Dharmesh Hirani,Jaco Selle,Virta Wagde,Oleksiy Klymenko,Celien Kuiper-Makris,Soula Danopoulos,Michele Donato,Stefanie Preuss,Mark Preuss,Sana Mujahid,Christina Vohlen,Kerstin Wulf,Silke van Koningsbruggen-Rietschel,Parvesh Khatri,Thomas Wunderlich,Manuel Koch,Stefan Rose-John,Jennifer M S Sucre,Denise Al-Alam,Werner Seeger,Jörg Dötsch,Richard D Bland,Marlene Rabinovitch,Miguel A Alejandre Alcazar
{"title":"Targeting IL6-Edn1-FoxO1 axis enables lung growth in mechanically ventilated newborn mice.","authors":"Dharmesh Hirani,Jaco Selle,Virta Wagde,Oleksiy Klymenko,Celien Kuiper-Makris,Soula Danopoulos,Michele Donato,Stefanie Preuss,Mark Preuss,Sana Mujahid,Christina Vohlen,Kerstin Wulf,Silke van Koningsbruggen-Rietschel,Parvesh Khatri,Thomas Wunderlich,Manuel Koch,Stefan Rose-John,Jennifer M S Sucre,Denise Al-Alam,Werner Seeger,Jörg Dötsch,Richard D Bland,Marlene Rabinovitch,Miguel A Alejandre Alcazar","doi":"10.1183/13993003.01580-2024","DOIUrl":"https://doi.org/10.1183/13993003.01580-2024","url":null,"abstract":"RATIONALEMechanical ventilation (MV) is a life-saving treatment for preterm infants that often leads to bronchopulmonary dysplasia (BPD). We previously demonstrated a reduced number of alveolar epithelial cells with a depletion of alveolar epithelial type 2 cells (AT2) in lungs of infants with BPD.OBJECTIVEInvestigate and target the mechanisms by which MV causes an arrest of alveolarisation.METHODSExperimental mouse model of neonatal ventilation-induced lung injury (nVILI) in wildtype mice, Il6 null mice, and pharmacological inhibition of IL-6 and Endothelin receptors. Complimentary, precision-cut lung slices (PCLS) and primary cells were analysed. Moreover, lungs of infants with BPD were studied.RESULTSMV leads to an AT2 depletion and arrest of alveolar growth. Transcriptomic profiling, measurement of gene and protein expression, immunofluorescent staining as well as cell culture studies identified an IL-6-mediated expression of Endothelin-1 (Edn1) and a nuclear sequestration of the anti-proliferative transcription factor FoxO1 in AT2. These findings were confirmed using murine PCLS, lung epithelial cells and transgenic mice with inducible constitutive active FoxO1. In vivo, Il6 null mice and pharmacological inhibition of IL-6 or endothelin A receptor [ET(A)] and ET(B) prevented nuclear sequestration of FoxO1, enabling thereby lung growth of newborn mice exposed to MV.CONCLUSIONMV causes an arrest of alveolarisation in newborn mice through an IL-6-mediated activation of Edn1 signaling and nuclear sequestration of FoxO1 in AT2. Thus, this study provides rationale for considering pharmacological inhibition of IL-6 and/or endothelin receptors as a therapeutic strategy for preterm newborns at risk for VILI-associated lung growth arrest.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"54 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254584","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}
Na'ama Avitzur, Madelyn Knaub, Francesca Thornton-Wood, Simon R Johnson, Christopher J Ryerson, R Gísli Jenkins, Iain Stewart, Kerri A Johannson
{"title":"The Impact of Pulmonary Fibrosis on Sex and Sexual Function - A Multinational Mixed Methods Study.","authors":"Na'ama Avitzur, Madelyn Knaub, Francesca Thornton-Wood, Simon R Johnson, Christopher J Ryerson, R Gísli Jenkins, Iain Stewart, Kerri A Johannson","doi":"10.1183/13993003.01039-2025","DOIUrl":"https://doi.org/10.1183/13993003.01039-2025","url":null,"abstract":"<p><strong>Rationale: </strong>Sex is an important part of life for many adults, yet sexual function may be impacted by chronic respiratory diseases such as pulmonary fibrosis (PF).</p><p><strong>Objectives: </strong>This multinational study sought to characterize the impact of PF on sex and sexual function, using mixed quantitative and qualitative methodology.</p><p><strong>Methods: </strong>We analyzed data from a patient registry, a clinical study, an online survey, and patient interviews to accomplish our objective and develop a conceptual framework for describing the effects of PF on sex-related quality of life. These cohorts used three distinct questionnaires; University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ), Sheffield Profile for Assessment and Referral to Care (SPARC) questionnaire, and the Changes in Sexual Function Questionnaire (CSFQ) to assess sexual dysfunction, respectively. Individual patient interviews were conducted and qualitatively evaluated using thematic analysis.