It may not be a boom trend, but more non-invasive diagnostic tests are coming to market as clinical laboratory tests that use breath as the specimen
Here’s a development that reinforces two important trends in diagnostics: non-invasive clinical laboratory assays and patient-self testing. Recently, the FDA expanded the clearance of one diagnostic test to allow patients to collect their own breath specimen at home under the supervision of the test manufacturer’s telehealth team.
Recently, however, the FDA announced it has “expanded the approval of the company’s 13C-Spirulina Gastric Emptying Breath Test (GEBT) to now include ‘at home’ administration under virtual supervision of Cairn Diagnostics.”
Self-administration of at-home tests by patients guided virtually by healthcare professionals is a major advancement in telehealth. But will this virtual-healthcare method be popular with both patients and their physicians?
Clinical Laboratory Diagnostics and Telehealth
Spurring a far greater acceptance of telehealth among patients and healthcare providers is one of the many ways the COVID-19 pandemic has impacted healthcare.
“Telehealth, particularly during the COVID-19 pandemic, has emerged as a preferred option for healthcare providers,” noted Kerry Bush, President and COO of Cairn Diagnostics, in a 2021 news release.
Cairn’s GEBT detects gastroparesis, a disease which, according to the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), affects 50 people in every 100,000. According to the CDC, it is also sometimes a complication of diabetes. Symptoms include nausea, heartburn, bloating, a feeling of fullness long after eating a meal, vomiting, belching, and pain in the upper abdomen, the NIDDK notes.
In people with gastroparesis—sometimes called “delayed gastric emptying”—muscles that normally move food from the stomach to the small intestine do not work as they should, and the food remains in the stomach for too long. The traditional diagnostic tool used to diagnose gastroparesis is scintigraphy. The patient consumes a meal that has radioactive material mixed in and the digestion process is observed using a nuclear medicine camera as the material is eliminated through the bowels.
Cairn Diagnostics’ C-Spirulina Gastric Emptying Breath Test (above) recently received an expansion to its initial 2015 FDA approval that enables patients to self-administer the test at-home while being virtually guided by the company’s telehealth team. GEBTs are interpreted by CLIA-certified clinical laboratories and the results sent to patients’ doctors within 24-48 hours after testing. (Photo copyright: Cairn Diagnostics.)
Virtual Telehealth GEBT versus Scintigraphy
The telehealth process for Cairn Diagnostic’s Gastric Emptying Breath Test (GEBT) differs significantly from traditional scintigraphy testing. Once a physician prescribes the test, Cairn’s telehealth team contacts the patient to describe the virtual process. The team then ships the at-home test kit to the patient. To complete the testing, Cairn provides the patient with a web-based link to a secure audio/video platform.
During administration of the GEBT, a Cairn technician coaches the patient and supervises via video. Once the test is complete, the patient returns the breath samples to the CLIA-certified clinical laboratory by overnight courier. The test results are sent to the prescribing physician within 24-48 hours after the lab receives the samples.
Discovering New Uses for Breath as a Specimen for Clinical Laboratory Testing
For obvious reasons, patients prefer diagnostics that use specimens obtained noninvasively. GEBT is the latest in a growing list of diagnostic tests that use breath as a specimen.
For example, at Johns Hopkins clinicians employ breath testing to diagnose several conditions, including:
Each of these tests involves the patient consuming a particular substance, technicians capturing breath samples at certain intervals, and clinical laboratory personnel analyzing the samples to look for indicators of disease or intolerance.
New Types of Breath Tests
Breath samples are commonly used to diagnose gastrointestinal issues, but researchers also are seeking methods of using them to diagnose and monitor respiratory conditions as well.
In a recent study published in Nature Nanotechnology, scientists explored how breath can be used to monitor respiratory disease, noting that although breath contains numerous volatile metabolites, it is rarely used clinically because biomarkers have not been identified.
“Here we engineered breath biomarkers for respiratory disease by local delivery of protease-sensing nanoparticles to the lungs. The nanosensors shed volatile reporters upon cleavage by neutrophil elastase, an inflammation-associated protease with elevated activity in lung diseases such as bacterial infection and alpha-1 antitrypsin deficiency,” the researchers wrote.
Indeed, the search for new ways to use breath as a biological sample is being pursued by numerous groups and organizations. Owlstone Medical in the UK, for example, is developing breathalyzer tests for the detection of cancer as well as inflammatory and infectious disease.
