ERJ Open Research最新文献

{"title":"Immortalisation of human airway epithelial cells for genome editing applications.","authors":"Emma J van Grinsven, Georgia N Ithakisiou, Pim Cleijpool, Bram M Bosch, Marinos Tziouvelis, Gimano D Amatngalim, Sam F B van Beuningen, Wilco Nijenhuis, Bahar Yetkin-Arik, Lukas C Kapitein, Jeffrey M Beekman, Anna Akhmanova","doi":"10.1183/23120541.01708-2025","DOIUrl":"https://doi.org/10.1183/23120541.01708-2025","url":null,"abstract":"<p><strong>Aim: </strong><i>In vitro</i> air-liquid interface (ALI) cultures of human airway epithelial cells are widely used to study respiratory biology and disease, as they recapitulate key features of the pseudostratified airway epithelium and reduce reliance on animal models and repeated patient biopsies. However, the limited proliferative capacity of primary airway basal cells restricts long-term studies and genome editing. This study aimed to generate stable, immortalised human airway basal cell lines that retain differentiation capacity and support genetic manipulation.</p><p><strong>Methods: </strong>Human airway epithelial basal cells from bronchial and nasal origin were immortalised by lentiviral expression of human telomerase reverse transcriptase (hTERT) followed by polyclonal expansion. A panel of cell lines derived from three independent nasal donors was established. Differentiation capacity was assessed in ALI cultures and compared with primary airway epithelial cells. Suitability for genetic manipulation was evaluated using lentiviral overexpression and CRISPR/Cas9-mediated gene knockout and knock-in strategies.</p><p><strong>Results: </strong>All immortalised cell lines displayed sustained proliferative capacity and efficiently differentiated into major airway epithelial cell types, including multiciliated and secretory cells. Differentiation patterns and functional characteristics closely resembled those of primary airway epithelial cultures. The cell lines supported efficient lentiviral transduction and CRISPR/Cas9-based genome editing, enabling stable gene overexpression, targeted gene disruption, and precise genomic modification.</p><p><strong>Conclusions: </strong>hTERT-immortalised human airway basal cell lines preserve key features of primary airway epithelium while enabling long-term culture and versatile genome editing. This resource provides a robust platform for airway biology research, disease modelling, and therapeutic development.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol consumption and mortality in COPD: a population-based cohort study.","authors":"Line Bjerrehave Nielsen, Signe Juul Riddersholm, Peter Ascanius Jacobsen, Jens Georg Hansen, Ulla Møller Weinreich","doi":"10.1183/23120541.00335-2026","DOIUrl":"https://doi.org/10.1183/23120541.00335-2026","url":null,"abstract":"<p><strong>Background: </strong>COPD is characterised by multimorbidity and high mortality. Although alcohol consumption is associated with comorbidities common in COPD, its impact on COPD outcomes is uncertain. We investigated associations between baseline alcohol consumption and 10-year mortality, stratified by COPD status and examined whether comorbidity prevalence differed across alcohol categories.</p><p><strong>Methods: </strong>COPD was defined by post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7; alcohol as ≤10 <i>versus</i> >10 units·week^-1. Comorbidities were ascertained from national registries. Cox models estimated mortality hazard ratios (HRs) adjusting for age, sex, smoking, education, body mass index and comorbidities. Inverse probability weighting addressed confounding. Logistic regression examined alcohol-comorbidity associations with false discovery rate correction.</p><p><strong>Results: </strong>In 2004-2006, 4528 Danish adults aged 45-84 years were recruited. Among 3468 participants with complete alcohol and COPD data (mean age 64 years; 65% male; 12% COPD), 593 deaths occurred over 10 years. Alcohol >10 units·week^-1 was not associated with mortality in unadjusted (HR 0.97 (95% CI 0.80-1.18)) or fully adjusted (HR 0.87 (95% CI 0.71-1.07)) models. COPD was strongly associated with mortality (adjusted HR 2.00 (95% CI 1.64-2.43)). No alcohol×COPD interaction was detected. Cardiovascular comorbidities were generally more prevalent among participants with COPD, although patterns varied. No associations between alcohol and individual comorbidities survived multiple testing correction.