Breath Analyzers: A Refreshing Diagnostic Tool.

As analytical instrument companies search for new areas of potential growth in their rapidly maturing industry, several have been turning towards applying their technologies to analyzing human breath to diagnose disease. Interestingly, the commercial potential for breath analysis instrumentation comes out of the very maturation process that instrument companies usually tend to find so distressing. As the old optimists' maxim goes, when a door shuts a window opens.

Since ancient times, health practitioners in various cultures have used breath in diagnosing illness, though it tended to be more of an art than a repeatable scientific technique. Western medical technology has focused more on testing body fluids such as blood and urine, or on other samples such as tissue or microbial cultures. But just as the last twenty years has seen wet chemistry techniques largely replaced with instrumentation, breath analysis instrumentation now shows promise of a movement towards making a significant impact in diagnosing disease.

As in the case of wet chemistry, the analysis of breath has been made possible by advances in the sensitivity and accuracy of instrumentation technologies. The improved technologies allow for detection of chemicals at the relatively low concentrations that are found in breath as compared to those levels usually found in body fluids or tissue.

There are several potential advantages of breath analysis over other forms of diagnostic techniques. Breath analysis techniques tend to be much less invasive, faster than competing techniques, and they can have substantial economic advantages. There are also cases where breath analysis can detect diseases that are difficult or impossible to detect by other means.

Several breath analysis instruments are now on the market that perform a variety of diagnostic tests, using several different technologies. However, there is much these products do not have in common. They don't use the same technologies, they don't necessarily perform the same tests, and they don't compete headlong in the same markets. But what they do have in common is their use of human breath as an analyte for diagnosing disease.

Breath analysis systems are currently being sold to address a number of diagnostic testing challenges, including bacterial overgrowth testing, measurement of intestinal transit time, urinary tract infections, carbohydrate absorption, and various gastrointestinal diagnostic applications, such as fat malabsorption, gastric emptying, lactose intolerance, amino acid oxidation, liver function, fatty acid oxidation and metabolic turnover. Breath analyzers can also test for minute amounts of bacteria that are difficult to diagnose using traditional blood tests.

Manual tests that mass spec-based breath analyzers are replacing or competing with include carbon-14 glycine cholate tests for bacterial overgrowth, carbon-14 lactose breath tests, carbon-14 stool excretion intestinal biopsies, intestinal intubations for culture intestinal perfusion, lactose barium radiography lactose tolerance tests, and stool pH tests for fecal reducing substances.

Technologies currently being used or developed commercially for breath analysis include specially customized GC/MS systems, quadrupole mass spec with chemical ionization, isotope ratio mass spec, ultrasensitive laser spectroscopy, selected ion flow tube (SIFT) based on modified quadrupole, and electronic noses.

Perhaps the area in which there is the most competition in breath analysis instrumentation is in the market for carbon 13 analyzers. Several companies have already entered this market, which appears to have significant potential. That potential is based on a fairly recent shift in medical thinking that places the blame for most ulcers on bacteria known as Helicobater pylori (H. pylori).

According to the Centers for Disease Control and Prevention (CDC), over 50% of the world's population is infected with H. pylori, and one out of ten Americans suffers from peptic ulcers, most of which are now believed to be caused by H. pylori. Peptic ulcer disease is estimated by the CDC to cost the United States $6 billion per year. Until fairly recently, it was believed the ulcers were mainly caused by spicy foods and stress, but now researchers believe that 90% of peptic ulcers are caused by H. pylori infection.

Long-term infection with H. pylori is also associated with gastric cancer, the world's second most common form of cancer. Healthcare providers can save a lot of money by attacking peptic ulcers with antibiotics rather than with acid-producing therapies or other treatments used in the past. A paper published by the CDC entitled Economics of Peptic Ulcer Disease and H. pylori Infection states that studies indicate that curing an ulcer with antibiotics takes far less time and costs less than one-tenth the amount of treating ulcer symptoms over a lifetime.

Breath analyzers are powerful weapons in fighting H. pylori infection because they can detect the bacteria accurately, quickly, non-invasively and with very good sensitivity. Breath analyzers are also effective in reducing the cost of treatments for peptic ulcers because they can determine accurately when the bacteria is no longer present and treatment can be stopped.

The instrument technique being used to detect H. pylori is isotope ratio mass spectrometry. This is an example of the strange ways in which shifting markets and technological advances can bring about enormous change in the analytical instrument industry. Isotope ratio mass spec has long been considered one of the most arcane techniques, of interest only to a small number of research scientists, particularly those involved in geochemical and nuclear applications. Now, with its new application in detecting H. pylori infection, isotope ratio mass spec has the potential to find a vast new market that includes an entirely different kind of consumer.

