About Breath Tests

(Adapted, in part, from "Breath tests in medicine" by Michael Phillips MD, FACP, Scientific American, July 1992, pages 74 to 79).

Since the time of Hippocrates in Ancient Greece, physicians have known that the aroma of human breath can provide clues to diagnosis. The astute clinician is alert for the sweet, fruity odor of acetone in patients with uncontrolled diabetes, the musty, fishy reek of advanced liver disease, the urine-like smell that accompanies failing kidneys and the putrid stench of a lung abscess.

Lavoisier, in eighteenth century France, was the pioneer of modern chemical analysis. He was the first to analyze breath and demonstrate that it contains carbon dioxide. This was the first scientific evidence that the body acts as a furnace which "burns" foodstuffs while consuming oxygen and generating carbon dioxide. In the nineteenth century, chemists developed breath tests for alcohol, and also for acetone which is increased in diabetes mellitus.

The modern era of breath testing commenced in 1971, when Nobel Prize winner Linus Pauling breathed through a very cold tube to "freeze out" the volatile organic compounds (VOCs). He then analyzed these frozen compounds by gas chromatography and found that normal human breath contains many different VOCs in very low concentrations.

We now know that a sample of normal human breath usually contains more than 200 different volatile organic compounds (VOCs), most of them in picomolar concentrations (around one part in a trillion).

Researchers suspected that some of these breath VOCs may be markers of disease, but this theory made only slow progress because of two major technical problems:

First, the concentrations of most breath VOCs are so low, they can only be detected with sensitive laboratory instruments. Outside a research laboratory, there was no easy way to collect a sample of breath and analyze it for VOCs.

Second, even after analyzing the breath VOCs, nobody understood what they signified. Which were normal and which were abnormal? This was not known, and most breath VOCs are not even mentioned in modern textbooks of medicine or biochemistry.

Research in the laboratories of Menssana Research has overcome these technical problems, and finally provided some answers to these questions.

We have developed a portable breath collection apparatus (BCA) which can collect breath samples virtually anywhere. A person sits breathing quietly into the BCA for two minutes, while it captures breath VOCs onto a small sorbent trap which looks like a stainless steel cigarette. This trap is then sent to the laboratory for analysis by gas chromatography and mass spectroscopy. Each analysis usually identifies more than 200 different VOCs. The assay is so sensitive that we also collect a sample of the room air at the same time as the breath sample, so that we can subtract the inhaled VOCs from the breath VOCs and calculate the "signal" coming from the body.

This breath test has identified a new and comprehensive set of markers of oxidative stress known as the breath methylated alkane contour (BMAC). Changes in the BMAC have revealed distinctive changes in a number of different diseases ö each can be identified with its own unique ãbreath fingerprintä.

This breath test is now being evaluated in several clinical studies, including:

lung cancer *
breast cancer *
heart transplant rejection *
kidney disease
ischemic heart disease
diabetes mellitus
development of the next-generation BCA *

* supported by grant funding from the United States National Institutes of Health

Institutions collaborating with the clinical studies include:

Barbarba Ann Karmanos Cancer Institute - Wayne State University, Michigan
Columbia Presbyterian College of Physicians and Surgeons, New York
Cornell Weill School of Medicine, New York
Danbury Hospital, Connecticut
Imperial College School of Medicine, London, England
Mt. Sinai Medical Center, New York
Newark Beth Israel Medical Center, New Jersey
New York University
Penn State-Geisenger Health Care System
Saint Vincents Medical Center, New York
Temple University, Philadelphia
University of Alabama at Birmingham
University of California Los Angeles

Physicians and patients of the 21st century may eventually come to think of a breath test in much the same way as we now think of a chest x-ray or a blood test: as an inexpensive and convenient screening test which can detect several diseases in their earliest and most treatable stages.