Semin Respir Crit Care Med 2006; 27(4): 337-349
DOI: 10.1055/s-2006-948288
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pathophysiology of Acute Lung Injury and the Acute Respiratory Distress Syndrome

Lorraine B. Ware1
  • 1Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Further Information

Publication History

Publication Date:
14 August 2006 (online)

ABSTRACT

Since the adult respiratory distress syndrome was first described substantial progress has been made in understanding the pathogenesis of this complex syndrome. This review summarizes our current understanding of the pathophysiology of what is now termed the acute respiratory distress syndrome (ARDS) and its less severe form acute lung injury (ALI), with an emphasis on cellular and molecular mechanisms of injury that may represent potential therapeutic targets. Although it is difficult to synthesize all of these abnormalities into a single, unified, pathogenetic pathway, a theme that emerges repeatedly is that of imbalance, be it between pro- and anti-inflammatory cytokines, oxidants and antioxidants, procoagulants and anticoagulants, neutrophil recruitment and activation and mechanisms of neutrophil clearance, or proteases and protease inhibitors. Future therapies aimed at restoring the overall balance of cytokines, oxidants, coagulants, and proteases may ultimately be successful where therapies that target individual cytokines or other mediators have not.

REFERENCES

  • 1 Ashbaugh D G, Bigelow D B, Petty T L et al.. Acute respiratory distress in adults.  Lancet. 1967;  2 319-323
  • 2 Ware L B, Matthay M A. Medical progress: the acute respiratory distress syndrome.  N Engl J Med. 2000;  342 1334-1349
  • 3 Lewis J F, Jobe A H. Surfactant and the adult respiratory distress syndrome.  Am Rev Respir Dis. 1993;  147 218-233
  • 4 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
  • 5 Nuckton T J, Alonso J A, Kallet R H et al.. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome.  N Engl J Med. 2002;  346 1281-1286
  • 6 Pelosi P, D'Onofrio D, Chiumello D et al.. Pulmonary and extrapulmonary acute respiratory distress syndrome are different.  Eur Respir J Suppl. 2003;  42 48S-56S
  • 7 Pratt P C, Vollmer R T, Shelburne J D et al.. Pulmonary morphology in a multihospital collaborative extracorporeal membrane oxygenation project.  Am J Pathol. 1979;  95 191-214
  • 8 Bachofen M, Weibel E R. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia.  Am Rev Respir Dis. 1977;  116 589-615
  • 9 Bachofen M, Weibel E R. Structural alterations of lung parenchyma in the adult respiratory distress syndrome.  Clin Chest Med. 1982;  3 35-56
  • 10 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
  • 11 Anderson W R, Thielen K. Correlative study of adult respiratory distress syndrome by light, scanning, and transmission electron microscopy.  Ultrastruct Pathol. 1992;  16 615-628
  • 12 Matthay M A, Broaddus V C. Fluid and hemodynamic management in acute lung injury.  Semin Respir Crit Care Med. 1994;  15 271-288
  • 13 Ware L B, Matthay M A. Clinical practice: acute pulmonary edema.  N Engl J Med. 2005;  353 2788-2796
  • 14 Matthay M A, Folkesson H G, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema.  Physiol Rev. 2002;  82 569-600
  • 15 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 1376-1383
  • 16 Prewitt R M, McCarthy J, Wood L DH. Treatment of acute low pressure pulmonary edema in dogs.  J Clin Invest. 1981;  67 409-418
  • 17 Zimmerman G A, Albertine K H, Carveth H J et al.. Endothelial activation in ARDS.  Chest. 1999;  116 18S-24S
  • 18 Raijmakers P GHM, Groeneveld A BJ, Teule G JJ et al.. The diagnostic value of the 67gallium pulmonary leak index in pulmonary edema.  J Nucl Med. 1996;  37 1316-1322
  • 19 Fein A, Grossman R F, Jones J G et al.. The value of edema protein measurements in patients with pulmonary edema.  Am J Med. 1979;  67 32-39
