NCT00910026

Brief Summary

The aim of the present study is to evaluate the effect of low (6 ml/kg) and high (12 ml/kg) tidal volume ventilation on inflammatory and oxidative stress biomarkers in the exhaled breath condensate (EBC) of ICU patients without lung injury. As the analysis of EBC is reflecting the composition of epithelial lining fluid (ELF), the study of EBC pH and inflammatory and oxidative stress markers could have the potential for assessing lung inflammation caused by mechanical ventilation. This study also aims to look at the possibility to identify selective profiles of biomarkers that might have a prognostic and/or diagnostic value in the follow up of these patients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started May 2009

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2009

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

May 28, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 29, 2009

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
Last Updated

October 25, 2013

Status Verified

November 1, 2009

Enrollment Period

4.3 years

First QC Date

May 28, 2009

Last Update Submit

October 24, 2013

Conditions

Inflammation

Keywords

EBC and mechanical ventilationlow tidal volume ventilationhigh tidal volume ventilationinflammatory and oxidative stress EBC biomarkersVentilator induced lung injury

Outcome Measures

Primary Outcomes (1)

  • Evaluation of the effect of low (6 ml/kg) and high (12 ml/kg) tidal volume ventilation on inflammatory and oxidative stress biomarkers in the exhaled breath condensate (EBC) of ICU patients without lung injury.

    2 years

Secondary Outcomes (1)

  • Evaluation of the prognostic role of exhaled biomarkers in the subsequent outcome of mechanically ventilated patients (length of ICU hospitalization, subsequent development of ALI or ARDS and morbidity and mortality in the ICU).

    2 years

Study Arms (2)

low tidal volume ventilation

EXPERIMENTAL

6 ml/kg tidal volume ventilation

Procedure: low tidal volume ventilation

high tidal volume ventilation

EXPERIMENTAL

12 ml/kg tidal volume ventilation

Procedure: high tidal volume ventilation

Interventions

low tidal volume ventilationPROCEDURE

6 ml/kg tidal volume ventilation

low tidal volume ventilation
high tidal volume ventilationPROCEDURE

12 ml/kg tidal volume ventilation

high tidal volume ventilation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ICU patients mechanically ventilated because of stroke, subarachnoid and/or intracerebral hemorrhage
  • Healthy respiratory system

You may not qualify if:

  • Pulmonary diseases

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Intensive Care Unit Department of University Hospital of Larissa

Larissa, Thessaly, 41110, Greece

Location

Related Publications (35)

  • Holz O. Catching breath: monitoring airway inflammation using exhaled breath condensate. Eur Respir J. 2005 Sep;26(3):371-2. doi: 10.1183/09031936.05.00071305. No abstract available.

    PMID: 16135713BACKGROUND

  • Hunt J. Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease. J Allergy Clin Immunol. 2002 Jul;110(1):28-34. doi: 10.1067/mai.2002.124966.

    PMID: 12110814BACKGROUND

  • Mutlu GM, Garey KW, Robbins RA, Danziger LH, Rubinstein I. Collection and analysis of exhaled breath condensate in humans. Am J Respir Crit Care Med. 2001 Sep 1;164(5):731-7. doi: 10.1164/ajrccm.164.5.2101032. No abstract available.

    PMID: 11549524BACKGROUND

  • Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med. 2001 Jun;163(7):1693-722. doi: 10.1164/ajrccm.163.7.2009041. No abstract available.

    PMID: 11401895BACKGROUND

  • Muller WG, Morini F, Eaton S, Peters M, Jaffe A. Safety and feasibility of exhaled breath condensate collection in ventilated infants and children. Eur Respir J. 2006 Sep;28(3):479-85. doi: 10.1183/09031936.06.00063505. Epub 2006 Apr 26.

    PMID: 16641124BACKGROUND

  • Moloney ED, Mumby SE, Gajdocsi R, Cranshaw JH, Kharitonov SA, Quinlan GJ, Griffiths MJ. Exhaled breath condensate detects markers of pulmonary inflammation after cardiothoracic surgery. Am J Respir Crit Care Med. 2004 Jan 1;169(1):64-9. doi: 10.1164/rccm.200307-1005OC. Epub 2003 Oct 9.

