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Acute Lung Injury
COORDINATOR: DR . ANDRÉS ESTEBAN
The following should be mentioned among this year’s major achievements of the Corporate Re- search Programme (PCI) for Acute Lung Injury:
We have considerably improved knowledge of the epidemiology of both mechanical ventilation in general and of patients with ARDS. Two of the groups in the PCI thus continue to exploit the two
We have developed an important model by means of intravital microscopy imaging, to monitor the migration in the vessels and, through these, of previously marked monocytes. The model used was that of haemorrhage and reperfusion in mice in order to have a situation of transfusion-related acute lung injury (TRALI). At the same time, we
Scientific Programmes
prospectively collected databases existing in this respect in the world.
From the progression point in the diagnosis of ARDS, a phenotype associated with the presence of ARDS with Diffuse Alveolar Damage as op- posed to the ones which have another alteration such as pneumonia has been described for the first time. Since we have a huge base of tissues from 700 clinical autopsies, we have been able to use the gold standard of histological findings and thus be able to establish the different groups of ARDS.
We have also carried out functional studies using luciferase in vitro and EMSA in the characterisa- tion of polymorphisms and its association with vulnerability to developing ARDS in three can- didate genes: PI3 (peptidase inhibitor 3), S1PR3 (sphingosine 1- phosphate receptor 3) and GADD45a (growth arrest DNA damage inducible alpha). At the same time, we have found the pres- ence of microRNA 27a associated with the pres- ence of ARDS with hyaline membranes. Lastly, we have studied the presence of proteins in the alve- olar cell attachment as a marker of the increase in permeability and thus of Acute Lung injury, as well as the measurement of Tryptase as a marker of the development of pulmonary fibrosis induced by acute lung injury induced by sepsis. To this end we have included 500 patients with severe sep- sis and ALI/ARDS admitted to the Intensive Care Units of 20 Spanish hospitals. We are now analys- ing this valuable database.
have worked on acquiring images of lungs using PET and TAC, particularly for evaluating pulmo- nary oedema.
After developing the programme for monitor- ing asynchronies between the ventilator and the patient we proceeded to quantify and associate these with the most important outcomes, such as duration of the mechanical ventilation, failure of disconnection and mortality.
In the area of cell signals and therapeutic targets we analysed the cell activation of DAMP and the potential therapeutic benefits, as well as the possibility of acid sphingomyelin derived from ceramide in order to induce the production of in- flammatory mediators and pulmonary vascular dysfunction.
In the area of tissue repair we have managed to develop an animal model in the mouse, in which we analysed the local response after intratracheal installation of stem cells in a decellularised lung scaffold and we verified the effect in hypoxia and hyperoxia conditions of the lung. We also ana- lysed the resulting differentiation with different mechanical stimuli.
CIBERES I Annual report 2015 I 23