Skip to main content
Top
Published in: Respiratory Research 1/2001

Open Access 01-12-2002 | Research

The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome

Authors: Panagiotis Agouridakis, Despina Kyriakou, Michael G Alexandrakis, Athanasios Prekates, Kostas Perisinakis, Nikolaos Karkavitsas, Demosthenes Bouros

Published in: Respiratory Research | Issue 1/2001

Login to get access

Abstract

Background

The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS).

Methods

We measured prospectively tumour necrosis factor alpha (TNF-α), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C).

Results

All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 – P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 – P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-α were negatively correlated to PaO2/FiO2 (all P < 0.05).

Conclusions

The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome.
Literature
1.
go back to reference Bernard G, Artigas A, Brigham K, Carlet J, Falke K, Judson L, Lamy M, Legal J, Morris A, Sprucg R: 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.CrossRefPubMed Bernard G, Artigas A, Brigham K, Carlet J, Falke K, Judson L, Lamy M, Legal J, Morris A, Sprucg R: 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.CrossRefPubMed
2.
go back to reference Pugin J, Ricou B, Steinberg KP, Suter RM, Martin TR: Proinflammatory activity in bronchoalveolar lavage fluid from patients with ARDS, a prominent role for interleukin 1. Am J Respir Crit Care Med 1996, 153:1850–1856.CrossRefPubMed Pugin J, Ricou B, Steinberg KP, Suter RM, Martin TR: Proinflammatory activity in bronchoalveolar lavage fluid from patients with ARDS, a prominent role for interleukin 1. Am J Respir Crit Care Med 1996, 153:1850–1856.CrossRefPubMed
3.
go back to reference Rinaldo JE, Christman JW: Mechanisms and mediators of the adult respiratory distress syndrome. Clin Chest Med 1990, 11:621–629.PubMed Rinaldo JE, Christman JW: Mechanisms and mediators of the adult respiratory distress syndrome. Clin Chest Med 1990, 11:621–629.PubMed
4.
go back to reference Torii K, Iida K, Miyazaki Y, Saga S, Kondoh Y, Taniguchi H, Taki F, Takagi K, Matsuyama M, Suzuki R: Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. Am J Respir Crit Care Med 1997, 155:43–46.CrossRefPubMed Torii K, Iida K, Miyazaki Y, Saga S, Kondoh Y, Taniguchi H, Taki F, Takagi K, Matsuyama M, Suzuki R: Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome. Am J Respir Crit Care Med 1997, 155:43–46.CrossRefPubMed
5.
go back to reference Meduri GU, Kanangat S, Stefan J, Tolley E, Schaberg D: Cytokines IL-1beta, IL-6, and TNF-alpha enhance in vitro growth of bacteria. Am J Respir Crit Care Med 1999, 160:961–967.CrossRefPubMed Meduri GU, Kanangat S, Stefan J, Tolley E, Schaberg D: Cytokines IL-1beta, IL-6, and TNF-alpha enhance in vitro growth of bacteria. Am J Respir Crit Care Med 1999, 160:961–967.CrossRefPubMed
6.
go back to reference Hierholzer C, Kalff JC, Omert L, Tsukada K, Loeffert JE, Watkins SC, Billiar TR, Tweardy DJ: IL-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury. Am J Physiol 1998, 275:L611-L621.PubMed Hierholzer C, Kalff JC, Omert L, Tsukada K, Loeffert JE, Watkins SC, Billiar TR, Tweardy DJ: IL-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury. Am J Physiol 1998, 275:L611-L621.PubMed
7.
go back to reference Johnson JL, Moore EE, Tamura DY, Zallen G, Biffl WL, Silliman CC: IL-6 augments neutrophil cytotoxic potential via selective enhancement of elastase release. J Surg Res 1998, 76:91–94.CrossRefPubMed Johnson JL, Moore EE, Tamura DY, Zallen G, Biffl WL, Silliman CC: IL-6 augments neutrophil cytotoxic potential via selective enhancement of elastase release. J Surg Res 1998, 76:91–94.CrossRefPubMed
8.
