Biomarkers of ALI/ARDS: Pathogenesis, discovery, and relevance to clinical trials

Seminars in Respiratory and Critical Care Medicine

Volumn 34, Issue 4, 2013, Pages 537-548

  Janz, David R ^a   Ware, Lorraine B ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

acute lung injury; acute respiratory distress syndrome; biomarker; genetics; genomics; metabolomics; proteomics

Indexed keywords

ADENOSINE; ANGIOPOIETIN 2; APOLIPOPROTEIN A1; BIOLOGICAL MARKER; CLARA CELL PROTEIN; GLUTATHIONE; HIGH MOBILITY GROUP B1 PROTEIN; INOSITOL; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 2 RECEPTOR; INTERLEUKIN 6; INTERLEUKIN 8; PHOSPHATIDYLSERINE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN C; PROTEIN S 100; SELECTIN; SOMATOMEDIN BINDING PROTEIN 3; SPHINGOMYELIN; SURFACTANT; THROMBOMODULIN; THROMBOPLASTIN; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN; VON WILLEBRAND FACTOR;

ACUTE LUNG INJURY; ADULT RESPIRATORY DISTRESS SYNDROME; ARTICLE; CAPILLARY WALL; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); DIAGNOSTIC VALUE; GENE EXPRESSION; INCIDENCE; INFLAMMATION; LUNG ALVEOLUS; LUNG ALVEOLUS EPITHELIUM; LUNG ENDOTHELIUM; MEASUREMENT; METABOLOMICS; OUTCOME ASSESSMENT; PATHOGENESIS; PRIORITY JOURNAL; PROGNOSIS; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEOMICS;

ACUTE LUNG INJURY; ANIMALS; BIOLOGICAL MARKERS; CLINICAL TRIALS AS TOPIC; GENE EXPRESSION PROFILING; HUMANS; METABOLOMICS; PATIENT SELECTION; PROGNOSIS; PROTEOMICS; RESPIRATORY DISTRESS SYNDROME, ADULT;

EID: 84881581885     PISSN: 10693424     EISSN: 10989048     Source Type: Journal    
DOI: 10.1055/s-0033-1351124     Document Type: Article

References (95)

