Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients

Abstract

Background: Preventing ventilator-associated lung injury (VALI) has become pivotal in mechanical ventilation of patients with acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS). In the present study we investigated whether plasma levels of lung-specific biological markers can be used to evaluate lung injury in patients with ALI/ARDS and patients without lung injury at onset of mechanical ventilation.

Methods: Plasma levels of surfactant protein D (SP-D), Clara Cell protein (CC16), KL-6 and soluble receptor for advanced glycation end-products (sRAGE) were measured in plasma samples obtained from 36 patients - 16 patients who were intubated and mechanically ventilated because of ALI/ARDS and 20 patients without lung injury at the onset of mechanical ventilation and during conduct of the study. Patients were ventilated with either a lung-protective strategy using lower tidal volumes or a potentially injurious strategy using conventional tidal volumes. Levels of biological markers were measured retrospectively at baseline and after 2 days of mechanical ventilation.

Results: Plasma levels of CC16 and KL-6 were higher in ALI/ARDS patients at baseline as compared to patients without lung injury. SP-D and sRAGE levels were not significantly different between these patients. In ALI/ARDS patients, SP-D and KL-6 levels increased over time, which was attenuated by lung-protective mechanical ventilation using lower tidal volumes (P = 0.02 for both biological markers). In these patients, with either ventilation strategy no changes over time were observed for plasma levels of CC16 and sRAGE. In patients without lung injury, no changes of plasma levels of any of the measured biological markers were observed.

Conclusion: Plasma levels of SP-D and KL-6 rise with potentially injurious ventilator settings, and thus may serve as biological markers of VALI in patients with ALI/ARDS.

Figure 1

Mechanical ventilation parameters. Mechanical ventilation parameters in patients with ALI/ARDS (circles) and without lung injury at onset of mechanical ventilation (squares). Open symbols: patients ventilated with a lung-protective mechanical ventilation strategy with lower tidal volumes; closed symbols: patients ventilated with a potentially lung-injurious strategy using conventional tidal volumes. V_T, tidal volume; P_max, maximum airway pressure.

Figure 2

Baseline biomarker levels and lung injury score. Scatter plots of baseline levels of surfactant protein D (SP-D), Clara cell protein (CC16), KL-6 and soluble receptor for advanced glycation end products (sRAGE) as a function of lung injury score (LIS). The correlation is expressed as Spearman's rho (ρ).

Figure 3

Biomarker levels per group at two time points. Levels of surfactant protein D (SP-D), Clara cell protein (CC16), KL-6 and soluble receptor for advanced glycation end products (sRAGE) in patients without lung injury at onset of mechanical ventilation (no lung injury) and ALI/ARDS patients (ALI/ARDS), ventilated with either lung-protective mechanical ventilation (open boxes) or potentially lung-injurious mechanical ventilation (grey boxes). In each group, the left bar represents T = 0 hours, the right bar represents T = 48 hours after inclusion. Box plots represent 25^th, 50^th and 75^th percentile; whiskers represent values within 10^th and 90^th percentile; "°" represent outliers and "*" represent extreme outliers. # P < 0.05 for difference in absolute values between groups at baseline; ‡ P < 0.05 for difference in increases over time between groups.