go back to reference Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, 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, 145:1016–1022.CrossRefPubMed Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, 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, 145:1016–1022.CrossRefPubMed
9.
go back to reference Donnelly SC, Strieter RM, Kundel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollok AJ, Haslett C: Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 1993, 341:643–647.CrossRefPubMed Donnelly SC, Strieter RM, Kundel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollok AJ, Haslett C: Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 1993, 341:643–647.CrossRefPubMed
10.
go back to reference Standiford TJ, Kunkel SL, Basha MA, Chensue SW, Lynch JP, Toews GB, Westwick J, Strieter RM: Interleukin-8 gene expression by pulmonary epithelial cell line. A model for cytokine networks in the lung. J Clin Invest 1990, 86:1945–1953.CrossRefPubMedPubMedCentral Standiford TJ, Kunkel SL, Basha MA, Chensue SW, Lynch JP, Toews GB, Westwick J, Strieter RM: Interleukin-8 gene expression by pulmonary epithelial cell line. A model for cytokine networks in the lung. J Clin Invest 1990, 86:1945–1953.CrossRefPubMedPubMedCentral
11.
go back to reference Strieter RM, Kunkel SL: Acute lung injury: the role of cytokines in the elicitation of neutrophils. J Investig Med 1994, 42:640–651.PubMed Strieter RM, Kunkel SL: Acute lung injury: the role of cytokines in the elicitation of neutrophils. J Investig Med 1994, 42:640–651.PubMed
12.
go back to reference Meduri GU, Chinn A, Leeper K, Wunderink RG, Tolley E, Winer-Muram HT, Khare V, Eltorky M: Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS: patterns of response and predictors of outcome. Chest 1994, 105:1516–1527.CrossRefPubMed Meduri GU, Chinn A, Leeper K, Wunderink RG, Tolley E, Winer-Muram HT, Khare V, Eltorky M: Corticosteroid rescue treatment of progressive fibroproliferation in late ARDS: patterns of response and predictors of outcome. Chest 1994, 105:1516–1527.CrossRefPubMed
13.
go back to reference Pugin J, Verghese G, Widmer MC, Matthay MA: The alveolar space is the site of intense inflammatory and profiberotic reaction in the early phase of acute respiratory distress syndrome. Crit Care Med 1999, 27:304–312.CrossRefPubMed Pugin J, Verghese G, Widmer MC, Matthay MA: The alveolar space is the site of intense inflammatory and profiberotic reaction in the early phase of acute respiratory distress syndrome. Crit Care Med 1999, 27:304–312.CrossRefPubMed
14.
go back to reference Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K: Persistent elevation of inflammatory cytokines predicts a poor outcome over time. Chest 1995, 107:1062–1073.CrossRefPubMed Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K: Persistent elevation of inflammatory cytokines predicts a poor outcome over time. Chest 1995, 107:1062–1073.CrossRefPubMed
15.
go back to reference Moss M, Gillespi MK, Ackerson L, Moore FA, Moore EE, Parson PE: Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome. Crit Care Med 1996, 24:1782–1786.CrossRefPubMed Moss M, Gillespi MK, Ackerson L, Moore FA, Moore EE, Parson PE: Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome. Crit Care Med 1996, 24:1782–1786.CrossRefPubMed
16.
go back to reference Armstrong L, Thickett DR, Christie SJ, Kendall H, Millar AB: Increased expression of functionally active membrane-associated tumor necrosis factor in acute respiratory distress syndrome. Am J Respir Cell Mol Biol 2000, 22:68–74.CrossRefPubMed Armstrong L, Thickett DR, Christie SJ, Kendall H, Millar AB: Increased expression of functionally active membrane-associated tumor necrosis factor in acute respiratory distress syndrome. Am J Respir Cell Mol Biol 2000, 22:68–74.CrossRefPubMed
17.
