December 10, 2024 | A number of research groups, companies, and collaboratives are pursuing breathalyzers aimed at tuberculosis, malaria, and other infectious diseases, as Diagnostics World recently reported. Some of those same entities, and others, have also set their sights on applying breath-based technologies to a variety of other health concerns, including breast cancer, liver disease, gastrointestinal conditions, and lung disease.
Canadian diagnostics developer Breathe BioMedical is working on a breath test for breast cancer, for example. The tool is meant to be used as an adjunctive test to mammography screening to help detect early-stage breast cancer in women with dense breast tissue.
Breathe BioMedical anticipates completion of test components and its Breast Cancer Breath Test in the year ahead, noted a news release. The company has plans to carry out verification and validation studies over the next two years, in addition to a large multi-center clinical study to evaluate safety and efficacy.
In addition to its tuberculosis and HIV efforts, UK-based Owlstone Medical is developing various breath tests for clinical and diagnostic use, including a liver disease breath test and tests for diagnosing and monitoring gastrointestinal conditions.
Its clinical tests for small intestinal bacterial overgrowth (SIBO) and carbohydrate malabsorption are already on the market in the UK, and the vision is to come up with a whole menu of digestive health tools that could be used to conduct research, assist clinicians as they make diagnoses, and help patients manage their symptoms.
Low-Hanging Fruit: Why Some are Starting with Lung Disease
Owlstone’s breath-based efforts include the development of a lung cancer test that is currently in clinical trials and involves an exogenous volatile organic compound (EVOC) approach. Similarly, Florida-based Detect-ION is looking to tackle cancer, beginning with lung cancer, in addition to its work focused on infectious diseases.
Detect-ION has announced a collaboration with the Moffitt Cancer Center that aims to evaluate point-of-care diagnostics for the early screening of lung cancer. The study will utilize Detect-ION’s mass spectrometry platform, called CLARION, to demonstrate VOC biomarkers capable of distinguishing lung cancer-positive patients from healthy controls.
The company views this pilot project as an opportunity to advance the diagnostic capabilities of point-of-care mass spectrometry. The goal is to identify VOC biomarkers in exhaled breath to come up with an inexpensive, user-friendly, at-home test.
“There is a pretty compelling body of research that has looked at many different types of cancers and tried to find a correlation of VOCs in your breath with the presence or the absence of those tumors,” Founder and CEO Ashish Chaudhary told Diagnostics World.
Lung cancer is reasonable place to start because it involves the organ where breath comes from and where metabolites are interacting with exhaled air, he explained. With that mindset, Detect-ION is “taking some optimism on already demonstrated biomarkers for lung cancer by much larger, beefier systems” that use the same sort of gas chromatograph mass spectrometer technology that his company has miniaturized.
Chaudhary said this was a compelling factor that initially led him to reach out to Moffitt and pursue this collaborative endeavor. He envisioned potential to dovetail into existing lung cancer programs and leverage the testing and clinical trials already taking place in order to evaluate his company’s technology “and see if we could come up with a clinically meaningful solution for early screening of lung cancer.”
The plan is to begin conservatively, he said, so the initial pilot study will focus on late-stage lung cancer patients who are already taking medicines and returning for checkups in an attempt to identify VOC biomarkers. If successful, the effort will involve a follow-up study with early-stage lung cancer patients to explore the potential for early detection. One underlying hope is that the data from this study could also help inform early detection and diagnosis efforts for other diseases, such as liver, pancreas, prostate, or colorectal cancer.
Meanwhile, recent research from Olivier Loudig and colleagues at the Hackensack Meridian Center for Discovery and Innovation (CDI) details their progress toward the development of an exhaled-breath test for the detection of lung diseases, including cancer. Loudig’s research and technology are the basis of Hackensack Meridian Health’s first spin-off company, called EValuate Diagnostics. His group’s approach is aimed at establishing a new method to lower the threshold for early detection, Loudig said.
Although additional work is needed to refine a range of biomarkers and show that this approach can be clinically relevant for humans, he and colleagues believe their line of work, detailed in recent studies, is paving the way.
Pair of Studies Lays Groundwork for Breath Test
Loudig has been targeting the nanoparticles released by cancer cells for early detection and diagnostics, and his group at CDI has developed a technology called EV-CATCHER for the isolation of cell-specific nanoparticles from biofluids. Their work focuses on capturing and identifying extracellular vesicles (EVs) that are released into serum, blood, and other biofluids.
Two papers published in 2024 by Loudig and colleagues demonstrate that they have gathered, separated, and profiled lung biomarkers from human breath, in addition to developing animal models to expand their analyses and identify markers for the early detection of metastatic lung tumors.
