ABSTRACT
The acute respiratory distress syndrome (ARDS) was first described by Ashbaugh and colleagues in 1967. However, despite considerable efforts, early progress in treatment was slowed by lack of consistent definitions and appropriately powered clinical trials. In 1994, the American-European Consensus Conference on ARDS established criteria defining ARDS as well as acute lung injury (ALI). Additionally, the conference established research directives and international coordination of clinical studies. Current incidence of ALI in the United States is estimated at 200,000 cases per year with a mortality rate approaching 40%. Mechanical ventilation, using positive end-expiratory pressure and reduced tidal volumes and inspiratory pressures, along with improved supportive care has increased survival rates. However, to date, pharmacological therapies have failed to improve survival in multicenter clinical trials. This article focuses on clinical treatments for ALI that have been tested in phase II and III clinical trials as well as a discussion of potential future therapies.
KEYWORDS
Acute respiratory distress syndrome - pulmonary edema - alveolar fluid clearance
REFERENCES
-
1
Ashbaugh D G, Bigelow D B, Petty T L et al..
Acute respiratory distress in adults.
Lancet.
1967;
2
319-323
-
2
Bernard G R.
Acute respiratory distress syndrome: a historical perspective.
Am J Respir Crit Care Med.
2005;
172
798-806
-
3
Milberg J A, Davis D R, Steinberg K P et al..
Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993.
JAMA.
1995;
273
306-309
-
4
Bernard G R, Artigas A, Brigham K L et al..
The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.
Am J Respir Crit Care Med.
1994;
149
818-824
-
5
Rubenfeld G D, Caldwell E, Peabody E et al..
Incidence and outcomes of acute lung injury.
N Engl J Med.
2005;
353
1685-1693
-
6
Webb H H, Tierney D F.
Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure.
Am Rev Respir Dis.
1974;
110
556-565
-
7
Dreyfuss D, Soler P, Basset G et al..
High inflation pressure pulmonary edema: respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure.
Am Rev Respir Dis.
1988;
137
1159-1164
-
8
Dreyfuss D, Saumon G.
Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation.
Am Rev Respir Dis.
1993;
148
1194-1203
-
9
Hickling K G, Walsh J, Henderson S et al..
Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study.
Crit Care Med.
1994;
22
1568-1578
-
10
Brower R G, Shanholtz C B, Fessler H E et al..
Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients.
Crit Care Med.
1999;
27
1492-1498
-
11
Brochard L, Roudot-Thoraval F, Roupie E et al..
Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.
Am J Respir Crit Care Med.
1998;
158
1831-1838
-
12
Stewart T E, Meade M O, Cook D J et al..
Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group.
N Engl J Med.
1998;
338
355-361
-
13
Amato M B, Barbas C S, Medeiros D M et al..
Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.
N Engl J Med.
1998;
338
347-354
-
14
Moran J L, Bersten A D, Solomon P J.
Meta-analysis of controlled trials of ventilator therapy in acute lung injury and acute respiratory distress syndrome: an alternative perspective.
Intensive Care Med.
2005;
31
227-235
-
15
Eichacker P Q, Gerstenberger E P, Banks S M et al..
Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes.
Am J Respir Crit Care Med.
2002;
166
1510-1514
-
16
Petrucci N, Iacovelli W.
Ventilation with smaller tidal volumes: a quantitative systematic review of randomized controlled trials.
Anesth Analg.
2004;
99
193-200
-
17
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.
N Engl J Med.
2000;
342
1301-1308
-
18
Fan E, Needham D M, Stewart T E.
Ventilatory management of acute lung injury and acute respiratory distress syndrome.
JAMA.
2005;
294
2889-2896
-
19
Oba Y, Salzman G A.
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury.
N Engl J Med.
2000;
343
813
author reply 813-814
-
20
Brower R G, Matthay M, Schoenfeld D.
Meta-analysis of acute lung injury and acute respiratory distress syndrome trials.
Am J Respir Crit Care Med.
2002;
166
1515-1517
-
21
Dellinger R P, Carlet J M, Masur H et al..
Serviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.
Intensive Care Med.
2004;
30
536-555
-
22
Sevransky J E, Levy M M, Marini J J.
Mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome: an evidence-based review.
Crit Care Med.
2004;
32
S548-S553
-
23
Nahum A, Hoyt J, Schmitz L et al..
Effect of mechanical ventilation strategy on dissemination of intratracheally instilled Escherichia coli in dogs.
Crit Care Med.
1997;
25
1733-1743
-
24
Brower R G, Lanken P N, MacIntyre N et al..
Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.
N Engl J Med.
