"abstract":"<p><strong>Background: </strong>Closed-loop oxygen control (CLOC) systems improve accuracy of oxygen delivery compared with standard manual oxygen adjustment. Determination of their efficacy in delivering oxygen noninvasively to adults, using different delivery methods and across different hospital locations, would enhance clinical practice.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis, searching Medline, Embase, Scopus Basic and Advanced, and Cochrane databases. Randomised controlled trials comparing time spent within a target peripheral oxygen saturation (<i>S</i> _pO₂ ) range between CLOC and manual oxygen control in hospitalised adults (>18 years) were included. Outpatient studies and studies using mechanical ventilation were excluded. The primary outcome was proportion of time spent within a target <i>S</i> _pO₂ range. Meta-regression was performed for pre-determined study-level covariates, including oxygen delivery mode and locations of care.</p><p><strong>Results: </strong>The search identified 3777 papers; of these, seven were included, with 635 participants. The mean proportion of time spent within the target <i>S</i> _pO₂ range was between 81.2 and 94.9% for CLOC and 51.3-84.0% for manual oxygen control. The mean difference was 21.2% (95% CI 18.5-23.8, p<0.0001), favouring CLOC. Evidence of heterogeneity (I²=87.9) was explained by three studies using low-flow oxygen therapy, mean difference 30.9% (95% CI 27.0-34.8, p<0.0001); compared with four studies using high-flow nasal oxygen therapy, mean difference 12.7% (95% CI 9.1-16.4, p<0.001).</p><p><strong>Conclusions: </strong>CLOC improves adherence to a target <i>S</i> _pO₂ range compared to manual oxygen control and is an effective approach for achieving a target <i>S</i> _pO₂ range when delivering oxygen noninvasively in hospitalised adults.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 182","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127112","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":"Bridging bench and bedside: translational omics of <i>Pseudomonas aeruginosa</i> to validate physiologically relevant models of chronic respiratory infection in cystic fibrosis.","authors":"Merel Wauters, Laura Bollé, Eva Van Braeckel, Aurélie Crabbé","doi":"10.1183/16000617.0282-2025","DOIUrl":"10.1183/16000617.0282-2025","url":null,"abstract":"<p><p>While culturing the opportunistic pathogen <i>Pseudomonas aeruginosa</i> in standard bacterial culture media has provided fundamental insights into its pathological properties such as virulence and antibiotic resistance, growing evidence suggests that these conditions fail to accurately reflect the <i>in vivo</i> bacterial physiology. In the lungs of people living with cystic fibrosis (pwCF), where <i>P. aeruginosa</i> is a major contributor to the disease process, bacteria reside within a complex physicochemical environment that drives their behaviour. Until recently, efforts to evaluate how well laboratory models mimic these <i>in vivo</i> conditions were hampered by limited data on the physiology of <i>P. aeruginosa</i> during chronic cystic fibrosis (CF) lung infections. However, several omics-based studies have now successfully characterised <i>P. aeruginosa</i> from human CF sputum, revealing unique adaptation patterns associated within this niche. This data enables evaluating the physiological relevance of <i>in vitro</i> and <i>in vivo</i> model systems, hereby highlighting the usefulness (and limitations) of models that mimic aspects of the physicochemical <i>in vivo</i> environment for studying <i>P. aeruginosa</i> infections in CF. In this review, we summarise a range of models of <i>P. aeruginosa</i> infection, including artificial sputum medium, air-liquid interface cell culture, <i>ex vivo</i> pig lung and mouse models, that have been evaluated for their physiological resemblance using omics-based approaches. We also address the current lack of proteomic and metabolomic validation approaches and outline key considerations and future directions to guide the continued refinement of experimental model systems.