Chest
Volume 130, Issue 6, December 2006, Pages 1906-1914
Journal home page for Chest

Postgraduate Education Corner: Contemporary Reviews in Critical Care Medicine
Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

https://doi.org/10.1378/chest.130.6.1906Get rights and content

For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis.

Section snippets

Biologic Markers of Inflammation in Clinical Studies

The role of the innate immune response and inflammation in the pathogenesis of VILI has been widely studied in recent years. Although some have suggested that inflammation may not be integral to the initiation of VILI, clearly a preponderance of data in this field support a major pathogenetic role for inflammation and lung neutrophil recruitment. The majority of biological markers identified in plasma, serum, pulmonary edema fluid, and BAL fluid in experimental studies are cytokines and

Experimental Studies of Ventilator-Attributable Injury

In an effort to understand and extend data from clinical trials, many investigators have attempted to model ventilator-attributable injury under more controlled experimental conditions. One of the most commonly used models is the VILI model in which normal lungs are injured with overtly harmful high or low lung volumes. Others have attempted to model the effects of more physiologic ventilator settings on previously injured lungs. This type of model, termed VALI, may more directly mimic the

Clinical Implications

Measurement of biological markers in experimental and clinical studies has provided insight into the pathogenesis of VALI. Both clinical and experimental data have characterized VALI as a condition of ongoing lung inflammation resulting from overdistention of the lung and potentially from excessively low lung volume. Although experimental studies have not been entirely concordant with clinical studies, there are several remarkable similarities. Temporal changes in plasma levels of IL-6, IL-8,

References (64)

  • ParsonsPE et al.

    Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury

    Crit Care Med

    (2005)
  • StuberF et al.

    Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury

    Intensive Care Med

    (2002)
  • ListaG et al.

    Impact of targeted-volume ventilation on lung inflammatory response in preterm infants with respiratory distress syndrome (RDS)

    Pediatr Pulmonol

    (2004)
  • ImaiY et al.

    Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome

    JAMA

    (2003)
  • YeSQ et al.

    Pre-B-cell colony enhancing factor as a potential novel biomarker in acute lung injury

    Am J Respir Crit Care Med

    (2005)
  • TremblayL et al.

    Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model

    J Clin Invest

    (1997)
  • ChengKC et al.

    Ventilation with negative airway pressure induces a cytokine response in isolated mouse lung

    Anesth Analg

    (2002)
  • ChiumelloD et al.

    Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome

    Am J Respir Crit Care Med

    (1999)
  • ImaiY et al.

    Intratracheal anti-tumor necrosis factor-α antibody attenuates ventilator-induced lung injury in rabbits

    J Appl Physiol

    (1999)
  • TakataM et al.

    Intraalveolar expression of tumor necrosis factor-α gene during conventional and high-frequency ventilation

    Am J Respir Crit Care Med

    (1997)
  • NaikAS et al.

    Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung

    Am J Respir Crit Care Med

    (2001)
  • HaitsmaJJ et al.

    Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-α

    Intensive Care Med

    (2000)
  • MurphyDB et al.

    Adverse ventilatory strategy causes pulmonary-to-systemic translocation of endotoxin

    Am J Respir Crit Care Med

    (2000)
  • KorneckiA et al.

    Lung development and susceptibility to ventilator-induced lung injury

    Am J Respir Crit Care Med

    (2005)
  • WilsonMR et al.

    High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury

    J Appl Physiol

    (2003)
  • GueryBP et al.

    Ventilation-induced lung injury is associated with an increase in gut permeability

    Shock

    (2003)
  • RibeiroSP et al.

    Heat stress attenuates ventilator-induced lung dysfunction in anex vivorat lung model

    Am J Respir Crit Care Med

    (2001)
  • NarimanbekovIO et al.

    Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model

    Exp Lung Res

    (1995)
  • CarusoP et al.

    Low tidal volume ventilation induces proinflammatory and profibrogenic response in lungs of rats

    Intensive Care Med

    (2003)
  • VreugdenhilHA et al.

    Ventilator-induced heat shock protein 70 and cytokine mRNA expression in a model of lipopolysaccharide-induced lung inflammation

    Intensive Care Med

    (2003)
  • AllenGB et al.

    Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury

    Am J Physiol Lung Cell Mol Physiol

    (2006)
  • MerzU et al.

    Partial liquid ventilation reduces release of leukotriene B4and interleukin-6 in bronchoalveolar lavage in surfactant-depleted newborn pigs

    Pediatr Res

    (2002)
  • Cited by (93)

    • Investigation of association between IL-6 level, il6 and il6r variants and community acquired pneumonia among Iranian children <5 years

      2022, Human Gene
      Citation Excerpt :

      They suggested that IL-6 is the main factor for the chronicization of brucella infection(Lin et al., 2020). Among the clinical value of IL-6 in the lung diseases, it has been reported that this cytokine can be used as the early biomarkers of lung injury and predictive factors of prolonged mechanical ventilation, organ dysfunctions, morbidity and mortality in acute respiratory distress syndrome (ARDS) (Frank et al., 2006; Vaporidi et al., 2008). Based on the binding to its soluble (sIL-6R) or membrane-bound receptor (IL-6R), IL-6 can trigger pro-inflammatory or anti-inflammatory signaling pathways(Wolf et al., 2014).

    View all citing articles on Scopus

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    The authors have no conflicts of interest to disclose.

    This work was supported by National Institutes of Health grants HL69900 (Dr. Frank) and HL51856 (Dr. Matthay).

    View full text