Companies currently active in this market include the Finnigan MAT division of ThermoQuest, Europa, Micromass, Analytical Precision and MERETEK. In addition to these companies, there are others that have developed or are in the process of developing products for breath analysis such as V&F Systems, a maker of process mass spectrometers that is using its Airsense 2000 quadrupole with chemical ionization for breath analysis.

The Finnigan MAT system is called the BreathMAT. Claimed by its maker to be the first dedicated 13C-UBT system, the BreathMAT is specifically designed for diagnosis of H. pylori infection. Finnigan also claims that the system has made 13C-UBTs affordable and easy-to-use, while adding an extra margin of security and reliability.

Although Finnigan claims to be the first system dedicated to H. pylori detection, several other companies make systems that specialize in 13C analysis from a sample of breath, which is virtually the same thing. Europa, which specializes in ion ratio systems, makes the ABCA Automated Breath 13 Carbon Analyzer. The manufacturer says it provides simplicity of operation and ease of maintenance on a budget. It includes a software integrated 200-position autosampler and bar code reader to automate the process of measuring 13C.

In addition, MERETEK markets a breath test kit, advertising it as "the first and only non-radioactive, non-invasive breath test available for the direct detection and post-treatment monitoring of H. pylori." The MERETEK system uses the Europa ion ratio mass spec for its analysis.

Micromass offers the MultiFlow, an automated multi-function sample preparation module for ion ratio mass spec. Micromass says the benchtop system is ideal for routine breath gas analysis with a high throughput of around two minutes per sample, automated analysis in excess of 250 samples per day, and unattended overnight runs with automatic quality checks.

Electronic noses could also have significant promise in diagnosing diseases. AromaScan is currently studying how to use its electronic nose technology to diagnose pneumonia through breath analysis. The company is also looking at several different ways to use its technology to diagnose other diseases through other sampling techniques.

Other uses for breath analysis are also beginning to emerge, such as the U.S. Air Force's use of breath analysis to analyze the effects of jet fuel exposure in personnel working in close contact with aircraft.

The challenge for instrument makers in approaching the breath analysis market is three-fold. First of all, companies must identify diagnostic challenges to which they can effectively apply their existing technologies or for which they can develop technologies relatively simply. It is not always obvious where analytical technology could be effective. Medical specialists may be entirely unfamiliar with the available technologies and have no idea that an instrumentation solution to a serious diagnostic problem may be quite simple. Instrument companies, used to focusing on entirely different markets, may be similarly unaware of diagnostic problems that their technologies might elegantly and profitably address. It will take a pioneering effort to locate the many potential diagnostic uses for analytical technology that are surely out there.

The second challenge is, once the potential has been discovered, to create an instrumentation product that not only addresses technical needs but is specifically tailored for the healthcare professionals who will use it. Again, if the company is used to selling to research physicists, an agricultural market, or to chemical quality control specialists, it must make sure that the product it is developing is attractive to the market at which it is aimed. The medical market has different standards of ergonomics, ease of use and training, as well as size and esthetics, and instrument makers must be sensitive to these differences.

The third challenge is to produce these products at a price point that will create a strong economic argument for using them. The healthcare marketplace is much bigger than the traditional analytical instrument industry. It is a marketplace that holds enormous potential for analytical instruments, but will certainly require a shift in thinking from instrument makers. If breath analyzers can be inexpensive enough to go into small clinics rather than only into major medical centers, the potential for large volumes of sales is very good. This is a nontrivial challenge since the present line-up of IRMS instrumemts used for breath analysis range in price from around $100,000 to over $200,000.

From a strategic point of view, breath analyzers are an indicator of where the future growth of the analytical instrument industry will come from. The implications go far beyond the companies currently or potentially competing in the breath analysis arena. The message for the industry as a whole is that as instruments become more sophisticated and sensitive, companies able to think beyond their traditional markets can find myriad new applications for what are generally considered to be mature technologies. Many of these potential markets could provide rapid growth and high profitability.

This newer market clearly illustrates the potential opportunities for rapid growth, particularly in the "traditional" analytical sectors with their maturing techniques. To compete effectively in this market, companies must not neglect their current markets, but they must also be aggressive and highly creative in discovering new ways in which their technologies can bring value to new customers.

Column Graph:  Breath Analysis Instrumentation Estimated Worldwide Market ($m)
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