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Exhaled breath as a matrix for biomarker measurement is a relatively new idea. The pace of research has accelerated since 2001 with most of the emphasis on compounds in breath condensate and Volatile Organic Compounds (VOC) in gas-phase breath.  Compounds in breath condensate include proteins, nucleic acids, cytokines, water-soluble volatiles, and various metabolites.  Over 6,000 VOC’s have been identified in gas-phase human breath using Mass Spectrometry.

The “breath test” idea is exemplified by the “breathalyzer” used by law enforcement for determining blood alcohol level. This basic concept, while successful for law enforcement, has persistently eluded both the medical establishment and segment entrepreneurs seeking to apply this analytical paradigm to other physiological conditions and disease diagnostics.  This is now changing fast.

There are three breath tests currently are approved by the FDA:

  • Exhaled Nitric Oxide (eNO) is a class II, product code MXA, regulation 862.3080
  • Urea breath test (UBT) is a class I, product code MSQ, JJQ, regulation 866.3110.  Another UBT is class I, product code LYR, regulation 866.3110.  A third UBT is class III, product code OZA, regulation 866.3110
  • Hearts Breath Test, a breath test for markers of oxidative stress, received Humanitarian Device Exemption (HOE) designation

Of these the most widely-used is eNO which is used to fine-tune the administration of certain asthma therapies.   The Urea Breath Test, also known as the H. Pylori breath test, is sometimes used to confirm that a previously-active H. Pylori infection has been rendered incactive.  The impact of these tests has been low to moderate in terms of the accepted standard of care, but they are all a great step forward.   A fourth test for measuring the rate of stomach emptying is also at or near approval but we could not find sufficient information on it at this time.

For a new breath test to be clinically useful it must:

  • Provide information currently unavailable to clinicians
    • Unavailable at all
    • Unavailable in the timeframe required to promptly guide diagnosis and therapy
    • Unavailable in a form which allows efficient, broad and immediate application to a patient population
  • Provide information that is actionable and significant to the well-being of the patient and/or the well-being of the community
  • Provide a way to recoup the cost of the test, directly or indirectly

Note that adding the convenience of a breath test as a substitute for a routine blood test is probably not a viable strategy in of itself. Barriers to success include medical inertia, spotty supporting laboratory infrastructure, and reimbursement.  However, there are some clear paths forward.

We believe that a breath test for non-volatile biomarkers exhaled in microscopic droplets can get clinical traction for evaluation of lung disease. This results from the organ specificity of such breath biomarkers that arise from airway epithelium and are less concentrated in blood than breath. These breath biomarkers don’t suffer from non-specificity of organ source as is the case with many biomarkers in blood.  The breath condensate matrix is rich in such biomarkers and many promising studies have been published.

Current research trends and prevailing medical thought support the exploration of VOC’s, particularly as biomarkers for cancer, infection, and other diseases. Additionally, breath tests targeting volatile markers are sensible development goals when assessing a systemic condition using continuous monitoring for which blood draws become prohibitive. A great example of this would be monitoring blood sugar for diabetes control.  The challenge with VOC’s is determining their source and relevance since they can reflect either the lung epithelium, the blood content of dissolved VOC’s, or other systemic and/or organ-specific physiology.

Headlines are emerging almost daily about new breath tests for cancer detection, malaria, and others.  We track these and retweet every major new headline and new publication at @BreathAnalysis.  Follow us for the latest in both non-volatile and volatile biomarkers in exhaled breath, and please contact us with any questions.  Our mission is to support all breath biomarker research and we look forward to speaking with you.


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