  • 20 Sprung C, Rackow E, Fein I et al.. The spectrum of pulmonary edema: differentiation of cardiogenic intermediate and noncardiogenic forms of pulmonary edema.  Am Rev Respir Dis. 1981;  124 718-722
  • 21 Matthay M A, Wiener-Kronish J P. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans.  Am Rev Respir Dis. 1990;  142 1250-1257
  • 22 Pittet J F, MacKersie R C, Martin T R et al.. Biological markers of acute lung injury: prognostic and pathogenetic significance.  Am J Respir Crit Care Med. 1997;  155 1187-1205
  • 23 Fagan K A, McMurtry I F, Rodman D M. Role of endothelin-1 in lung disease.  Respir Res. 2001;  2 90-101
  • 24 Pittet J F, Morel D R, Hemsen A et al.. Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis.  Ann Surg. 1991;  213 261-264
  • 25 Morel D R, Lacroix J S, Hemsen A et al.. Increased plasma and pulmonary lymph levels of endothelin during endotoxin shock.  Eur J Pharmacol. 1989;  167 427-428
  • 26 Miyauchi T, Yanagisawa M, Tomizawa T et al.. Increased concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction.  Lancet. 1989;  2 53-54
  • 27 Druml W, Steltzer H, Waldhausl W et al.. Endothelin-1 in adult respiratory distress syndrome.  Am Rev Respir Dis. 1993;  148 1169-1173
  • 28 Langleben D, Demarchie M, Laporta D et al.. Endothelin-1 in acute lung injury and the adult respiratory distress syndrome.  Am Rev Respir Dis. 1993;  148 1646-1650
  • 29 Sanai L, Haynes W G, Mackenzie A et al.. Endothelin production is sepsis and the adult respiratory distress syndrome.  Intensive Care Med. 1996;  22 52-56
  • 30 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 2325-2331
  • 31 Ware L B, Eisner M D, Thompson B T et al.. Significance of von Willebrand factor in septic and non-septic patients with acute lung injury.  Am J Respir Crit Care Med. 2004;  170 766-772
  • 32 Hurley J V. Types of pulmonary microvascular injury.  Ann NY Acad Sci. 1982;  384 269-286
  • 33 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;  88 864-875
  • 34 Baker C S, Evans T W, Randle B J et al.. Damage to surfactant-specific protein in acute respiratory distress syndrome.  Lancet. 1999;  353 1232-1237
  • 35 Bitterman P B. Pathogenesis of fibrosis in acute lung injury.  Am J Med. 1992;  92 39S-43S
  • 36 Matthay M A, Eschenbacher W C, Goetzl E J. Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with adult respiratory distress syndrome.  J Clin Immunol. 1984;  4 479-483
  • 37 Parsons P E, Fowler A A, Hyers T et al.. Chemotactic activity in bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome.  Am Rev Respir Dis. 1985;  132 490-493
  • 38 Steinberg K P, Milberg J A, Martin T R et al.. Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome.  Am J Respir Crit Care Med. 1994;  150 113-122
  • 39 Warshawski F J, Sibbald W, Driedger A et al.. Abnormal neutrophil-pulmonary interaction in the adult respiratory distress syndrome: qualitative and quantitative assessment of pulmonary-neutrophil kinetics in humans with in vivo indium-111 neutrophil scintigraphy.  Am Rev Respir Dis. 1986;  133 792-804
  • 40 Matthay M A. Conference summary: acute lung injury.  Chest. 1999;  116 119S-126S
  • 41 Prescott S M, McIntyre T M, Zimmerman G. Two of the usual suspects, platelet-activating factor and its receptor, implicated in acute lung injury.  J Clin Invest. 1999;  104 1019-1020
  • 42 Laufe M D, Simon R H, Flint A et al.. Adult respiratory distress syndrome in neutropenic patients.  Am J Med. 1986;  80 1022-1026
  • 43 Worthen G S, Downey G P. Mechanisms of neutrophil mediated injury. In: Evans TW, Haslett C ARDS Acute Respiratory Distress in Adults. London, UK; Chapman & Hall 1996: 99-114
  • 44 Doerschuk C M, Quinlan W M, Doyle N A et al.. The role of P-selectin and ICAM-1 in acute lung injury as determined using blocking antibodies and mutant mice.  J Immunol. 1996;  157 4609-4614
