The Role of the Host Defense Response in the Progression and Outcome of ARDS

  • G. U. Meduri
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1998)


Acute respiratory distress syndrome (ARDS) describes the clinical syndrome associated with the morphologic lesion termed diffuse alveolar damage (DAD). At presentation, (early) ARDS manifests with acute and diffuse injury to the endothelial and epithelial lining of the terminal respiratory units and causes increased vascular permeability with protein-rich exudative edema. In non-survivors of ARDS, DAD rapidly advances through three histological phases (exudative, fibroproliferative, and fibrotic) with different clinico-physiologic features. The objective of this review is to describe systematically the pathophysiology of unresolving ARDS relating to mechanisms of its development, structural alterations induced in the lung, and functional consequences of these morphologic changes.


Idiopathic Pulmonary Fibrosis Systemic Inflammatory Response Syndrome Acute Respiratory Distress Syndrome Disseminate Intravascular Coagulation Adult Respiratory Distress Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Meduri GU (1996) The role of the host defense response in the progression and outcome of ARDS: pathophysiological correlations and response to glucocorticoid treatment. Eur Respir J 9: 2650–2670PubMedCrossRefGoogle Scholar
  2. 2.
    Meduri GU (1993) Late ARDS. New Horizons 1: 563–577PubMedGoogle Scholar
  3. 3.
    Headley AS, Tolley E, Meduri GU (1997) Infections and the inflammatory response in acute respiratory distress syndrome. Chest 111: 1306–1321PubMedCrossRefGoogle Scholar
  4. 4.
    Cerami A (1992) Inflammatory cytokines. Clin Immunol Immunopathol 62: S3–S10PubMedCrossRefGoogle Scholar
  5. 5.
    Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15: 74–80PubMedCrossRefGoogle Scholar
  6. 6.
    Meduri GU, Headley S, Kohler G, et al (1995) Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-lß and IL-6 are consistent and efficient predictors of outcome over time. Chest 107: 1062–1073PubMedCrossRefGoogle Scholar
  7. 7.
    Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A (1995) Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 108: 1303–1314PubMedCrossRefGoogle Scholar
  8. 8.
    Vadas P, Pruzanski W, Stefanski E, et al (1988) Concordance of endogenous Cortisol and phos- pholipase A2 levels in gram-negative septic shock: a prospective study. J Lab Clin Med 111: 584–590PubMedGoogle Scholar
  9. 9.
    Romaschin AD, DeMajo WC, Winton T, et al (1992) Systemic phospholipase A2 and cachectin levels in adult respiratory distress syndrome and multiple-organ failure. Clin Biochem 25: 55–60PubMedCrossRefGoogle Scholar
  10. 10.
    Robbins RA, Russ WD, Rasmussen JK, Clayton MM (1987) Activation of the complement system in the adult respiratory distress syndrome. Am Rev Respir Dis 135: 651–658PubMedGoogle Scholar
  11. 11.
    Meduri GU, ElTorky M, Winer-Muram HT (1995) The fibroproliferative phase of late adult respiratory distress syndrome. Semin Respir Infect 10: 154–175PubMedGoogle Scholar
  12. 12.
    Meduri GU, Headley S, Tolley E, Shelby M, Stentz F, Postlethwaite A (1995) Plasma and BAL cytokine response to corticosteroid rescue treatment in late ARDS. Chest 108: 1315 - 1325PubMedCrossRefGoogle Scholar
  13. 13.
    Idell S (1994) Extravascular coagulation and fibrin deposition in acute lung injury. New Horizons 2: 566–574PubMedGoogle Scholar
  14. 14.
    Idell S, Koenig KB, Fair DS, Martin TR, McLarty J, Maunder RJ (1991) Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. Am J Physiol 261: L240–L248PubMedGoogle Scholar
  15. 15.
    Fuchs-Buder T, de Moerloose P,Ricou B,et al (1996) 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 153: 163–167Google Scholar
  16. 16.
    Carvalho AC (1985) Blood alterations during ARDS. In: Zapol WM, Falke KJ (eds) Acute respiratory failure. Marcel Dekker, New York, pp 303–346Google Scholar
  17. 17.
    Schneider RC, Zapol WM, Carvalho AC (1980) Platelet consumption and sequestration in severe acute respiratory failure. Am Rev Respir Dis 122: 445–451PubMedGoogle Scholar
  18. 18.
    Quinn DA, Carvalho AC, Geller E, et al (1987) 99mTc-fibrinogen scanning in adult respiratory distress syndrome. Am Rev Respir Dis 135: 100–106Google Scholar
  19. 19.
    Taylor FB (1994) The inflammatory-coagulant axis in the host response to gram-negative sepsis:regulatory roles of proteins and inhibitors of tissue factor. New Horizons 2: 555–565PubMedGoogle Scholar
  20. 20.
