EXHALED BREATH
ANALYSIS
Breath analysis offers a window on lung physiology and disease and is
rapidly evolving as a new frontier in medical testing for disease states in the
lung and beyond. Breath analysis is now used to diagnose and monitor asthma, to
check for transplant organ rejection, and to detect lung cancer, among other
applications.
With each breath we exhale,
thousands of molecules are expelled in our breath, and each one of us has a
“smellprint” that can tell a lot about our state of health. Hippocrates
described fetor oris and fetor hepaticus in his treatise on
breath aroma and disease. In 1784, Lavoisier and Laplace showed that
respiration consumes oxygen and eliminates carbon dioxide. In the mid-1800s,
Nebelthau showed that individuals with diabetes emit breath acetone. And in
1874, Anstie isolated ethanol from breath (which is the basis of breath alcohol
testing today).
In addition to the known
respiratory gases (oxygen and carbon dioxide) and water vapor, exhaled breath
contains a multitude of other substances, including elemental gases such as
nitric oxide (NO) and carbon monoxide (CO) and volatile organic compounds
(VOCs). Exhaled breath also carries aerosolized drop- lets that can be
collected as “exhaled breath condensate” (EBC), which contain nonvolatile
compounds such as proteins dissolved in them as well.
A major breakthrough in the
scientific study of breath started in the 1970s when Linus Pauling demonstrated
the presence of 250 substances in exhaled breath. With modern mass spectrometry
(MS) and gas chromatography mass spectrometry (GC-MS) instruments, we can now
identify more than 1000 unique substances in exhaled breath. There are
currently commercially available analyzers that can measure NO levels in
exhaled breath to the parts per billion (ppb) range and CO to the parts per
million (ppm) range. Sensitive mass spectrometers can measure volatile
compounds on breath down to the parts per trillion (ppt) range.
Aerosolized droplets in exhaled
breath can be captured by a variety of methods and analyzed for a wide range of
biomarkers from metabolic end products to proteins to a variety of cytokines
and chemokines, and the possibilities continue to expand.
Advances in the field of breath
analysis require close multidisciplinary collaboration. One great example of
how the collaboration between technical, medical, and commercial professionals
has resulted in a clinically useful tool is the measurement of NO in exhaled
breath for monitoring airway inflammation. The advent of chemiluminescence
analyzers in the early 1990s allowed the detection of low (ppb) levels of NO in
exhaled breath. This was quickly followed by the observation that patients with
asthma had higher than normal levels of NO in their exhaled breath, which was
later linked to eosinophilic airway inflammation. Standardization of the gas
collection methods and measurement techniques allowed the industry to build the
next generation of analyzers suitable for use in the clinical setting. In 2003,
the Food and Drug Administration approved the first desktop NO analyzer for
monitoring airway inflammation in individuals with asthma. The use of exhaled NO
in monitoring asthma is useful for several reasons. It is noninvasive, it can
be performed repeatedly, and it can be used in children and patients with
severe airflow obstruction in whom other techniques are difficult or impossible
to perform. Exhaled NO may also be more sensitive than currently available
tests in detecting airway inflammation, which may allow more optimum
therapy.
