ABSTRACT
The importance of pulmonary surfactant in maintaining normal lung function, and the observations that alterations in endogenous surfactant contribute to the lung dysfunction associated with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), provide a rationale for administering exogenous surfactant in this setting. The results of clinical trials have been variable, however, in part due to the various surfactant preparations used, the different delivery and dosing methods employed, and the types of patients targeted for this therapy. Based on the insight gained from these studies, ongoing trials have modified these factors to optimize outcome, including one trial that is focusing on patients with direct lung insults such as pneumonia and aspiration.
The future of surfactant therapy may well take advantage of the recently described host defense functions of this material. Based on extensive in vitro data as well as in vivo animal studies demonstrating the anti-inflammatory and antibacterial functions of various surfactant components, administration of surfactant earlier in the course of the disease, when lung inflammation is present but before severe lung dysfunction occurs, may prove to be optimal.
This review discusses both the biophysical and host defense functions of surfactant in the context of novel therapeutic approaches for patients with ALI/ARDS.
KEYWORDS
Surfactant - lung injury - ARDS - host defense
REFERENCES
-
1
Goerke J.
Pulmonary surfactant: functions and molecular composition.
Biochim Biophys Acta.
1998;
1408
79-89
-
2
Robertson B.
Background to neonatal respiratory distress syndrome and treatment with exogenous surfactant.
Dev Pharmacol Ther.
1989;
13
159-163
-
3
Enhorning G, Shennan A, Possmayer F, Dunn M, Chen C P, Milligan J.
Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial.
Pediatrics.
1985;
76
145-153
-
4
Lewis J F, Jobe A H.
Surfactant and the adult respiratory distress syndrome.
Am Rev Respir Dis.
1993;
147
218-233
-
5
Frerking I, Gunther A, Seeger W, Pison U.
Pulmonary surfactant: functions, abnormalities and therapeutic options.
Intensive Care Med.
2001;
27
1699-1717
-
6
Lewis J F, Veldhuizen R.
The role of exogenous surfactant in the treatment of acute lung injury.
Annu Rev Physiol.
2003;
65
613-642
-
7
Gregory T J, Longmore W J, Moxley M A et al..
Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.
J Clin Invest.
1991;
88
1976-1981
-
8
Hallman M, Maasilta P, Sipila I, Tahvanainen J.
Composition and function of pulmonary surfactant in adult respiratory distress syndrome.
Eur Respir J Suppl.
1989;
3
104s-108s
-
9
Davidson W J, Dorscheid D, Spragg R, Schulzer M, Mak E, Ayas N T.
Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis.
Crit Care.
2006;
10(2)
R41
-
10
Pison U, Max M, Neuendank A, Weissbach S, Pietschmann S.
Host defence capacities of pulmonary surfactant: evidence for “non-surfactant” functions of the surfactant system.
Eur J Clin Invest.
1994;
24
586-599
-
11
Crouch E, Wright J.
Surfactant proteins A and D and pulmonary host defense.
Annu Rev Physiol.
2001;
63
521-554
-
12
Yu S, Harding P G, Smith N, Possmayer F.
Bovine pulmonary surfactant: chemical composition and physical properties.
Lipids.
1983;
18
522-529
-
13
Veldhuizen R, Nag K, Orgeig S, Possmayer F.
The role of lipids in pulmonary surfactant.
Biochim Biophys Acta.
1998;
1408
90-108
-
14
Possmayer F.
A proposed nomenclature for pulmonary surfactant-associated proteins.
Am Rev Respir Dis.
1988;
138
990-998
-
15
Possmayer F, Nag K, Rodriguez K, Qanbar R, Schurch S.
Surface activity in vitro: role of surfactant proteins.
Comp Biochem Physiol A Mol Integr Physiol.
2001;
129
209-220
-
16
Crouch E, Hartshorn K, Ofek I.
Collectins and pulmonary innate immunity.
Immunol Rev.
2000;
173
52-65
-
17
Cockshutt A M, Weitz J, Possmayer F.
Pulmonary surfactant-associated protein A enhances the surface activity of lipid extract surfactant and reverses inhibition by blood proteins in vitro.
