As a physician doing a fellowship in the 1970s at the University of California San Francisco, Michael Phillips, MD, became very interested in breath testing. He knew that the technology existed to detect the use of certain drugs using a breath test, so he thought surely it ought to be possible to detect diseases the same way.
So, with the "optimism of youth," as he tells Medical Device Daily, Phillips went on to create a company called Menssana Research (Fort Lee, New Jersey) with the goal of developing tests capable of detecting diseases in their earliest, most treatable, states simply by analyzing breath samples. And, as Phillips says, "it only took me 20 years" to get somewhere with it.
In February 2004 the FDA approved the company's Heartsbreath test for heart transplant rejection and it appears that Menssana is well on its way to developing a similar test to detect active pulmonary tuberculosis (TB). A study that will soon be published in the journal Tuberculosis shows that the new breath test can detect active pulmonary TB.
Phillips said the breath test was 85% accurate in detecting patients with active pulmonary tuberculosis in a study of 226 patients in San Diego, London and the Philippines. The patients in the study were symptomatic patients at high risk for TB, he noted. The National Institutes of Health funded the study, said Phillips, who in addition to being the founder/CEO of Menssana is also a professor of clinical medicine at New York Medical College (Valhalla, New York).
This wasn't the first time the NIH had supported Menssana's research in this area. Prior to the most recent study, the agency awarded the company a Phase I SBIR grant to test the feasibility of the idea. During that study, the company analyzed breath volatile organic compounds (VOCs) in hospitalized patients who were being screened for pulmonary TB at New York University Medical Center. Menssana also analyzed the VOCs made by Mycobacteria grown in the laboratory at Saint Vincents Medical Center (New York). The feasibility study showed that breath biomarkers of oxidative stress clearly distinguished between the "sick" hospitalized patients and normal controls. Also, breath VOCs accurately identified the patients whose sputum samples grew Mycobacteria – the VOC biomarkers in breath and in sputum cultures were very similar, according to the company.
"We were delighted and surprised to see" such results, Phillips said. It was based on these findings that the NIH awarded Menssana a Phase II SBIR grant to validate the breath test for pulmonary TB in this most recent, larger multicenter international study.
Phillips said the test appears to detect volatile organic compounds made by the infecting organism that causes the disease, Mycobacterium tuberculosis. He said the test detects a signal from Mycobacteria in the lungs, and thus is "probably a better test than skin tests or a blood test for tuberculosis that measures the body's immune response to infection."
Another advantage is that the breath test is safe, painless, and non-invasive, as a patient breathes gently for two minutes for a sample collection, Menssana noted.
According to the study, the researchers used a portable breath collection apparatus (BCA) to capture the VOCs in 1.0 liters breath and 1.0 liters room air on to separate sorbent traps. The geometry of the breath reservoir of the BCA ensured that the sample comprised greater than 99% alveolar breath. Subjects wore a nose-clip and respired normally for 2 minutes through a disposable and previously unused valved mouthpiece with a bacterial filter to prevent Mycobacterial contamination of the instrument. The mouthpiece and filter presented low resistance to respiration, ensuring that samples were collected without discomfort to patients, the authors wrote.
The company said the breath test might offer a new way to detect tuberculosis, a major cause of death, especially in developing countries.
"Essentially the diagnosis of tuberculosis has not really changed in the last 50 years, which is amazing when you think about it," Phillips told MDD. He said one reason the technology for TB has not advanced much in recent history is because it is not a very common disease in developed countries, such as the U.S. However, he noted that the disease is making somewhat of a comeback because of the immigrant population and others who are high risk for TB, such as those with HIV or AIDS.
"For years doctors have diagnosed tuberculosis with a chest X-ray or sputum culture or sputum microscopy," Phillips said. "These are okay as far as they go, but they've got severe limitations."
He added that these tests often produce false negative results and, especially with chest X-rays, a lot of false positives as well. "So you can't always trust the results," he said.
Phillips emphasized the urgent need for better diagnostic technology for TB, especially in less developed countries, because the treatments for the disease exist. It's just a matter of determining accurately whether or not a patient has it, he said.
Menssana has been developing its breath test technology since the 1980s and has been working on the TB indication for about five years, Phillips said.
One limitation with the breath test techniques Menssana has been using so far is that they are laboratory-based and use expensive instruments, Phillips said. "The methods we're using are really to slow and to expensive for clinical use," he said.
But that will hopefully change soon, he added. The U.S. Air Force recently awarded Menssana a contract to evaluate a new point-of-care breath test for pulmonary TB, studying patients in Africa, Great Britain and the Philippines. If successful, a patient could learn within minutes whether they are infected with tuberculosis, the company said.
Phillips hopes that physicians and patients will eventually consider a breath test in the same way as they 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.
Menssana is also developing breath tests for several other diseases, the company noted, including lung cancer, breast cancer, and ischemic heart disease.
"The platform of breath testing can be applied right across the board for many type of diseases," Phillips said.
Amanda Pedersen, 229-471-4212;