1729. Elevated Carbon Monoxide in the Exhaled Breath of Mice During a Systemic Bacterial Infection or Endotoxicosis
Session: Poster Abstract Session: Studies of the Interface of Host-Microbial Interaction
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 1729_IDWPOSTERweb.pdf (3.7 MB)
  • Background: Blood is the specimen of choice for most laboratory tests for diagnosis and disease monitoring. Sampling exhaled breath is a noninvasive alternative to phlebotomy and has the potential for real-time monitoring at the bedside. To evaluate breath analysis as a biomarker for infection and sepsis under experimental conditions, we crafted a means for noninvasively collecting breath samples from individual awake animals. 

    Methods: Containers flushed with ultra-pure air were used to collect breath samples from nose-only manifolds, and the contents were subjected to gas chromatography and mass spectrometry procedures developed for analysis of trace volatile organic compounds (VOCs) in the atmosphere. We first evaluated the system with experimental infections of BALB/c scid mice with the bacterium Borrelia hermsii. Infected mice had high density bacteremia by day 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations acute phase reactants and of both inflammatory and anti-inflammatory cytokines.

    Results: Whereas breath samples from individual infected and uninfected animals did not significantly differ for 72 different VOCs, carbon monoxide (CO) was elevated in samples from infected mice, with a mean (95% confidence limits) effect size of 4.2 (2.8-5.6), when differences in CO2 in the breath were taken into account (CO/CO2). CO/CO2 values declined to the uninfected range after 1 day of ceftriaxone. CO was not elevated in B. hermsii culture headspaces. CO/CO2 in the breath also increased dose dependently within 4 hr of a single injection of purified Escherichia coli endotoxin in wildtype BALB/c mice, and these elevations persisted for several hours. Correlated with elevated CO in breath samples were blood levels of heme oxygenase-1 protein as measured by ELISA and HMOX1 cDNA as measured by PCR.

    Conclusion: Our findings with single, unanesthetized animals with masses of 20-30 grams provide a rationale for further studies of CO in the human breath as a biomarker that is informative for diagnosis, staging, and monitoring effects of resuscitation and therapy of systemic infection and sepsis.

    Alan Barbour, MD, Arash Ghalyanchi Langeroudi, DVM, PhD, Charlotte Hirsch, BS, Azadeh Shojaee Estabragh, DVM, Eric Lewis, BS, Simone Meinardi, PhD and Donald Blake, PhD, University of California Irvine, Irvine, CA

    Disclosures:

    A. Barbour, None

    A. Ghalyanchi Langeroudi, None

    C. Hirsch, None

    A. Shojaee Estabragh, None

    E. Lewis, None

    S. Meinardi, None

    D. Blake, None

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.