  • 45 Folkesson H G, Matthay M A. Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation in rabbits.  J Appl Physiol. 1997;  82 1743-1750
  • 46 Mulligan M S, Polley M J, Bayer R J. Neutrophil-dependent acute lung injury: requirement for P-selectin (GMP-140).  J Clin Invest. 1992;  90 1600-1607
  • 47 Nagase T, Ohga E, Sudo E et al.. Intercellular adhesion molecule-1 mediates acid aspiration-induced lung injury.  Am J Respir Crit Care Med. 1996;  154 504-510
  • 48 Doerschuk C M. Mechanisms of leukocyte sequestration in inflamed lungs.  Microcirculation. 2001;  8 71-88
  • 49 Worthen G S, Schwab B, Elson E L et al.. Mechanics of stimulated neutrophils: cell stiffening induces retention in capillaries.  Science. 1989;  245 183-185
  • 50 Lavkan A H, Astiz M E, Rackow E C. Effects of proinflammatory cytokines and bacterial toxins on neutrophil rheologic properties.  Crit Care Med. 1998;  26 1677-1682
  • 51 Erzurum S, Downey G, Doherty D et al.. Mechanisms of lipopolysaccharide induced neutrophil retention.  J Immunol. 1992;  149 154-162
  • 52 Inano H, English D, Doerschuk C. Effect of zymosan activated plasma on deformability of rabbit polymorphonuclear leukocytes.  J Appl Physiol. 1992;  73 1370-1376
  • 53 Puneet P, Moochhala S, Bhatia M. Chemokines in acute respiratory distress syndrome.  Am J Physiol Lung Cell Mol Physiol. 2005;  288 L3-15
  • 54 Moraes T J, Zurawska J H, Downey G P. Neutrophil granule contents in the pathogenesis of lung injury.  Curr Opin Hematol. 2006;  13 21-27
  • 55 Suzuki T, Moraes T J, Vachon E et al.. Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells.  Am J Respir Cell Mol Biol. 2005;  33 231-247
  • 56 Donnelly S C, MacGregor I, Zamani A et al.. Plasma elastase levels and the development of the adult respiratory distress syndrome.  Am J Respir Crit Care Med. 1995;  151 1428-1433
  • 57 Gando S, Kameue T, Nanzaki S et al.. Increased neutrophil elastase, persistent intravascular coagulation, and decreased fibrinolytic activity in patients with posttraumatic acute respiratory distress syndrome.  J Trauma. 1997;  42 1068-1072
  • 58 Christner P, Fein A M, Goldberg S et al.. Collagenase in the lower respiratory tract of patients with adult respiratory distress syndrome.  Am Rev Respir Dis. 1985;  131 690-695
  • 59 Delclaux C, d'Ortho M P, Delacourt C et al.. Gelatinases in epithelial lining fluid of patients with adult respiratory distress syndrome.  Am J Physiol. 1997;  272 L442-L51
  • 60 Pugin J, Verghese G, Widmer M-C et al.. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of ARDS.  Crit Care Med. 1999;  27 304-312
  • 61 Ricou B, Nicod L, Lacaraz S et al.. Matrix metalloproteinases and TIMP in acute respiratory distress syndrome.  Am J Respir Crit Care Med. 1996;  154 346-352
  • 62 Weiland J E, Davis B, Holter J F et al.. Lung neutrophils in the adult respiratory distress syndrome: clinical and pathophysiologic significance.  Am Rev Respir Dis. 1986;  133 218-225
  • 63 Lee C T, Fein A M, Lipmann M et al.. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory distress syndrome.  N Engl J Med. 1981;  304 192-196
  • 64 McGuire W W, Spragg R C, Cohen A B et al.. Studies on the pathogenesis of the adult respiratory distress syndrome.  J Clin Invest. 1982;  69 543-553
  • 65 Suter P M, Suter S, Girardin E et al.. 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 1016-1022
  • 66 Fowler A A, Walchak S, Giclas P C et al.. Characterization of antiprotease activity in the adult respiratory distress syndrome.  Chest. 1982;  81 50S-51S
  • 67 Idell S, Kucich U, Fein A et al.. Neutrophil elastase releasing factors in bronchoalveolar lavage from patients with adult respiratory distress syndrome.  Am Rev Respir Dis. 1985;  132 1098-1105
  • 68 Gadek J E, Pacht E R. The interdependence of lung antioxidants and antiprotease defense in ARDS.  Chest. 1996;  110 273S-277S
