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Early Acute Lung Injury: Criteria for Identifying Lung Injury Prior to the Need for Positive Pressure Ventilation*

Levitt, Joseph E. MD, MS1; Calfee, Carolyn S. MD2; Goldstein, Benjamin A. PhD, MPH3; Vojnik, Rosemary MS1; Matthay, Michael A. MD2

doi: 10.1097/CCM.0b013e31828a3d99
Clinical Investigations

Objective: Mortality associated with acute lung injury remains high. Early identification of acute lung injury prior to onset of respiratory failure may provide a therapeutic window to target in future clinical trials. The recently validated Lung Injury Prediction Score identifies patients at risk for acute lung injury but may be limited for routine clinical use. We sought to empirically derive clinical criteria for a pragmatic definition of early acute lung injury to identify patients with lung injury prior to the need for positive pressure ventilation.

Design: Prospective observational cohort study.

Setting: Stanford University Hospital.

Patients: We prospectively evaluated 256 patients admitted to Stanford University Hospital with bilateral opacities on chest radiograph without isolated left atrial hypertension.

Interventions: None.

Measurements and Main Results: Of the 256 patients enrolled, 62 patients (25%) progressed to acute lung injury requiring positive pressure ventilation. Clinical variables (through first 72 hr or up to 6 hr prior to acute lung injury) associated with progression to acute lung injury were analyzed by backward regression. Oxygen requirement, maximal respiratory rate, and baseline immune suppression were independent predictors of progression to acute lung injury. A simple three-component early acute lung injury score (1 point for oxygen requirement > 2–6 L/min or 2 points for > 6 L/min; 1 point each for a respiratory rate ≥ 30 and immune suppression) accurately identified patients who progressed to acute lung injury requiring positive pressure ventilation (area under the receiver-operator characteristic curve, 0.86) and performed similarly to the Lung Injury Prediction Score. An early acute lung injury score greater than or equal to 2 identified patients who progressed to acute lung injury with 89% sensitivity and 75% specificity. Median time of progression from early acute lung injury criteria to acute lung injury requiring positive pressure ventilation was 20 hours.

Conclusions: This pragmatic definition of early acute lung injury accurately identified patients who progressed to acute lung injury prior to requiring positive pressure ventilation. Pending further validation, these criteria could be useful for future clinical trials targeting early treatment of acute lung injury.

Supplemental Digital Content is available in the text.

1Division of Pulmonary/Critical Care, Stanford University, Stanford, CA.

2Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, CA.

3Department of Medicine, Stanford University, Stanford, CA.

*See also p. 2046.

This study was performed at Stanford University Hospital.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Dr. Levitt received a research grant K23HL091334 from the National Heart, Lung and Blood Institute. Dr. Levitt also received support for traveling to meetings for the study: NIH/NHLBI Travel the International Conference of the American Thoracic Society to present data. Dr. Calfee received grant/pending: NIH, Flight Attendant Medical Reseach Institute, GlaxoSmithKline, board membership: Ikaria, GlaxoSmithKline, Cerus Corp. Dr. Goldstein received a grant from the NIH. Dr. Vojnik received a grant from the NIH-NIH K-23 award supplemented most of his time during preparation for this manuscript, employment: Boehringer-Ingelheim, InterMune. Dr. Matthay received a grant from the NHLBI, and is a consultant for GlaxoSmithKline.

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© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins