Coordinator: Dr. José Ángel Lorente Balanza
Acute hypoxemic respiratory failure (AHRF) is a common condition in the Intensive Care Unit (ICU) that is associated with a high mortality rate. Unlike other acute conditions in critical care, AHRF lacks specific biomarkers, its pathogenesis is incompletely understood, and there is no known pharmacological treatment. On the other hand, the magnitude of the health care problem of AHRF for the National Health System is not known. Under the diagnosis of AHFR (and also under acute respiratory distress syndrome -ARDS-, a common related condition) different heterogenous subgroups of patients (subphenotypes) are included. This heterogeneity seems to contribute to the so far unsuccessful trials, as patients who do not share the same pathophysiology are not likely to respond to the same treatment. Thus there is an urgent need for advances in the understanding of the pathogenesis of the syndrome, the discovery of biomarkers, the definition of undisclosed subphenotypes, and the identification of novel therapeutic targets.
In the present grant we plan to (1) define the magnitude of the health problem of AHRF and its (evolving) treatment; (2) define the magnitude of COVID-19 as a major cause of AHRF; (3) better understand the syndrome, unraveling complex pathogenic mechanisms; (4) better identify the syndrome by the discovery of new biomarkers of lung injury; (5) better characterize the syndrome by the definition of subphenotypes that allow personalized precision medicine; (6) better treat AHRF by carrying out prospective randomized clinical trials.
Large observational studies will determine the magnitude of the health care problem of AHRF (incidence, long term outcomes, treatments received) collecting real world data (RWD) and real world evidence (RWE) on the effectiveness of the treatments used. Samples will be collected for further analysis. In addition, the existing Government funded project CIBERESUCICOVID will be completed within the present grant, as the large database of patients with COVID-19 admitted to the ICU continues to be analyzed.
Existing models of disease in which the investigators have ample experience (lung-in-a-chip, cell models, animal models of AHRF) will be used to define key pathogenic mechanisms related to the role of the extracellular matrix in the functionality of stem cells, coagulation activation and other cell biological processes, and the modulation of the function of key miRNAs.
Samples from human and preclinical studies will be used for analysis using -omic science (genomics, transcriptomics, proteomics) to determine biomarkers and define subphenotypes within AHRF.
Finally, PRCTs will be conducted to define the appropriate dose of dexamethasone in patients with AHRF (DEXA-REVISE-COVID-19 among others).
The successful achievement of the proposed objectives will imply break through advancements in the way AHRF is diagnosed, prognosticated an treated. The availability of biomarkers and the definition of subphenotypes will profoundly change clinical practice.
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Participant Group |
Participant Organisation |
Principal Investigator |
|
CB06/06/0026 |
Universidad de Barcelona |
Isaac Almendros |
|
CB06/06/1088 |
Fundación Canaria Instituto de Investigación Sanitaria de Canarias |
Jesús Villar |
|
CB06/06/1084 |
Universidad Complutense |
Francisco Pérez |
|
CB06/06/1090 |
Asociación Centro de Investigación Cooperativa en biomateriales, CIC biomaGUNE |
Jesús Ruiz |
|
CB06/06/1097 |
Fundación Instituto de Investigación e innovación Parc Taulí |
Lluis Blanch |
|
CB06/06/0028 |
Hospital Clinico y Provincial de Barcelona. |
Antonio Torres |
|
CB17/06/00021
|
Fundación para la Investigación e Innovacion Biosanitaria en el Principado de Asturias (FINBA) |
Guillermo Muñiz |
|
CB06/06/0044 |
Hospital Universitario de Getafe |
José A. Lorente |