“Whilst we are still in this discovery stage it is time to refine our study designs so that we can make progress towards tailored clinical application,” they wrote. “Breathomics is perhaps at the ‘end of the beginning’ for asthma at least; it has a ‘sexy’ name, some promising and consistent findings, and the key questions are at least being recognized.”
Better for Patients, Clinicians, and Clinical Laboratories
Virtual telehealth tests, ordered by physicians, administered at home, and interpreted in CLIA-certified clinical laboratories, is a trend pathologists may want to watch carefully, along with the development of other tests that use human breath as the specimen.
Less invasive, more personalized diagnostic tools that can be administered at home are better for patients. When those tools also provide detailed information, clinicians can make better decisions regarding care. Clinical laboratories that approach the use of at-home tests creatively, and which can accurately and quickly process these new types of tests, may have a market advantage and an opportunity to expand and grow.
Noninvasive diagnostic technology developed for space travelers and warfighters might eventually be used by clinical laboratories and physician office labs
To solve the problem of how to perform clinical laboratory tests on astronauts living for months at a time in the International Space Station (ISS), researchers associated with the National Aeronautics and Space Administration (NASA) are developing diagnostic tests that use human breath as the specimen. Last month, the research team unveiled the aptly named “E-Nose,” a prototype device designed to perform diagnostic tests using breath specimens
Clinical laboratory professionals and pathologists know that breath contains biological specimens which are useful biomarkers for detecting specific diseases, and that diagnostic tests based on breath have been around for a long time.
For example, the link between Helicobacter pylori (H pylori), a spiral bacterium, and stomach ulcers was discovered in the mid-1990s. Today, a diagnostic test that identifies the presence of ammonia and other volatile chemicals produced by H pylori is based on analysis of breath specimens.
Another biomarker is nitrogen oxide (NO), which when found in higher-than-normal concentrations in breath, could be an indicator of asthma. Other volatile biomarkers in breath may indicate infection, metabolic conditions, and inflammatory diseases.
Diagnosing a ‘Battery of Illnesses and Abnormalities’
In October, NASA demonstrated its new hand-held device—fully dubbed the E-Nose Breath Analyzer. Though still under development, the E-Nose device “will have the capability of analyzing compounds found within a person’s breath to diagnose a battery of illnesses and abnormalities including respiratory illnesses, infectious diseases, and cardiovascular conditions,” according to an Air Force news release.
If it develops into a standard diagnostic tool for doctors, could E-Nose have an impact on the revenue of clinical laboratories that perform traditional diagnostic testing?
“The [E-Nose] technology is designed to make rapid measurements—in less than five minutes, at the point of care—in a way that is completely non-invasive. When fully realized, the NASA E-Nose will open a new realm of medical care to both the warfighter and potential space travelers,” Loftus said.
Jing Li, PhD (above), Principal Investigator and Senior Scientist at NASA’s Ames Research Center, demonstrated the E-NOSE breathalyzer during a meeting with members of the 60th Medical Group at Travis Air Force Base. The smartphone-size medical device detects a wide range of volatile biochemicals linked to various diseases and illnesses and could pose competition for clinical laboratories that perform tradition diagnostic testing. (Photo copyright: US Air Force.)
Can NASA Advance E-Nose for Clinical Use?
According to NASA research presented at the DGMC, the E-Nose “utilizes an array of chemical sensors combined with humidity, temperature and pressure” for its real-time breath analysis. E-nose can detect 16 different chemicals in seconds at room temperature, including:
Methane
Hydrazine
Nitrogen dioxide
Hydrazoic acid
Sulfur trioxide
Hydrogen chloride
Formaldehyde
Acetone
Benzene
Chlorine gas
Hydrogen cyanide
Malathion
Diazinon
Toluene
Nitro toluene
Hydrogen peroxide
According to NASA’s presentation materials, the E-Nose underwent extensive research and development:
Work started at the NASA Ames Research Center in 2002.
The device includes the most well-developed Nano Chemical Sensor System in the world to date, which was tested aboard a Navy Satellite in 2007 for 12 months; deployed on the International Space Station (cabin air quality monitor); and field-tested by the Department of Homeland Security for various threats.
It was featured in 35 peer-reviewed journals, and
Involves nine United States patents.
