Display options
Share it on

Open Forum Infect Dis. 2014 Sep 18;1(2):ofu085. doi: 10.1093/ofid/ofu085. eCollection 2014 Sep.

Elevated carbon monoxide to carbon dioxide ratio in the exhaled breath of mice treated with a single dose of lipopolysaccharide.

Open forum infectious diseases

Arash Ghalyanchi Langeroudi, Charlotte M Hirsch, Azadeh Shojaee Estabragh, Simone Meinardi, Donald R Blake, Alan G Barbour

Affiliations

  1. Departments of Medicine ; Microbiology and Molecular Genetics.
  2. Chemistry , University of California, Irvine.

PMID: 25734151 PMCID: PMC4281777 DOI: 10.1093/ofid/ofu085

Abstract

BACKGROUND: Analysis of volatile organic chemicals in breath holds promise for noninvasive diagnosis and monitoring of patients, but investigation of this in experimental mouse models has been limited. Of particular interest is endogenous production of carbon monoxide as a biomarker of inflammation and, more particularly, during sepsis.

METHODS: Using a nose-only collection procedure for unanesthetized individual adult mice and sensitive gas chromatography of carbon monoxide (CO) and carbon dioxide (CO2) of sampled breath, we investigated the responses of mice to one-time injections with different doses of purified Escherichia coli lipopolysaccharide. Two strains of mice were examined: BALB/c and C3H, including an endotoxin-resistant mutant (HeJ) as well as the wild type (HOuJ).

RESULTS: The CO to CO2 ratio increased in a dose-responsive manner within hours in treated BALC/c mice but not control mice. The CO/CO2 values declined to the range of control mice within 48-72 h after the injection of lipopolysaccharide. Breath CO/CO2 values correlated with systemic inflammation biomarkers in serum and heme oxygenase-1 gene expression in blood. C3H/HOuJ mice, but not the HeJ mice, had similar increases of the CO/CO2 ratio in response to the endotoxin.

CONCLUSIONS: Carbon monoxide concentrations in exhaled breath of at least 2 strains of mice increase in response to single injections of endotoxin. The magnitude of increase was similar to what was observed with a bacteremia model. These findings with an experimental model provide a rationale for further studies of normalized CO concentrations in human breath as an informative biomarker for staging and monitoring of sepsis.

Keywords: biomarker; breath analysis; endotoxin; heme oxygenase; sepsis

References

  1. PLoS One. 2013 Jul 31;8(7):e69802 - PubMed
  2. Clin Infect Dis. 2013 Apr;56(7):996-1002 - PubMed
  3. Trends Mol Med. 2013 Jan;19(1):3-11 - PubMed
  4. Am J Respir Crit Care Med. 2001 Apr;163(5):1113-6 - PubMed
  5. J Clin Invest. 2008 Jan;118(1):239-47 - PubMed
  6. Am J Physiol. 1994 Jan;266(1 Pt 2):R125-35 - PubMed
  7. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15613-8 - PubMed
  8. Trends Immunol. 2013 Mar;34(3):129-36 - PubMed
  9. Respir Med. 2001 Dec;95(12):1003-5 - PubMed
  10. Crit Care Med. 2014 Mar;42(3):625-31 - PubMed
  11. Prog Cardiovasc Dis. 2012 Jul-Aug;55(1):34-43 - PubMed
  12. Am J Respir Crit Care Med. 2011 Sep 1;184(5):602-15 - PubMed
  13. Am J Physiol. 1978 Nov;235(5):R219-27 - PubMed
  14. J Breath Res. 2011 Sep;5(3):037108 - PubMed
  15. Addiction. 2005 Feb;100(2):159-67 - PubMed
  16. Expert Rev Mol Diagn. 2011 Jun;11(5):487-96 - PubMed
  17. Physiol Rev. 2006 Apr;86(2):583-650 - PubMed
  18. Anal Chem. 2001 Aug 1;73(15):3723-31 - PubMed
  19. N Engl J Med. 2013 Aug 29;369(9):840-51 - PubMed
  20. Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37 - PubMed

Publication Types

Grant support