Biochemistry.
1990;
29
8424-8429
-
18
Cochrane C G, Revak S D, Merritt T A et al..
The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome.
Am J Respir Crit Care Med.
1996;
153
404-410
-
19
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
-
20
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
-
21
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
-
22
Wright J R, Hawgood S.
Pulmonary surfactant metabolism.
Clin Chest Med.
1989;
10
83-93
-
23
Rooney S A.
Regulation of surfactant secretion.
Comp Biochem Physiol A Mol Integr Physiol.
2001;
129
233-243
-
24
Mason R J, Voelker D R.
Regulatory mechanisms of surfactant secretion.
Biochim Biophys Acta.
1998;
1408
226-240
-
25
Schurch S, Green F H, Bachofen H.
Formation and structure of surface films: captive bubble surfactometry.
Biochim Biophys Acta.
1998;
1408
180-202
-
26
Bastacky J, Lee C Y, Goerke J et al..
Alveolar lining layer is thin and continuous: low-temperature scanning electron microscopy of rat lung.
J Appl Physiol.
1995;
79
1615-1628
-
27 Goerke J, Clements J A. Alveolar surface tension and lung surfactant. In: Fishman AP, Geiger SR Handbook of Physiology: The Respiratory System. Bethesda; American Physiological Society 1985: 247-261
-
28
Gross N J.
Extracellular metabolism of pulmonary surfactant: the role of a new serine protease.
Annu Rev Physiol.
1995;
57
135-150
-
29
Wright J R.
Clearance and recycling of pulmonary surfactant.
Am J Physiol.
1990;
259
L1-12
-
30
Magoon M W, Wright J R, Baritussio A et al..
Subfractionation of lung surfactant: implications for metabolism and surface activity.
Biochim Biophys Acta.
1983;
750
18-31
-
31
Lewis J F, Ikegami M, Jobe A H.
Altered surfactant function and metabolism in rabbits with acute lung injury.
J Appl Physiol.
1990;
69
2303-2310
-
32
Gross N J, Kellam M, Young J, Krishnasamy S, Dhand R.
Separation of alveolar surfactant into subtypes: a comparison of methods.
Am J Respir Crit Care Med.
2000;
162(2 Pt 1)
617-622
-
33
Putz G, Goerke J, Clements J A.
Surface activity of rabbit pulmonary surfactant subfractions at different concentrations in a captive bubble.
J Appl Physiol.
1994;
77
597-605
-
34
Yamada T, Ikegami M, Jobe A H.
Effects of surfactant subfractions on preterm rabbit lung function.
Pediatr Res.
1990;
27
592-598
-
35
Wright J R, Clements J A.
Metabolism and turnover of lung surfactant.
Am Rev Respir Dis.
1987;
136
426-444
-
36
McCormack F X, Whitsett J A.
The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung.
J Clin Invest.
2002;
109
707-712
-
37
Ferguson J S, Voelker D R, McCormack F X, Schlesinger L S.
Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages.
J Immunol.
1999;
163
312-321
-
38
Allen M J, Voelker D R, Mason R J.
Interactions of surfactant proteins A and D with Saccharomyces cerevisiae and Aspergillus fumigatus
.
Infect Immun.
2001;
69
2037-2044
-
39
Arias-Diaz J, Garcia-Verdugo I, Casals C, Sanchez-Rico N, Vara E, Balibrea J L.
Effect of surfactant protein A (SP-A) on the production of cytokines by human pulmonary macrophages.
Shock.
2000;
14
300-306
-
40
Barr F E, Pedigo H, Johnson T R, Shepherd V L.
Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages.
Am J Respir Cell Mol Biol.
2000;
23
586-592
-
41
Blau H, Riklis S, Van Iwaarden J F, McCormack F X, Kalina M.
Nitric oxide production by rat alveolar macrophages can be modulated in vitro by surfactant protein A.
Am J Physiol.
1997;
272(6 Pt 1)
L1198-L1204
-
42
Haagsman H P.
Interactions of surfactant protein A with pathogens.
Biochim Biophys Acta.
