Ultra-sensitive breath tests aim to identify disease

By JEFFREY GOLD
Associated Press Writer

August 20, 2005, 9:43 AM EDT

NEWARK, N.J. -- Breath tests aren't just for drunken drivers anymore.

They now can help determine if a heart transplant is being rejected and potentially will cut down on the number of biopsies transplant patients must endure.

The new test was developed by a New Jersey researcher, Dr. Michael Phillips, who expects his patient-friendly method will one day be used to detect lung cancer, breast cancer, kidney disease and diabetes.

And one day, he hopes, giving a breath sample will be as common as a blood or urine test.

"I could see a screening breath test as part of a routine medical exam," said Phillips, founder and CEO of Menssana Research Inc., which is based in Fort Lee and has its lab in Newark.

Experts caution, however, that while breath tests are a promising diagnostic technique, it does not appear that they will completely replace trusted methods such as biopsies and CT scans.

In the meantime, Phillips is looking to license a company to produce and market his Heartsbreath test to doctors and hospitals, since such a nationwide effort cannot be undertaken by his four-person firm.

Analyzing breath to diagnose disease is a concept that dates back two millennia, Phillips said, noting that ancient physicians found that a diabetic's breath smelled like rotten apples. And while a police Breathalyzer is designed to detect just one substance _ alcohol _ the acetone that causes diabetic breath is among the 200 compounds that the Heartsbreath technology can identify.

In addition, Phillips said, his technology can determine

the levels of each compound, being about a billion times more sensitive than police machines.

By taking samples from thousands of ill people, "We've identified a number of compounds that are the 'fingerprint' of a disease," Phillips said.

Because illnesses produce high amounts of free radicals, which oxidize cell membranes and release certain compounds, each disease has a unique "fingerprint," he said.

Part of Phillips' contribution has been developing the computer software to extract the fingerprint from a mass of data provided by two standard pieces of lab equipment that analyze the breath samples: a gas chromatograph and mass spectrometer.

The samples reveal a lot about an individual, said Renee Cataneo, a Menssana research associate. "I can tell if they were drinking the night before, or if they're hungry," she said. An empty stomach, it seems, gives higher readings of acetone.

Following several years of clinical trials funded by federal grants, the Heartsbreath test was approved in 2004 by the Food and Drug Administration to be used along with biopsies to determine if a donor heart is being rejected. If rejection is detected, anti-rejection drugs can be adjusted.

There are some 2,000 U.S. heart transplant patients annually, and each traditionally has about 20 biopsies in the first year after their transplant, Phillips said.

The biopsy, done under local anesthesia, involves threading a tube down a neck vein and into the heart, where it snips several tiny pieces of the heart and removes them so they can be examined by a pathologist. It costs about $2,500.

In the Heartsbreath test, the patient puts on a nose clip and breathes into a tube for two minutes. The sample is captured in a 4-inch steel tube the width of a pencil, which is stuffed with absorbent material.

The contents of the tube, along with those of another tube that has collected air from around the patient, are analyzed by the chromatograph and spectrometer.

The Heartsbreath test is likely to reduce many of the routine biopsies given to transplant patients, said Judith Massicot-Fisher, who manages heart transplant research grants for the Heart, Lung, and Blood Institute of the National Institutes of Health.

"They're always talking about wanting a noninvasive way to do it," she said.

However, should the breath test show signs of rejection, the patient would require a biopsy to confirm the diagnosis and determine the severity before altering anti-rejection therapy, she said.

The Heartsbreath test isn't the only option to biopsies. Transplant patients also can use a blood test that examines certain genes in white blood cells for signs of rejection.

Phillips, 62, of Fort Lee, said it is premature to provide cost estimates for the test, but said the collection device would be well within the reach of a clinic or hospital. He expects that the "off-the-shelf" machines to analyze the samples would generally be bought by testing labs, which would also purchase the Menssana software to interpret the data.

Dr. Norman H. Edelman, chief medical officer for the American Lung Association, said it would be an "enormous advance" if a breath test could provide early detection of lung cancer.

CT scans are often used now, he said. Such tests are very sensitive _ finding nodules that are only 2 millimeters big _ but do not generally reveal which are cancerous, Edelman said.

"If this (breath test) adds specificity, it could be useful," he said.

"They talk about using it as a screening test, and I think they have some hurdles," he added. "He would have to prove that a negative test using this method is sufficiently sensitive to avoid using a CT scan."

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On the Net:

Menssana Research: http://www.menssanaresearch.com/

National Heart, Lung, and Blood Institute: http://www.nhlbi.nih.gov/

American Lung Association: http://www.lungusa.org/