We are all about respiratory research, and I mean that in the generic sense. Our breath research community strives to answer a single basic question: how can we diagnose disease using exhaled biomarkers? Most of us focus on endogenously produced compounds such as VOC’s in gas-phase breath and non-volatile markers in breath condensate. While there are an abundance of studies and papers supporting the incredible potential of this approach, a different class of breath tests is working its way into the standard of care almost unnoticed.
I call these the “drug-device breath tests”. These are in some ways very similar to the “standard approach” breath tests:
- They measure a substance in exhaled breath
- They use various technologies such as GC-MS, near-infrared absorption, and custom “electronic noses”
- They are coded and/or billable in the clinical and/or consumer setting
Examples of these “standard approach” breath tests include FeNO, end tidal CO2, and in the consumer space, Hydrogen Sulfide and ethanol. Each of these is proven, useful, and has a payment structure to support its use.
However, the drug-device breath tests are fundamentally different. They don’t directly measure biomarkers of disease. Instead, they measure metabolites of ingested compounds, and in some cases, the time decay of the ingested compounds themselves. A well-known example of this is the H. pylori breath test. Simply put, the patient ingests a liquid and exhales into a breath bag. At the lab, the metabolism of that liquid by ulcer-causing bacteria is detected and quantified to establish bacterial activity. This test has been around for more than a decade, is FDA-approved, has a CPT code, and is in widespread use.
Several new breath tests are now making or have made their way through FDA and have the potential to become standard of care. These include the Gastric Emptying Breath Test which can replace nuclear scintigraphy in the diagnosis of gastroparesis, and the Smart Medication Monitoring System® which confirms medication adherence in the context of large pharmaceutical clinical trials. Both of these tests measure exhaled metabolites of a specific food additive with well-known and consistently-predictable signatures.
- Patient inhales a nebulized solution of urea laced with a carbon isotope
- The tuberculosis-causing bacteria metabolize this into an isotope of carbon dioxide
- A spectrophotometer measures the isotope of carbon dioxide in the exhaled breath
This test is very similar to the H. pylori test in that both measure isotopes of carbon dioxide in the exhaled breath following administration of isotope-laced urea. Unlike the H. pylori test, urea is introduced into the lung, not the stomach, and the detection is performed at the point of care in under 10 minutes. While this test is not yet FDA approved, initial clinical trials appear very promising.
The common thread with each of these is that they are poised for success and were created from a multi-disciplinary approach to creating a total diagnostic solution. And yet as I read most every abstract I can find on breath research (and post article links to my twitter feed ) rarely do I see any reference to this type of solution. What might this mean? We in the breath research community may benefit by broadening our teams to include chemists, pharmacologists, microbiologists, engineers, the patient community, and of course, physicians. As an engineer I am awed and fascinated by my physician friends and have been most surprised to find they feel the same way about me. We each bring something unique and powerful to this field, and harnessing this collective power would create great teams.
Would this generate new ideas and new approaches? Sure. Would any of these be clinically viable? Probably. Worth a try? Heck yeah. Matching the disease to the metabolite to the biomarker to the detection technology to the patient experience to the payment infrastructure as a single multi-disciplinary effort certainly holds potential. For a distinguished set of entrepreneurial research teams, this is already working.