Soluble Forms and Ligands of RAGE in ALI/ARDS (SoLiRAGE).
Condition: Acute Lung Injury; Acute Respiratory Distress Syndrome; Mechanical Ventilation
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
Study type: Observational

Summary: 
      RAGE, the receptor for advanced glycation end products, is a novel marker of alveolar
      epithelial type I cell injury. Soluble RAGE (sRAGE) is elevated in the plasma and in the
      pulmonary edema fluid from patients with ALI/ARDS, but one should acknowledge that the
      RAGE/NF-B axis is also involved in the pathophysiology of various other conditions. Few data
      are available about the levels of soluble forms and ligands of RAGE in the setting of
      ALI/ARDS. The purpose of this observational prospective study is to describe soluble forms
      (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in ICU patients with
      ALI/ARDS.
    

Detailed description: 
      BACKGROUND:

      The receptor for advanced glycation end products (RAGE) is now identified as a marker of
      alveolar type I cell injury. RAGE is a member of the immunoglobulin superfamily that acts as
      a multiligand receptor and is involved in propagating inflammatory responses. While the
      precise function of RAGE remains unclear, the elevated levels of RAGE, and its soluble
      isoform sRAGE, correlate with severity of ALI/ARDS in human and animal studies, and RAGE
      levels could reflect impaired alveolar fluid clearance. Frequently, the biology of RAGE
      coincides with settings in which ligands of the receptor accumulate, especially in a
      proinflammatory environment. More work is needed for us to understand the mechanisms by which
      RAGE is regulated during ALI/ARDS, especially with regard to the expression of its soluble
      forms and the involvement of its potential ligands.

      DESIGN NARRATIVE:

      This observational prospective clinical study will describe and compare soluble forms (sRAGE,
      esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in the alveolar edema fluid and in
      the plasma from ICU patients enrolled within the first 24 hours after onset of ALI/ARDS, and
      from patients under mechanical ventilation (control group).

      Edema fluid and plasma samples will be collected simultaneously on day 1, day 3 and day 6, in
      order to describe kinetics of evolution of soluble forms and ligands of RAGE levels.
      Undiluted pulmonary edema fluid samples will be collected in intubated patients only, and
      blood samples will be simultaneously gathered from indwelling arterial and central venous
      catheters. The concentrations of soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1,
      S100A12, AGEs) will be measured in duplicate by ELISA.
    

Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Defined population
      
Keywords: Receptor for advanced glycation end products (RAGE); Soluble RAGE (sRAGE); Endogenous secretory RAGE (esRAGE); High-mobility group box-1 protein (HMGB-1); Extracellular newly-identified RAGE-binding protein (EN-RAGE or S100A12); Advanced glycation endproducts (AGEs); Pentosidine; N--carboxymethyllysine; Acute lung injury (ALI); Acute respiratory distress syndrome (ARDS); Alveolar epithelium; Mechanical ventilation; Intensive Care Unit (ICU)