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 182","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127116","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":"Effects of opioids and stimulants on the respiratory system.","authors":"Christina Lildharrie, Faith N Veenker, Kylee B Miller, Michele-Vera Yonga, Sarah Abey, Gene-Jack Wang, Sung Won Kim, Sukru B Demiral, Nora D Volkow","doi":"10.1183/16000617.0092-2026","DOIUrl":"10.1183/16000617.0092-2026","url":null,"abstract":"<p><p>Drug overdose remains an urgent public health concern as it is a leading cause of fatal injury in the United States, with approximately 90% being attributed to opioid-induced respiratory depression from synthetic opioids. This statistic is primarily driven by the rise in the use of fentanyl, a potent synthetic opioid and its increased use in combination with stimulant drugs. The rise in the combined use of opioids and stimulants raises questions about pharmacological and physiological interactions, and its implication for the treatment of their addictive consequences and of overdoses. Though opioid-related fatalities are due to respiratory depression and stimulant fatalities predominantly from cardiac disruption, co-use creates interactions that remain under studied. Similarly, how medications designed to treat opioid use disorder impact respiration has been mostly neglected. Here, we review preclinical and clinical studies on the effects of opioids and stimulants on respiration, focusing on brainstem respiratory nuclei, and explore implications for advancing prevention and treatment strategies for drug-related overdose.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 182","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127096","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":"Pulmonary arterial hypertension with signs of venous/capillary involvement in connective tissue diseases: paradigms and paradoxes.","authors":"Ghadi Zebian, Jessica Giordano, Peter Dorfmüller, Elisa Hivin, Nicolas Lamblin, Olivier Sitbon, Marc Humbert, Vincent Sobanski, Eric Hachulla, David Launay, François Pontana, David Montani, Sébastien Sanges","doi":"10.1183/16000617.0159-2026","DOIUrl":"10.1183/16000617.0159-2026","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) with features of venous and/or capillary involvement, formerly pulmonary veno-occlusive disease (PVOD), represents a rare and severe subset of pulmonary hypertension. While PVOD is typically idiopathic, heritable or drug/toxin-induced, \"PVOD-like\" features have long been recognised in PAH associated with connective tissue diseases (CTDs), especially systemic sclerosis (SSc). This review synthesises the available evidence on this phenotype, integrating published data with an unreported cohort of 25 patients. Venular remodelling is a frequent histological finding in SSc-PAH lung explants, but high-resolution computed tomography (HRCT) signs of PVOD are inconsistently observed at PAH presentation, reflecting a progression of the lung vasculopathy and/or an unmasking effect of pulmonary vasodilators. Patients often exhibit major functional limitation, profound impairment in gas transfer and severe haemodynamic compromise. Assessing venular involvement in SSc-PAH poses unique challenges, due to possible lung fibrosis on HRCT and differential diagnosis with an occult post-capillary component. Despite the lack of robust evidence, PAH-approved therapies are commonly used, although with caution due to a high risk of pulmonary oedema with pulmonary vasodilators. As these patients also display significant arteriolar involvement, which can benefit from these drugs, dedicated treatment strategies warrant further investigation. Prognosis remains dismal, with a 5-year survival around 45-50%. Similar PVOD-like patterns have also anecdotally been reported in systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome and inflammatory myopathies, with comparable features. Overall, PVOD-like disease in CTD-PAH constitutes a high-risk phenotype with unresolved pathogenic and management challenges, requiring refined patient stratification and improved therapeutic strategies.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 181","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029586","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":"Thymic neuroendocrine tumours: molecular landscape, immune microenvironment and therapeutic perspectives.","authors":"Jing Ding, Xuefeng Leng, Yongtao Han, Tongyu Lin","doi":"10.1183/16000617.0016-2026","DOIUrl":"10.1183/16000617.0016-2026","url":null,"abstract":"<p><strong>Background: </strong>Thymic neuroendocrine tumours (T-NETs) are rare, aggressive malignancies with distinct biology and poor outcomes. Current management is extrapolated from other neuroendocrine tumours (NETs), highlighting a critical need for a synthesised understanding of their unique molecular and immune landscape.</p><p><strong>Methods: </strong>We conducted a comprehensive narrative review (2000-2026) of T-NETs, interrogating PubMed, Embase, Web of Science and Scopus. Focus was placed on clinicopathology, molecular alterations, tumour immune microenvironment and therapeutic outcomes.