2004;
351
327-336
-
25
Lapinsky S E, Aubin M, Mehta S et al..
Safety and efficacy of a sustained inflation for alveolar recruitment in adults with respiratory failure.
Intensive Care Med.
1999;
25
1297-1301
-
26
Rimensberger P C, Cox P N, Frndova H et al..
The open lung during small tidal volume ventilation: concepts of recruitment and “optimal” positive end-expiratory pressure.
Crit Care Med.
1999;
27
1946-1952
-
27
Foti G, Cereda M, Sparacino M E et al..
Effects of periodic lung recruitment maneuvers on gas exchange and respiratory mechanics in mechanically ventilated acute respiratory distress syndrome (ARDS) patients.
Intensive Care Med.
2000;
26
501-507
-
28
Kloot T E, Blanch L, Melynne Youngblood A et al..
Recruitment maneuvers in three experimental models of acute lung injury: effect on lung volume and gas exchange.
Am J Respir Crit Care Med.
2000;
161
1485-1494
-
29
Brower R G, Morris A, MacIntyre N et al..
Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure.
Crit Care Med.
2003;
31
2592-2597
-
30
Marini J J.
Are recruiting maneuvers needed when ventilating acute respiratory distress syndrome?.
Crit Care Med.
2003;
31
2701-2703
-
31
Lessard M R, Guerot E, Lorino H et al..
Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome.
Anesthesiology.
1994;
80
983-991
-
32
Rappaport S H, Shpiner R, Yoshihara G et al..
Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure.
Crit Care Med.
1994;
22
22-32
-
33
Esteban A, Alia I, Gordo F et al..
Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure Collaborative Group.
Chest.
2000;
117
1690-1696
-
34
Kallet R H, Campbell A R, Dicker R A et al..
Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: a comparison between volume and pressure-regulated breathing modes.
Respir Care.
2005;
50
1623-1631
-
35
Zapol W M, Snider M T, Hill J D et al..
Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study.
JAMA.
1979;
242
2193-2196
-
36
Morris A H, Wallace C J, Menlove R L et al..
Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.
Am J Respir Crit Care Med.
1994;
149
295-305
-
37
Hemmila M R, Rowe S A, Boules T N et al..
Extracorporeal life support for severe acute respiratory distress syndrome in adults.
Ann Surg.
2004;
240
595-605
discussion 605-597
-
38
Meduri G U, Chinn A J, Leeper K V et al..
Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS: patterns of response and predictors of outcome.
Chest.
1994;
105
1516-1527
-
39
Meduri G U, Tolley E A, Chrousos G P et al..
Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids.
Am J Respir Crit Care Med.
2002;
165
983-991
-
40
Meduri G U, Headley S, Tolley E et al..
Plasma and BAL cytokine response to corticosteroid rescue treatment in late ARDS.
Chest.
1995;
108
1315-1325
-
41
Meduri G U, Headley A S, Golden E et al..
Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.
JAMA.
1998;
280
159-165
-
42
The National Heart L, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network .
Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. 10.1056/NEJMoa051693.
N Engl J Med.
2006;
354
1671-1684
-
43
Hamm H, Fabel H, Bartsch W.
The surfactant system of the adult lung: physiology and clinical perspectives.
Clin Investig.
1992;
70
637-657
-
44
Wright J R.
Pulmonary surfactant: a front line of lung host defense.
J Clin Invest.
2003;
111
1453-1455
-
45
Enhorning G, Duffy L C, Welliver R C.
Pulmonary surfactant maintains patency of conducting airways in the rat.
Am J Respir Crit Care Med.
1995;
151
554-556
-
46
Mercier C E, Soll R F.
Clinical trials of natural surfactant extract in respiratory distress syndrome.
Clin Perinatol.
1993;
20
711-735
-
47
Gregory T J, Steinberg K P, Spragg R et al..
Bovine surfactant therapy for patients with acute respiratory distress syndrome.
Am J Respir Crit Care Med.
1997;
155
1309-1315
-
48
Weg J G, Balk R A, Tharratt R S et al..
Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome.
JAMA.
1994;
272
1433-1438
-
49
Walmrath D, Grimminger F, Pappert D et al..
Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics.
Eur Respir J.
2002;
19
805-810
-
50
Walmrath D, Gunther A, Ghofrani H A et al..
Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis.
Am J Respir Crit Care Med.
1996;
154
57-62
-
51
Anzueto A, Baughman R P, Guntupalli K K et al..
Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group.
N Engl J Med.
1996;
334
1417-1421
-
52
Spragg R G, Lewis J F, Wurst W et al..
Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant.
Am J Respir Crit Care Med.