1998;
1408
264-277
-
43
Tonks A, Morris R H, Price A J, Thomas A W, Jones K P, Jackson S K.
Dipalmitoylphosphatidylcholine modulates inflammatory functions of monocytic cells independently of mitogen activated protein kinases.
Clin Exp Immunol.
2001;
124
86-94
-
44
Borron P, Veldhuizen R AW, Lewis J F et al..
Surfactant associated protein-A inhibits human lymphocyte proliferation and IL-2 production.
Am J Respir Cell Mol Biol.
1996;
15
115-121
-
45
Kuzmenko A I, Wu H, McCormack F X.
Pulmonary collectins selectively permeabilize model bacterial membranes containing rough lipopolysaccharide.
Biochemistry.
2006;
45
2679-2685
-
46
Kuzmenko A I, Wu H, Wan S, McCormack F X.
Surfactant protein A is a principal and oxidation-sensitive microbial permeabilizing factor in the alveolar lining fluid.
J Biol Chem.
2005;
280
25913-25919
-
47
Reid K B, Clark H, Palaniyar N.
Surfactant and lung inflammation.
Thorax.
2005;
60
620-622
-
48
Palaniyar N, Clark H, Nadesalingam J, Hawgood S, Reid K B.
Surfactant protein D binds genomic DNA and apoptotic cells, and enhances their clearance, in vivo.
Ann NY Acad Sci.
2003;
1010
471-475
-
49
Clark H, Palaniyar N, Strong P, Edmondson J, Hawgood S, Reid K B.
Surfactant protein D reduces alveolar macrophage apoptosis in vivo.
J Immunol.
2002;
169
2892-2899
-
50
Korfhagen T R, LeVine A M, Whitsett J A.
Surfactant protein A (SP-A) gene targeted mice.
Biochim Biophys Acta.
1998;
1408
296-302
-
51
Botas C, Poulain F, Akiyama J et al..
Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein d.
Proc Natl Acad Sci USA.
1998;
95
11869-11874
-
52
Wert S, Jones T, Korfhagen T, Fisher J, Whitsett J.
Spontaneous emphysema in surfactant protein D gene-targeted mice.
Chest.
2000;
117(5 Suppl 1)
248S
-
53
LeVine A M, Kurak K E, Bruno M D, Stark J M, Whitsett J A, Korfhagen T R.
Surfactant protein-A-deficient mice are susceptible to Pseudomonas aeruginosa infection.
Am J Respir Cell Mol Biol.
1998;
19
700-708
-
54
LeVine A M, Kurak K E, Wright J R et al..
Surfactant protein-A binds group B Streptococcus enhancing phagocytosis and clearance from lungs of surfactant protein-A-deficient mice.
Am J Respir Cell Mol Biol.
1999;
20
279-286
-
55
Wu Y, Adam S, Hamann L et al..
Accumulation of inhibitory kappaB-alpha as a mechanism contributing to the anti-inflammatory effects of surfactant protein-A.
Am J Respir Cell Mol Biol.
2004;
31
587-594
-
56
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
-
57
Ashbaugh D G, Bigelow D B, Petty T L, Levine B E.
Acute respiratory distress in adults.
Lancet.
1967;
2
319-323
-
58
Petty T L, Ashbaugh D G.
The adult respiratory distress syndrome clinical features, factors influencing prognosis and principles of management.
Chest.
1971;
60
233-239
-
59
Pison U, Gono E, Joka T, Obertacke U.
Phospholipid lung profile in adult respiratory distress syndrome evidence for surfactant abnormality.
Prog Clin Biol Res.
1987;
236A
517-523
-
60
Holm B A, Keicher L, Liu M Y, Sokolowski J, Enhorning G.
Inhibition of pulmonary surfactant function by phospholipases.
J Appl Physiol.
1991;
71
317-321
-
61
Hite R D, Seeds M C, Jacinto R B, Balasubramanian R, Waite M, Bass D.
Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2.
Am J Physiol.
1998;
275
L740-L747
-
62
Pison U, Tam E K, Caughey G H, Hawgood S.
Proteolytic inactivation of dog lung surfactant-associated proteins by neutrophil elastase.