</p><p><strong>Conclusions: </strong>In this cohort with predominantly moderate consumption, alcohol intake >10 units·week^-1 was not associated with 10-year mortality in adults with or without COPD, whereas COPD conferred excess risk independent of comorbidity and lifestyle factors. These findings should not be interpreted as evidence that alcohol consumption is safe.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety and efficacy of lumacaftor/ivacaftor in children aged ≥12 months of age with cystic fibrosis: a 96-week open-label study.","authors":"Edith T Zemanick, Susanna A McColley, Rachel W Linnemann, Jonathan H Rayment, William T Harris, Bonnie Ramsey, Edward F McKone, Elizabeth Tullis, Marcus A Mall, Jennifer L Taylor-Cousar, Patrick R Sosnay, Neil Ahluwalia, Lingyun Liu, Mark Jennings, Margaret Rosenfeld","doi":"10.1183/23120541.00214-2026","DOIUrl":"https://doi.org/10.1183/23120541.00214-2026","url":null,"abstract":"<p><strong>Aims: </strong>We evaluated long-term safety and efficacy of lumacaftor (LUM)/ivacaftor (IVA) in children aged 12 to <24 months with cystic fibrosis (CF) homozygous for <i>F508del</i>.</p><p><strong>Methods: </strong>This international, 96-week, phase 3, open-label study enrolled children who completed parent study 809-122 (after 2-week washout) or were LUM/IVA-naïve. The primary end-point was safety and tolerability. The secondary efficacy end-point was change from baseline in sweat chloride concentration.</p><p><strong>Results: </strong>52 children (39 from 809-122; 13 LUM/IVA-naïve) participated. Mean±sd exposure to LUM/IVA was 597±162 days. All children had at least one adverse event, which were mostly mild (32.7%) or moderate (55.8%) in severity and consistent with common manifestations of CF or early childhood illnesses. One child (1.9%) discontinued study drug due to a treatment-emergent adverse event of increased alanine/aspartate aminotransferases that resolved after discontinuation. 12 (23.1%) children had serious adverse events, none of which was considered related to LUM/IVA. At week 96, mean absolute change from pre-treatment baseline in sweat chloride concentration was -21.0 (95% CI -27.6 to -14.3) mmol·L^-1. Growth parameters, which did not change significantly, were in the normal range throughout the 96-week treatment period. Improvements from baseline were observed in mean fecal elastase-1, fecal calprotectin, and serum immunoreactive trypsinogen.</p><p><strong>Conclusions: </strong>LUM/IVA remained generally safe and well-tolerated over 96 weeks. Improvements in sweat chloride concentration and markers of pancreatic function and intestinal inflammation were consistent with the parent study. These results demonstrate the long-term safety and efficacy of LUM/IVA in the 12 to 24-month-old population.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible baseline lung allograft dysfunction within the first year defines a high-risk and potentially reversible state after lung transplantation.","authors":"Michael Gerckens, Aorchie Siddiqui, Julian Schlatzer, Gamze Kasman, Paola Arnold, Jürgen Barton, Tobias Veit, Teresa Kauke, Christian Schneider, Sebastian Michel, Michael Zoller, Ali Önder Yildirim, Jürgen Behr, Nikolaus Kneidinger, Carlo Mümmler","doi":"10.1183/23120541.00548-2026","DOIUrl":"https://doi.org/10.1183/23120541.00548-2026","url":null,"abstract":"<p><strong>Background: </strong>Baseline lung allograft dysfunction (BLAD) has been associated with impaired long-term outcomes. However, BLAD within the first post-transplant year represents a potentially dynamic state. This is the first study evaluating a provisional Possible BLAD state, investigating risk factors and evolution to normal baseline lung function or confirmed BLAD.</p><p><strong>Methods: </strong>Possible BLAD was defined as failure to reach baseline forced expiratory volume in 1 s and forced vital capacity (FVC) ≥lower limit of normal within the first post-transplant year. Association of Possible BLAD and BLAD with allograft failure was investigated using multivariate time-dependent Cox regression analysis.