European Respiratory Journal最新文献

{"title":"Survival benefit of tofacitinib in interstitial lung disease associated with anti-MDA5-positive dermatomyositis: a need for further validation.","authors":"Chih-Wei Tseng,James Cheng-Chung Wei","doi":"10.1183/13993003.00306-2025","DOIUrl":"https://doi.org/10.1183/13993003.00306-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"94 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming cystic fibrosis care: the impact of elexacaftor/tezacaftor/ivacaftor.","authors":"Alexander Moeller,Elias Seidl","doi":"10.1183/13993003.00793-2025","DOIUrl":"https://doi.org/10.1183/13993003.00793-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"679 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival trends in patients with chronic thromboembolic pulmonary hypertension: an observational study.","authors":"Takatoyo Kiko, Ryotaro Asano, Yusuke Yoshikawa, Hiroyuki Endo, Shinya Fujisaki, Ryo Takano, Mitsumasa Akao, Naruhiro Nishi, Hiroya Hayashi, Soshiro Ogata, Akiyuki Kotoku, Hiroki Horinouchi, Yosuke Inoue, Jin Ueda, Yoshimasa Seike, Akihiro Tsuji, Tetsuya Fukuda, Kunihiro Nishimura, Hitoshi Matsuda, Takeshi Ogo","doi":"10.1183/13993003.02268-2024","DOIUrl":"10.1183/13993003.02268-2024","url":null,"abstract":"<p><strong>Background: </strong>Treatment options for patients with chronic thromboembolic hypertension (CTEPH) have increased over the past decade. However, it is unknown whether the outcomes of patients with CTEPH have changed as well.</p><p><strong>Methods: </strong>This retrospective study analysed the data of 834 patients with CTEPH, categorised into early (April 1980-December 1999), middle (January 2000-September 2010) and current (October 2010-December 2023) eras. The primary end-point was all-cause mortality. Multivariable Cox proportional hazards models were used to assess changes in all-cause mortality after adjusting for confounding variables.</p><p><strong>Results: </strong>95, 210 and 529 patients were from the early, middle and current eras, respectively. The proportion of patients who did not receive CTEPH therapy decreased from 65% in the early era to 36% and 3% in the middle and current eras, respectively. Meanwhile, the adoption of multimodal treatment increased from 0% to 58% over time. The Kaplan-Meier analysis revealed significant improvements in overall survival (log-rank p<0.001). The 5-year survival rates improved from 68% in the early era to 85% and 93% in the middle and current eras, respectively. The adjusted hazard ratios for mortality were 0.291 (95% CI 0.154-0.550; p<0.001) for the early <i>versus</i> middle era, 0.447 (95% CI 0.249-0.804; p=0.007) for the middle <i>versus</i> current era and 0.130 (95% CI 0.067-0.254; p<0.001) for the early <i>versus</i> current era.</p><p><strong>Conclusion: </strong>The long-term prognosis of patients with CTEPH has significantly improved in recent decades.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572575","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":"Risk of rifampicin resistance emergence after incomplete first-line tuberculosis treatment.","authors":"Genevieve N Dupuis, Mariia Dolynska, Silvia S Chiang, C Robert Horsburgh, Helen R Stagg, Natasha R Rybak, Vasyl Petrenko, Helen E Jenkins","doi":"10.1183/13993003.00902-2025","DOIUrl":"10.1183/13993003.00902-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-33, inflammation and mucus in COPD: the final FRONTIER?","authors":"James D Chalmers,Merete B Long","doi":"10.1183/13993003.00831-2025","DOIUrl":"https://doi.org/10.1183/13993003.00831-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"109 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Inhibition of Epac1 Protects against Pulmonary Fibrosis by Blocking FoxO3a Neddylation.","authors":"Katherine Jankowski, Sarah E Lemay, Daniel Lozano-Ojalvo, Leticia Perez-Rodriguez, Mélanie Sauvaget, Sandra Breuils-Bonnet, Karina Formoso, Vineeta Jagana, Maria T Ochoa, Shihong Zhang, Javier Milara, Julio Cortijo, Irene C Turnbull, Steeve Provencher, Sebastien Bonnet, Jordi Ochando, Frank Lezoualc'h, Malik Bisserier, Lahouaria Hadri","doi":"10.1183/13993003.02250-2024","DOIUrl":"10.1183/13993003.02250-2024","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic Pulmonary Fibrosis (IPF) is marked by progressive lung scarring with no existing cure, emphasizing the need for new therapeutic targets. Current evidence suggests that cyclic adenosine monophosphate (cAMP) mitigates lung fibroblast proliferation <i>via</i> the PKA pathway, but the impact of Epac1, a cAMP-activated protein, on IPF remains unexplored.