</p><p><strong>Results: </strong>T-NETs encompass a spectrum from well-differentiated carcinoids to high-grade carcinomas. Their molecular drivers are grade-specific, featuring TP53 (tumour protein p53)/RB1 (retinoblastoma 1) loss and chromosomal instability in high-grade tumours, alongside prevalent chromatin remodelling and PI3K (phosphatidylinositol 3-kinase)-mTOR (mechanistic target of rapamycin) dysregulation. The immune microenvironment is predominantly \"inflamed\", with heterogeneous PD-L1 (programmed death-ligand 1)/VISTA (V-domain Ig suppressor of T-cell activation) expression and T-cell infiltration that is often restrained by a myeloid-rich stroma. For clinical management, surgical resection is curative for localised disease. In advanced stages, therapy is extrapolated from other NETs and includes somatostatin analogues (for somatostatin receptor-positive tumours), everolimus, temozolomide-based regimens and, in selected cases, peptide receptor radionuclide therapy. Immunotherapy and novel combinations represent emerging investigational avenues.</p><p><strong>Conclusion: </strong>T-NETs are biologically distinct thymic malignancies. Improved care will require thymus-specific molecular and immune profiling, standardised diagnostic criteria, and prospective collaborative studies to move beyond extrapolated treatment paradigms.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 181","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029757","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 ventricular-protective ventilation in acute respiratory distress syndrome: phenotypes, monitoring and ventilatory management.","authors":"Chengchao Peng, Le Yang, Yongran Wu, You Shang, Xiaojing Zou","doi":"10.1183/16000617.0038-2026","DOIUrl":"10.1183/16000617.0038-2026","url":null,"abstract":"<p><p>Despite the widespread implementation of lung-protective ventilation, mortality in acute respiratory distress syndrome (ARDS) remains substantial, underscoring the importance of extrapulmonary determinants of outcome. Right ventricular (RV) dysfunction is recognised as a frequent and clinically meaningful complication of ARDS, affecting a sizeable proportion of patients and consistently associated with adverse outcomes. ARDS-related pulmonary vascular injury, including hypoxic pulmonary vasoconstriction, hypercapnia and acidosis, microangiopathy, and an imbalance in vasoconstrictor/vasodilator signalling, reduces the functional pulmonary vascular bed and increases pulmonary vascular resistance, thereby imposing an acute afterload challenge on the thin-walled right ventricle. Mechanical ventilation may further exacerbate RV stress through alveolar overdistension, increased intrathoracic pressure and decreased venous return, promoting RV dilation, RV-pulmonary arterial uncoupling and circulatory collapse in severe cases. In this review, we summarise the pathophysiological basis of RV injury in ARDS and propose a physiology-informed clinical framework integrating RV phenotyping with multimodal monitoring. This includes echocardiography as the bedside cornerstone, selected invasive haemodynamic assessments and emerging noninvasive techniques such as electrical impedance tomography, as well as advanced cardiac imaging modalities and serological biomarkers for complementary assessment. We further discuss key components of RV-protective ventilation, including limitation of tidal volume and airway pressures, haemodynamics and recruitability-guided positive end-expiratory pressure titration, cautious use of permissive hypercapnia, avoidance of excessive mean airway pressure, prone positioning, appropriate application of spontaneous breathing and extracorporeal support to facilitate ultra-protective lung ventilation. Finally, we highlight unresolved clinical questions and emphasise the need for prospective studies incorporating standardised RV phenotypes and RV-centred end-points.