</p><p><strong>Findings: </strong>Dyspnea with sexual activity affected 2054/2759 (74%) of registry patients, associated with male sex, lower forced vital capacity (FVC%), lower diffusion capacity of the lung for carbon monoxide (DLCO%), and worse cough. Distress due to the effect of PF on their sex life was reported in 52/225 (23%) of the clinical cohort, associated with younger age, male sex, lower DLCO%, and worse cough. Sexual dysfunction was common, affecting 56/67 (83%) of female and 63/73 (86%) male survey respondents. Qualitative analysis of patient interviews identified several themes including sex life limitations, changes in inter-personal relationships, quality of life. All patients wanted to discuss sex with trusted healthcare providers.</p><p><strong>Conclusions: </strong>In this multinational study, patients with PF reported engaging in sex and sexual activities but were adversely impacted by the effect of PF on sex life, with both physical and psychological limitations. Sexual dysfunction was common, driven by multiple disease domains. Sexual health appears to be an important component of comprehensive patient care.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257624","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":"Characteristics, treatment, and lung function outcomes of pulmonary exacerbations in cystic fibrosis: insights from the BEAT-CF cohort.","authors":"Parveen Fathima,Edward Pan,Julie Marsh,Shivanthan Shanthikumar,Sheila Sivam,Adam Jaffe,Hiran Selvadurai,Ameneh Khatami,Geshani Jayasuriya,Richard Norman,Andrew Tai,Lucy Burr,Siobhain Mulrennan,Tom Snelling,André Schultz","doi":"10.1183/13993003.01349-2025","DOIUrl":"https://doi.org/10.1183/13993003.01349-2025","url":null,"abstract":"BACKGROUNDPulmonary exacerbations pose a significant clinical burden on people with cystic fibrosis (pwCF). Whether management of exacerbations should change in the context of modulator therapy is unclear. We describe the characteristics, treatment and lung function outcomes of pulmonary exacerbations requiring intravenous antibiotic therapy (PERITs) in a contemporary Australian cohort of pwCF, in an era of rapidly broadening access to modulator therapy.METHODSPwCF receiving care at 11 Australian specialist centres were prospectively enrolled between 14 October 2020 and 9 October 2024. Spirometry data and treatments received during a PERIT were collected systematically.RESULTSA total of 982 pwCF were enrolled, with 593 PERITs recorded in 323 individuals. The median age at PERIT start was 12 years (IQR:7-17) and the mean baseline ppFEV1 across PERITs was 80% (sd:21%). Approximately 62% (n=366) of PERITs occurred in people receiving modulator therapy. Intravenous tobramycin (63%) and piperacillin-tazobactam (43%) were the most frequently used antibiotics. Among participants with spirometry at baseline and at Day7 (n=296) or Day60 (n=383), 41% (n=120) and 44% (n=169) were below their baseline at Day7 and Day60 after commencing treatment, respectively; 8% were >10% below their baseline ppFEV1 at both timepoints. Recovery patterns were consistent regardless of baseline lung function, Pseudomonas aeruginosa colonisation, or modulator use.CONCLUSIONThe pattern and magnitude of lung function impairment during PERITs is similar among those receiving and not receiving modulator therapy. This underscores the continued need for evidence to help clinicians balance treatment burden against the risk of irreversible loss of lung function.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"25 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254582","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}
Catherine Drai,Hanneke J van der Woude,Anne J Lexmond,Tineke van den Hoorn,Peter G M Mol,Finbarr P Leacy,Agnieszka Przybyszewska,Bruno Sepodes,Thomas Castelnovo
{"title":"The European Medicines Agency's review of Kaftrio (elexacaftor-tezacaftor-ivacaftor): extending its use to all people with CF aged 2 years and older who do not have two class I CFTR variants.","authors":"Catherine Drai,Hanneke J van der Woude,Anne J Lexmond,Tineke van den Hoorn,Peter G M Mol,Finbarr P Leacy,Agnieszka Przybyszewska,Bruno Sepodes,Thomas Castelnovo","doi":"10.1183/13993003.01506-2025","DOIUrl":"https://doi.org/10.1183/13993003.01506-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"126 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254578","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}
Imran Howell,Mahdi Mahdi,Hafiz R Mahmood,Laura Bermejo-Sanchez,Catherine Borg,Sanjay Ramakrishnan,James Melhorn,Gabriel Lavoie,Nayia Petousi,Timothy S C Hinks,Mona Bafadhel,Ian D Pavord
