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Health Care in a Huff: Breath Tests for Diseases

Breathalyzers, long a tool in police officers' quivers, may be coming soon to a doctor's office near you



COURTESY OF MENSSANA RESEARCH, INC.

Most of us associate Breathalyzers with drunk-driving arrests. But breath tests can reveal a lot more than how many alcoholic beverages a person chugged. They're also used to diagnose some medical conditions, including jaundice in babies, lactose intolerance and ulcers, as well as to monitor whether asthma drugs are effective. And researchers say breath analyzers may one day be used to quickly identify a slew of other disorders, including cancer, leading to early detection and treatment.

The way these tests work: Every time you take a breath, you inhale oxygen and exhale carbon dioxide (CO2), along with at least a thousand other chemicals that actually provide a so-called "breathprint," or unique breath profile of your health. The first person to recognize—or at least write about—this phenom was Hippocrates (460 B.C. to 377 B.C.), considered to be the father of medicine, who suggested that bad breath was a sign of disease. But it was not until late last century that scientists actually identified many of these chemicals.

In 1971, researchers led by Nobel Prize winning chemist Linus Pauling identified about 250 breath chemicals using gas–liquid partition chromatography (which  separates molecules based on their boiling points and polarity, or unequal electrical charges).

Thanks to improvements in laboratory techniques, scientists have since identified at least 1,000 different chemicals in human breath, a few of which have become the basis of medical tests. The U.S. Food and Drug Administration (FDA) has approved six medical breath tests, according to Terence Risby, a professor of environmental health science at Johns Hopkins Bloomberg School of Public Health in Baltimore.

The most common is one used to determine whether breathing tubes are correctly positioned in patients' lungs (occasionally doctors accidentally thread the tube through the esophagus and into the stomach), according to Raed Dweik, a pulmonologist and director of the Pulmonary Vascular Program at the Cleveland Clinic in Ohio. If the tube is properly placed, CO2 moves from the lungs and out through the tube; if not, carbon dioxide will not flow out. A golf ball-size CO2 detector changes color when it picks up the gas, signaling to doctors that the tube is positioned correctly. Another type of carbon dioxide detector known as a capnograph is routinely used in hospitals to continuously monitor the amount of CO2 exhaled by patients anesthetized for surgery or hooked up to ventilators to help them breath. Dweik says that doctors can determine if patients are getting enough oxygen by the amount of carbon dioxide leaving their bodies. 

Physicians now also use a breath test to determine whether asthma meds are working by measuring the amount of nitric oxide a patient with the respiratory illness exhales. According to Dweik, people with asthma, which is marked by chronic inflammation of the airways and difficulty breathing, exhale abnormally high levels of nitric oxide, a gas  that regulates blood flow but may damage cells and cause inflammation if overproduced in the airways: The nitric oxide content of an asthmatic's breath can be as high as 100 or 200 parts per billion or ppb (100 nitric oxide molecules in every billion exhaled molecules) compared with the 10 to 20 ppb in each breath of a nonasthmatic person.

If an asthma patient is not exhaling normal nitric oxide levels within days of beginning a treatment, it indicates the therapy is not effective and another one should be tried. "The whole test takes about five minutes," Dweik says, noting that a patient breathes into a tube attached to a breath analyzer, which produces an electronic readout of nitric oxide concentrations.

Physicians can diagnose lactose intolerance with a test that identifies abnormally high levels of hydrogen in the breath produced by gut bacteria that gobble lactose when the body fails to break down the milk sugar on its own. In addition, jaundice in babies can be confirmed with a test that scans the breath for high levels of carbon monoxide produced when the liver is not functioning properly, and there's a breath test that identifies the presence of the ulcer-promoting intestinal bacteria Helicobacter pylori (H. pylori).
 


Another breath test determines whether a transplanted organ is taking or being rejected by a patient. If a patient's body is rejecting a new heart, the breath test will detect alkanes in the breath; alkanes are the by-products of chemical reactions set off by free radicals (unstable, cell-damaging molecules) that are produced by the body when it rejects donated organs.

There are many reasons breath tests could be the next frontier in medical diagnosis, Risby says, noting that they are  relatively inexpensive to administer, safe (the only requirement is that a person is breathing), and noninvasive (there's no need to stick patients with needles or take a slice of tissue to biopsy).

A research team led by physicist Jun Ye at the University of Colorado at Boulder (U.C.B.) is currently testing a breath analyzer that scans for abnormally high levels of about 10 disease-related molecules within two minutes. Among them: ammonia (a marker for liver and kidney disease); acetone (an indicator of diabetes); and ethane, a potential cancer marker.

The liver and the kidneys normally filter ammonia from the blood.  If these organs are not doing their jobs properly, ammonia builds up in the body and is exhaled at unusually high levels, says Michael Thorpe, a physicist in Ye's lab group. He notes that the team's breath analyzer also screens for elevated levels of acetone, a marker for diabetes, a disease in which cells cannot efficiently absorb glucose, their primary fuel source. When the body cannot get energy from glucose, it breaks down fat for fuel; acetone is one of the by-products of fat breakdown.

The experimental breath analyzer also searches for ethane. Ethane tends to accumulate in the body when cells are damaged by free radicals, which may lead to  cancer, Thorpe says.  But he says more research is needed to identify a collection of breath chemicals associated with cancer, given that ethane may also be linked to other conditions such as Alzheimer's disease and arteriosclerosis (hardening of the heart arteries that can lead to heart attacks).

Menssana Research in Newark, N.J., is currently conducting a clinical trial on a breath test for lung cancer. Founder and CEO Michael Phillips (profiled by Scientific American in 2003) has developed a technology that  screens a set of 10 to 15 molecules typically released in the breath of lung cancer sufferers. Scientists suspect toxins (such as components of tobacco) activate a system of enzymes (proteins) that work to expel the poisons, producing chemical by-products released in the breath. (People with types of cancer other than lung also emit telltale cancer molecules from their bodies—in fact, dogs may be able to identify people with various types of cancer by sniffing their skin and breath, studies suggest).

Phillips says Breathalyzers could reduce the need for computerized tomography (CT) scanning, which is currently used to screen high-risk patients (smokers and former smokers) for lung cancer:  The x-rays not only expose patients to potentially dangerous amounts of radiation, but they cost around $1,500 to $2,000 a pop to administer compared with $150 to $200 for a breath test. He notes that Breathalyzers would not replace CT scans, but that doctors could use them to determine whether CT scans are necessary to confirm – or dispute – results.

"I believe very strongly," Ddweik  says, that breath analyzers are "the future of medical tests."

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