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


CONCLUSIONS
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.
Determann
Rogier M
RM
Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. r.m.determann@amc.uva.nl
Royakkers
Annick A N M
AA
Haitsma
Jack J
JJ
Zhang
Haibo
H
Slutsky
Arthur S
AS
Ranieri
V Marco
VM
Schultz
Marcus J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D012189:Retrospective Studies; D013990:Tidal Volume; D016896:Treatment Outcome; D014598:Uteroglobin / Q000097:blood
D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1; D037663:Pulmonary Surfactant-Associated Protein D; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C556389:SCGB1A1 protein, human; D014598:Uteroglobin