Biochim Biophys Acta.
1989;
992
251-257
-
63
Holm B A, Enhorning G, Notter R H.
A biophysical mechanism by which plasma proteins inhibit lung surfactant activity.
Chem Phys Lipids.
1988;
49
49-55
-
64
Seeger W, Stohr G, Wolf H R, Neuhof H.
Alteration of surfactant function due to protein leakage special interaction with fibrin monomer.
J Appl Physiol.
1985;
58
326-338
-
65
Cockshutt A M, Possmayer F.
Lysophosphatidylcholine sensitizes lipid extracts of pulmonary surfactant to inhibition by serum proteins.
Biochim Biophys Acta.
1991;
1086
63-71
-
66
Veldhuizen R A, McCaig L A, Akino T, Lewis J F.
Pulmonary surfactant subfractions in patients with the acute respiratory distress syndrome.
Am J Respir Crit Care Med.
1995;
152
1867-1871
-
67
Gunther A, Siebert C, Schmidt R et al..
Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema.
Am J Respir Crit Care Med.
1996;
153
176-184
-
68
Ito Y, Veldhuizen R AW, Yao L-J, McCaig L A, Bartlett A J, Lewis J F.
Ventilation strategies affect surfactant aggregate conversion in acute lung injury.
Am J Respir Crit Care Med.
1997;
155
493-499
-
69
Malloy J L, Veldhuizen R A, Lewis J F.
Effects of ventilation on the surfactant system in sepsis-induced lung injury.
J Appl Physiol.
2000;
88
401-408
-
70
Veldhuizen R A, Yao L, Lewis J F.
An examination of the different variables affecting surfactant aggregate conversion in vitro.
Exp Lung Res.
1999;
25
127-141
-
71
Veldhuizen R AW, Marcou J, Yao L-J, McCaig L, Ito Y, Lewis J F.
Alveolar surfactant aggregate conversion in ventilated normal and injured rabbits.
Am J Physiol.
1996;
270
L152-L158
-
72
Gunther A, Kalinowski M, Rosseau S, Seeger W.
Surfactant incorporation markedly alters mechanical properties of a fibrin clot.
Am J Respir Cell Mol Biol.
1995;
13
712-718
-
73
Nag K, Rodriguez-Capote K, Panda A K et al..
Disparate effects of two phosphatidylcholine binding proteins, C-reactive protein and surfactant protein A, on pulmonary surfactant structure and function.
Am J Physiol Lung Cell Mol Physiol.
2004;
287
L1145-L1153
-
74
Rodriguez-Capote K, Manzanares D, Haines T, Possmayer F.
Reactive oxygen species inactivation of surfactant involves structural and functional alterations to surfactant proteins SP-B and SP-C.
Biophys J.
2006;
90(8)
2808-2821
-
75
Rodriguez-Capote K, McCormack F X, Possmayer F.
Pulmonary surfactant protein-A (SP-A) restores the surface properties of surfactant after oxidation by a mechanism that requires the Cys6 interchain disulfide bond and the phospholipid binding domain.
J Biol Chem.
2003;
278
20461-20474
-
76
Haddad I Y, Ischiropoulos H, Holm B A, Beckman J S, Baker J R, Matalon S.
Mechanisms of peroxynitrite-induced injury to pulmonary surfactants.
Am J Physiol.
1993;
265(6 Pt 1)
L555-L564
-
77
Andersson S, Kheiter A, Merritt T A.
Oxidative inactivation of surfactants.
Lung.
1999;
177
179-189
-
78
Veldhuizen R AW, Yao L-J, Hearn S A, Possmayer F, Lewis J F.
Surfactant-associated protein A is important for maintaining large aggregate forms during surface area cycling.
Biochem J.
1996;
313
835-840
-
79
Gross N J, Narine K R.
Surfactant subtypes of mice metabolic relationships and conversion in vitro.
J Appl Physiol.
1989;
67
414-421
-
80
Lee C T, Fein A M, Lippmann M, Holtzman H, Kimbel P, Weinbaum G.
Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome.
N Engl J Med.
