European Respiratory Journal最新文献

{"title":"Extracorporeal Photopheresis for the prevention of rejection after lung transplantation - a prospective randomized controlled trial.","authors":"Alberto Benazzo, Ara Cho, Sophia Auner, Stefan Schwarz, Zsofia Kovacs, Dariga Ramazanova, Vera Kolovratova, Manuela Branka, Gabriela Muraközy, Elisabeth Hielle-Wittmann, Clemens Aigner, Konrad Hoetzenecker, Thomas Wekerle, Nina Worel, Robert Knobler, Peter Jaksch","doi":"10.1183/13993003.00733-2024","DOIUrl":"https://doi.org/10.1183/13993003.00733-2024","url":null,"abstract":"<p><strong>Rationale: </strong>Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD).</p><p><strong>Objective: </strong>To investigate the efficacy of ECP as a prophylactic treatment to prevent acute cellular rejection (ACR), CMV infections and reduce the risk of CLAD.</p><p><strong>Methods: </strong>Single-center prospective randomized controlled trial conducted at Medical University of Vienna between 2018 and 2020. It included 31 COPD recipients per group. Treatment group underwent extracorporeal photopheresis in addition to standard triple-drug immunosuppression protocol after lung transplantation. Control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation.</p><p><strong>Results: </strong>In the control group, 19 patients (61.3%) achieved the primary combined endpoint, compared with only 6 patients (19.4%) in the treatment group (p<0.001). Freedom from high-grade ACR was significantly greater in the ECP group (p=0.045). Cumulative A scores were significantly lower in the ECP group than in the control group at 3 months (0.18±0.44 <i>versus</i> 0.56±0.94, p<0.05) and at 12 months (0.25±0.48 <i>versus</i> 1.0±1.45, p=0.002). The rate of infections was lower in the ECP group with 5 cases and 67 cumulative hospital days compared to 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at three years was significantly greater in the ECP group (p=0.015).</p><p><strong>Conclusion: </strong>Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784405","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":"Glycerolipids disrupt regulatory T-cells in asthma.","authors":"Fatma Betul Oktelik, Mehdi Benamar","doi":"10.1183/13993003.01386-2024","DOIUrl":"https://doi.org/10.1183/13993003.01386-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784629","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":"Is asthma remission an important clinical outcome in asthma management?","authors":"Marcia M M Pizzichini, Emílio Pizzichini","doi":"10.1183/13993003.01908-2024","DOIUrl":"https://doi.org/10.1183/13993003.01908-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784673","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":"LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T-cells.","authors":"Abudureyimujiang Aili, Yuqing Wang, Ying Shang, Lijiao Zhang, Huan Liu, Zemin Li, Lixiang Xue, Yahong Chen, Yongchang Sun, Xu Zhang, Rong Jin, Chun Chang","doi":"10.1183/13993003.01752-2023","DOIUrl":"10.1183/13993003.01752-2023","url":null,"abstract":"<p><strong>Background: </strong>The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms.</p><p><strong>Methods: </strong>Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms <i>in vivo.</i> The effects of LPG 18:0 on CD4⁺ T-cell differentiation, proliferation and apoptosis were assessed <i>in vitro</i> by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species and ATP production measurements. The intracellular mechanism of LPG 18:0 in regulatory T-cells (Tregs) was investigated using small-molecule inhibitors.</p><p><strong>Results: </strong>The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. <i>In vivo</i> and <i>in vitro</i> studies revealed that LPG 18:0 impaired naïve CD4⁺ T-cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG 18:0 treatment reduced the FOXP3 protein level <i>via</i> SIRT1-mediated deacetylation during Treg differentiation.</p><p><strong>Conclusions: </strong>This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function <i>via</i> the NAD⁺/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG 18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987722","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":"Uncovering early COPD? The T-slope as a novel CT biomarker for evaluating airway narrowing.","authors":"Miranda Kirby, Grace Parraga","doi":"10.1183/13993003.01849-2024","DOIUrl":"https://doi.org/10.1183/13993003.01849-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784729","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":"A novel <i>in vitro</i> tubular model to recapitulate features of distal airways: the bronchioid.","authors":"Elise Maurat, Katharina Raasch, Alexander M Leipold, Pauline Henrot, Maeva Zysman, Renaud Prevel, Thomas Trian, Tobias Krammer, Vanessa Bergeron, Matthieu Thumerel, Pierre Nassoy, Patrick Berger, Antoine-Emmanuel Saliba, Laetitia Andrique, Gaëlle Recher, Isabelle Dupin","doi":"10.1183/13993003.00562-2024","DOIUrl":"10.1183/13993003.00562-2024","url":null,"abstract":"<p><strong>Background: </strong>Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerous <i>in vitro</i> models of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems.</p><p><strong>Methods: </strong>We developed a so-called bronchioid model by encapsulating human bronchial adult stem cells derived from clinical samples in a tubular scaffold made of alginate gel.</p><p><strong>Results: </strong>This template drives the spontaneous self-organisation of epithelial cells into a tubular structure. Fine control of the level of contraction is required to establish a model of the bronchiole, which has a physiologically relevant shape and size. Three-dimensional imaging, gene expression and single-cell RNA-sequencing analysis of bronchioids made of bronchial epithelial cells revealed tubular organisation, epithelial junction formation and differentiation into ciliated and goblet cells. Ciliary beating was observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid could be infected by rhinovirus. An air-liquid interface was introduced that modulated gene expression.