“As with past technology that has been developed by the Air Force at DGMC, NASA medical research can improve civilian care throughout the country,” Bradley Williams, MD, 60th Medical Group Clinical Research Administrator, said in the Air Force statement. “The Air Force and NASA share the same altruistic medical research mission. Together, we seek to develop the future medical care which will be needed by the US Space Force, and which will also be very useful to the rest of the nation’s hospitals.”
Medical laboratory and pathology group managers would be wise to keep a close eye on the development of the E-Nose Breath Analyzer and similar technologies that have the potential to cut into diagnostic testing revenue streams. Especially if these devices can detect everything from infections to cancer.
It has been regularly demonstrated in recent decades that human breath contains elements that could be incorporated into clinical laboratory tests, so the decision to use this “breath biopsy” test in a therapeutic drug trial will be closely watched
When a major pharma company pays attention to a breath test, implications for clinical laboratories are often forthcoming. Such may be the case with GlaxoSmithKline (GSK). The global healthcare company has selected Owlstone Medical’s Breath Biopsy technology for use in its Phase II clinical trial of danirixin (DNX), a respiratory drug under development by GSK for treatment of chronic obstructive pulmonary disease (COPD), an Owlstone Medical news release announced.
Anatomic pathologists and medical laboratory leaders will be intrigued by GSK’s integration of breath-based specimens in a clinical trial of a respiratory drug. The partners in the trial aim to analyze breath samples to better understand the drug’s treatment effects and to discover personalized medicine (AKA, precision medicine) opportunities.
GSK (NYSE:GSK), headquartered in the UK but with a large presence in the US, researches and develops pharmaceutical medicines, vaccines, and other consumer health products.
Owlstone Medical, a diagnostic company, is developing a breathalyzer for disease and says it is on a mission to save 100,000 lives and $1.5 billion in healthcare costs. Dark Daily previously reported on Owlstone Medical’s Breath Biopsy platform. The Cambridge, England-based company has raised significant funding ($23.5 million) and already garnered credible cancer trial collaborators including the UK’s National Health Service (NHS).
Now, Owlstone Medical has brought its breath analysis technology to bear on chronic disease outside of cancer diagnostics development. A pharmaporum article called Owlstone’s Medical’s work with GSK an “additional boost of confidence” in the company’s technology, as well as a means for revenue.
Billy Boyle, co-founder and Chief Executive Officer, Owlstone Medical (above), shown with the company’s ReCIVA Breath Sampler device. This will be used by GSK in its Phase II respiratory disease clinical trial of danirixin to “capture VOC biomarkers in breath samples.” (Photo copyright: Business Weekly UK.)
GSK Studying Future Treatments for Respiratory Diseases
COPD affects about 700 million people worldwide, an increase of about 65% since 1990, GSK pointed out. In September 2017, GSK presented respiratory disease data and its pipeline medications at the European Respiratory Society in Milan, Italy. Included was information on danirixin (an oral CXCR2 antagonist), which is part of the company’s focus on COPD disease modification, according to a GSK news release.
“Each of our studies sets the bar for our future research and innovation,” noted Neil Barnes, MA Cantab, FRCP, FCCP(Hon), Vice President, Global Franchise Medical Head, GSK Respiratory, in the GSK press release.
Clinical Trial Aimed at Identifying the ‘Right’ Patients
With Owlstone Medical’s breathalyzer, GSK plans to explore how volatile organic compounds (VOCs) can help identify patients who will benefit most from the company’s medications, as well as evaluate Danirixin’s effects. A critical element of personalized medicine.
“It’s part of our efforts to identify the right patient for the right treatment,” said Ruth Tal-Singer, PhD, GSK’s Vice President of Medicine Development Leader and Senior Fellow, Respiratory Research and Development, in the Owlstone Medical news release.
VOCs in breath will be captured in a non-invasive way from patients who wear Owlstone Medical’s ReCIVA Breath Sampler, which, according to Owlstone Medical, has CE-mark clearance, a certification noting conformity with European health and safety standards. The VOCs breath samples will then be sent to Owlstone Medical’s lab for high-sensitivity analysis.
“Non-invasive Breath Biopsy can establish a role in precision medicine applications such as patient stratification and monitoring treatment response,” said Billy Boyle, Owlstone Medical’s co-Founder and Chief Executive Officer.
VOC Biomarkers in Respiratory Disease
VOC profiles can be characteristic of COPD as well as other respiratory diseases including asthma, tuberculosis, and cystic fibrosis, reported Science/Business.