</p><p><strong>Objective: </strong>To investigate the role of Epac1 in IPF progression.</p><p><strong>Methods: </strong>We examined lung samples from IPF patients and controls, and from a bleomycin-induced mouse model of pulmonary fibrosis (PF). Epac1's effects were analysed in knock-out mice and through modulation using viral vectors. The Epac1-specific small compound inhibitor AM-001 was evaluated <i>in vitro</i> using lung fibroblasts from patients with IPF, <i>in vivo</i> in bleomycin mice, and <i>ex vivo</i> in IPF precision cut lung slices.</p><p><strong>Results: </strong>Increased Epac1 expression was observed in lung tissues from IPF patients, fibrotic fibroblasts, and bleomycin-challenged mice. Genetic or pharmacological inhibition of Epac1 with AM-001 decreased proliferation in normal and IPF fibroblasts, and reduced expression of pro-fibrotic markers such as α-SMA, TGF-β/SMAD2/3, and IL-6/STAT3 pathways. Epac1-specific inhibition consistently protected against bleomycin-induced lung injury and fibrosis, suggesting a significant therapeutic potential. Global gene expression profiling indicated reduced pro-fibrotic gene signature and neddylation pathway components in Epac1-deficient fibroblasts and human-derived lung cells. Mechanistically, the protective effects may involve inhibiting the neddylation pathway and preventing NEDD8 activation, which in turn reduces the degradation of FoxO3a by NEDD8. Additionally, these effects may be enhanced while also limiting the proliferation of lung-infiltrating monocytes.</p><p><strong>Conclusions: </strong>Our findings demonstrate that Epac1 regulates fibroblast activity in pulmonary fibrosis, and that targeting Epac1 with the pharmacological specific inhibitor AM-001 offers a promising therapeutic approach for treating IPF disease.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen-targeted PET/CT Imaging of Tuberculosis Patients.","authors":"Alvaro A Ordonez,Mboyo-di-Tamba Willy Vangu,Anisha Rajaratnam,Nomsa Mofokeng,Lungile Gabuza,Pholo Maenetje,Mariane Le Fur,Sydney B Montesi,Peter Caravan,Sara C Auld,Gregory P Bisson","doi":"10.1183/13993003.00195-2025","DOIUrl":"https://doi.org/10.1183/13993003.00195-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"37 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of infiltrating CD206-positive macrophages restricts progression of pulmonary lymphangioleiomyomatosis (LAM).","authors":"Heng-Jia Liu,Remi Diesler,Joelle Chami,Boxiang Wu,Heng Du,Yue Jin,Melissa Daou,Nicola Alesi,Damir Khabibullin,Caroline Leroux,Vincent Cottin,Lloyd G Cantley,Udo Rudloff,Elizabeth P Henske","doi":"10.1183/13993003.00084-2025","DOIUrl":"https://doi.org/10.1183/13993003.00084-2025","url":null,"abstract":"RATIONALELymphangioleiomyomatosis (LAM) is a low-grade neoplasm caused by the proliferation of tuberous sclerosis complex (TSC)1 or TSC2-deficient LAM cells, resulting in progressive cystic lung disease. The currently approved treatment for LAM delays disease progression but the disease recurs if treatment is discontinued. Therefore, new therapeutic targets and/or strategies are necessary for a cure. Immunosuppressive M2-like macrophages are involved in the progression of various cancers, but their role in the pathophysiology of LAM and as a putative therapeutic target is unknown.METHODSTo identify the different immune cells populations involved in LAM, we generated a single-cell transcriptomic map of pulmonary LAM. Interactions between macrophages and LAM cells were studied using the Visium spatial transcriptomic platform and