  • 69 Geerts L, Jorens P G, Willems J et al.. Natural inhibitors of neutrophil function in acute respiratory distress syndrome.  Crit Care Med. 2001;  29 1920-1924
  • 70 Matute-Bello G, Liles W C, Radella II F et al.. Neutrophil apoptosis in the acute respiratory distress syndrome.  Am J Respir Crit Care Med. 1997;  156 1969-1977
  • 71 Lesur O, Kokis A, Hermans C et al.. Interleukin-2 involvement in early acute respiratory distress syndrome: relationship with polymorphonuclear neutrophil apoptosis and patient survival.  Crit Care Med. 2000;  28 3814-3822
  • 72 Sookhai S, Wang J J, McCourt M et al.. A novel therapeutic strategy for attenuating neutrophil-mediated lung injury in vivo.  Ann Surg. 2002;  235 285-291
  • 73 Hussain N, Wu F, Zhu L et al.. Neutrophil apoptosis during the development and resolution of oleic acid-induced acute lung injury in the rat.  Am J Respir Cell Mol Biol. 1998;  19 867-874
  • 74 Goodman R, Pugin J, Lee J S et al.. Cytokine mediated inflammation in acute lung injury.  Cytokine Growth Factor Rev. 2003;  14 523-535
  • 75 Nathan C F. Secretory products of macrophages.  J Clin Invest. 1987;  79 319-326
  • 76 Miller E J, Cohen A B, Matthay M A. Increased interleukin-8 concentrations in the pulmonary edema fluid of patients with acute respiratory distress syndrome from sepsis.  Crit Care Med. 1996;  24 1448-1454
  • 77 Folkesson H G, Matthay M A, Hebert C A et al.. Acid aspiration induced lung injury in rabbits is mediated by interleukin-8 dependent mechanisms.  J Clin Invest. 1995;  96 107-116
  • 78 Yokoi K, Mukaida N, Harada A et al.. Prevention of endotoxemia-induced acute respiratory distress syndrome-like lung injury in rabbits by a monoclonal antibody to IL-8.  Lab Invest. 1997;  76 375-384
  • 79 Martin T R. Cytokines and the acute respiratory distress syndrome (ARDS): a question of balance.  Nat Med. 1997;  3 272-273
  • 80 Parsons P E. Interleukin-10: the ambiguity in sepsis continues.  Crit Care Med. 1998;  26 818-819
  • 81 Kurdowska A, Noble J M, Steinberg K P et al.. Anti-interleukin 8 autoantibody: interleukin 8 complexes in the acute respiratory distress syndrome.  Am J Respir Crit Care Med. 2001;  163 463-468
  • 82 Kurdowska A, Miller E J, Noble J M et al.. Anti-IL-8 autoantibodies in alveolar fluid from patients with the adult respiratory distress syndrome.  J Immunol. 1996;  157 2699-2706
  • 83 Fan J, Ye R D, Malik A B. Transcriptional mechanisms in acute lung injury.  Am J Physiol Lung Cell Mol Physiol. 2001;  281 L1037-L50
  • 84 Christman J W, Sadikot R T, Blackwell T. The role of nuclear factor-κ B in pulmonary diseases.  Chest. 2000;  117 1482-1487
  • 85 Lum H, Roebuck K A. Oxidant stress and endothelial cell dysfunction.  Am J Physiol Cell Physiol. 2001;  280 C719-C741
  • 86 Waters C M, Savla U, Panos R J. KGF prevents hydrogen peroxide-induced increases in airway epithelial cell permeability.  Am J Physiol. 1997;  272 L681-L9
  • 87 Hu P, Ischiropoulos H, Beckman J S et al.. Peroxynitrite inhibition of oxygen consumption and sodium transport in alveolar type II cells.  Am J Physiol. 1994;  266 L628-L34
  • 88 Haddad J J. Oxygen homeostasis, thiol equilibrium and redox regulation of signalling transcription factors in the alveolar epithelium.  Cell Signal. 2002;  14 799-810
  • 89 Chabot F, Mitchell J A, Gutteridge J MC et al.. Reactive oxygen species in acute lung injury.  Eur Respir J. 1998;  11 745-757
  • 90 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
  • 91 Dreyfuss D, Basset G, Soler P et al.. Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats.  Am Rev Respir Dis. 1985;  132 880-884
  • 92 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
  • 93 Bowton D L, Kong D L. High tidal volume ventilation produces increased lung water in oleic acid-injured rabbit lungs.  Crit Care Med. 1989;  17 908-911
