Pathogenetic Significance of Biological Markers of Ventilator-Associated Lung Injury in Experimental and Clinical Studies

Abstract

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. Keywords ARDS; critical care; ventilation; ventilator-induced lung injuryAlthough clinicians and researchers have been interested in ventilator-induced lung injury (VILI) for at least 30 years, the reduction in mortality associated with low tidal volume ventilation in patients with acute lung injury (ALI) and ARDS 1 has directed increasing scientific interest toward the mechanisms of VILI. One of the greatest difficulties in clinical studies has been distinguishing the underlying lung injury responsible for the patient's respiratory failure from the lung injury resulting from the particular settings of the mechanical ventilator. Consequently, investigators have searched for biological markers that will reflect ventilator-attributable lung injury. The term VILI generally refers to experimental models in which lung injury in induced directly by an injurious ventilation strategy. Ventilator-associated lung injury (VALI) refers to the additional injury imposed on a previously injured lung by mechanical ventilation in either the clinical setting or in experimental studies. For the purposes of this review, the term ventilator-attributable injury encompasses all of these types of injury. Researchers have used a variety of experimental models to determine the effects of mechanical ventilation or mechanical strain on the expression of biological markers of inflammation or Biologic Markers of Inflammation in Clinical StudiesThe 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 chemokines. Although none of these mediator...

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

“…These chemoattractants have been shown to be important mediators in the development of VILI (Frank et al, 2006) and to be elevated (IL-6) after injurious short-term ventilation in healthy mice (Allen et al, 2006). In line with results from others (Frank et al, 2005;Allen et al, 2006) application of RMs producing transient elevations in peak P ao did not increase cytokine concentrations in BALF.…”

Elevated Plasma and Alveolar Levels of Soluble Receptor for Advanced Glycation Endproducts Are Associated with Severity of Lung Dysfunction in ARDS Patients

“…It remains to be determined whether sRAGE is only a marker of lung injury or a causal factor, as for many other biomarkers (Latini et al 2004). Higher sRAGE levels were related to higher tidal volumes: even though patients with more severe lung injury might have been supported with lower tidal volumes (our ICU ventilation protocol only imposes to keep tidal volumes ≤ 6 ml/ kg), our finding may also suggest that sRAGE plays a role in one important cause of lung dysfunction associated with ALI/ARDS: ventilator-induced lung injury (VILI) (Frank et al 2006). Stretch and strain caused by mechanical ventilation on the stiff ALI/ARDS lungs are known to activate inflammation (VILI) through pro-inflammatory sensors (biotrauma) (Chen et al 2008) and direct cells wall disruption (barotrauma) (Sarge and Talmor 2009).…”

Sodium Nitrite Mitigates Ventilator-induced Lung Injury in Rats

“…This is in contrast to several studies suggesting release of proinflammatory cytokines in response to excessive mechanical strain by high tidal volumes contributes to VILI. 36 In a critical reappraisal of these data, Ricard et al pointed out that most of these studies were done in preinjured lungs or in ex vivo lung preparations. 37 Furthermore, they could not reproduce in vivo the increase in cytokine concentrations measured ex vivo in isolated, unperfused lungs.…”