immunofluorescence staining on human pulmonary LAM specimens. Direct co-culture models were used to characterize the influence of TSC2-deficient cells on macrophage differentiation. The efficacy of targeting M2-like macrophages was assessed in preclinical mouse models of TSC2-deficient subcutaneous tumors treated with RP-182, a synthetic peptide which reprograms macrophages towards an anti-tumor M1-like phenotype.RESULTSSingle-cell RNA-seq analysis revealed that the majority of macrophages in pulmonary LAM display immunosuppressive markers, including CD206/MRC1 and CD163. Spatial transcriptomic and immunofluorescence analyses showed that M2 macrophages are in close proximity to LAM cells and that LAM cells which are in close proximity to macrophages highly express macrophage homing factor chemokine ligand CXCL12. In vitro, co-culture of human and mouse macrophages with TSC2-deficient cells resulted in the upregulation of M2 markers expressed macrophages. Targeting M2 macrophages via treatment with the CD206 modulator RP-182 impaired the growth of TSC2-deficient tumors in vivo.CONCLUSIONLAM cells recruit and polarize macrophages towards an M2 phenotype. M2-like CD206high macrophages may represent a potential therapeutic target in LAM.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"149 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuated Benefit to Vasodilators in Pulmonary Arterial Hypertension with high HFpEF probability.","authors":"Yogesh N V Reddy,Robert P Frantz,Hilary M Dubrock,Anna R Hemnes,Evelyn M Horn,Teresa De Marco,Charles Burger,Stephen C Mathai,Steven M Kawut,Barry A Borlaug, ","doi":"10.1183/13993003.00880-2025","DOIUrl":"https://doi.org/10.1183/13993003.00880-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"22 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-derived biomarkers in bronchiectasis: identifying a common therapeutic target.","authors":"James D Chalmers,Marcus A Mall,Kim G Nielsen,Anne B Chang,Stefano Aliberti,Francesco Blasi,Brice Korkmaz,Natalie Lorent,Clifford C Taggart,Michael R Loebinger","doi":"10.1183/13993003.00081-2025","DOIUrl":"https://doi.org/10.1183/13993003.00081-2025","url":null,"abstract":"Bronchiectasis is a chronic respiratory disease that can lead to a substantial decline in lung function, ultimately leading to a significantly increased risk of morbidity and mortality. Despite the increasing global impact of bronchiectasis, no specific (or licensed) treatment for the disease currently exists, with most available therapies, though beneficial, focusing on symptom management and infection control. In part, the lack of specific treatments for bronchiectasis may be due to a lack of established biomarkers for the disease. Because bronchiectasis varies so widely in its clinical presentation and can be caused by various aetiologies, the establishment of validated biomarkers has proven challenging. However, identifying key biomarkers in bronchiectasis is crucial to developing appropriate diagnosis and management plans, as well as to measuring effective responses to treatment. While there is a multitude of potential biomarkers in bronchiectasis, almost all instances of bronchiectasis are underpinned by chronic neutrophilic inflammation. The imbalance in neutrophil serine proteases (NSPs) and their endogenous inhibitors has been strongly linked to the lung destruction, mucosal-related defects, infection and worsening of clinical outcomes that are frequently observed in bronchiectasis. In this review, we discuss the various biomarkers linked to bronchiectasis, with a specific focus on NSPs as the most validated biomarkers in bronchiectasis, given their marked role in the pathogenesis of the disease. Lastly, we touch on potential therapeutic approaches aimed at reducing NSP activity in bronchiectasis, showing that, to date, indirect NSP inhibition appears to be the strategy that most effectively addresses chronic neutrophilic inflammation in bronchiectasis.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"194 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}