1. Ware L. B., Matthay M. A. The acute respiratory distress syndrome. N Engl J Med: 2000; 342 18 1334 1349 (Pubitemid 30408719)
2. Rubenfeld G. D., Caldwell E., Peabody E., et al. Incidence and outcomes of acute lung injury. N Engl J Med: 2005; 353 16 1685 1693 (Pubitemid 41464707)
3. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther: 2001; 69 3 89 95
4. WHO International Programme on Chemical Safety Biomarkers in risk assessment: validity and validation. 2001. http://www.inchem.org/documents/ehc/ ehc/ehc155.htm
5. Eisner M. D., Parsons P., Matthay M. A., Ware L., Greene K. Acute Respiratory Distress Syndrome Network Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury. Thorax: 2003; 58 11 983 988 (Pubitemid 37392811)
6. McClintock D. E., Ware L. B., Eisner M. D., Wickersham N., Thompson B. T., Matthay M. A. National Heart, Lung, and Blood Institute ARDS Network Higher urine nitric oxide is associated with improved outcomes in patients with acute lung injury. Am J Respir Crit Care Med: 2007; 175 3 256 262 (Pubitemid 46203129)
7. Suratt B. T., Eisner M. D., Calfee C. S., et al. NHLBI Acute Respiratory Distress Syndrome Network Plasma granulocyte colony-stimulating factor levels correlate with clinical outcomes in patients with acute lung injury. Crit Care Med: 2009; 37 4 1322 1328
8. Ware L. B., Eisner M. D., Thompson B. T., Parsons P. E., Matthay M. A. Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med: 2004; 170 7 766 772 (Pubitemid 39298992)
9. Parsons P. E., Eisner M. D., Thompson B. T., et al. NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med: 2005; 33 1 1 6, discussion 230-232 (Pubitemid 40116529)
10. Ware L. B., Fang X., Matthay M. A. Protein C and thrombomodulin in human acute lung injury. Am J Physiol Lung Cell Mol Physiol: 2003; 285 3 L514 L521 (Pubitemid 37022850)
11. Parsons P. E., Matthay M. A., Ware L. B., Eisner M. D. National Heart, Lung, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol: 2005; 288 3 L426 L431 (Pubitemid 40229507)
12. Calfee C. S., Eisner M. D., Parsons P. E., et al. NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury. Intensive Care Med: 2009; 35 2 248 257
13. Calfee C. S., Ware L. B., Eisner M. D., et al. NHLBI ARDS Network Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury. Thorax: 2008; 63 12 1083 1089
14. Ware L. B., Fremont R. D., Bastarache J. A., Calfee C. S., Matthay M. A. Determining the aetiology of pulmonary oedema by the oedema fluid-to-plasma protein ratio. Eur Respir J: 2010; 35 2 331 337
15. Matthay M. A., Zemans R. L. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol: 2011; 6 147 163
16. Zimmerman G. A., Albertine K. H., Carveth H. J., et al. Endothelial activation in ARDS. Chest: 1999; 116 (1, Suppl): 18S 24S (Pubitemid 29340184)
17. Staub N. C. Pulmonary edema due to increased microvascular permeability. Annu Rev Med: 1981; 32 291 312
18. Fiedler U., Augustin H. G. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol: 2006; 27 12 552 558 (Pubitemid 44780853)
19. Parikh S. M., Mammoto T., Schultz A., et al. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med: 2006; 3 3 e46
20. Fiedler U., Reiss Y., Scharpfenecker M., et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med: 2006; 12 2 235 239 (Pubitemid 43214752)
21. Bhandari V., Choo-Wing R., Lee C. G., et al. Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nat Med: 2006; 12 11 1286 1293 (Pubitemid 44706931)
22. van der Heijden M., van Nieuw Amerongen G. P., Koolwijk P., van Hinsbergh V. W., Groeneveld A. B. Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patients. Thorax: 2008; 63 10 903 909
23. Gallagher D. C., Parikh S. M., Balonov K., et al. Circulating angiopoietin 2 correlates with mortality in a surgical population with acute lung injury/adult respiratory distress syndrome. Shock: 2008; 29 6 656 661 (Pubitemid 351769925)
24. Calfee C. S., Gallagher D., Abbott J., Thompson B. T., Matthay M. A. NHLBI ARDS Network Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance. Crit Care Med: 2012; 40 6 1731 1737
25. Langer H. F., Chavakis T. Leukocyte-endothelial interactions in inflammation. J Cell Mol Med: 2009; 13 7 1211 1220
26. Newman W., Beall L. D., Carson C. W., et al. Soluble E-selectin is found in supernatants of activated endothelial cells and is elevated in the serum of patients with septic shock. J Immunol: 1993; 150 2 644 654 (Pubitemid 23133642)
27. Gearing A. J., Newman W. Circulating adhesion molecules in disease. Immunol Today: 1993; 14 10 506 512 (Pubitemid 23301002)
28. Okajima K. Regulation of inflammatory responses by natural anticoagulants. Immunol Rev: 2001; 184 258 274 (Pubitemid 34123781)
29. Okajima K., Harada N., Sakurai G., et al. Rapid assay for plasma soluble E-selectin predicts the development of acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. Transl Res: 2006; 148 6 295 300 (Pubitemid 44880039)
30. Donnelly S. C., Haslett C., Dransfield I., et al. Role of selectins in development of adult respiratory distress syndrome. Lancet: 1994; 344 8917 215 219 (Pubitemid 24229007)
31. Franchini M., Lippi G. Von Willebrand factor and thrombosis. Ann Hematol: 2006; 85 7 415 423 (Pubitemid 44283106)