    PMID: 14551168BACKGROUND

  • Horvath I, Hunt J, Barnes PJ, Alving K, Antczak A, Baraldi E, Becher G, van Beurden WJ, Corradi M, Dekhuijzen R, Dweik RA, Dwyer T, Effros R, Erzurum S, Gaston B, Gessner C, Greening A, Ho LP, Hohlfeld J, Jobsis Q, Laskowski D, Loukides S, Marlin D, Montuschi P, Olin AC, Redington AE, Reinhold P, van Rensen EL, Rubinstein I, Silkoff P, Toren K, Vass G, Vogelberg C, Wirtz H; ATS/ERS Task Force on Exhaled Breath Condensate. Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J. 2005 Sep;26(3):523-48. doi: 10.1183/09031936.05.00029705.

    PMID: 16135737BACKGROUND

  • Thammanomai A, Majumdar A, Bartolak-Suki E, Suki B. Effects of reduced tidal volume ventilation on pulmonary function in mice before and after acute lung injury. J Appl Physiol (1985). 2007 Nov;103(5):1551-9. doi: 10.1152/japplphysiol.00006.2007. Epub 2007 Aug 9.

    PMID: 17690203BACKGROUND

  • Halter JM, Steinberg JM, Gatto LA, DiRocco JD, Pavone LA, Schiller HJ, Albert S, Lee HM, Carney D, Nieman GF. Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability. Crit Care. 2007;11(1):R20. doi: 10.1186/cc5695.

    PMID: 17302983BACKGROUND

  • Del Sorbo L, Slutsky AS. Year in review 2007: Critical Care--respirology. Crit Care. 2008;12(5):231. doi: 10.1186/cc6953. Epub 2008 Oct 14.

    PMID: 18983706BACKGROUND

  • Dreyfuss D, Saumon G. From ventilator-induced lung injury to multiple organ dysfunction? Intensive Care Med. 1998 Feb;24(2):102-4. doi: 10.1007/s001340050529. No abstract available.

    PMID: 9539065BACKGROUND

  • Parker JC, Hernandez LA, Peevy KJ. Mechanisms of ventilator-induced lung injury. Crit Care Med. 1993 Jan;21(1):131-43. doi: 10.1097/00003246-199301000-00024.

    PMID: 8420720BACKGROUND

  • Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. doi: 10.1056/NEJM199802053380602.

    PMID: 9449727BACKGROUND

  • Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Sep;138(3):720-3. doi: 10.1164/ajrccm/138.3.720. No abstract available.

    PMID: 3202424BACKGROUND

  • Pelosi P, Negrini D. Extracellular matrix and mechanical ventilation in healthy lungs: back to baro/volotrauma? Curr Opin Crit Care. 2008 Feb;14(1):16-21. doi: 10.1097/MCC.0b013e3282f25162.

    PMID: 18195621BACKGROUND

  • Vaughan J, Ngamtrakulpanit L, Pajewski TN, Turner R, Nguyen TA, Smith A, Urban P, Hom S, Gaston B, Hunt J. Exhaled breath condensate pH is a robust and reproducible assay of airway acidity. Eur Respir J. 2003 Dec;22(6):889-94. doi: 10.1183/09031936.03.00038803.

    PMID: 14680074BACKGROUND

  • Kostikas K, Papatheodorou G, Ganas K, Psathakis K, Panagou P, Loukides S. pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med. 2002 May 15;165(10):1364-70. doi: 10.1164/rccm.200111-068OC.

    PMID: 12016097BACKGROUND

  • Kostikas K, Papatheodorou G, Psathakis K, Panagou P, Loukides S. Oxidative stress in expired breath condensate of patients with COPD. Chest. 2003 Oct;124(4):1373-80. doi: 10.1378/chest.124.4.1373.

    PMID: 14555568BACKGROUND

  • van Beurden WJ, Harff GA, Dekhuijzen PN, van den Bosch MJ, Creemers JP, Smeenk FW. An efficient and reproducible method for measuring hydrogen peroxide in exhaled breath condensate. Respir Med. 2002 Mar;96(3):197-203. doi: 10.1053/rmed.2001.1240.

    PMID: 11908513BACKGROUND

  • Razola SS, Ruiz BL, Diez NM, Mark HB Jr, Kauffmann JM. Hydrogen peroxide sensitive amperometric biosensor based on horseradish peroxidase entrapped in a polypyrrole electrode. Biosens Bioelectron. 2002 Dec;17(11-12):921-8. doi: 10.1016/s0956-5663(02)00083-0.

    PMID: 12392940BACKGROUND

  • Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, Barnes PJ. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1175-7. doi: 10.1164/ajrccm.162.3.2001063.

