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Lesión Pulmonar Aguda (LPA)
 
Coordinator: Andrés Esteban, Hospital Universitario de Getafe. Madrid
 

EARLY DIAGNOSIS AND NOVEL THERAPEUTIC STRATEGIES FOR ACUTE LUNG INJURY

Having a strong scientific interest, the present ALI CRP is endowed with a clear translational relevance, aiming at solving questions of great social impact. Indeed, most citizens will eventually require in their lifetime an intensive care unit (ICU) admission. About one third of them require mechanical ventilation, of which over two thirds have acute respiratory failure as the admitting diagnosis. Common causes of acute respiratory failure are the conditions termed acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The social and economic impact of ALI and ARDS is documented by the high associated mortality rate -around 50%-, as well as the important sequelae of these patients, that often require prolonged rehabilitation treatment. This high mortality is comparable to the mortality of other conditions such as acute myocardial infarction, cancer or sepsis. However, funding from public or private agencies in this area is far from enough. This paradox implies a huge social and economic problem, given the severity of the disease, and the elevated cost of treatment, rehabilitation and work loss. The insufficient research in this field will not help solve these nationwide problems. Specifically, the present corporative research project (CRP) is designed to help solving the clinical and social problem of the early diagnosis and treatment of ALI.

 Different groups of scientific excellence will participate in this research project, collaborating to accomplish a common objective: how to diagnose earlier and treat better patients with ALI and ARDS in order to decrease their high morbidity and mortality. Research questions include: (a) is there a specific diagnostic biomarker?; (b) which are the intracellular signalling pathways involved in the development and repair of ALI?; (c) which are the potential therapeutic targets based on involved pathways relevant to pathogenesis?; (d) can we define specific patient subgroups that could benefit from novel therapeutic approaches that will arise over the next 5 years?

 The different research groups will collaborate with an integrated systems biology approach. Biological samples from participating patients with ALI and ARDS (i. e., serum, BAL fluid, etc.) will be collected for use in future investigations. These samples will be stored in and managed by the CIBERES’ Biobank Platform.

 The CRP is built on a limited number of WPs, defined to orchestrate in an efficient manner the different research areas, aiming at the common objective of diagnosis and treatment of ALI/ARDS.

 

Aims and objectives:

1. To identify genes/processes that are deregulated in preclinical models of ALI (assessed by functional genomics), or that constitute hits in genome-wide association studies being conducted. To examine whether genetic variants of those genes are associated with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) development and outcome (mortality or protection). To find new enigmatic genes that can explain the diversity of clinical presentation of ALI/ARDS, the response to current medical treatment, and the individual’s genetic predisposition.

2. To discover biomarkers of ALI among the three most relevant families of markers (i.e., inflammation-cytokine, endothelial related and epithelial derived markers). Determine the utility of MRS and MS as biomarkers of ALI. To validate volatile organic compounds in airway fluid and exhaled breath samples collected by non-invasive or minimally invasive as biomarkers of ALI/ARDS. To determine specific biomarkers for the early detection of alterations in CNS function in ALI/ARDS at the local brain level (alterations in tissue architecture, and mapping of biological markers related to neuronal activation of early genes, apoptosis and inflammation); and to define their correlation with systemic biomarkers.

3. To demonstrate a key role of TLR/NLR receptor activation in the pathogenesis of ALI. These effects will be studied in animal models of ALI and in serum from patients with ALI, as well as in different cell types and in isolated ventilated perfused lung model.

4. To define the relationship of asynchronies to clinically relevant outcomes in patients with ALI, in order to define therapeutic targets based on ventilatory management and to define ventilatory management strategies

5. To explore lung repair mechanisms that are initiated immediately following the insult leading to ALI/ARDS (i.e. sepsis, VILI). To study interactions between initiating factors, structural pulmonary elements, and signalling pathways that are involved in lung repair.

To define biochemical factors determining changes in surfactant function and structure in a rat model of ALI. To define mechanisms of alveolar repair, by means of stem cells, in decellularized lung scaffolds and in a lung-on-a-chip model. To use of adult stem cells in treatment.

6.  To spread knowledge and evidence providing new insights and training on acute lung injury mechanisms and lung repair.

Tabla de proyectos y cronograma:

 

Line

Project

Groups

2011

2012

2013

2014

1

ALI-Mech

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1

ALI-ORG

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1

VILI-FIB

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1

ALI-Cells

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1

OLA

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2

ALI-EXP

6

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2

ALI-HUMANS

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

3

ARDS-Gen

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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