title: Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury.
abstract: BACKGROUND
  Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury (ALI). The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation.
  
  
  METHODS
  A prospective observational cohort study was conducted in the intensive care unit of a tertiary care university hospital. Twenty-five intubated, mechanically ventilated patients with ALI were enrolled. Physiologic data and serum samples were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6, IL-8, intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons.
  
  
  RESULTS
  Before endotracheal intubation, all of the biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the spontaneously breathing patients with ALI. After intubation and the institution of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body weight), none of the biological markers was significantly increased at either an early (3 +/- 2 hours) or later (21 +/- 5 hours) time point. However, the levels of IL-8 were significantly decreased at the later time point (21 +/- 5 hours) after intubation. During the 24-hour period after intubation, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio significantly increased and the plateau airway pressure significantly decreased.
  
  
  CONCLUSIONS
  Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation. The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury. The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI.
authors.affiliation: The Cardiovascular Research Institute and the Departments of Medicine and Anesthesia, University of California, San Francisco, 505 Parnassus Avenue, M917, San Francisco, CA 94143-0624, USA. magdac72@yahoo.com
authors.forename: Magda
authors.initials: M
authors.lastname: Cepkova
authors.forename: Sandra
authors.initials: S
authors.lastname: Brady
authors.forename: Anil
authors.initials: A
authors.lastname: Sapru
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Gwynne
authors.initials: G
authors.lastname: Church
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines