Skip to main content
Premium Trial:

Request an Annual Quote

Using Biomarkers in Breath, Zeteo Tech Aims to Find Respiratory Infections Sooner

Premium
Ventilator

NEW YORK – By capturing and identifying biological particles in exhaled breath, Zeteo Tech plans to bring to market tests to identify within about two hours whether patients have lower respiratory tract infections and aid decisions whether to start antimicrobial treatments.

The Maryland-based biodefense and medical device firm has been developing a testing system that uses breath samples that are collected from a ventilator or CPR-type mask. Then leveraging mass spectrometry, a user can identify protease biomarkers of infections including early-stage infections in asymptomatic patients. Company officials recently reported in PNAS Nexus that they used the techniques in a proof-of-concept study to detect the increased release of human neutrophil elastase (HNE) from intubated patients who had ventilator-associated pneumonia.

While the company's initial tests will not be used to identify the type of pathogen that is causing an infection, company officials said that clinicians can still use the results to aid decisions whether to begin antibiotic treatments by helping them to determine earlier whether a patient has an active infection. They noted that ventilator-associated infections, for example, are likely to be caused by bacteria.

In an award abstract for a $967,000 Small Business Innovation Research grant from the National Science Foundation, the company said that short-course antibiotic therapies are typically used to treat patients following the diagnosis of lower respiratory tract infection, but current tests, including PCR assays, are unable to distinguish between colonization and infection. The company intends to use its technologies to aid the diagnosis of infections as well as predict the risk that patients will develop infections.

"Our work would largely assist decision-making for clinicians regarding antibiotic treatment and dramatically improve patients' clinical outcomes by limiting antibiotic treatments and minimizing harmful exposure to unnecessary antibiotic treatment," the company said in the SBIR grant.

In the PNAS Nexus article, the authors reported that their quantitative test for HNE as a biomarker of lower respiratory tract infection achieved area under the receiver operating characteristic curve of 0.987 with a sensitivity of 1 and a specificity of 0.867.

Mike McLoughlin, Zeteo Tech chief technology officer, said the company's BreathBiomics sample collection device is used to capture proteins and peptides from the breath of intubated patients in about one hour. The same device, however, also could be used to collect samples from patients in an ambulance in about five to 10 minutes because of the higher flow rate of patient breaths under those conditions.

"It's well established that earlier intervention with antibiotics is helpful. However, there's great concern over overuse of antibiotics," McLoughlin said. "So, what they're really looking for is a better tool set so that they can, number one, detect an active infection early."

The sample collection system leverages chemical affinity to capture biological targets. In the recent study, the collection column was attached to the ventilator exhaust tubing of critical care patients at Johns Hopkins Hospital in Baltimore and integrated into a CPR-use face mask for the collection of samples from healthy volunteers.

McLoughlin said that the company extracted the captured particulate from a filter and mixed it with a sensor molecule. HNE was detected through a distinctive mass shift after a reaction between HNE and the sensor molecule caused the release of a reporter molecule, he said.

The researchers reported that their approach allowed the detection of ultralow protease concentrations through mass spectrometry, while McLoughlin noted that the methods used in the study also could be applied to the development of multiplex tests with sensor molecules for multiple proteases.

While the company's focus has been on lower respiratory tract infections, he said that the technology has the potential for a wider range of applications.

"Even if you're not on a ventilator, you're still going to be expressing those molecules, so we think that there's great applicability for not only detecting lung infections but, ultimately, for things like managing [chronic obstructive pulmonary disease], asthma, and other chronic lung diseases where inflammation response is a major indicator that there's a potential issue," he said.

Zeteo Tech CEO Wayne Bryden said the firm plans to assess which of the dozens of other proteases that are expelled in breath could be used to assess the response to infection or provide more information about the health of a patient's lungs. Dapeng Chen, principal investigator on the recent study, said that some of those proteases may help to differentiate between viral, bacterial, and fungal infections, while Bryden said that some could be used to distinguish between infections with Gram-positive and Gram-negative bacteria, identify bacterial species, or provide information that could be used to predict drug resistances.

Meanwhile, Bryden said that the confirmation that a patient has an infection also could trigger the use of a PCR assay or culture-based test to determine the causes of infection.

Albert Rizzo, chief medical officer of the American Lung Association, said that a diagnosis of lower respiratory tract infection is typically reached through the assessment of clinical presentation such as coughing, sputum production, and shortness of breath along with physical examination and, often, a chest X-ray. While monitoring intubated patients in an ICU, doctors may have to decide whether the shadows and other visual changes that they see on radiographs are infections that require treatment, and he noted that the recent study results suggest that elevated HNE release is correlated with active infection.

Rizzo, who is not connected with Zeteo Tech or the company's research, said that tests that can help to more closely determine the cause of the infection are going to help healthcare providers to tailor antibiotic treatments to patients earlier rather than after starting them on empirical treatments. He noted that treatment plans are typically developed through the evaluation of a combination of factors including whether the patient is in an outpatient or inpatient setting, whether they are hospitalized in the ICU, the severity of disease, and their recent medical history. Diagnostic tests may be used to distinguish whether a patient who develops pneumonia during cold and flu season, for example, has a viral or bacterial infection.

McLoughlin said that Zeteo Tech has requested a pre-submission meeting with the US Food and Drug Administration, although the company remains early in its regulatory and commercialization processes. He said the company, though, is already experienced at building small and robust mass spectrometers and tests through its prior biodefense contracts.

Zeteo Tech announced late last year that the US Department of Homeland Security had awarded the company an SBIR Phase III contract for at least $1.9 million and up to $5.9 million for the development and testing of its DigitalMALDI sensor technology that is used for the detection of dangerous aerosolized biological agents including bacteria, viruses, and toxins.

Bryden noted that the company's previous work also includes Bill and Melinda Gates Foundation-funded research in South Africa on the use of the company's technology to detect tuberculosis through breath samples and mass spectrometry.

As for the company's BreathBiomics technology, Bryden said that the firm's analysis so far suggests that its breath-based tests have promising market potential, and it is gathering additional data to continue developing its commercialization plans.

"We are working as hard as we can to try to figure that out and to move forward," he said.