CRITICAL CARE

Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury

M D Eisner^1,2, P Parsons³, M A Matthay^1,4, L Ware⁵, K Greene⁶ the Acute Respiratory Distress Syndrome Network

¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, USA
² Division of Occupational and Environmental Medicine, Department of Medicine, University of California San Francisco, USA
³ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Fletcher Allen Health Care, University of Vermont, USA
⁴ Department of Anaesthesia, University of California, Cardiovascular Research Institute, San Francisco, USA
⁵ Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University, USA
⁶ Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, USA

Correspondence to:
Correspondence to:
Dr M D Eisner, Division of Occupational and Environmental Medicine & Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, 350 Parnassus Avenue, Suite 609, San Francisco, CA 94117, USA;
eisner{at}itsa.ucsf.edu

Background: Because injury to the alveolar epithelial barrier is a characteristic feature of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), plasma surfactant protein levels may have prognostic value. To test this hypothesis plasma surfactant proteins A and D (SP-A and SP-D) levels were measured in patients with ALI or ARDS enrolled in the NHLBI sponsored multicentre ARDS Network randomised controlled trial of a 6 ml/kg v 12 ml/kg tidal volume strategy.

Methods: Data from 565 participants in the clinical trial were used. Plasma levels of SP-A and SP-D were measured at baseline and on day 3 after the start of the mechanical ventilation protocol. The longitudinal impact of baseline plasma surfactant protein levels on clinical outcomes was examined by multivariate analysis, controlling for mechanical ventilation group, APACHE III score, and other clinical covariates. The effect of 6 ml/kg tidal volume ventilation on plasma SP-A and SP-D levels was evaluated using analysis of covariance.

Results: Baseline plasma SP-A levels were not related to any clinical outcome. In contrast, higher baseline plasma SP-D levels were associated with a greater risk of death (OR 1.21 per 100 ng/ml increment; 95% CI 1.08 to 1.35), fewer ventilator-free days (mean decrease -0.88 days; p=0.001), and fewer organ failure-free days (mean decrease -1.06 days; p<0.0001). The 6 ml/kg tidal volume strategy had no effect on the rise in plasma SP-A levels (p=0.91) but attenuated the rise in plasma SP-D levels (p=0.0006).

Conclusions: Early in the course of ALI/ARDS an increased level of plasma SP-D is associated with a worse clinical outcome. The 6 ml/kg tidal volume strategy attenuated the rise of SP-D early in the clinical course. Taken together, these observations indicate that plasma SP-D, a product of alveolar type II cells, is a valuable biomarker in ALI/ARDS.

Keywords: acute respiratory distress syndrome; acute lung injury; plasma surfactant associated proteins

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