According to Owlstone Medical’s Website, VOCs are gaseous molecules produced by the human body’s metabolism that are suitable for Breath Biopsy. Their research suggests that exhaled breath reflects molecular processes responsible for chronic inflammation. Thus, VOCs captured through Breath Biopsy offer insight into respiratory disease biomarkers.
Breath also includes VOCs that originate from circulation, which can provide information on a patient’s response to medications.
How the Breath Biopsy Platform Works
Owlstone Medical’s platform relies on its patented Field Asymmetric Ion Mobility Spectrometry (FAIMS) technology, which “has the ability to rapidly monitor a broad range of VOC biomarkers from breath, urine and other bodily fluids with high sensitivity and selectivity,” according to the company’s website. During the process:
Gases are exchanged between circulating blood and inhaled fresh air in the lungs;
VOC biomarkers pass from the circulation system into the lungs along with oxygen, carbon dioxide, and other gases;
Exhaled breath contains exiting biomarkers.
It takes about a minute for blood to flow around the body. So, a breath sample during that time makes possible collection and analysis of VOC biomarkers from any part of the body touched by the circulatory system.
The medical analysis is enabled by software in the Owlstone Medical lab, Boyle told the Cambridge Independent.
“There’s an analogy with blood prints—you get the blood and can look for different diseases, and we’ve developed core hardware and technology to analyze the breath sample,” he said.
Another Breath Sample Device
The ReCIVA Breath Sampler is not the only breathalyzer focused on multiple diseases. Dark Daily reported on research conducted by Technion, Israel’s Institute of Technology, into a breath analyzer that can detect up to 17 cancers, and inflammatory and neurological diseases.
But Owlstone Medical stands out due, in part, to its noteworthy partners: the UK’s National Health Service, as well as the:
And now the company can add collaboration with GSK to its progress. Though some question the reliability of breath tests as biomarkers in the areas of sensitivity and specificity required for cancer diagnosis, Owlstone Medical appears to have the wherewithal to handle those hurdles. It is a diagnostics company that many pathologists and medical laboratory professionals may find worth watching.
Owlstone Medical’s breath biopsy platform takes aim at breath biomarkers for an earlier diagnosis of cancer; could it supplant tissue biopsies sent to pathology labs?
For many years, medical laboratory scientists and pathologists have known that human breath contains molecules and substances that have the potential to be used as biomarkers for detecting different diseases and health conditions. The challenge was always how to create clinical laboratory test technology that could use human breath samples to produce accurate and clinically useful information.
Stated differently, breath, the essence of life, may contain medical laboratory test biomarkers that could provide early-detection advantages to pathology groups in their fight against cancer. Now diagnostics company Owlstone Medical—developer of the Breath Biopsy platform—is about to conduct a clinical study in collaboration with the United Kingdom’s (UK’s) National Health Service (NHS) and others to demonstrate the effectiveness of its breath-based diagnostic tests.
Anatomic pathology groups and clinical laboratory leaders know human breath contains volatile organic compounds (VOCs) that can be useful diagnostic biomarkers for medical laboratory testing. Many possible breath tests have been researched. One such test, the urea breath test for detecting Helicobacter pylori (H. pylori), has been in clinical use for 20 years. As part of the test, patients with suspect stomach ulcers or other gastric concerns, swallow a tablet with urea and exhale carbon dioxide that is measured for H. pylori bacteria.
According to an Owlstone Medical news release, the new study, called the “PAN Cancer Trial for Early Detection of Cancer in Breath,” will explore the ability of Owlstone Medical’s Breath Biopsy platform to detect cancers of the:
Current medical care standards call for these cancers to be diagnosed by analyzing biopsied tissue specimens. If Owlstone Medical’s breath test performs well during trial, it could provide advantages over traditional tissue-based cancer testing that include:
A non-invasive approach to finding cancer earlier;
A lower price point as compared to a tissue biopsy cancer test; and
Faster return of test results, since tissue would not need to be collected from patients during surgical procedures and sent to medical laboratories for analysis.
“By 2030, the number of new cancer cases per year is expected to rise to around 22-million globally. Some cancers are diagnosed very late when there are few treatment options available. Non-invasive detection of cancer in breath could make a real difference to survival,” stated Richard Gilbertson, PhD, Li Ka Shing Chair of Oncology, Director of the CRUK Cambridge Center, and Oncology Department Head at University of Cambridge, in the news release.