</p><p><strong>Conclusion: </strong>Here, we provide a proof of concept of a perfusable bronchioid with proper mucociliary and contractile functions. The key advantages of our approach, such as the air‒liquid interface, lumen accessibility, recapitulation of pathological features and possible assessment of clinically relevant end-points, will make our pulmonary organoid-like model a powerful tool for preclinical studies.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132270","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":"Airway-derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD.","authors":"Yan Hu, Qianjiang Hu, Meshal Ansari, Kent Riemondy, Ricardo Pineda, John Sembrat, Adriana S Leme, Kenny Ngo, Olivia Morgenthaler, Kellie Ha, Bifeng Gao, William J Janssen, Maria C Basil, Corrine R Kliment, Edward Morrisey, Mareike Lehmann, Christopher M Evans, Herbert B Schiller, Melanie Königshoff","doi":"10.1183/13993003.02071-2023","DOIUrl":"10.1183/13993003.02071-2023","url":null,"abstract":"<p><p>Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of COPD that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific subpopulation of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single-cell RNA sequencing and <i>in situ</i> localisation revealed that asATII cells co-express the alveolar marker surfactant protein C and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII subpopulation derived from club cells was also identified in mouse COPD models using lineage labelling. Human and mouse ATII subpopulations formed 80-90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987791","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":"A breath of the future: a novel human model for COPD and beyond.","authors":"Maja C Funk, Janna Nawroth, Mareike Lehmann","doi":"10.1183/13993003.01531-2024","DOIUrl":"https://doi.org/10.1183/13993003.01531-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784621","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":"Childhood interstitial lung disease survivors in adulthood: a European collaborative study.","authors":"Effrosyni D Manali, Matthias Griese, Nadia Nathan, Yurdagül Uzunhan, Raphael Borie, Katarzyna Michel, Nicolaus Schwerk, Justyna Fijolek, Elżbieta Radzikowska, Felix Chua, Rishi Pabary, Nesrin Mogulkoc, Cormac McCarthy, Maria Kallieri, Andriana I Papaioannou, Nural Kiper, Martina Koziar Vasakova, Ladislav Lacina, Maria Molina-Molina, Alba Torrent-Vernetta, Theofanis Tsiligiannis, Bulent Karadag, Maria Kokosi, Elisabetta A Renzoni, Coline Hm van Moorsel, Ilaria Campo, Elisabeth Bendstrup, Thomas Skovhus Prior, Antje Prasse, Francesco Bonella, Vincent Cottin, Rémi Diesler, Antoine Froidure, Lykourgos Kolilekas, Lampros Fotis, Konstantinos Douros, Athanasios G Kaditis, Florence Jeny, Simon Chauveau, Hilario Nunes, Azrine Dahbia, Francesca Mariani, Joanne J van der Vis, Karlijn Groen, Ela Erdem Eralp, Yasemin Gokdemir, Derya Kocakaya, Sehnaz Olgun Yildizeli, Ebru Yalçın, Nagehan Emiralioğlu, Halime Nayir Buyuksahin, Helen O'Brien, Oguz Karcıoglu, Demet Can, Alper Ezircan, Gokcen Kartal Ozturk, Nesrin Ocal, Hasan Yuksel, Sedef Narin Tongal, Martina Safrankova, Katerina Kourtesi, Camille Louvrier, Caroline Kannengiesser, Aurelie Fabre, Marie Legendre, Bruno Crestani, Petr Pohunek, Andrew Bush, Spyros A Papiris","doi":"10.1183/13993003.00680-2024","DOIUrl":"https://doi.org/10.1183/13993003.00680-2024","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD) is rarer in children (chILD) than adults, but with increasing diagnostic awareness, more cases are being discovered. chILD prognosis is often poor, but increasing numbers are now surviving into adulthood.</p><p><strong>Aim: </strong>To characterize chILD-survivors and identify their impact on adult-ILD centers.</p><p><strong>Methods: </strong>European study (34 adult-ILD and chILD centers) reporting incident/prevalent cases of chILD-survivors from January to July 2023. Epidemiological, clinical, physiological and genetic data were collected.</p><p><strong>Results: </strong>244 patients were identified with median (years) (IQR) age at diagnosis 12.5 (6-16), age at study inclusion 25 (22-33), 51% male, 86% non-smokers, median %-predicted FVC and DLCO 70 (47-89) and 48 (32-75) respectively; 32% were prescribed long-term oxygen; 227 (93%) were followed-up in adult centers whereas 17 (7%) never transitioned. Commonest diagnoses (82%) were chILD category B1, 35% (sarcoidosis, hemosiderosis, connective tissue disorders, vasculitis); A4, 21% (surfactant-related); B2, 14% (bronchiolitis obliterans, hypersensitivity pneumonitis); Bz, 13% (unclassified-ILD). Bz patients had the worst functional status. 60% of all patients were still being prescribed corticosteroids. Re-specification of diagnosis and treatment were made after transition for 9.8% and 16% of patients respectively. Not all chILD diagnoses were recognized in adult-ILD classifications.</p><p><strong>Conclusion: </strong>chILD survivors are seen in most adult-ILD centers and only a minority continue follow-up in pediatric centers. Survivors have a significant loss of lung function. The heterogeneity of their etiologies and therapeutic requirements has a real impact on adult-ILD centers. Re-specification of diagnosis and treatment may contribute to precision and personalization of management.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785027","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":"Relieving dyspnoea through the brain.","authors":"Andreas von Leupoldt, Carine Karachi, Valentina Jelinčić","doi":"10.1183/13993003.01828-2024","DOIUrl":"https://doi.org/10.1183/13993003.01828-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784679","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}