2003;
167
1562-1566
-
53
Spragg R G, Lewis J F, Walmrath H D et al..
Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.
N Engl J Med.
2004;
351
884-892
-
54
Willson D F, Thomas N J, Markovitz B P et al..
Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial.
JAMA.
2005;
293
470-476
-
55
Rossaint R, Falke K J, Lopez F et al..
Inhaled nitric oxide for the adult respiratory distress syndrome.
N Engl J Med.
1993;
328
399-405
-
56
Dellinger R P, Zimmerman J L, Taylor R W et al..
Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group.
Crit Care Med.
1998;
26
15-23
-
57
Troncy E, Collet J P, Shapiro S et al..
Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study.
Am J Respir Crit Care Med.
1998;
157
1483-1488
-
58
Michael J R, Barton R G, Saffle J R et al..
Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS.
Am J Respir Crit Care Med.
1998;
157
1372-1380
-
59
Taylor R W, Zimmerman J L, Dellinger R P et al..
Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial.
JAMA.
2004;
291
1603-1609
-
60
Lundin S, Mang H, Smithies M et al..
Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide.
Intensive Care Med.
1999;
25
911-919
-
61
McIntyre Jr R C, Pulido E J, Bensard D D et al..
Thirty years of clinical trials in acute respiratory distress syndrome.
Crit Care Med.
2000;
28
3314-3331
-
62
Holcroft J W, Vassar M J, Weber C J.
Prostaglandin E1 and survival in patients with the adult respiratory distress syndrome: a prospective trial.
Ann Surg.
1986;
203
371-378
-
63
Abraham E, Park Y C, Covington P et al..
Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo-controlled, randomized, double-blind, multicenter clinical trial.
Crit Care Med.
1996;
24
10-15
-
64
Abraham E, Baughman R, Fletcher E et al..
Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group.
Crit Care Med.
1999;
27
1478-1485
-
65
Bone R C, Slotman G, Maunder R et al..
Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group.
Chest.
1989;
96
114-119
-
66
Vincent J L, Brase R, Santman F et al..
A multi-centre, double-blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome.
Intensive Care Med.
2001;
27
1578-1583
-
67
Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network.
JAMA.
2000;
283
1995-2002
-
68
Bernard G R, Wheeler A P, Arons M M et al..
A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group.
Chest.
1997;
112
164-172
-
69
Domenighetti G, Suter P M, Schaller M D et al..
Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study.
J Crit Care.
1997;
12
177-182
-
70
Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome. The ARDS Network.
Crit Care Med.
2002;
30
1-6
-
71
Brochard L, Mancebo J, Wysocki M et al..
Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.
N Engl J Med.
1995;
333
817-822
-
72
Levitt M A.
A prospective, randomized trial of BiPAP in severe acute congestive heart failure.
J Emerg Med.
2001;
21
363-369
-
73
Ferrer M, Esquinas A, Leon M et al..
Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial.
Am J Respir Crit Care Med.
2003;
168
1438-1444
-
74
Hilbert G, Gruson D, Vargas F et al..
Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure.
N Engl J Med.
2001;
344
481-487
-
75
Antonelli M, Conti G, Bufi M et al..
Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial.
JAMA.
2000;
283
235-241
-
76
Confalonieri M, Calderini E, Terraciano S et al..
Noninvasive ventilation for treating acute respiratory failure in AIDS patients with Pneumocystis carinii pneumonia.
Intensive Care Med.
2002;
28
1233-1238
-
77
Wysocki M, Tric L, Wolff M A et al..
Noninvasive pressure support ventilation in patients with acute respiratory failure: a randomized comparison with conventional therapy.
Chest.
1995;
107
761-768
-
78
Antonelli M, Conti G, Rocco M et al..
A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure.
N Engl J Med.
1998;
339
429-435
-
79
Guerin C, Gaillard S, Lemasson S et al..
Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial.
JAMA.
2004;
292
2379-2387
-
80
Voggenreiter G, Aufmkolk M, Stiletto R J et al..
Prone positioning improves oxygenation in post-traumatic lung injury: a prospective randomized trial.
J Trauma.
2005;
59
333-341
discussion 341-333
-
81
Gattinoni L, Tognoni G, Pesenti A et al..
Effect of prone positioning on the survival of patients with acute respiratory failure.
N Engl J Med.
2001;
345
568-573
-
82
Curley M A, Hibberd P L, Fineman L D et al..
Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial.
JAMA.
2005;
294
229-237
-
83
Henderson-Smart D J, Bhuta T, Cools F et al..
Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants.
Cochrane Database Syst Rev.
2003;
(4)
CD000104
-
84
Bollen C W, van Well G T, Sherry T et al..
High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].
