Hill and Colleagues’ IDeA Research Yields Breath Test for Lung Infections
- By Joshua E. Brown
Police nab criminals by their fingerprints – and soon doctors may be able to nab bacteria by their “breathprint.”
Researchers at the University of Vermont have been developing technologies that detect disease-causing bacteria in the lung by simply measuring what’s in the breath. The research has potential for creating a fast and easy breath test to detect common infections like tuberculosis.
Traditional tests to diagnose bacterial infections in the lungs can take days or weeks, says Jane Hill, Ph.D., an assistant professor of engineering who co-led the new study, “but we can measure breath in one minute.”
The new technique profiles volatile organic compounds (VOCs) – gases swirling in the air exhaled from the lungs – to generate a distinctive chemical signature for differing types of infectious bacteria.
Led by UVM graduate student Jiangjiang Zhu, the UVM team – including members from the School of Engineering, the College of Medicine’s Department of Microbiology and Molecular Genetics, and the Vermont Lung Center – successfully distinguished between species of bacteria, as well as strains of the same bacteria, in the lungs of infected laboratory mice.
Their results were presented in the Journal of Breath Research, published online by the Institute of Physics, on January 11, 2013.
Clinicians see breath-testing as an attractive method for diagnosing disease; it’s easy to use, not invasive, and potentially inexpensive. Scientists have already investigated breath-based diagnostics for multiple cancers, asthma, and diabetes.
In this study, the researchers analyzed the VOCs given off by Pseudomonas aeruginosa and Staphylococcus aureus, both of which are common in lung infections associated with pneumonia and other diseases including cystic fibrosis and chronic obstructive pulmonary disease (COPD).
The scientists first infected mice with the two bacteria and sampled their breath after 24 hours. Then they ionized the samples and sprayed them through a mass spectrometer to analyze the presence and concentrations of various VOCs.
The technique is called secondary electrospray ionization mass spectrometry, or SESI-MS, which is capable of detecting VOCs down to parts-per-trillion.
The UVM team found that there was a significant difference between the breath profiles of mice infected with the bacteria and mice that were uninfected. The two different species of bacteria could also be distinguished, as could the two different strains of the P. aeruginosa that were used.
The researchers hypothesize that bacteria in the lungs produce unique VOCs that are not found in regular human breath due to their differing metabolism.
“Bacteria, when they get in your lung, are eating the body as their source of nutrients,” says Hill. “This releases byproducts — a particular suite of volatiles, which are unique to the bacterium. And that’s the basis for this research. Every bacterium has its own set of metabolic enzymes and its own interaction with the host which allows us to distinguish between one bacterium and another during infection.”
And this real-world, real-body aspect of the research is important, since the VOC profile of bacteria grown in laboratory dishes can look dramatically different than those living in host organisms. The new study reported only a 25 to 34 percent overlap in the VOC profile of the same bacteria strains grown in a lab culture versus when grown in mice.
The UVM team – which, in addition to Hill and Zhu, includes Laurie Leclair, M.D., associate professor of medicine and pulmonologist, Matthew Wargo, Ph.D., assistant professor of microbiology and molecular genetics, and engineering researcher Heather Bean – is moving the laboratory research toward human clinical trials, including an upcoming study in collaboration with Massachusetts General Hospital.
“I suspect that we will also be able to distinguish between bacterial, viral and fungal infections of the lung,” says Hill, who is among the junior faculty receiving support from the College of Medicine’s Center for Immunology and Infectious Diseases IDeA grant.
The World Health Organization estimates that one-third of the world’s population carries tuberculosis and that this lung disease causes more than a million deaths each year.
“TB takes about six weeks to diagnose,” says Hill, allowing an infected person to spread it unwittingly. “Faster diagnosis of the disease would allow for faster treatment decisions and would also decrease disease transmission.”
She anticipates a time when patients could visit a physician, breathe into an instrument and know within minutes, “what you’re infected with,” she says, and, perhaps, “whether your antibiotic regime is effective, whether you need different antibiotics, and whether you have more then one bug causing your problem.”
The new research has drawn the attention of international media including the BBC and Scientific American.
This research was supported by the UVM College of Medicine’s Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (grant 8 P20 GM103496-07) within the National Institutes of Health; the Cystic Fibrosis Foundation; and NASA EPSCoR.
(Portions of this story were written by Michael Bishop, Institute of Physics.)