</p><p><strong>Results: </strong>Among lung allograft recipients in the Munich Lung Transplant cohort, Possible BLAD occurred in a substantial share of lung allograft recipients. Possible BLAD was independently associated with a markedly increased risk of allograft failure (HR 4.76, 95% CI 2.64-8.61). Patients who recovered from Possible BLAD to normal baseline lung function had similar survival compared to lung allograft recipients directly reaching normal baseline lung function. A four-item clinical score at timepoint of first spirometry predicted recovery from possible BLAD (area under the curve (AUC) 0.83 for double lung allograft recipients, AUC 0.88 for single lung allograft recipients).</p><p><strong>Conclusion: </strong>Possible BLAD is associated with a markedly increased risk of mortality. A share of patients with Possible BLAD may recover to normal baseline lung function, while others progress to BLAD. Possible BLAD characterisation improves early risk stratification and might provide further insight into modifiable mechanisms underlying impaired allograft performance.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: A novel method to assess airway eosinophilia using sputum plugs.","authors":"Einat Fireman-Klein, Elizabeth Fireman","doi":"10.1183/23120541.00428-2026","DOIUrl":"https://doi.org/10.1183/23120541.00428-2026","url":null,"abstract":"<p><p><b>A simplified method to detect eosinophils from induced sputum</b> https://bit.ly/4eD4Ik2.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligonucleotide correction of a rare <i>CFTR</i> intron 12 splicing variant from a cystic fibrosis patient.","authors":"Aiguo Ni, Yan L Dang, Susan E Boyles, John T Minges, Deborah M Cholon, Marianne S Muhlebach, Carla M P Ribeiro, Martina Gentzsch, Silvia M Kreda","doi":"10.1183/23120541.00561-2026","DOIUrl":"https://doi.org/10.1183/23120541.00561-2026","url":null,"abstract":"<p><p><b>SSOs corrected rare <i>CFTR</i> splicing mutations unresponsive to modulators, restoring functional CFTR in patient airway epithelial cells - even under epithelial inflammation - highlighting SSOs as a promising precision therapy for cystic fibrosis</b> https://bit.ly/3U156kG.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to comment on: A novel method to assess airway eosinophilia using sputum plugs.","authors":"Kalliopi Domvri, Zil Patel, Manali Mukherjee","doi":"10.1183/23120541.00933-2026","DOIUrl":"https://doi.org/10.1183/23120541.00933-2026","url":null,"abstract":"<p><p><b>SSIMPLE histological processing complements the cytological gold standard by enabling FFPE archival storage, immunohistochemical validation and integration into existing pathology infrastructure, expanding access to airway inflammation monitoring</b> https://bit.ly/4vDKP27.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protracted lung repair after mild breakthrough Omicron SARS-CoV-2 infection: the storm beneath the calm.","authors":"Shreya M Kanth, Honghui Wang, Xin Tian, Julio A Huapaya, Salina Gairhe, Cumhur Y Demirkale, Maura J O'Neill, Thorkell Andresson, Junfeng Ma, Chunyan Hou, David Regenold, Anthony F Suffredini","doi":"10.1183/23120541.00350-2026","DOIUrl":"https://doi.org/10.1183/23120541.00350-2026","url":null,"abstract":"<p><p><b>Proteomic analysis of serial bronchoalveolar lavage from 24 patients recovering from mild, self-limited Omicron-variant SARS-CoV-2 infection revealed a protracted pulmonary host repair response at a median of 281 days after symptom onset</b> https://bit.ly/4uk5bwC.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heart failure-related pleural effusion: determinants of pleural drainage and predictors of mortality in a cohort of 1372 patients.","authors":"José M Porcel, Alena Belokopytova, Juan C Pineda, Laura Porcel, Silvia Bielsa","doi":"10.1183/23120541.01853-2025","DOIUrl":"https://doi.org/10.1183/23120541.01853-2025","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is one of the most common causes of pleural effusion, yet data on its management and prognosis in patients undergoing diagnostic thoracentesis are limited. The significance of invasive pleural interventions remains uncertain.