go back to reference Sterner-Kock A, Braun RK, Schrenzel MD, Hyde DM: Recombinant tumor necrosis factor-alpha and platelet-activating factor synergistically increase intercellular adhesion molecule-1 and E-selectin-dependent neutrophil adherence to endothelium in vitro. Immunology 1996, 87:454–460.PubMedPubMedCentral Sterner-Kock A, Braun RK, Schrenzel MD, Hyde DM: Recombinant tumor necrosis factor-alpha and platelet-activating factor synergistically increase intercellular adhesion molecule-1 and E-selectin-dependent neutrophil adherence to endothelium in vitro. Immunology 1996, 87:454–460.PubMedPubMedCentral
18.
go back to reference Shanley TP, Warner RL, Ward PA: The role of cytokines and adhesion molecules in the development of inflammatory injury. Mol Med Today 1995, 1:40–45.CrossRefPubMed Shanley TP, Warner RL, Ward PA: The role of cytokines and adhesion molecules in the development of inflammatory injury. Mol Med Today 1995, 1:40–45.CrossRefPubMed
19.
go back to reference Zissel G, Baumer I, Schlaak M, Muller-Quernheim J: In vitro release of interleukin-15 bronchoalveolar lavage cells and peripheral blood mononuclear cells from patients with different lung diseases. Eur Cytokine Netw 2000, 11:105–112.PubMed Zissel G, Baumer I, Schlaak M, Muller-Quernheim J: In vitro release of interleukin-15 bronchoalveolar lavage cells and peripheral blood mononuclear cells from patients with different lung diseases. Eur Cytokine Netw 2000, 11:105–112.PubMed
20.
go back to reference Cassatella MA, McDonald PP: Interleukin-15 and its impact on neutrophil function. Curr Opin Hematol 2000, 7:174–177.CrossRefPubMed Cassatella MA, McDonald PP: Interleukin-15 and its impact on neutrophil function. Curr Opin Hematol 2000, 7:174–177.CrossRefPubMed
21.
go back to reference Fowler AA, Hamman RF, Good JT, Benson K, Baird M, Eberle DJ, Petty TL: Adult respiratory distress syndrome: risk with common predispositions. Ann Intern Med 1983, 98:593–597.CrossRefPubMed Fowler AA, Hamman RF, Good JT, Benson K, Baird M, Eberle DJ, Petty TL: Adult respiratory distress syndrome: risk with common predispositions. Ann Intern Med 1983, 98:593–597.CrossRefPubMed
22.
go back to reference Vincent JL, Bihari DJ, Suter PM, Bruing HA, White J, Nicolas-Chanoin MH, Wolff M, Spencer RC, Hemmer M: Prevalence of nosocomial infection in Intensive Care Units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) study. EPIC International Advisory Committee. JAMA 1995, 274:639–644.CrossRefPubMed Vincent JL, Bihari DJ, Suter PM, Bruing HA, White J, Nicolas-Chanoin MH, Wolff M, Spencer RC, Hemmer M: Prevalence of nosocomial infection in Intensive Care Units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) study. EPIC International Advisory Committee. JAMA 1995, 274:639–644.CrossRefPubMed
23.
go back to reference Bone R, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knous WA, Schein RM, Sibbald WJ: The ACCP/SCCM Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20:864–874.CrossRef Bone R, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knous WA, Schein RM, Sibbald WJ: The ACCP/SCCM Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992, 20:864–874.CrossRef
24.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13:818–829.CrossRefPubMed Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13:818–829.CrossRefPubMed
25.
go back to reference Baldwin DR, Wise R, Andrews JM, Honeybourne D: Microlavage: a technique for determining the volume of epithelial lining fluid. Thorax 1991, 46:658–662.CrossRefPubMedPubMedCentral Baldwin DR, Wise R, Andrews JM, Honeybourne D: Microlavage: a technique for determining the volume of epithelial lining fluid. Thorax 1991, 46:658–662.CrossRefPubMedPubMedCentral
27.