  • 94 Corbridge T C, Wood L DH, Crawford G P et al.. Adverse effects of large tidal volumes and low PEEP in canine acid aspiration.  Am Rev Respir Dis. 1990;  142 311-315
  • 95 Tremblay L, Valenza F, Ribeiro S P et al.. Injurious ventilatory strategies increase cytokines and c-fos mRNA expression in an isolated rat lung model.  J Clin Invest. 1997;  99 944-952
  • 96 Pardo A, Ridge K, Segura L et al.. Gelatinase A and interstitial collagenase are upregulated during high tidal volume mechanical ventilation [abstract].  Am J Respir Crit Care Med. 1996;  153 A531
  • 97 Howard A B, Alexander R, Nerem R et al.. Cyclic strain induces an oxidative stress in endothelial cells.  Am J Physiol. 1997;  272 C421-C427
  • 98 Slutsky A S, Tremblay L N. Multiple system organ failure: is mechanical ventilation a contributing factor?.  Am J Respir Crit Care Med. 1998;  157 1721-1725
  • 99 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 1301-1308
  • 100 Ranieri V M, Suter P M, Tortorella C et al.. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome.  JAMA. 1999;  282 54-61
  • 101 Ware L B, Bastarache J A, Wang L. Coagulation and fibrinolysis in human acute lung injury: new therapeutic targets?.  Keio J Med. 2005;  54 142-149
  • 102 Idell S. Anticoagulants for acute respiratory distress syndrome: can they work?.  Am J Respir Crit Care Med. 2001;  164 517-520
  • 103 Abraham E. Coagulation abnormalities in acute lung injury and sepsis.  Am J Respir Cell Mol Biol. 2000;  22 401-404
  • 104 Seeger W, Hubel J, Klapettek K et al.. Procoagulant activity in bronchoalveolar lavage of severely traumatized patients-relation to development of acute respiratory distress.  Thromb Res. 1991;  61 53-64
  • 105 Fuchs-Buder T, deMoerloose 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;  153 163-167
  • 106 Idell S, Koenig K, Fair D et al.. Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome.  Am J Physiol. 1991;  261 L240-L8
  • 107 Idell S, Gonzalez K, Bradford H et al.. Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome.  Am Rev Respir Dis. 1987;  136 1466-1474
  • 108 Idell S, James K, Levin E et al.. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.  J Clin Invest. 1989;  84 695-705
  • 109 Ware L B, Matthay M A. Lower plasma protein C is associated with worse clinical outcomes in patients with acute lung injury [abstract].  Am J Respir Crit Care Med. 2002;  165 A476
  • 110 Bertozzi P, Astedt B, Zenzius L et al.. Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome.  N Engl J Med. 1990;  322 890-897
  • 111 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 predict the outcome of clinical acute lung injury.  Am J Physiol: Lung Cell Mol Physiol. 2003;  285(1) L20-L28
  • 112 McDonald J. The yin and yang of fibrin in the airways.  N Engl J Med. 1990;  322 929-931
  • 113 Idell S. Extravascular coagulation and fibrin deposition in acute lung injury.  New Horiz. 1994;  2 566-574
  • 114 Matthay M. Severe sepsis-a new treatment with both anticoagulant and anti-inflammatory properties.  N Engl J Med. 2001;  344 759-762
  • 115 Vincent J-L. New therapeutic implications of anticoagulation mediator replacement in sepsis and acute respiratory distress syndrome.  Crit Care Med. 2000;  28 S83-S5
  • 116 Lo S, Lai L, Ja C et al.. Thrombin-induced generation of neutrophil activating factors in the blood.  Am J Pathol. 1988;  130 22-32
  • 117 Kaplanski G, Fabrigoule M, Boulay V et al.. Thrombin induces endothelial type II activation in vitro: IL-1 and TNF-alpha-independent IL-8 secretion and E-selectin expression.  J Immunol. 1997;  158 5435-5441
  • 118 Coughlin S. Thrombin signaling and protease-activated receptors.  Nature. 2000;  407 258-264
  • 119 Bernard G, 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
