Joint BTS/BALR/A+L UK Early Career Investigator Symposium最新文献

{"title":"T4 Novel lung organoid model reveals crucial role of lung resident mesenchymal stromal cells in COPD pathogenesis","authors":"DM Butler, I. Heijink, A. Krasnodembskaya","doi":"10.1136/thorax-2022-btsabstracts.4","DOIUrl":"https://doi.org/10.1136/thorax-2022-btsabstracts.4","url":null,"abstract":"T4 Figure 1Cellular condensation of primary distal lung cells;epithelial, endothelial, and mesenchymal stromal cells in Matrigel results in a large multicellular structure that matures over a period of 21 d to resemble the normal human alveoli. A Whole organoid imaging reveleas protruding bulbous structures projecting away from the main organoid body, are composed of SPC+ epithelial cells and are connected by a basic network of CD31+endothelial cells. Scale bar: 250 μm. Blue: DAPI, Green: SPC, Magenta: CD31. B Alveolar-like spheres are composed of SPC+ (green) and AQP5+ (red)cells. Scale bar: 100 μm. Blue: DAPI, Green: SPC, Red: AQP5. C Organoids formed with the seeding of MSCs isolated from healthy lungs (top) and MSCs isolated from lungs of COPD (bottom). Replacement of healthy MSCs with COPD MSCs results in loss of organoid symmetry and reduced size. Scale bar 1000 μm D HGF secretion levels are significantly lower in the organoids formed with COPD MSCs compared to organoids with healthy MSCs (P<0.05, Kurskal-Wallis)[Figure omitted. See PDF]ConclusionCondensation of primary pulmonary cells provides a physiologically relevant distal lung organoid model that features endothelial cell presence. COPD lung MSCs are not able to support growth of endothelial cells and induce irregular spatial organisation of alveolar epithelial cells.FundingMRC UK MR/S009426/1 to Dr. Anna KrasnodembskayaPlease refer to page A208 for declarations of interest related to this .","PeriodicalId":347633,"journal":{"name":"Joint BTS/BALR/A+L UK Early Career Investigator Symposium","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123060363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T2 Subphenotypes in patients with severe acute respiratory failure requiring extracorporeal membrane oxygenation","authors":"K. Reddy, JE Millar, M. Malfertheiner, P. Sinha, D. Antcliffe, C. Calfee, C. O’Kane, T. Müller, D. McAuley","doi":"10.1136/thorax-2022-btsabstracts.2","DOIUrl":"https://doi.org/10.1136/thorax-2022-btsabstracts.2","url":null,"abstract":"","PeriodicalId":347633,"journal":{"name":"Joint BTS/BALR/A+L UK Early Career Investigator Symposium","volume":"148 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129289509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T3 Altered neutrophil proteomes in COVID19 patients 29-days post hospital admission are associated with delayed recovery: results from the PREDICT-COVID19 study","authors":"M. Long, AJ Brenes, A. Howden, H. Keir, C. Rollings, Y. Giam, T. Pembridge, L. Delgado, H. Abo-Leyah, A. Lloyd, G. Sollberger, R. Hull, A. Gilmour, C. Hughes, S. Gallant, D. Cassidy, B. New, D. Connell, H. Richardson, A. Shoemark, AI Lamond, D. Cantrell, J. Chalmers","doi":"10.1136/thorax-2022-btsabstracts.3","DOIUrl":"https://doi.org/10.1136/thorax-2022-btsabstracts.3","url":null,"abstract":"Introduction and ObjectivesNeutrophils are increasingly recognised for a role in acute COVID19, contributing to hyperinflammatory responses, immunothrombosis and tissue damage. However, less is known about the cellular changes occurring within neutrophils in acute disease, as well as neutrophil function in patients recovering from COVID19. Mass spectrometry-based proteomics of neutrophils from hospitalised COVID19 patients sampled longitudinally was utilised to characterise these cells in both acute and long COVID19 (i.e. symptoms for ≥4 weeks).MethodsProspective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May 2020–December 2020). Patients were enrolled within 96 hours of admission, with longitudinal sampling up to day 29. Control groups comprised hospitalised patients with non-COVID19 acute respiratory infection and age-matched non-infected controls. Neutrophils isolated from peripheral blood were processed for mass spectrometry. COVID19 severity was defined using the WHO 7-point ordinal scale.Results84 COVID19 patients were included (mean age±SD 65.5±14.6 years;52.4% male), 91 non-COVID19 respiratory infection patients (age 65.7±16.7 years;49.5% male) and 42 non-infected controls (age 58.5±17.9;40% male). 