go back to reference Kyriakou DS, Alexandrakis MG, Tzardi M, Stephanaki K, Eliopoulos GD: Downregulation of CD43 in RAEB and RAEB-T patients. Am J Hematol 2000, 63:20–27.CrossRefPubMed Kyriakou DS, Alexandrakis MG, Tzardi M, Stephanaki K, Eliopoulos GD: Downregulation of CD43 in RAEB and RAEB-T patients. Am J Hematol 2000, 63:20–27.CrossRefPubMed
28.
go back to reference Grassi G, Frobert Y, Pradelles PH, Chercuitte F, Gruaz D, Dayer JM, Poubelle PE: Production of monoclonal antibodies against IL-1a and IL-1b: development of the two-enzyme immunometric assays (EIA) using acetylcholinesterase and their application to biological media. J Immunol Meth 1989, 123:193–210.CrossRef Grassi G, Frobert Y, Pradelles PH, Chercuitte F, Gruaz D, Dayer JM, Poubelle PE: Production of monoclonal antibodies against IL-1a and IL-1b: development of the two-enzyme immunometric assays (EIA) using acetylcholinesterase and their application to biological media. J Immunol Meth 1989, 123:193–210.CrossRef
29.
go back to reference Kyriakou DS, Papadaki HA, Eliopoulos AG, Foundoulakis A, Alexandrakis MG, Eliopoulos GD: Serum soluble IL-6 receptor concentrations correlate with stages of multiple myeloma defined by serum beta 2-microglobulin and C-reactive protein. Int J Hematol 1997, 66:367–371.CrossRefPubMed Kyriakou DS, Papadaki HA, Eliopoulos AG, Foundoulakis A, Alexandrakis MG, Eliopoulos GD: Serum soluble IL-6 receptor concentrations correlate with stages of multiple myeloma defined by serum beta 2-microglobulin and C-reactive protein. Int J Hematol 1997, 66:367–371.CrossRefPubMed
30.
go back to reference Zweig MH, Campbell G: Receiver operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993, 39:561–577.PubMed Zweig MH, Campbell G: Receiver operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993, 39:561–577.PubMed
31.
go back to reference Heffner JE, Brown LK, Barbieri CA: Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Chest 1997, 111:970–980.CrossRefPubMed Heffner JE, Brown LK, Barbieri CA: Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Chest 1997, 111:970–980.CrossRefPubMed
32.
go back to reference Hyers TM, Tricomi SM, Detterimeier PA, Fowler AA: Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1991, 144:268–271.CrossRefPubMed Hyers TM, Tricomi SM, Detterimeier PA, Fowler AA: Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1991, 144:268–271.CrossRefPubMed
33.
go back to reference Suter RM, Suter S, Girardin E, Roux-Lombard P, Grau GE, 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, 145:1016–1022.CrossRefPubMed Suter RM, Suter S, Girardin E, Roux-Lombard P, Grau GE, 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, 145:1016–1022.CrossRefPubMed
34.
go back to reference Kiehl MG, Ostermann H, Thomas M, Muller C, Cassens U, Kienast J: Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome. Crit Care Med 1998, 26:1194–1199.CrossRefPubMed Kiehl MG, Ostermann H, Thomas M, Muller C, Cassens U, Kienast J: Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome. Crit Care Med 1998, 26:1194–1199.CrossRefPubMed
35.
go back to reference Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A: Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 1995, 108:1303–1314.CrossRefPubMed Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A: Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 1995, 108:1303–1314.CrossRefPubMed
Metadata
Title
The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome
Authors
Panagiotis Agouridakis
Despina Kyriakou
Michael G Alexandrakis
Athanasios Prekates
Kostas Perisinakis
Nikolaos Karkavitsas
Demosthenes Bouros
Publication date
01-12-2002
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2001
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/rr193

Other articles of this Issue 1/2001

Respiratory Research 1/2001 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.