Monday, August 5, 2013

Breathalyzer Detects Infections in Mice; May Replace Blood Testing in Humans


Breath analysis may prove to be an accurate, noninvasive way to quickly determine the severity of bacterial and other infections, according to a UC Irvine study appearing online today in the open-access journal PLOS ONE.

Employing a chemical analysis method developed for air pollution testing, UC Irvine microbiologists and chemists were able to correlate inflammation levels in laboratory mice to the amount of naturally produced carbon monoxide and other gases in breath samples.

The findings point to human applications of this technology in emergency rooms and intensive care units, potentially augmenting or replacing blood tests.

"Breath analysis has been showing promise as a diagnostic tool in a number of chronic diseases," said Dr. Alan Barbour, professor of microbiology & molecular genetics and medicine. "This study provides the first evidence … that it can be used for rapid clinical assessment of infections, which can lead to prompt institution of effective treatments."

Barbour collaborated with UC Irvine chemist Donald Blake, utilizing a gas analysis method devised for the Rowland-Blake lab's atmospheric chemistry research, which measures the level of trace gases that contribute to local and regional air pollution. It's one of the few research groups in the world recognized for its ability to gauge precisely at the parts-per-trillion level. Previous breath sampling work by the Rowland-Blake lab has involved diabetes, cystic fibrosis and kidney failure.

Barbour believed that breath analysis could additionally be used on infections, which elicit strong inflammatory responses in the body. Several compounds, or "biomarkers," are by-products of these responses. They can be identified in blood but also detected in exhaled breath.

Studying mice with bacterial blood infections, the researchers found that increases in the severity of infection elicited significantly higher amounts of carbon monoxide in relation to carbon dioxide in breath samples, making carbon monoxide a reliable biomarker for the presence and intensity of infection. Importantly, the carbon monoxide returned to normal levels soon after an antibiotic was given.

"Using a breath analysis method like this could help physicians in the emergency room and ICU make critical decisions about serious infections more quickly than if they had to wait for blood tests to come back from the lab," Barbour said.

He and Blake will next expand their research to human breath samples. Their diagnostic method is currently under patent review.

Charlotte Hirsch, Arash Ghalyanchi Langeroudi, Simone Meinardi, Eric Lewis and Azadeh Shojaee Estabragh of UC Irvine also contributed to the study, which was funded by a National Institute of Allergy & Infectious Diseases grant to the Pacific Southwest Regional Center of Excellence for Biodefense & Emerging Infectious Diseases (AI-065359).

REFERENCE

Alan G. Barbour, Charlotte M. Hirsch, Arash Ghalyanchi Langeroudi, Simone Meinardi, Eric R. G. Lewis, Azadeh Shojaee Estabragh, Donald R. Blake. Elevated Carbon Monoxide in the Exhaled Breath of Mice during a Systemic Bacterial Infection. PLoS ONE, 2013; 8 (7): e69802 DOI: 10.1371/journal.pone.0069802

ABSTRACT

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. Improved instrumentation has advanced breath analysis for several gaseous compounds from humans. However, application to small animal models of diseases and physiology has been limited. To extend breath analysis to mice, we crafted a means for collecting nose-only breath samples from groups and individual animals who were awake. Samples were subjected to gas chromatography and mass spectrometry procedures developed for highly sensitive analysis of trace volatile organic compounds (VOCs) in the atmosphere. We evaluated the system with experimental systemic infections of severe combined immunodeficiency Mus musculus with the bacterium Borrelia hermsii. Infected mice developed bacterial densities of ~107 per ml of blood by day 4 or 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations of both inflammatory and anti-inflammatory cytokines. While 12 samples from individual infected mice on days 4 and 5 and 6 samples from uninfected mice 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. Normalized CO values declined to the uninfected range after one day of treatment with the antibiotic ceftriaxone. Strongly correlated with CO in the breath were levels of heme oxygenase-1 protein in serum and HMOX1 transcripts in whole blood. These results (i) provide further evidence of the informativeness of CO concentration in the exhaled breath during systemic infection and inflammation, and (ii) encourage evaluation of this noninvasive analytic approach in other various other rodent models of infection and for utility in clinical management.

Source: PLOS ONE and Science Daily

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