1981;
304
192-196
-
81
McGuire W W, Spragg R G, Cohen A B, Cochrane C G.
Studies on the pathogenesis of the adult respiratory distress syndrome.
J Clin Invest.
1982;
69
543-553
-
82
Hite R D, Seeds M C, Jacinto R B, Grier B L, Waite B M, Bass D A.
Lysophospholipid and fatty acid inhibition of pulmonary surfactant non-enzymatic models of phospholipase A2 surfactant hydrolysis.
Biochim Biophys Acta.
2005;
1720
14-21
-
83
Hite R D, Seeds M C, Safta A M et al..
Lysophospholipid generation and phosphatidylglycerol depletion in phospholipase A(2)-mediated surfactant dysfunction.
Am J Physiol Lung Cell Mol Physiol.
2005;
288
L618-L624
-
84
Veldhuizen R AW, Ito Y, Marcou J, Yao L J, McCaig L, Lewis J F.
Effects of lung injury on pulmonary surfactant aggregate conversion in vivo and in vitro.
Am J Physiol.
1997;
16
L872-L878
-
85
Higuchi R, Lewis J, Ikegami M.
In vitro conversion of surfactant subtypes is altered in alveolar surfactant isolated from injured lungs.
Am Rev Respir Dis.
1992;
145
1416-1420
-
86
Nicholas T E, Doyle I R, Bersten A D.
Surfactant replacement therapy in ARDS white knight or noise in the system?.
Thorax.
1997;
52
195-197
-
87
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
-
88
Lachmann B.
Animal models and clinical pilot studies of surfactant replacement in adult respiratory distress syndrome.
Eur Respir J Suppl.
1989;
3
98S-103S
-
89
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;
224
1417-1421
-
90
Evans D A, Wilmott R W, Whitsett J A.
Surfactant replacement therapy for adult respiratory distress syndrome in children.
Pediatr Pulmonol.
1996;
21
328-336
-
91
Wiswell T E, Smith R M, Katz L B et al..
Bronchopulmonary segmental lavage with Surfaxin (KL(4)-surfactant) for acute respiratory distress syndrome.
Am J Respir Crit Care Med.
1999;
160
1188-1195
-
92
Walmrath D, Gunther A, Ardeschir H 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
-
93
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
-
94
Lewis J F, Veldhuizen R AW.
Factors influencing efficacy of exogenous surfactant in acute lung injury.
Biol Neonate.
1995;
67(Suppl 1)
48-60
-
95
Hall S B, Venkitaraman A R, Whitsett J A, Holm B A, Notter R H.
Importance of hydrophobic apoproteins as constituents of clinical exogenous surfactants.
Am Rev Respir Dis.
1992;
145
24-30
-
96
Cummings J J, Holm B A, Hudak M L, Hudak B B, Ferguson W H, Egan E A.
A controlled clinical comparison of four different surfactant preparations in surfactant-deficient preterm lambs.
Am Rev Respir Dis.
1992;
145
999-1004
-
97
Balaraman V, Meister J, Ku T L et al..
Lavage administration of dilute surfactants after acute lung injury in neonatal piglets.
Am J Respir Crit Care Med.
1998;
158
12-17
-
98
Lewis J, McCaig L, Hafner D, Spragg R, Veldhuizen R, Kerr C.
Dosing and delivery of a recombinant surfactant in lung-injured adult sheep.
Am J Respir Crit Care Med.
1999;
159
741-747
-
99
Taeusch W H, Lu K, Goerke J, Clements J.
Nonionic polymers reverse inactivation of surfactant by meconium and other substances.
Am J Respir Crit Care Med.
1999;
159
1391-1395
-
100
Kobayashi T, Ohta K, Tashiro K et al..
Dextran restores albumin-inhibited surface activity of pulmonary surfactant extract.
J Appl Physiol.
1999;
86
1778-1784
-
101
Lu J J, Yu L M, Cheung W W et al..
Poly(ethylene glycol) (PEG) enhances dynamic surface activity of a bovine lipid extract surfactant (BLES).
Colloids Surf B Biointerfaces.