  • 120 Fukuda Y, Ishizaki M, Masuda Y et al.. The role of intra-alveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage.  Am J Pathol. 1987;  126 171-182
  • 121 Martin C, Papazian L, Payan M J et al.. Pulmonary fibrosis correlates with outcome in the adult respiratory distress syndrome.  Chest. 1995;  107 196-200
  • 122 Zapol W M, Trelstad R L, Coffey J W et al.. Pulmonary fibrosis in severe acute respiratory failure.  Am Rev Respir Dis. 1979;  119 547-554
  • 123 Pugin J, Ricou B, Stenberg K P et al.. Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1.  Am J Respir Crit Care Med. 1996;  153 1850-1856
  • 124 Chesnutt A N, Matthay M A, Tibayan F A et al.. Early detection of type III procollagen peptide in acute lung injury.  Am J Respir Crit Care Med. 1997;  156 840-845
  • 125 Clark J G, Milberg J A, Steinberg K P et al.. Type III procollagen peptide in the adult respiratory distress syndrome.  Ann Intern Med. 1995;  122 17-23
  • 126 Lindroos P M, Coin P G, Osornio-Vargas A R et al.. Interleukin-1β (IL-1β) and the IL-1β alpha 2-macroglobulin complex upregulate the platelet-derived growth factor alpha on rat pulmonary fibroblasts.  Am J Respir Cell Mol Biol. 1995;  13 455-465
  • 127 Martinet Y, Menard O, Vaillant P et al.. Cytokines in human lung fibrosis.  Arch Toxicol Suppl. 1996;  18 127-139
  • 128 Marshall R, Bellingan G, Webb S et al.. Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome.  Am J Respir Crit Care Med. 2000;  162 1783-1788
  • 129 Olman M A, White K E, Ware L et al.. Microarray analysis indicates that pulmonary edema fluid from patients with acute lung injury mediates inflammation, mitogen gene expression, and fibroblast proliferation through bioactive interleukin-1.  Chest. 2002;  121 69S-70S
  • 130 Jurkovich G J, Rivara F P, Gurney J G et al.. The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma.  JAMA. 1993;  270 51-56
  • 131 Hudson L D, Milberg J A, Anardi D et al.. Clinical risks for development of the acute respiratory distress syndrome.  Am J Respir Crit Care Med. 1995;  151 293-301
  • 132 Moss M, Bucher B, Moore F A et al.. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults.  JAMA. 1996;  275 50-54
  • 133 Moss M, Parsons P E, Steinberg K P et al.. Chronic alcohol abuse is associated with an increased incidence of acute respiratory distress syndrome and severity of multiple organ dysfunction in patients with septic shock.  Crit Care Med. 2003;  31 869-877
  • 134 Moss M, Burnham E L. Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction.  Crit Care Med. 2003;  31 S207-S12
  • 135 Guidot D M, Roman J. Chronic ethanol ingestion increases susceptibility to acute lung injury: role of oxidative stress and tissue remodeling.  Chest. 2002;  122(Suppl 6) 309S-314S
  • 136 Holguin F, Moss I, Brown L A et al.. Chronic ethanol ingestion impairs alveolar type II cell glutathione homeostasis and function and predisposes to endotoxin-mediated acute edematous lung injury in rats.  J Clin Invest. 1998;  101 761-768
  • 137 Velasquez A, Bechara R I, Lewis J F et al.. Glutathione replacement preserves the functional surfactant phospholipid pool size and decreases sepsis-mediated lung dysfunction in ethanol-fed rats.  Alcohol Clin Exp Res. 2002;  26 1245-1251
  • 138 Moss M, Guidot D M, Wong-Lambertina M et al.. The effects of chronic alcohol abuse on pulmonary glutathione homeostasis.  Am J Respir Crit Care Med. 2000;  161 414-419
  • 139 Bunnell E, Pacht E R. Oxidized glutathione is increased in the alveolar fluid of patients with the adult respiratory distress syndrome.  Am Rev Respir Dis. 1993;  148 1174-1178
  • 140 Pacht E R, Timerman A P, Lykens M G et al.. Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome.  Chest. 1991;  100 1397-1404
  • 141 Brown L A, Harris F L, Bechara R et al.. Effect of chronic ethanol ingestion on alveolar type II cell: glutathione and inflammatory mediator-induced apoptosis.  Alcohol Clin Exp Res. 2001;  25 1078-1085
