Medical Device Daily Associate

The electronic nose, a device long used for safety and quality control in the food, wine and perfume industries, also can be used to detect early evidence of lung cancer, according to research conducted at the Cleveland Clinic (Cleveland).

Known as the Cyranose, the electronic nose is a hand-sized device that uses biosensor technology to produce what is known as a "smellprint" of the volatile organic compounds that comprise human breath and other scents.

The device's mechanism of action is similar to that of the Breathalyzer used in blood alcohol content detection.

The technology involves an array of polymer composite sensors composed of different polymers filled with conductive particles. When these sensors come in contact with a vapor, the polymer expands like a sponge, changing the resistance of the composite. This change in resistance is transmitted to a processor, and the pattern of change of the sensor array is used to determine the vapor sensed.

Led by Serpil Erzurum, MD, chairman of the department of pathobiology at the Cleveland Clinic's Lerner Research Institute, researchers speculated the electronic nose could be used to detect and distinguish between lung diseases, particularly lung cancer. Testing their theory, they found the exhaled breath of lung cancer patients had specific characteristics that, in fact, could be detected with the device. Their findings will be published in the American Journal of Respiratory Medicine later this spring.

"Our work indicates that the electronic nose can be used as a non-invasive tool for the early diagnosis of lung cancer and to monitor the effectiveness of treatment on lung cancer patients," Erzurum said in a statement. "Use of the electronic nose could enable physicians to determine the appropriate course for a lung cancer patient's treatment at an earlier stage, rather than after the cancer has spread to other parts of the body and is more difficult to treat. The small, portable nature of the electronic nose also makes it easy to use in physician offices and outpatient settings."

The Cyranose technology is based on work originally conducted at the California Institute of Technology (Pasadena, California) involving polymer composite sensors.

That technology was originally licensed to a company called Cyrano Sciences (also Pasadena) in 1997. That company, in turn, was bought by the Smiths Group (London) in March of last year for $15 million plus an earn-out. Cyrano Sciences then became part of that company's Smiths Detection (Watford, UK) division and the name was changed to Smiths Detection Inc., retaining its offices in Pasadena.

A spokeswoman for Smiths Detection explained how the Cyranose works. "Different types of diseases create different metabolites in the body," she told Medical Device Daily. As the impetus for this type of research, she cited early medical observations of canines being able to detect cancer through urine samples and diabetics who don't have their condition under control having the distinct smell of acetone on their breath. "Those types of things caused [doctors] to think that maybe there were other diseases out there that have distinct odors," the spokeswoman said.

Aside from lung cancer, the spokeswoman said that the company has investigated other areas for detection including sinusitis and ventilator-associated pneumonia, and ongoing studies for both of those conditions are currently being conducted at the Hospital of the University of Pennsylvania (Philadelphia).

An iteration of the technology also is being used as a tool on the war on terror, specifically to detect chemical and biologic agents, and the company last year received a roughly $4.5 million development grant from the U.S. Department of Defense to further its efforts in that area.

Peter Mazzone, MD, a staff physician in the Cleveland Clinic's department of pulmonary allergy and a member of the study's research team, explained why the clinic chose lung cancer as its area of study. He told MDD that his organization was already aware of some prior studies over the past 10 to 15 years using a more complicated gas analysis system called a GC Mass Spectrometry that had looked at lung cancer in the past and shown there are distinct patterns of these chemicals in the breath.

"Knowing that there were distinct chemicals in the breath of lung cancer patients, having an opportunity to use these easier-to-use systems, we just married those two ideas together and started with lung cancer," Mazzone said.

In the Cleveland Clinic study, researchers examined the exhaled breath of 14 lung cancer patients and 45 healthy patients. The electronic nose was programmed to detect certain characteristics in breath and used algorithms to create patterns viewable on a computer screen. Researchers found the pattern characterizing the breath of lung cancer patients was distinctly different from that of healthy patients and of people with other lung diseases.

"Patients are frequently found to have shadows on chest X-rays or CT [computed tomography] scans that may or may not represent lung cancer," said Mazzone. "Currently we rely on expensive imaging tests or invasive procedures with potential complications to determine whether these shadows represent cancer. An accurate, inexpensive and non-invasive test for lung cancer, such as the electronic nose, would be tremendously helpful."

While he said he could possibly see the Cyranose system or some next-generation product being used by both a general practitioner and a specialist such as a pulmonologist, Mazzone said researchers are still "a ways away from knowing how best to use it." He noted that such a system would probably be used as an adjunct to other diagnostic imaging technologies such as the aforementioned X-ray or CT scan, "[but] in the algorithm of which would come first and what would come second, it will take a little bit of time to determine."

Additionally, he acknowledged that such a system could one day test for more than one disease or condition. He said that the more cumbersome GC Mass Spectrometry device also has been used in other diseases – "things that you might never imagine would cause certain characteristics in someone's breath – for example, breast cancer, schizophrenia, things that have nothing to do with the lungs really somehow produced different chemical signatures in the breath. It's possible that as the technology advances and our understanding advances, we'll see more than just a use for this in diagnosing lung cancer.'

Aside from the Cyranose, Mazzone said that his research team also is investigating another sensor technology from ChemSensing (Northbrook, Illinois) for its lung disease studies to determine which of the two might be more accurate or useful in a clinical setting. That technology, called the Cosat system, employs an array of colored dots, with the colors changing based on the type of chemicals that the sensor comes in contact with.

Lung cancer is the leading cause of death from cancer in both men and women, and currently no screening guidelines exist for it, said Tarek Mekhail, director of the lung cancer medical oncology program at the clinic's Taussig Cancer Center. "Given the impact early diagnosis can have on treatment and on patient survival, researchers will intensify their efforts to find an easy, non-expensive and reliable screening tool," Mekhail said.