    PMID: 10988150BACKGROUND

  • Ganas K, Loukides S, Papatheodorou G, Panagou P, Kalogeropoulos N. Total nitrite/nitrate in expired breath condensate of patients with asthma. Respir Med. 2001 Aug;95(8):649-54. doi: 10.1053/rmed.2001.1117.

    PMID: 11530952BACKGROUND

  • 23. Hammerschmidt S., Meybaum M., Schauer J. et. al; Effect of tidal volume and end expiratory pressure on pulmonary NO release in an isolated lung model (abstract); Eur.Respir.J. 2001;18(suppl):366s.

    BACKGROUND

  • Berg JT, Deem S, Kerr ME, Swenson ER. Hemoglobin and red blood cells alter the response of expired nitric oxide to mechanical forces. Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2947-53. doi: 10.1152/ajpheart.2000.279.6.H2947.

    PMID: 11087251BACKGROUND

  • Francoeur C, Denis M. Nitric oxide and interleukin-8 as inflammatory components of cystic fibrosis. Inflammation. 1995 Oct;19(5):587-98. doi: 10.1007/BF01539138.

    PMID: 8543373BACKGROUND

  • Jang AS, Choi IS, Lee S, Seo JP, Yang SW, Park KO, Lee KY, Lee JU, Park CS, Park HS. Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects. Clin Exp Allergy. 1999 Aug;29(8):1136-42. doi: 10.1046/j.1365-2222.1999.00595.x.

    PMID: 10457119BACKGROUND

  • Edwards YS, Sutherland LM, Murray AW. NO protects alveolar type II cells from stretch-induced apoptosis. A novel role for macrophages in the lung. Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1236-42. doi: 10.1152/ajplung.2000.279.6.L1236.

    PMID: 11076814BACKGROUND

  • Gessner C, Hammerschmidt S, Kuhn H, Lange T, Engelmann L, Schauer J, Wirtz H. Exhaled breath condensate nitrite and its relation to tidal volume in acute lung injury. Chest. 2003 Sep;124(3):1046-52. doi: 10.1378/chest.124.3.1046.

    PMID: 12970036BACKGROUND

  • Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ. Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. Chest. 2002 Oct;122(4):1162-7. doi: 10.1378/chest.122.4.1162.

    PMID: 12377837BACKGROUND

  • Sack U, Scheibe R, Wotzel M, Hammerschmidt S, Kuhn H, Emmrich F, Hoheisel G, Wirtz H, Gessner C. Multiplex analysis of cytokines in exhaled breath condensate. Cytometry A. 2006 Mar;69(3):169-72. doi: 10.1002/cyto.a.20231.

    PMID: 16496377BACKGROUND

  • Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E, Ottersbach G, Fischer M, Uhlig S, Putensen C. The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg. 2004 Mar;98(3):775-81, table of contents. doi: 10.1213/01.ane.0000100663.11852.bf.

    PMID: 14980936BACKGROUND

  • Wrigge H, Zinserling J, Stuber F, von Spiegel T, Hering R, Wetegrove S, Hoeft A, Putensen C. Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function. Anesthesiology. 2000 Dec;93(6):1413-7. doi: 10.1097/00000542-200012000-00012.

    PMID: 11149435BACKGROUND

  • Koner O, Celebi S, Balci H, Cetin G, Karaoglu K, Cakar N. Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass. Intensive Care Med. 2004 Apr;30(4):620-6. doi: 10.1007/s00134-003-2104-5. Epub 2004 Jan 13.

    PMID: 14722635BACKGROUND

  • Bonetto C, Terragni P, Ranieri VM. Does high tidal volume generate ALI/ARDS in healthy lungs? Intensive Care Med. 2005 Jul;31(7):893-5. doi: 10.1007/s00134-005-2668-3. Epub 2005 Jun 2. No abstract available.

    PMID: 15931524BACKGROUND

  • Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. 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 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

    PMID: 10793162BACKGROUND

MeSH Terms

Conditions

InflammationVentilator-Induced Lung Injury

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsLung InjuryLung DiseasesRespiratory Tract Diseases

Study Officials

  • Olympia I. Apostolopoulou, MD

    University of Thessaly

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

May 28, 2009

First Posted

May 29, 2009

Study Start

May 1, 2009

Primary Completion

September 1, 2013

Study Completion

September 1, 2013

Last Updated

October 25, 2013

Record last verified: 2009-11

Locations

GR(1)