  • 142 Brown L A, Harris F L, Guidot D M. Chronic ethanol ingestion potentiates TNF-alpha-mediated oxidative stress and apoptosis in rat type II cells.  Am J Physiol Lung Cell Mol Physiol. 2001;  281 L377-L386
  • 143 Guidot D M, Modelska K, Lois M et al.. Ethanol ingestion via glutathione depletion impairs alveolar epithelial barrier function in rats.  Am J Physiol Lung Cell Mol Physiol. 2000;  279 L127-L135
  • 144 Burnham E, Brown L AS, Eaton S et al.. Prolonged glutathione deficiency and increased total protein concentrations in the epithelial lining fluid of chronic alcoholics [abstract].  Am J Respir Crit Care Med. 2001;  163 A816
  • 145 Baughman R P, Roselle G A. Surfactant deficiency with decreased opsonic activity in a guinea pig model of alcoholism.  Alcohol Clin Exp Res. 1987;  11 261-264
  • 146 Greenberg S S, Zhao X, Hua L et al.. Ethanol inhibits lung clearance of Pseudomonas aeruginosa by a neutrophil and nitric oxide-dependent mechanism, in vivo.  Alcohol Clin Exp Res. 1999;  23 735-744
  • 147 Omidvari K, Casey R, Nelson S et al.. Alveolar macrophage release of tumor necrosis factor-alpha in chronic alcoholics without liver disease.  Alcohol Clin Exp Res. 1998;  22 567-572
  • 148 Looney M R, Gropper M A, Matthay M A. Transfusion-related acute lung injury: a review.  Chest. 2004;  126 249-258
  • 149 Kopko P M, Marshall C S, MacKenzie M R et al.. Transfusion-related acute lung injury: report of a clinical look-back investigation.  JAMA. 2002;  287 1968-1971
  • 150 Silliman C C, Boshkov L K, Mehdizadehkashi Z et al.. Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.  Blood. 2003;  101 454-462
  • 151 Popovsky M A, Moore S B. Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.  Transfusion. 1985;  25 573-577
  • 152 Kopko P M, Holland P V. Transfusion-related acute lung injury.  Br J Haematol. 1999;  105 322-329
  • 153 Silliman C C, Paterson A J, Dickey W O et al.. The association of biologically active lipids with the development of transfusion-related acute lung injury: a retrospective study.  Transfusion. 1997;  37 719-726
  • 154 Zallen G, Offner P J, Moore E E et al.. Age of transfused blood is an independent risk factor for postinjury multiple organ failure.  Am J Surg. 1999;  178 570-572
  • 155 Purdy F R, Tweeddale M G, Merrick P M. Association of mortality with age of blood transfused in septic ICU patients.  Can J Anaesth. 1997;  44 1256-1261
  • 156 Dobbs L G, Gonzalez R, Matthay M A et al.. Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung.  Proc Natl Acad Sci USA. 1998;  95 2991-2996
  • 157 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
  • 158 Folkesson H G, Matthay M A, Westrom B R et al.. Alveolar epithelial clearance of protein.  J Appl Physiol. 1996;  80 1431-1445
  • 159 Kim C F, Jackson E L, Woolfenden A E et al.. Identification of bronchioalveolar stem cells in normal lung and lung cancer.  Cell. 2005;  121 823-835
  • 160 Ware L B, Matthay M A. Keratinocyte and hepatocyte growth factors in the lung: roles in lung development, inflammation and repair.  Am J Physiol Lung Cell Mol Physiol. 2002;  282 L924-L40
  • 161 Atabai K, Ishigaki M, Geiser T, Ueki I, Matthay M A, Ware L B. Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic mechanisms.  Am J Physiol: Lung Cell Mol Physiol. 2002;  283 L163-L169
  • 162 Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration.  Nat Med. 2003;  9 702-712
  • 163 Burnham E L, Taylor W R, Quyyumi A A et al.. Increased circulating endothelial progenitor cells are associated with survival in acute lung injury.  Am J Respir Crit Care Med. 2005;  172 854-860

Lorraine B WareM.D. 

Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, T1218 MCN

1161 21st Ave. S., Nashville, TN 37232-2650

Email: lorraine.ware@vanderbilt.edu

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