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 181","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029625","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":"Maternal and fetal outcomes associated with CFTR modulator use during pregnancy: a scoping review.","authors":"Zihanjiao Wang, Rasa Ruseckaite, Aleksandar Dobric, Danni Li, Zhengzheng Liu, Peter Wark, Andre Schultz, Imogen Felton, Sian Bentley, Jane Davies, Jamie Duckers, Peter G Middleton, Jennifer L Taylor-Cousar, Luke Richardson, Daniel L Rolnik, Ellen Menkhorst, Elena K Schneider-Futschik","doi":"10.1183/16000617.0273-2025","DOIUrl":"10.1183/16000617.0273-2025","url":null,"abstract":"<p><p>With major therapeutic advances driven by cystic fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRm), increasing numbers of women with cystic fibrosis (CF) are living into adulthood and pursuing pregnancy. Women with CF may face pregnancy-related challenges that influence maternal and fetal outcomes. However, long-term data regarding the safety and effectiveness of CFTRm use during pregnancy remain limited.This scoping review aimed to evaluate the existing literature on the effects of CFTRm use in women with CF during pregnancy and the postpartum period, as well as the potential impact on the developing fetus. We analysed clinical studies, registry data and related literature published between 2003 and 2025 to assess reported differences in lung function, birth weight, pregnancy and neonatal complications, mode of delivery and screening biomarkers among pregnancies in women with CF treated with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor or elexacaftor/tezacaftor/ivacaftor, compared with pregnancies not exposed to CFTRm.Available evidence suggests that elexacaftor/tezacaftor/ivacaftor may improve maternal health through better lung function and nutritional status, while inadvertent fetal drug exposure has not been clearly associated with serious adverse outcomes. Reported fetal and neonatal outcomes following maternal CFTRm therapy have generally been reassuring. However, long-term effects in exposed children remain uncertain. There is also insufficient evidence to establish the safety of infant exposure or prolonged maternal CFTRm use during lactation. This review highlights the need for future studies evaluating dose optimisation, long-term follow-up of infants and children, and integration of registry data to better define the safety and effectiveness of CFTRm use during pregnancy.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 181","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029620","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":"The gut-lung axis in early life: microbiome-associated mechanisms and clinical relevance.","authors":"Lara Klischke, Alexandros Rahn, Ingmar Fortmann, Marie-Theres Dammann, Isabell Ricklefs, Fumi Sugihara, Kirsten Glaser, Claus Klingenberg, Christoph Härtel, Sabine Pirr","doi":"10.1183/16000617.0147-2026","DOIUrl":"10.1183/16000617.0147-2026","url":null,"abstract":"<p><p>The early-life microbiome is increasingly recognised as a contributor to immune maturation and respiratory health. Early-life microbial colonisation is highly dynamic and shaped by multiple factors. Recently, the gut-lung axis has emerged as a framework describing bidirectional communication between the intestinal microbiota and the respiratory system <i>via</i> microbial metabolites, immune mediators and neuroimmune pathways. Although current evidence is largely derived from studies of bacterial communities, emerging data suggest that other microbial components, including fungi and viruses, may also contribute to gut-lung interactions. This review synthesises current mechanistic and clinical evidence on the gut-lung axis with a specific focus on neonatology. We discuss how early microbiome composition may influence immune regulation, lung development and inflammatory response. Associations between intestinal microbiota alterations and major neonatal morbidities, including bronchopulmonary dysplasia, are discussed, as well as emerging evidence linking early-life microbial imbalance to long-term respiratory outcomes such as recurrent infections and asthma. We further examine emerging translational opportunities, including microbiome- and metabolome-based biomarkers for early risk stratification, and microbiota-targeted interventions. Attention is given to the strengths and limitations of the current evidence base, including the predominance of observational human studies and preclinical animal models. Overall, available evidence suggests that the developing microbiome represents a potentially important mediator of gut-lung communication in early life. However, substantial gaps remain regarding causality, underlying mechanisms and clinical applicability. Further longitudinal and interventional studies are needed to define the role of microbiome-targeted strategies in improving neonatal and long-term respiratory outcomes.</p>","PeriodicalId":12166,"journal":{"name":"European Respiratory Review","volume":"35 181","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029811","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}