1,748 proteins were significantly different (q-value≤0.05) in COVID19 neutrophils compared to those of non-infected controls. Major differences included a robust interferon response at baseline, with markers of neutrophil immaturity (CD10, CD71), increased neutrophil activation (CD64), and changes in metabolism which associated with COVID19 disease severity. Delayed recovery (WHO score 2–3) at day 29 was associated with significant changes in 1,107 proteins compared to the control population. Features of non-recovery included significantly reduced abundance of migratory receptors (e.g. C3AR1, LTB4R), integrins (CD11b, CD18), inhibitory molecules (e.g. SHP-1, SHIP-1) and indications of increased activation (CD64). Overall, ficolin and specific granule content was decreased in COVID19 patient neutrophils at day 29 compared with controls, however, comparing those who had recovered and those who had not, granule content was found to be significantly lower in the non-recovery group.ConclusionNeutrophils undergo significant changes in acute COVID19 associated with disease severity. Neutrophil proteomics revealed that these cells may have an ongoing role in non-recovered patients, including profiles associated with increased potential for neutrophil activation and reduced migratory capacity, highlighting neutrophils as potential therapeutic targets in long COVID19.","PeriodicalId":347633,"journal":{"name":"Joint BTS/BALR/A+L UK Early Career Investigator Symposium","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129001344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T1 Genetic overlap study between acute respiratory distress syndrome and idiopathic pulmonary fibrosis","authors":"B. Guillen-Guio, R. Allen, O. Leavy, T. Hernández-Beeftink, E. Suarez-Pajes, R. Jenkins, C. Flores, L. Wain","doi":"10.1136/thorax-2022-btsabstracts.1","DOIUrl":"https://doi.org/10.1136/thorax-2022-btsabstracts.1","url":null,"abstract":"Introduction and ObjectiveAcute respiratory distress syndrome (ARDS) is a critical lung condition induced by a systemic inflammatory response. A subset of ARDS patients can also develop pulmonary fibrosis (i.e. lung scarring). Idiopathic pulmonary fibrosis (IPF) is the most common cause of pulmonary fibrosis in the general population. Genome-wide association studies (GWAS) of IPF and post-sepsis ARDS suggest that these phenotypes could share genetic risk factors. Here we performed the first genetic overlap study between IPF and ARDS to identify shared genetic risk loci that might be informative about development of lung fibrosis after ARDS.MethodsWe used summary statistics from large meta-GWASs of IPF risk (4,125 cases, 20,464 controls) and post-sepsis ARDS (716 cases, 4,399 controls), as well as individual-level data from a subset of individuals from the ARDS GWAS (321 cases, 3,249 controls). We performed polygenic risk score (PRS) analyses to assess if IPF GWAS variants could be used to predict ARDS risk. We constructed PRSs as the weighted sum of variants reaching different p-value thresholds in the IPF meta-GWAS, and tested their association with ARDS risk, whilst adjusting for age, sex and population stratification. We also assessed individual genetic signals to identify variants shared between both traits. We conducted colocalisation analyses to determine whether the same causal variant was driving both phenotypes, and studied the association of overlapping variants with gene expression.ResultsThe PRS calculated from IPF variants that passed the best p-value threshold (i.e. p=0.0011) predicted ARDS risk (p=4.07x10-04, OR[95%CI]=1.24[1.10, 1.39]). We also found that the ARDS protective allele at HLA-DQA2 was associated with IPF risk (p=1.28x10-04) and that the IPF risk allele at ATP11A conferred protection from post-sepsis ARDS (p=0.003). The latter was associated with protection from severe COVID-19 in previous studies. Colocalisation analyses were inconclusive, likely due to the limited ARDS sample size.ConclusionsOur risk score analyses suggest that there may be shared biological processes underlying IPF and ARDS risk. However, we note opposite directions of effect on IPF and ARDS risk for some loci. Further studies are needed to assess if these results are also informative about fibrotic sequelae of ARDS.Please refer to page A208 for declarations of interest related to this .","PeriodicalId":347633,"journal":{"name":"Joint BTS/BALR/A+L UK Early Career Investigator Symposium","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124572530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T6 Elevated serum Cathepsin K is associated with disease activity in Lymphangioleiomyomatosis and Cathepsin K inhibition is beneficial in vitro and in vivo","authors":"S. Miller, R. Babaei‐Jadidi, D. Clements, VP Krymskaya, S. Johnson","doi":"10.1136/thorax-2022-btsabstracts.6","DOIUrl":"https://doi.org/10.1136/thorax-2022-btsabstracts.6","url":null,"abstract":"","PeriodicalId":347633,"journal":{"name":"Joint BTS/BALR/A+L UK Early Career Investigator Symposium","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133601962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}