2005;
41
145-151
-
102
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
-
103
Herridge M S, Slutsky A S, Colditz G A.
Has high-frequency ventilation been inappropriately discarded in adult acute respiratory distress syndrome?.
Crit Care Med.
1998;
26
2073-2077
-
104
Kerr C L, Veldhuizen R A, Lewis J F.
Effects of high-frequency oscillation on endogenous surfactant in an acute lung injury model.
Am J Respir Crit Care Med.
2001;
164
237-242
-
105
Lewis J, Ikegami M, Higuchi R, Jobe A, Absolom D.
Nebulized vs. instilled exogenous surfactant in an adult lung injury model.
J Appl Physiol.
1991;
71
1270-1276
-
106
Lewis J F, Goffin J, Yue P, McCaig L A, Bjarneson D, Veldhuizen R AW.
Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.
J Appl Physiol.
1996;
80
1156-1164
-
107
Lewis J F, McCaig L A.
Aerosolized versus instilled exogenous surfactant in a nonuniform pattern of lung injury.
Am Rev Respir Dis.
1993;
148
1187-1193
-
108
Willson D F, Jiao J H, Bauman L A et al..
Calf's lung surfactant extract in acute hypoxemic respiratory failure in children.
Crit Care Med.
1996;
24
1316-1322
-
109
Livingston D H, Mosenthal A C, Deitch E A.
Sepsis and multiple organ dysfunction syndrome: a clinical-mechanistic overview.
New Horiz.
1995;
3
257-264
-
110
Hite R D, Morris P E.
Acute respiratory distress syndrome: pharmacological treatment options in development.
Drugs.
2001;
61
897-907
-
111
Crimi E, Slutsky A S.
Inflammation and the acute respiratory distress syndrome.
Best Pract Res Clin Anaesthesiol.
2004;
18
477-492
-
112
Ito Y, Goffin J, Veldhuizen R et al..
Timing of exogenous surfactant administration in a rabbit model of acute lung injury.
J Appl Physiol.
1996;
80
1357-1364
-
113
Krause M F, Hoehn T.
Timing of surfactant administration determines its physiologic response in a rabbit model of airway lavage.
Biol Neonate.
2000;
77
196-202
-
114
Montgomery A B, Stager M A, Carrico C J, Hudson E D.
Causes of mortality in patients with the adult respiratory distress syndrome.
Am Rev Respir Dis.
1985;
132
485-489
-
115
Maier R V.
Pathogenesis of multiple organ dysfunction syndrome: endotoxin, inflammatory cells, and their mediators: cytokines and reactive oxygen species.
Surg Infect (Larchmt).
2000;
1
197-205
-
116
Bone R C.
Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation.
Crit Care Med.
1996;
24
163-172
-
117
Dos Santos C C, Slutsky A S.
The contribution of biophysical lung injury to the development of biotrauma.
Annu Rev Physiol.
2006;
68
585-618
-
118
Tremblay L N, Slutsky A S.
Ventilator-induced injury: from barotrauma to biotrauma.
Proc Assoc Am Physicians.
1998;
110
482-488
-
119
Bone R C.
Multiple system organ failure and the sepsis syndrome.
Hosp Pract (off Ed).
1991;
26(11)
101-109
discussion 109-126
-
120
Hawgood S, Shiffer K.
Structures and properties of the surfactant-associated proteins.
Annu Rev Physiol.
1991;
53
375-394
-
121
Haagsman H P.
Surfactant proteins A and D.
Biochem Soc Trans.
1994;
22
100-106
-
122
Ito Y, Manwell S EE, Kerr C L et al..
Effect of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.
Am J Respir Crit Care Med.
1998;
157
149-155
-
123
Tremblay L, Valenza F, Ribeiro S P, Li J, Slutsky A S.
Injurious ventilatory strategies increase cytokines and c-fos mRNA expression in an isolated rat lung model.
J Clin Invest.
1997;
99
944-952
James F LewisM.D. F.R.C.P.C.
St. Joseph's Health Centre, University of Western Ontario
268 Grosvenor St., London, Ontario, N6A 4V2, Canada
Email: jflewis@uwo.ca