    Greene R, Zapol WM, Snider MT, et al (1981) Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis 124: 593–601PubMedGoogle Scholar
  21. 21.
    Tomaseski JF, Davies P, Boggis C, Greene R, Zapol WM, Reid LM (1983) The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol 112: 112–126Google Scholar
  22. 22.
    Leavell KJ, Peterson MW, Gross TJ (1996) The role of fibrin degradation products in neutrophil recruitment to the lung. Am J Respir Cell Mol Biol 14: 53–60PubMedGoogle Scholar
  23. 23.
    McDonald JA (1990) The yin and yang of fibrin in the airways. N Engl J Med 322: 929–931PubMedCrossRefGoogle Scholar
  24. 24.
    Kuhn C III, Boldt J, King TE, Crouch E, Vartio T, McDonald JA (1989) An immuno histochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. Am Rev Respir Dis 140: 1693–1703PubMedCrossRefGoogle Scholar
  25. 25.
    Fukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O, Masugi Y (1987) The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol 126: 171–182PubMedGoogle Scholar
  26. 26.
    Lamy M, Fallat RL, Koeniger E, et al (1976) Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis 114: 267–284PubMedGoogle Scholar
  27. 27.
    Bachofen M, Weibel ER (1977) Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116: 589–615PubMedGoogle Scholar
  28. 28.
    Kovacs EJ, Dipietro LA (1994) Fibrogenic cytokines and connective tissue production. FASEB J 8: 854–861PubMedGoogle Scholar
  29. 29.
    Meduri GU, Chinn AJ, Leeper KV, et al (1994) Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS. Patterns of response and predictors of outcome. Chest 105: 1516–1527PubMedCrossRefGoogle Scholar
  30. 30.
    Entzian P, Huckstadt A, Kreipe H, Barth J (1990) Determination of serum concentrations of type III procollagen peptide in mechanically ventilated patients. Pronounced augmented concentrations in the adult respiratory distress syndrome. Am Rev Respir Dis 142: 1079–1082PubMedGoogle Scholar
  31. 31.
    Kropf J, Grobe E, Knoch M, Lammers M, Gressner AM, Lennartz H (1991) The prognostic value of extracellular matrix component concentrations in serum during treatment of adult respiratory distress syndrome with extracorporeal C02 removal. Eur J Clin Chem Clin Biochem 29: 805–812PubMedGoogle Scholar
  32. 32.
    Waydhas C, Nast-Kolb D, Trupka A, et al (1993) Increased serum concentrations of procollagen type III peptide in severely injured patients: An indicator of fibrosing activity? Crit Care Med 21: 240–247PubMedCrossRefGoogle Scholar
  33. 33.
    Clark JG, Milberg JA, Steinberg KP, Hudson LD (1995) Type III procollagen peptide in the adult respiratory distress syndrome. Association of increased peptide levels in bronchoalveolar lavage fluid with increased risk for death. Ann Intern Med 122: 17–23PubMedGoogle Scholar
  34. 34.
    Shimada Y, Yoshiya I, Tanaka K, Sone S, Sakurai M (1979) Evaluation of the progress and prognosis of adult respiratory distress syndrome: simple respiratory physiologic measurement. Chest 76: 180–186PubMedCrossRefGoogle Scholar
  35. 35.
    Bernard GR, Luce JM, Sprung CL, et al (1987) High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 317: 1565––1570PubMedCrossRefGoogle Scholar
  36. 36.
    Holter JF, Weiland JE, Pacht ER, Gadek JE, Davis WB (1986) Protein permeability in the adult respiratory distress syndrome. Loss of size selectivity of the alveolar epithelium. J Clin Invest 78: 1513–1522PubMedCrossRefGoogle Scholar
  37. 37.
    Sinclair DG, Braude S, Haslam PL, Evans TW (1994) Pulmonary endothelial permeability in patients with severe lung injury. Chest 106: 535–539PubMedCrossRefGoogle Scholar
  38. 38.
    Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE (1986) Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. Am RevRespir Dis 133: 218–225PubMedGoogle Scholar
  39. 39.
    Miller EJ, Cohen AB, Magao S, et al (1992) Elevated levels of NAP-l/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 146: 427–432PubMedGoogle Scholar
  40. 40.
    Steimberg KP, Milberg JA, Martin TR, Maunder RJ, Cockrill BA, Hudson LD (1994) Evolution of bronchoalveolar lavage cell population in the adult respiratory distress syndrome. Am J Respir Crit Care Med 150: 113–122Google Scholar
  41. 41.
    Gunther K, Baughman RP, Rashkin M, Pattishall E (1993) Bronchoalveolar lavage results in patients with sepsis-induced adult respiratory distress syndrome: evaluation of mortality and inflammatory response. Am Rev Respir Dis 147: A346 (Abst)Google Scholar
  42. 42.
    Kelly CA, Fenwick JD, Corris PA, Fleetwood A, Hendrick DJ, Walters EH (1988) Fluid dynamics during bronchoalveolar lavage. Am Rev Respir Dis 138: 81–84PubMedCrossRefGoogle Scholar