32. Rubin D. B., Wiener-Kronish J. P., Murray J. F., et al. Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest: 1990; 86 2 474 480 (Pubitemid 20271879)
33. Ware L. B., Conner E. R., Matthay M. A. von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury. Crit Care Med: 2001; 29 12 2325 2331 (Pubitemid 34038167)
34. Bajaj M. S., Tricomi S. M. Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome. Intensive Care Med: 1999; 25 11 1259 1266
35. Moss M., Ackerson L., Gillespie M. K., Moore F. A., Moore E. E., Parsons P. E. von Willebrand factor antigen levels are not predictive for the adult respiratory distress syndrome. Am J Respir Crit Care Med: 1995; 151 1 15 20
36. Muller W. A. Mechanisms of transendothelial migration of leukocytes. Circ Res: 2009; 105 3 223 230
37. Conner E. R., Ware L. B., Modin G., Matthay M. A. Elevated pulmonary edema fluid concentrations of soluble intercellular adhesion molecule-1 in patients with acute lung injury: biological and clinical significance. Chest: 1999; 116 (1, Suppl): 83S 84S (Pubitemid 29340222)
38. McClintock D., Zhuo H., Wickersham N., Matthay M. A., Ware L. B. Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury. Crit Care: 2008; 12 2 R41
39. Flori H. R., Ware L. B., Glidden D., Matthay M. A. Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med: 2003; 4 3 315 321
40. Medford A. RL, Millar A. B. Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm? Thorax: 2006; 61 7 621 626 (Pubitemid 44035144)
41. Ware L. B., Kaner R. J., Crystal R. G., et al. VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema. Eur Respir J: 2005; 26 1 101 105 (Pubitemid 40945937)
42. Wiener-Kronish J. P., Albertine K. H., Matthay M. A. Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin. J Clin Invest: 1991; 88 3 864 875
43. Ware L. B., Matthay M. A. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med: 2001; 163 6 1376 1383 (Pubitemid 32506602)
44. Lewis J. F., Jobe A. H. Surfactant and the adult respiratory distress syndrome. Am Rev Respir Dis: 1993; 147 1 218 233 (Pubitemid 23025945)
45. Kurahashi K., Kajikawa O., Sawa T., et al. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest: 1999; 104 6 743 750 (Pubitemid 29536359)
46. Bitterman P. B. Pathogenesis of fibrosis in acute lung injury. Am J Med: 1992; 92 6A 39S 43S
47. Pastva A. M., Wright J. R., Williams K. L. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc: 2007; 4 3 252 257 (Pubitemid 47036444)
48. Chroneos Z. C., Sever-Chroneos Z., Shepherd V. L. Pulmonary surfactant: an immunological perspective. Cell Physiol Biochem: 2010; 25 1 13 26
49. Greene K. E., Wright J. R., Steinberg K. P., et al. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med: 1999; 160 6 1843 1850 (Pubitemid 30004685)
50. Greene K. E., Ye S., Mason R. J., Parsons P. E. Serum surfactant protein-A levels predict development of ARDS in at-risk patients. Chest: 1999; 116 (1, Suppl): 90S 91S (Pubitemid 29340228)
51. Bersten A. D., Hunt T., Nicholas T. E., Doyle I. R. Elevated plasma surfactant protein-B predicts development of acute respiratory distress syndrome in patients with acute respiratory failure. Am J Respir Crit Care Med: 2001; 164 4 648 652 (Pubitemid 32801671)
52. Shirasawa M., Fujiwara N., Hirabayashi S., et al. Receptor for advanced glycation end-products is a marker of type I lung alveolar cells. Genes Cells: 2004; 9 2 165 174 (Pubitemid 38312960)
53. Uchida T., Shirasawa M., Ware L. B., et al. Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. Am J Respir Crit Care Med: 2006; 173 9 1008 1015
54. Calfee C. S., Budev M. M., Matthay M. A., et al. Plasma receptor for advanced glycation end-products predicts duration of ICU stay and mechanical ventilation in patients after lung transplantation. J Heart Lung Transplant: 2007; 26 7 675 680 (Pubitemid 47001705)
55. Broeckaert F., Bernard A. Clara cell secretory protein (CC16): characteristics and perspectives as lung peripheral biomarker. Clin Exp Allergy: 2000; 30 4 469 475 (Pubitemid 30253184)
56. Determann R. M., Millo J. L., Waddy S., Lutter R., Garrard C. S., Schultz M. J. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study. BMC Pulm Med: 2009; 9 49
57. Kropski J. A., Fremont R. D., Calfee C. S., Ware L. B. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest: 2009; 135 6 1440 1447
58. The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med: 2000; 342 18 1301 1308
59. Meduri G. U., Headley S., Kohler G., et al. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest: 1995; 107 4 1062 1073
60. Park W. Y., Goodman R. B., Steinberg K. P., et al. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med: 2001; 164 10 Pt 1 1896 1903 (Pubitemid 33152327)
61. Takala A., Jousela I., Takkunen O., et al. A prospective study of inflammation markers in patients at risk of indirect acute lung injury. Shock: 2002; 17 4 252 257
62. Parsons P. E., Moss M., Vannice J. L., Moore E. E., Moore F. A., Repine J. E. Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients. Am J Respir Crit Care Med: 1997; 155 4 1469 1473 (Pubitemid 27172800)
63. Bouros D., Alexandrakis M. G., Antoniou K. M., et al. The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome. BMC Pulm Med: 2004; 4 6
64. Pittet J. F., Mackersie R. C., Martin T. R., Matthay M. A. Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med: 1997; 155 4 1187 1205 (Pubitemid 27172758)
