Stratified interventions in ARDS (EMINENT)
Lead Research Organisation:
University of Cambridge
Department Name: Medicine
Abstract
There is an urgent and unmet need to define disease pathogenesis in acute respiratory distress syndrome (ARDS), and to develop rapid diagnostics to aid patient stratification and support targeted intervention. This is a programmatic approach to define disease pathogenesis in ARDS, and to develop rapid diagnostics to aid patient stratification and support targeted intervention.
Technical Summary
WP1: ARDS: in whom to intervene? This will involve an unbiased informatics-based analysis of existing (HARP2, REST, MOSAIC, GALAXY, ARDS.NET) and new patient cohorts to define ARDS endotypes
WP2: ARDS: when to intervene? Undertake prospective analysis of trans-pulmonary cytokine, genomic/epigenomic and neutrophil and monocyte phenotyping/migration signatures, and novel imaging modalities (SPECT/CT, PET/CT) to define the optimal time for intervention in the above cohorts, and to develop rapid ('by lunchtime') diagnostic platforms. This WP will specifically test the concepts generated in well-established and highly refined animal, human lung slice and EVLP models of ALI
WP3: ARDS with what to intervene? The collaborative network established above will, together with GSK, be ideally positioned to deliver Phase IIa experimental POC studies, using existing assets in the specific subtypes identified; endpoints (e.g. vascular leak, cell migration, physiological indices, biomarkers) will be determined by the endotype under study
WP2: ARDS: when to intervene? Undertake prospective analysis of trans-pulmonary cytokine, genomic/epigenomic and neutrophil and monocyte phenotyping/migration signatures, and novel imaging modalities (SPECT/CT, PET/CT) to define the optimal time for intervention in the above cohorts, and to develop rapid ('by lunchtime') diagnostic platforms. This WP will specifically test the concepts generated in well-established and highly refined animal, human lung slice and EVLP models of ALI
WP3: ARDS with what to intervene? The collaborative network established above will, together with GSK, be ideally positioned to deliver Phase IIa experimental POC studies, using existing assets in the specific subtypes identified; endpoints (e.g. vascular leak, cell migration, physiological indices, biomarkers) will be determined by the endotype under study
Publications
Vogt KL
(2019)
The clinical consequences of neutrophil priming.
in Current opinion in hematology
Samanta RJ
(2019)
Translational Research in Intensive Care Unit: Novel Approaches for Drug Development and Personalized Medicine.
in Seminars in respiratory and critical care medicine
Vogt K
(2019)
The clinical consequences of neutrophil priming.
Mehta P
(2020)
Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities.
in The Lancet. Respiratory medicine
Thwaites R
(2021)
Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19
in Science Immunology
Bos LDJ
(2021)
Precision medicine in acute respiratory distress syndrome: workshop report and recommendations for future research.
in European respiratory review : an official journal of the European Respiratory Society
Stacey D
(2022)
Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.
in Nature communications
Dunmore B
(2023)
Reduced circulating BMP9 and pBMP10 in hospitalized COVID-19 patients
in Pulmonary Circulation
Description | Stratified interventions in ARDS: EMINENT ARDS Work Package 2. |
Amount | £952,329 (GBP) |
Funding ID | MR/X005070/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 12/2022 |
End | 11/2025 |
Description | Collaboration with GlaxoSmithKline |
Organisation | GlaxoSmithKline (GSK) |
Department | Research and Development GSK |
Country | United Kingdom |
Sector | Private |
PI Contribution | This programme grant is via the MRC-GSK EMINENT network. Alongside the programme is a GSK-NIHR BRC co-funded PhD clinical research training fellowship. |
Collaborator Contribution | GSK have provided expertise, technical support, compounds, training and hosting of research team members. The research fellow has spent 6 months FTE embedded at GSK R&D. |
Impact | Follow-on funding is pending. Publications about to be submitted, |
Start Year | 2018 |
Description | Rachel Chambers / UCL via EMINENT |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Partner in EMINENT-ARDS programme. |
Collaborator Contribution | Joint development/delivery of validation work stream for EMINET-ARDS programme, |
Impact | None as yet. |
Start Year | 2020 |