Acute Lung Injury (ALI)

Coordinator: Dr. José Ángel Lorente Balanza

Biomarker Discovery and Innovative Therapies for Acute Respiratory Distress Syndrome (ARDS).

ARDS/ acute lung injury (ALI) is a lethal syndrome frequently developed by critically ill patients, characterized by a high mortality, prolonged ICU stay, lack of effective pharmacologic treatment, and, for those who survive their illness, slow recovery and prolonged rehabilitation. Thus ARDS is associated with an immense social and economic 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.

ARDS portrays: acute lung inflammation, endothelial and alveolar cell injury, alveolocapillary hyperpermeability pulmonary edema, and hallmark histological findings (diffuse alveolar damage, DAD); pulmonary vascular dysfunction and pulmonary hypertension and progression to pulmonary fibrosis.

However, genetic determinants, and mechanisms and effective therapies of these ominous pathophysiological changes are largely unknown, in clear contrast to the current state of knowledge in other areas of pulmonary medicine. Advances in this field are desperately needed. 

The present ALI line research project at CIBERES is to develop cutting edge research of excellence to accomplish objectives of clear translational relevance. Both investigators and clinicians feel the lack of knowledge in the field of ARDS, particularly the lack of ability to identify patients with the hallmark pathophysiology and histology of ARDS (alveolocapillary hyperpermeability and diffuse alveolar damage), to treat vascular dysfunction in the context of pulmonary hypertension, and to identify patients who develop or are likely to develop pulmonary fibrosis. Thus, the present research is aimed at answering specific questions of clinical interest by the collaboration of basic scientists, clinical investigators and clinicians.

The present project was prepared based on previous experience and results of the participating investigators within the Spanish Biomedical Research Network in Respiratory Diseases (CIBERES). Principal investigators leading the participating groups are internationally recognized experts in the area of respiratory failure, including genetic risk factors, epidemiology, mechanisms of lung injury, mechanisms of vascular dysfunction, tissue engineering, the use of mesenchymal stem cells for the treatment of the acute lung injury and cell-matrix crosstalk in lung repair.

 

Objectives

  1. Aims for the present project 2016-2019:
  2. To identify relevant genetic risk factors.
  3. To identify biomarkers of the pathophysiological changes associated with the syndrome (i.e., alveolocapillary hyperpermeability, DAD, pulmonary hypertension, fibrosis) based on miRNAs sequencing.
  4. To test targeted therapies based on biomarker discovery.
  5. To discover the relationship between pathophysiological and histological changes associated with the syndrome and advanced imaging techniques (e.g., FDG-PET-CT).
  6. To test the efficacy of new modes of mechanical ventilation and oxygenation.
  7. To define optimal conditions for the efficacy of novel cell based therapies.