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.