Loudig explained the role of EVs in cancer, describing them as nanoparticles secreted by cells to exchange material and communicate. Cancer cells essentially hijack the EV system to poison cells and shut down the immune system, he said, which makes EVs a valuable target for detecting tumors.
His group’s research uses exhaled breath condensates (EBCs) to detect lung cancer. They have developed a non-invasive method to collect and analyze EBCs, which can detect tumors in mice and in humans with advanced lung cancer.
“You breathe in, and you breathe out, and when you breathe out there’s some moisture that comes out of your breath,” Loudig told Diagnostics World. “We have devices that we’ve tested—one that is disposable—that allows us to condense that moisture that comes out of the breath and has material coming from the deep lung.”
The researchers have found that EBCs contains EVs from tumors, which can be used for early detection. Loudig aims to commercialize this technology, focusing on early detection and monitoring post-treatment.
In a mouse model study published in Extracellular Vesicles and Circulating Nucleic Acids (DOI: 10.20517/evcna.2023.77), Loudig and colleagues detected human-derived tumor cell microRNAs using EV-CATCHER to obtain human exhaled lung tumor EVs from exhaled breath.
The mouse model utilized metastatic breast cancer cells injected into mice, which seed in the lung and form tumors within roughly six weeks. The EBCs test can detect the presence of lung tumors in mice within just one to two weeks following injection, potentially providing a quick and non-invasive method for early detection.
The lung is a hub for circulation, he explained, which makes it an ideal site for detecting metastatic cancer cells. He highlighted the possible application of EBC testing for detecting cancers that metastasize to the lung, such as breast, colorectal, prostate, and bladder cancers.
Loudig said the mouse study is complementary to a separate but related human study that his research group conducted, which confirmed the detection of tumors by analyzing EBCs. In a paper that appeared in the Journal of Extracellular Vesicles (DOI: 10.1002/jev2.12440), the researchers examined five types of airway samples.
They detected lung cancer by analyzing the breath collected from 18 subjects, including 12 healthy participants and six who had been diagnosed with stage IV lung cancer. They found that exhaled EVs contain microRNA expression profiles that are consistent with those gathered through more invasive methods.
The thought process behind this human study’s approach was to look at two different ends of the spectrum: healthy controls and patients with advanced disease. “If we can’t distinguish those two ends of the spectrum, it’s going to be really hard to pitch that we can detect disease really early,” Loudig explained.
What they found is that they can, indeed, distinguish patients with advanced lung cancer from healthy controls that do not have any lung cancer, he continued, so there is now a desire to find consenting patients at different stages of disease, build up a collection of specimens, and determine whether they can detect at earlier stages.
Loudig pointed out that his group’s work, which focuses on non-volatile organic compounds (non-VOCs) in EBCs, differs from other methods that focus on VOCs in breath. Notably, the non-volatile approach allows for the collection and storage of EBCs, he said, which enables the development of a biorepository.
He explained that one tube of blood amounts to about 10 milliliters. By comparison, collecting exhaled breath leads to about two milliliters of material within 10 minutes. The idea is that you wind up with an actual biofluid, like blood, which makes it possible to build up a cohort of samples and initiate a study.
“But you’re just breathing,” he added. “You’re not doing anything different.” In other words, the approach is “very practical and non-invasive.”
Emerging Tech Award Recognizes Biomarker Discovery Efforts
Loudig’s accomplishments have garnered recent attention. On November 21, he was honored with the Research & Development Council of New Jersey’s inaugural Emerging Tech Award at the 45th annual Edison Patent Awards Ceremony and Reception.
The Emerging Tech Award is presented to a person, team, or organization in New Jersey whose early-stage innovations or inventions could potentially “make a significant impact on the marketplace,” according to a news release.
The award recognized Loudig’s development of research programs focused on biomarker discovery. Along with senior research associate Megan Mitchell, they have developed technologies and earned patents for the isolation of circulating EVs contained in EBCs, which could help enable the early detection of lung diseases and cancers.
“Olivier Loudig’s work is a great example of the CDI’s science accelerating discoveries into innovations to change lives as soon as possible,” said Ihor Sawczuk, Hackensack Meridian Health’s president of Academics, Research and Innovation.
“We are thrilled that the discovery and innovation of Olivier Loudig continues to earn support, and accolades, from the scientific community,” added David Perlin, chief scientific officer and executive vice president of Hackensack Meridian’s CDI.
Looking ahead, Loudig’s startup company hopes to commercialize its tool and collaborate with pharmaceutical companies for clinical trials, he told Diagnostics World, and the long-term goal is to change the way lung diseases are diagnosed.
Paul Nicolaus is a freelance writer specializing in science, nature, and health. Learn more at www.nicolauswriting.com.