How the Breath Biopsy Platform Works
The Breath Biopsy platform relies on Owlstone Medical’s Field Asymmetric Ion Mobility Spectrometry (FAIMS) technology, which the diagnostics company explains is a “fast means to identifying volatile organic compound biomarkers in breath.”
Billy Boyle (above), co-founder and Chief Executive Officer at Owlstone Medical, demonstrates the ReCIVA Breath Sampler. “Positive results from the PAN cancer trial could be game-changing in the fight against cancer,” he noted in the news release. “Success in this study supports our vision of saving 100,000 lives and $1.5 billion in healthcare costs.” This technology has the potential to be disruptive to anatomic pathology, which relies on the analysis of biopsied tissue to detect cancer. (Photo copyright: Owlstone Medical.)
Here is how FAIMS works in the Breast Biopsy platform, according to the Owlstone Medical website:
Gases are exchanged between circulating blood and inhaled fresh air in the lungs;
VOC biomarkers in the body’s circulation system pass into air in the lungs, along with oxygen, carbon dioxide, and other gases;
Exhaled breath contains those biomarkers exiting the body;
Because it takes one minute for blood to flow around the body, a breath sample during that time makes possible collection and analysis of VOC biomarkers of any part of the body touched by the circulatory system.
One publication compared the capture of VOCs to liquid biopsies, another possible non-invasive cancer diagnostic technique being widely researched.
“The advantage to VOCs is that they can be picked up earlier than signatures searched for in liquid biopsies, meaning cancer can be diagnosed earlier and treated more effectively,” reported Pharmaphorum in its analysis of five technology companies fighting cancer.
As part of the clinical trial, breath samples will be collected in clinic settings with the hand-held Owlstone Medical ReCIVA Breath Sampler (equipped with a dime-sized FAIMS silicon chip). The samples will come from people with a suspected cancer diagnosis who are seeking care at Cambridge University Hospital’s Addenbrooke’s Hospital. To test reliability of the biomarkers, breath samples from patients with cancer and without cancer will be analyzed.
“You’re seeing a convergence of technology now, so we can actually run large-scale clinical studies to get the data to prove odor analysis has real utility,” stated Owlstone Medical co-founder and Chief Executive Officer Billy Boyle, in a New York Times article.
Breath Tests Popular Area for Research
The company’s Breath Biopsy platform is also being tested in a clinical trial for lung cancer being funded by the UK’s NHS. The study involves 3,000 people, the New York Times article reported.
Breath tests in general—because they generally are non-invasive, fast, and cost-effective—have been the subject of several other Dark Daily e-briefings as well, including those about:
Owlstone Medical’s ability to get backing from Britain’s NHS, as well as investments to the tune of $23.5 million (the most recent coming from Aviva Ventures) is a positive sign. That Owlstone Medical’s Breath Biopsy platform is credible enough to attract such respected collaborators in the cancer trials as the Cancer Research UK Cambridge Institute (CRUK), University of Cambridge, and Cambridge University Hospitals (CUH) NHS Foundation Trust is evidence that the company’s diagnostic technology is considered to have good potential for use in clinical care.
Medical laboratory managers and pathology group stakeholders will want to monitor these developments closely. Once proven in clinical trials such as those mentioned above, breath tests have the potential to supplant other medical laboratory diagnostics and perhaps lower the number of traditional biopsies sent to labs for diagnosis of cancer.
The Technion breathalyzer would give pathology groups and medical laboratories unprecedented ability to support physicians in diagnosing and treating cancers, chronic diseases, and other illnesses
Readers of Dark Daily know that several pathology research teams in America and the UK are developing breath analyzer tests that can detect everything from lung cancer to early-stage infections. Clinical laboratories will soon have a plethora of breath-related tests from which to choose. Now there’s a new kid on the block. A breathalyzer test that can detect up to 17 distinct cancerous, inflammatory, and neurological diseases!
Assuming the cost per test was at a competitive level to existing technologies, what would give this new diagnostic system appeal to physicians and patients alike is that it would be a non-invasive way to diagnose disease. Only a sample of the patient’s breath would be needed to perform the assays.
Researchers at the Israel Institute of Technology, or Technion, published the results of their study in ACS Nano, a monthly journal of the American Chemical Society devoted to “nanoscience and nanotechnology research at the interfaces of chemistry, biology, materials science, physics, and engineering.” (more…)