Crit Care.
2005;
9
R430-R439
-
85
Derdak S, Mehta S, Stewart T E et al..
High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial.
Am J Respir Crit Care Med.
2002;
166
801-808
-
86
Doctor A, Ibla J C, Grenier B M et al..
Pulmonary blood flow distribution during partial liquid ventilation.
J Appl Physiol.
1998;
84
1540-1550
-
87
Thomassen M J, Buhrow L T, Wiedemann H P.
Perflubron decreases inflammatory cytokine production by human alveolar macrophages.
Crit Care Med.
1997;
25
2045-2047
-
88
Hirschl R B, Tooley R, Parent A et al..
Evaluation of gas exchange, pulmonary compliance, and lung injury during total and partial liquid ventilation in the acute respiratory distress syndrome.
Crit Care Med.
1996;
24
1001-1008
-
89
Kawamae K, Pristine G, Chiumello D et al..
Partial liquid ventilation decreases serum tumor necrosis factor-alpha concentrations in a rat acid aspiration lung injury model.
Crit Care Med.
2000;
28
479-483
-
90
Hirschl R B, Croce M, Gore D et al..
Prospective, randomized, controlled pilot study of partial liquid ventilation in adult acute respiratory distress syndrome.
Am J Respir Crit Care Med.
2002;
165
781-787
-
91
Leach C L, Greenspan J S, Rubenstein S D et al..
Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The LiquiVent Study Group.
N Engl J Med.
1996;
335
761-767
-
92
Kacmarek R M, Wiedemann H P, Lavin P T et al..
Partial liquid ventilation in adult patients with the acute respiratory distress syndrome.
Am J Respir Crit Care Med.
2006;
173
882-889
-
93
Bernard G R, Vincent J L, Laterre P F et al..
Efficacy and safety of recombinant human activated protein C for severe sepsis.
N Engl J Med.
2001;
344
699-709
-
94
Abraham E, Laterre P F, Garg R et al..
Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.
N Engl J Med.
2005;
353
1332-1341
-
95
Finigan J H, Dudek S M, Singleton P A et al..
Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation.
J Biol Chem.
2005;
280
17286-17293
-
96
Choi G, Schultz M J, van Till J W et al..
Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection.
Eur Respir J.
2004;
24
786-789
-
97
Gunther A, Mosavi P, Heinemann S et al..
Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia: comparison with the acute respiratory distress syndrome.
Am J Respir Crit Care Med.
2000;
161
454-462
-
98
Schultz M J, Millo J, Levi M et al..
Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia.
Thorax.
2004;
59
130-135
-
99
van der Poll T, Levi M, Nick J A et al..
Activated protein C inhibits local coagulation after intrapulmonary delivery of endotoxin in humans.
Am J Respir Crit Care Med.
2005;
171
1125-1128
-
100
Nick J A, Coldren C D, Geraci M W et al..
Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis.
Blood.
2004;
104
3878-3885
-
101
Paine III R, Wilcoxen S E, Morris S B et al..
Transgenic overexpression of granulocyte macrophage-colony stimulating factor in the lung prevents hyperoxic lung injury.
Am J Pathol.
2003;
163
2397-2406
-
102
Presneill J J, Harris T, Stewart A G et al..
A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction.
Am J Respir Crit Care Med.
2002;
166
138-143
-
103
Perkins G D, McAuley D F, Richter A et al..
Bench-to-bedside review: beta2-agonists and the acute respiratory distress syndrome.
Crit Care.
2004;
8
25-32
-
104
Maris N A, de Vos A F, Dessing M C et al..
Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by healthy volunteers.
Am J Respir Crit Care Med.
2005;
172
878-884
-
105
Manocha S, Gordon A C, Salehifar E et al..
Inhaled beta-2 agonist salbutamol and acute lung injury: an association with improvement in acute lung injury.
Crit Care.
2006;
10
R12
-
106
Perkins G D, McAuley D F, Thickett D R et al..
The beta-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial.
Am J Respir Crit Care Med.
2006;
173
281-287
-
107
The National Heart L, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network .
Wiedeman HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury.
N Engl J Med.
2006;
354
2564-2575
-
108
The National Heart L, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network .
Wiedeman HP, Wheeler AP, Bernard GR, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.
N Engl J Med.
2006;
354
2213-2224
-
109
Matthay M A, Zimmerman G A, Esmon C et al..
Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group.
Am J Respir Crit Care Med.
2003;
167
1027-1035
Joseph E LevittM.D.
Stanford University Medical Center
300 Pasteur Dr., H3147, MC 5236, Stanford, CA 94305
eMail: josephlevitt@msn.com