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Determining which molecules to measure // Fine-tuning instruments to find them // Drawing the line between health and disease

Breath Tests: In One Breath

By Anita Slomski // Photographs by Grant Cornett // Summer 2013
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mouth breathing

Grant Cornett for Proto

Using breath to divine the inner workings of the human body is a practice as ancient as Hippocrates, who described the fetor hepaticus of liver failure that manifested itself in the fishy odor of patients’ exhalations. Other revelations from breath, just as distinctive, are also well known to clinicians: the fruity smell of acetone in uncontrolled diabetes, the freshly baked–bread vapors of typhoid fever, the ammonia reek of kidney disease. And although breath as a clue to disease was long ago replaced by more precise diagnostic tests, scientists have recently returned to breath’s rich repository of chemicals—about 3,000 compounds have been measured so far—to look for markers that could indicate the presence of a particular disease or gauge how well a patient is responding to treatment.

Breath has several potential advantages as an analytic tool. Unlike blood and urine, it can be sampled frequently and noninvasively, it’s never in short supply, it generates little or no infectious wastes, and results could be produced in real time using newer technology that can collect breath and parse its compounds instantly. Breath tests might be used, for example, for fast, inexpensive screening of large populations for exposure to a flu strain. And breath may hold a surprising trove of information in addition to the expected gases from the environment and metabolism. “We can collect microdroplets of water and particles to give us access to substances we could find only in blood and urine, such as fragments of DNA, messenger proteins, inflammatory cytokines, bacteria and cellular material,” says Joachim Pleil, research physical scientist at the Environmental Protection Agency, who studies molecules in breath to distinguish between those emanating from human physiology and inhaled compounds in the environment.

At June’s International Conference on Breath Research in Germany, scientists presented research on breath tests for Parkinson’s disease, bacterial infections in cystic fibrosis, cancer, diabetes and other conditions. During the past two decades, thousands of articles have been published on breath’s potential biomarkers. But in this young field, researchers have often had to depend on jerry-rigged instruments and ad hoc methods to collect and analyze breath, and the quality of much of the work has been suspect. Because people wrongly believe it’s easy to collect breath samples, there have been a lot of bad studies, and that has led many scientists to dismiss breath research as fringe science, according to Terence Risby, professor emeritus of environmental health sciences at Johns Hopkins University.

Now, however, that attitude may be changing, thanks in part to more accurate, commercially available instruments that collect breath as well as to advanced statistical algorithms that enable researchers to find associations between what they are measuring and clinical outcomes. “The instruments we use to analyze breath can detect compounds in our breath in concentrations measured in parts per billion,” says Raed Dweik, professor of medicine and director of the pulmonary vascular program at the Cleveland Clinic. “That’s the equivalent of finding one red Ping-Pong ball in a baseball stadium full of white Ping-Pong balls.” Such sensitivity is crucial, because abnormal physiology may announce itself through extremely subtle fluctuations in the normal range of a compound in breath.

Despite recent progress, only a handful of breath tests have made their way into common use. But researchers have been energized by the widespread acceptance of a breath test that measures concentrations of nitric oxide to reveal airway inflammation and show whether a patient needs corticosteroid treatment and is likely to respond to the therapy. Dweik notes that testing blood only gradually became standard practice, “and there’s still much we don’t understand about blood,” he says. He believes breath analysis could eventually ascend to prominence as a new frontier in medical testing.

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1. “Single Exhaled Breath Metabolomic Analysis Identifies Unique Breathprint in Patients with Acute Decompensated Heart Failure,” by Michael A. Samara et al., Journal of the American College of Cardiology, April 2013. By analyzing the breath of 61 patients with heart disease, researchers were able to identify which patients would develop heart failure—a development that could allow physicians to modify patients’ medications to prevent it.

2. “Smart Sensor Systems for Human Health Breath Monitoring Applications,” by G.W. Hunter et al., Journal of Breath Research, September 2011. To revolutionize health care diagnostics, breath tests will need to be portable and inexpensive so patients can monitor their health status at home or in the clinic. The authors describe one approach to miniaturizing a breath monitoring system for asthma.

3. “Current Status of Clinical Breath Analysis,” by T.H. Risby and S.F. Solga, Applied Physics B: Lasers and Optics, May 2006. This review article makes recommendations for how breath analysis can advance more quickly, which includes standardizing protocols for breath collection and correcting for ambient air.

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