65. Suter P. M., Suter S., Girardin E., Roux-Lombard P., Grau G. E., Dayer J. M. High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis: 1992; 145 5 1016 1022
66. Donnelly S. C., Strieter R. M., Kunkel S. L., et al. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet: 1993; 341 8846 643 647 (Pubitemid 23083243)
67. Goodman R. B., Strieter R. M., Martin D. P., et al. Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med: 1996; 154 3 Pt 1 602 611 (Pubitemid 26327279)
68. Cohen M. J., Brohi K., Calfee C. S., et al. Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion. Crit Care: 2009; 13 6 R174
69. Bastarache J. A., Ware L. B., Bernard G. R. The role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome. Semin Respir Crit Care Med: 2006; 27 4 365 376 (Pubitemid 44272605)
70. Prabhakaran P., Ware L. B., White K. E., Cross M. T., Matthay M. A., Olman M. A. Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol: 2003; 285 1 L20 L28 (Pubitemid 36736464)
71. Ware L. B., Matthay M. A., Parsons P. E., Thompson B. T., Januzzi J. L., Eisner M. D. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med: 2007; 35 8 1821 1828 (Pubitemid 47220354)
72. Idell S., Koenig K. B., Fair D. S., Martin T. R., McLarty J., Maunder R. J. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol: 1991; 261 4 Pt 1 L240 L248
73. Fuchs-Buder T., de Moerloose P., Ricou B., et al. Time course of procoagulant activity and D dimer in bronchoalveolar fluid of patients at risk for or with acute respiratory distress syndrome. Am J Respir Crit Care Med: 1996; 153 1 163 167 (Pubitemid 26026844)
74. Günther 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 2 Pt 1 454 462 (Pubitemid 30129452)
75. Bastarache J. A., Wang L., Geiser T., et al. The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor. Thorax: 2007; 62 7 608 616 (Pubitemid 47056889)
76. Fremont R. D., Koyama T., Calfee C. S., et al. Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis. J Trauma: 2010; 68 5 1121 1127
77. Calfee C. S., Ware L. B., Glidden D. V., et al. National Heart, Blood, and Lung Institute Acute Respiratory Distress Syndrome Network Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury. Crit Care Med: 2011; 39 4 711 717
78. Ware L. B., Koyama T., Billheimer D. D., et al. NHLBI ARDS Clinical Trials Network Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. Chest: 2010; 137 2 288 296
79. Lacy P. Metabolomics of sepsis-induced acute lung injury: a new approach for biomarkers. Am J Physiol Lung Cell Mol Physiol: 2011; 300 1 L1 L3
80. 1H-nuclear magnetic resonance quantitative metabolomics and computational analysis. Am J Physiol Lung Cell Mol Physiol: 2011; 300 1 L4 L11
81. Schnapp L. M., Donohoe S., Chen J., et al. Mining the acute respiratory distress syndrome proteome: identification of the insulin-like growth factor (IGF)/IGF-binding protein-3 pathway in acute lung injury. Am J Pathol: 2006; 169 1 86 95
82. de Torre C., Ying S. X., Munson P. J., Meduri G. U., Suffredini A. F. Proteomic analysis of inflammatory biomarkers in bronchoalveolar lavage. Proteomics: 2006; 6 13 3949 3957 (Pubitemid 44081167)
83. Ware L. B., Matthay M. A. Beyond fishing: the role of discovery proteomics in mechanistic lung research. Am J Physiol Lung Cell Mol Physiol: 2009; 296 1 L12 L13
84. Christie J. D., Wurfel M. M., Feng R., et al. Trauma ALI SNP Consortium (TASC) investigators Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma. PLoS ONE: 2012; 7 1 e28268
85. Howrylak J. A., Dolinay T., Lucht L., et al. Discovery of the gene signature for acute lung injury in patients with sepsis. Physiol Genomics: 2009; 37 2 133 139
86. Wang Z., Beach D., Su L., Zhai R., Christiani D. C. A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS. Am J Respir Cell Mol Biol: 2008; 38 6 724 732 (Pubitemid 351841574)
87. Wang Z., Chen F., Zhai R., et al. Plasma neutrophil elastase and elafin imbalance is associated with acute respiratory distress syndrome (ARDS) development. PLoS ONE: 2009; 4 2 e4380
88. Brun-Buisson C., Minelli C., Bertolini G., et al. ALIVE Study Group Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study. Intensive Care Med: 2004; 30 1 51 61 (Pubitemid 38147107)
89. 2-agonist for treatment of acute lung injury. Am J Respir Crit Care Med: 2011; 184 5 561 568
90. Rice T. W., Wheeler A. P., Thompson B. T., deBoisblanc B. P., Steingrub J., Rock P. NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA: 2011; 306 14 1574 1581
91. Rice T. W., Wheeler A. P., Thompson B. T., et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA: 2012; 307 8 795 803
92. Brower R. G., Lanken P. N., MacIntyre N., et al. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med: 2004; 351 4 327 336
93. Steinberg K. P., Hudson L. D., Goodman R. B., et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med: 2006; 354 16 1671 1684
94. Wiedemann H. P., Wheeler A. P., Bernard G. R., et al. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Comparison of two fluid-management strategies in acute lung injury. N Engl J Med: 2006; 354 24 2564 2575 (Pubitemid 43882352)
95. Ware L. B. Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design. Crit Care Med: 2005; 33 (3, Suppl) S217 S222 (Pubitemid 40365612)