{"title":"Exhaled nitric oxide (FeNO) and the response to prednisolone for asthma attacks in patients treated with anti-IL5/5Rα therapy: a prospective observational study.","authors":"Imran Howell,Mahdi Mahdi,Hafiz R Mahmood,Laura Bermejo-Sanchez,Catherine Borg,Sanjay Ramakrishnan,James Melhorn,Gabriel Lavoie,Nayia Petousi,Timothy S C Hinks,Mona Bafadhel,Ian D Pavord","doi":"10.1183/13993003.01229-2025","DOIUrl":"https://doi.org/10.1183/13993003.01229-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"29 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254583","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":"Large-scale proteomic profiling identifies distinct inflammatory phenotypes in Acute Respiratory Distress Syndrome (ARDS): A multi-center, prospective cohort study.","authors":"Mengna Lin,Feixiang Xu,Yiyu Deng,Ying Wei,Feng Shi,Yun Xie,Cuiying Xie,Chen Chen,Jianfeng Song,Yao Shen,Yiyan Lin,Hailin Ding,Yannan Zhou,Su Lu,Yumei Chen,Lulu Lan,Wenxin Zhao,Jing Zhu,Zhongshu Kuang,Wei Pang,Sijin Que,Xiaoyu Fang,Ran Ji,Chenyang Dong,Jiancheng Zhang,Qi Liu,Zhaocai Zhang,Chengjin Gao,Lei Chen,Yuanlin Song,Liying Zhan,Lihong Huang,Xueling Wu,Ruilan Wang,Zhenju Song, ","doi":"10.1183/13993003.00933-2025","DOIUrl":"https://doi.org/10.1183/13993003.00933-2025","url":null,"abstract":"BACKGROUNDHost responses during ARDS are highly heterogeneous, contributing to inconsistent therapeutic outcomes. Proteome-based phenotyping may identify biologically and clinically distinct phenotypes to guide precision therapy.METHODSIn this multicenter cohort study, we used latent class analysis (LCA) of targeted serum proteomics to identify ARDS phenotypes. Serum samples were collected within 72 h of diagnosis to capture early-phase profiles. Validation was conducted in external cohorts. Pathway enrichment assessed molecular heterogeneity. Lung CT scans were analyzed using machine learning-based radiomics to explore phenotypic distinctions. Heterogeneous treatment effects (HTEs) for glucocorticoids and ventilation strategies were evaluated using inverse probability of treatment weighting (IPTW) adjusted Cox regression. A multinomial XGBoost model was developed to classify phenotypes.RESULTSAmong 1048 patients, three inflammatory phenotypes (C1, C2, C3) were identified and validated in two independent cohorts. The phenotype C1 with a larger proportion of poorly/non-inflated lung compartments had the highest 90-day mortality, shock incidence, and fewest ventilator-free days, followed by C3, while C2 patients had the best outcomes (p<0.001). Phenotype C1 was characterized by intense innate immune activation, cytokine amplification, and metabolic reprogramming. Phenotype C2 demonstrated immune suppression, enhanced tissue repair, and restoration of anti-inflammatory metabolism. Phenotype C3, comprising the oldest patients, reflected an intermediate state with moderate immune activation and partial immune resolution. Glucocorticoids therapy and higher positive end-expiratory pressure (PEEP) ventilation improved 90-day outcomes in C1 but increased mortality in C2 patients (P interaction<0.05). Finally, a 12-biomarker classifier can accurately distinguish phenotypes.CONCLUSIONSWe identified and validated three proteome-based ARDS phenotypes with distinct clinical, radiographic, and molecular profiles. Their differential treatment responses highlight the potential of biomarker-driven strategies for ARDS precision medicine.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"114 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254581","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}
Eleni Bacopanos, Douglas L Forrester, Ella Girdler, Francesca Gonnelli, Jennifer K Quint, Vidya Navaratnam
{"title":"The increasing burden of bronchiectasis in the UK.","authors":"Eleni Bacopanos, Douglas L Forrester, Ella Girdler, Francesca Gonnelli, Jennifer K Quint, Vidya Navaratnam","doi":"10.1183/13993003.00909-2025","DOIUrl":"10.1183/13993003.00909-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948313","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":"Decoding the eosinophil connection: implications for precision treatment of emphysematous in COPD.","authors":"Wen Sun","doi":"10.1183/13993003.01403-2025","DOIUrl":"https://doi.org/10.1183/13993003.01403-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"80 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241003","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}