Exhaled breath analysis: the new frontier in medical testing

With each breath we exhale, thousands of molecules are expelled in our breath and each one of us has a 'breathprint' that can tell a lot about his or her state of health. While this may be news to some, it should not be to people in medicine. For one can argue that the field of breath analysis is as old as the field of medicine itself. Hippocrates described fetor oris and fetor hepaticus in his treatise on breath aroma and disease, Lavoisier and Laplace in 1784 showed that respiration consumes oxygen and eliminates carbon dioxide [1], Nebelthau in the mid 1800s showed that diabetics emit breath acetone [2], and Anstie in 1874 isolated ethanol from breath (which is the basis of breath alcohol testing today) [3].The end of the 20th century and the beginning of the 21st century, however, have arguably witnessed a revolution in our understanding of the constituents of exhaled breath and the development of the field of breath analysis and testing. A major breakthrough in the scientific study of breath started in the 1970s when Linus Pauling demonstrated that there is more to exhaled breath than the classic gases of nitrogen, oxygen, carbon dioxide and water vapor, a lot more. Based on gas–liquid partition chromatography analysis, Linus Pauling reported the presence of 250 substances in exhaled breath [4]. 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. These substances include elemental gases like nitric oxide and carbon monoxide and a multitude of volatile organic compounds. Exhaled breath also carries aerosolized droplets collected as 'exhaled breath condensate' that have non-volatile compounds like proteins dissolved in them as well.We now have the technology to test for any and all of these components. Thanks to major breakthroughs in new technologies (infrared, electrochemical, chemiluminescence, and others) and the availability of very sensitive mass spectrometers, the field of breath analysis has made considerable advances in the 21st century. Several methods are now in clinical use or about ready to enter that arena. There are currently commercially available analyzers that can measure NO levels in exhaled breath to the parts per billion (ppb) range and carbon monoxide to the parts per million (ppm) range [5]. Sensitive mass spectrometers can measure volatile compounds on breath down to the parts per trillion (ppt) range. Aerosolized