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About Breath Testing: A Brief History

(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. (Photo: http://en.wikipedia.org/wiki/File:Hippocrates_rubens.jpg)

Antoine 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. (Photo: http://upload.wikimedia.org/wikipedia/commons/b/
b1/Lavoiser_humanexp.jpg
)

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. (Photo: http://upload.wikimedia.org/
wikipedia/commons/d/db/Pauling.jpg
.)

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:

1. 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.

2. 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 golf pencil. This trap is then sent to the laboratory for analysis by gas chromatography and mass spectrometry. 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 - each can be identified with its own unique "breath fingerprint".

Like the BCA system, our BreathscannerTM system collects breath samples for two minutes, but the main difference is that it also connects to our BreathLinkTM system, which concentrates breath samples and then immediately delivers them to our servers for analysis. Once we confirm the accuracy of our BreathscannerTM/BreathLinkTM systems, we will be able to offer point-of-care breath analysis in a matter of minutes, before the patient even leaves the doctor's office.

Both our BCA and BreathLinkTM systems are in use for several clinical studies:

Testing with the BCA

Radiation (funded by BARDA)
- NYU
- Seattle Swedish
- MD Anderson (Orlando)
- PNNL

Lung cancer
-Seattle Swedish
-NYU
-MD Anderson (Orlando)

Testing with BreathLinkTM
and the BCA

Pulmonary tuberculosis
-Homerton Hospital, London
-Mumbai
-Manila
-Cavite
-UMDNJ

Heart transplant rejection
-Cedars Sinai
-Columbia (NY Presbyterian)
-Drexel
-Newark Beth Israel
-Stanford University

Breast cancer
-St. Michael´┐Żs, Newark NJ
-Columbia (NY Presbyterian)
-Seattle Swedish
-Weill Cornell
-Maastricht

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.