  43. 43.
    Meduri GU, Belenchia JM, Massey JD, ElTorky M (1996) 67Ga scintigraphy in diagnosing sources of fever in ventilated patients. Intensive Care Med 22: 395–403Google Scholar
  44. 44.
    Meduri GU, Belenchia JM, Estes RJ, Wunderink RG, ElTorky M, Leeper KV Jr (1991) Fibroproliferative phase of ARDS. Clinical findings and effects of corticosteroids. Chest 100: 943–952PubMedCrossRefGoogle Scholar
  45. 45.
    Hooper RG, Kearl RA (1990) Established ARDS treated with a sustained course of adrenocortical steroids. Chest 97: 138–143PubMedCrossRefGoogle Scholar
  46. 46.
    Hooper RG, Kearl RA (1996) Established adult respiratory distress syndrome successfully treated with corticosteroids. South Med J 89: 359–364PubMedCrossRefGoogle Scholar
  47. 47.
    Zapol WM, Snider MT (1977) Pulmonary hypertension in severe acute respiratory failure. N Engl J Med 296: 476–480PubMedCrossRefGoogle Scholar
  48. 48.
    Snow RL, Davies P, Pontoppidan W, Zapol WM, Reid L (1982) Pulmonary vascular remodeling in adult respiratory distress syndrome. Am Rev Respir Dis 126: 887–892PubMedGoogle Scholar
  49. 49.
    Sloane PJ, Gee MH, Gottlieb JE, et al (1992) A multicenter registry of patients with acute respiratory distress syndrome. Am Rev Respir Dis 146: 419–426PubMedGoogle Scholar
  50. 50.
    Langleben D, Demarchie M, Laporta D, et al (1993) Endothelin-1 in acute lung injury and the adult respiratory distress syndrome. Am Rev Respir Dis 148: 1646–1650PubMedCrossRefGoogle Scholar
  51. 51.
    Gattinoni L, Bombino M, Pelosi P, et al (1994) Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA 271: 1772–1779PubMedCrossRefGoogle Scholar
  52. 52.
    Rouby JJ, Lherm T,, de Lassale EM et al (1993) Histologie aspects of pulmonary barotrauma in critically ill patients with acute respiratory failure. Intensive Care Med 19: 383–389PubMedCrossRefGoogle Scholar
  53. 53.
    Tomasheski JR Jr (1990) Pulmonary pathology of the adult respiratory distress syndrome. Clin Chest Med 11: 593–619Google Scholar
  54. 54.
    Kristiansson M, Soop M, Saraste L, Sundqvist KS (1993) Post-operative circulating cytokine patterns - the influence of infection. Intensive Care Med 19: 395–400PubMedCrossRefGoogle Scholar
  55. 55.
    Meduri GU (1994) Fever in late adult respiratory distress syndrome: Etiology, pathophysiology, and diagnostic evaluation. Semin Respir Med 15: 308–324CrossRefGoogle Scholar
  56. 56.
    Lefering R, Neugebauer EAM (1995) Steroid controversy in sepsis and septic shock: A meta-analysis. Crit Care Med 23: 1294–1303PubMedCrossRefGoogle Scholar
  57. 57.
    Ashbaugh DG, Maier RV (1985) Idiopathic pulmonary fibrosis in adult respiratory distress syndrome. Diagnosis and treatment. Arch Surg 120: 530–535PubMedCrossRefGoogle Scholar
  58. 58.
    Meduri GU, Headley AS, Golden E, et al (1998) Prolonged methylprednisolone treatment improves lung function and outcome in patients with unresolving acute respiratory distress syndrome. Results of a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med (In press)Google Scholar
  59. 59.
    Meduri GU, Headley EA, Tolley A, Chin A, Stentz F, Postlethwaite A (1998) Plasma and BAL procollagen type I and III levels during ARDS and in response to prolonged methylprednisolone treatment. Am J Resp Crit Care Med (In Press)Google Scholar
  60. 60.
    Simmons RS, Berdine GG, Seidenfeld J J, et al (1994) Fluid balance and the adult respiratory distress syndrome. Am Rev Respir Dis 135: 924–929Google Scholar
  61. 61.
    Groeneveld ABJ, Raijmakers PGHM, Hack CE, Thijs LG (1995) Interleukin 8-related neutrophil elastase and the severity of the adult respiratory distress syndrome. Cytokine 7: 746–752PubMedCrossRefGoogle Scholar
  62. 62.
    Baughman RP, Gunther KL, Rashkin MC, Keeton DA, Pattishall EN (1996) Changes in the inflammatory response of the lung during acute respiratory distress syndrome: Prognostic indicators. Am J Resp Crit Care Med 154: 76–81PubMedGoogle Scholar
  63. 63.
    Gando S, Nakanishi Y, Tedo I (1995) Cytokines and plasminogen activator inhibitor-1 in post- trauma disseminated intravascular coagulation: Relationship to multiple organ dysfunction syndrome. Crit Care Med 23: 1835–1842PubMedCrossRefGoogle Scholar
  64. 64.
    Lötz M,Guerne PA (1991) Interleukin-6 induces the synthesis of tissue inhibitor of metallo- proteinases- 1/erythroid potentiating activity (TIMP-1/EPA). J Biol Chem 266: 2017–2020Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • G. U. Meduri

There are no affiliations available

Personalised recommendations