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of a prospectively maintained pleural database, including consecutive patients with HF-related pleural effusion who underwent diagnostic thoracentesis. Clinical characteristics, pleural findings, need for invasive pleural management (therapeutic thoracentesis or indwelling pleural catheter (IPC)), and mortality were assessed. Fine-Gray competing-risk models and Cox regression were applied.</p><p><strong>Results: </strong>A total of 1372 patients were included (median age 85 years). During follow-up, 726 (53%) patients required at least one therapeutic thoracentesis and 81 (6%) received an IPC. In the competing-risk analysis, effusion size equal to or more than half hemithorax (sudistribution hazard ratio (sHR) 2.33), bilateral effusion (sHR 1.37), pleural fluid albumin >1.2 g·dL^-1 (sHR 1.23), and male sex (sHR 1.20) were independently associated with invasive pleural management. Median survival was 14 months, with mortality rates of 50% at 1 year and 70% at 2 years. Mortality was independently associated with advanced age, elevated serum N-terminal pro-brain natriuretic peptide, renal dysfunction, and hypoalbuminemia, whereas pleural characteristics and invasive pleural management were not.</p><p><strong>Conclusion: </strong>In patients with HF-related pleural effusion undergoing diagnostic thoracentesis, mortality is high and primarily driven by systemic markers of advanced HF. Invasive pleural interventions are frequently required in patients with large or bilateral effusions. In descriptive comparisons, survival was similar regardless of pleural intervention status, although causal inference is precluded by the observational design and time-dependent nature of intervention.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-related quality of life assessment using KBILD in fibrotic interstitial lung diseases receiving antifibrotic therapy: a prospective longitudinal study.","authors":"Yuzo Suzuki, Masato Kono, Sayomi Matsushima, Shinpei Kato, Kosuke Suzuki, Kazuki Tanaka, Keigo Koda, Toshihiro Masuda, Miho Kanai, Masaki Ikeda, Mitsuru Niwa, Yusuke Kaida, Hiroyuki Matsuda, Masanori Harada, Dai Hashimoto, Kazuhiro Asada, Koshi Yokomura, Mikio Toyoshima, Kazutaka Mori, Yusuke Inoue, Hideki Yasui, Hironao Hozumi, Masato Karayama, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Naoki Inui, Takafumi Suda","doi":"10.1183/23120541.00402-2026","DOIUrl":"https://doi.org/10.1183/23120541.00402-2026","url":null,"abstract":"<p><strong>Background: </strong>Patients with fibrotic interstitial lung diseases (ILDs) experience impaired health-related quality of life (HRQoL). The King's Brief Interstitial Lung Disease (KBILD) questionnaire was designed to evaluate disease-specific HRQoL; however, its practical application in real-world clinical settings has not been thoroughly investigated.</p><p><strong>Methods: </strong>This prospective longitudinal study included 289 patients with fibrotic ILD initiated antifibrotic therapy. Their HRQoL was evaluated using the KBILD questionnaire at baseline, 6 months and 1 year. A total of 289, 164 and 159 patients completed the KBILD assessment at the aforementioned time points, respectively. The associations between the KBILD scores, clinical parameters and mortality risk were evaluated.</p><p><strong>Results: </strong>The KBILD Total score demonstrated a moderate correlation with dyspnoea scale but a weak or no correlation with pulmonary function test parameters and ILD aetiology. Interestingly, more than 20% of the patients showed significant improvement (≥5 points) at 6 months and 1 year. A lower baseline KBILD Total score was associated with disease progression and reduced survival, independent of the ILD-gender-age-physiology index. In addition, longitudinal assessment showed that the cross-sectional KBILD Total score at 6 months and 1 year and longitudinal decreases in the KBILD Total score at 1 year were associated with increased mortality risk.</p><p><strong>Conclusion: </strong>Antifibrotic therapy has a positive impact on HRQoL in a subset of patients with fibrotic ILDs. Repeated KBILD assessment may aid in monitoring mortality risk, independent of lung function tests.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"12 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13699368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149264530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}