Decoding the exposome through breath biomarkers

An interview with Prof. Joachim D. Pleil, US Environmental Protection Agency, conducted by April Cashin-Garbutt, MA (Cantab)

What is the human exposome and how much do we know about the interaction between our genes and the environment?

The human exposome is probably best defined as “everything that is not the genome.” This is a bit tongue in cheek, but basically, the exposome is comprised of all of the chemicals in your body from the environment, food, consumer products, their metabolites, the endogenous “housekeeping” chemicals, the cellular wastes from energy production, as well as all of the messenger compounds and life supporting chemicals.

Unlike the genome, which is relatively stable throughout life, the exposome is a moving target depending on your current and past environment, as well as your activity, health state, nutrition, and stress, and consumption of food.

We are learning a lot about the gene x environment interaction, but honestly, it will be a long research path before we fully understand it. However, we need to remember why this is important.

It is generally accepted that 70-90 percent of long-term latency and chronic human diseases are associated with environmental factors.

Breath analysis is at the forefront of public health research and protection – it is a non-invasive window in the human health state, and has potential for broad applications at the community level.

cold breath

How can biomarkers in breath be used to decode the human exposome?

Breath is actually an interesting biological medium that tends to be overlooked in favor of the traditional media (blood and urine), when it comes to understanding the exposome.

People only think of the gas-phase when they consider breath analysis. Sure, gas exchange with the blood is the primary function of breathing, and so we consider the breath to be a non-invasive window into understanding how respiration affects the dissolved gases in the blood.

What is not quite as recognized, is that breath also contains vapors, aerosols, and particles. By modifying purely gas-phase collection methods, we gain access to the semi- and non-volatile fraction of breath, as well as a host of dissolved water soluble chemicals otherwise missed in gas-analysis.

As such, the breath exposome is expanded beyond the volatile compounds into the realm of proteins, bacteria, viruses, inorganic compounds, inflammatory markers, and larger compounds such as fatty acids and lipids.

How many different analytes can be measured from breath?

Traditional chemical breath analysis goes back to Linus Pauling who proposed that there are hundreds to thousands of different volatile organic chemicals accessible in exhaled breath. These numbers are increasing everyday as instrumentation becomes more sensitive and capable of greater specificity.

I focused the early part of my career on assessing environmental chemical exposures — examining exposure to compounds like benzene, toluene, carbon tetrachloride, chloroform, etc. that are related to adverse health outcomes.

We then started cataloguing endogenous chemicals like alcohols, ketones, and aldehydes more likely to represent current metabolism, and possibly health state.

Today, the “gold standard” for gas-phase breath discovery analysis is the GCxGC–ToFMS or Orbitrap style high-resolution equipment.

My understanding is that tens-of-thousands (possibly more) distinct features can be identified in a single breath sample. Furthermore, we have access to the exhaled breath condensate fraction, which contains the particles, aerosols, and all sorts of dissolved materials.

Here, researchers can apply all types of liquid chromatography, genetic analysis, direct Mass Spectrometry (SELDI, MALDI, PTR, SIFT) and immunochemistry to assess pretty much everything coming from the human body.

For example, in my lab, we have focused on assessing pro- and anti-inflammatory cytokines in exhaled breath condensate using second-generation robotic immunochemistry platforms.

What advances in GC-MS and LC-MS have aided your research?

To me, the most interesting recent development is the ability to use standard (modest) GC –MS systems with simultaneous SIM/Scan acquisition. Much of the gas-phase breath analysis in environmental and toxicological research is based on pharmacokinetics, that is, we track the progression of compounds throughout an organism from exposure to excretion, or sometimes infer previous exposures from compounds currently being excreted.

Usually, this style of pragmatic research is conducted with specific target compounds in mind. The cool thing about simultaneous SIM/Scan is that we don’t sacrifice discovery analysis, and if something out of the ordinary occurs in our breath samples, we can catch it.

What further developments would you like to see from GC-MS and LC-MS instruments?

Personally, I think the new high-end analytical instrumentation is so advanced that the capability is often beyond our more parochial needs.

The one thing I’d like to see is further development of the standard bench top (code for inexpensive) GC-ToF-MS detector. This may be in the works, but smaller laboratories could use modest systems similar to the existing single-quads, but with higher, (maybe 0.01 to 0.001 Dalton) mass resolution for volatile compounds.

Can you please outline your upcoming talk at Pittcon 2017?

I actually have two symposium talks at Pittcon, both breath related. The first, on Monday, considers that part of breath research impacted by cellular level “respiration.” Here the symposium delves into different aspects of disease/infection diagnosis, pharmaceutical development, human toxicology, and food safety based on what we now call “cell breath.”

My own talk outlines cellular level research for assessing toxicity of chemicals and assessing differential contributions to exhaled breath from human cells vs. human microbiota in the gut and lungs.

The second talk takes place on Thursday in a symposium dealing with the human metabolome. Here, I’m presenting the basics of breath discovery analysis and current exhaled breath research for assessing fire fighters’ protective gear, and the concept of using canine olfaction as a guide for developing laboratory methods for toxicology and disease diagnosis.

What are you looking forward to at Pittcon 2017?

There are a lot of opportunities at Pittcons to explore new ideas. My biggest issue is always how to split my time between the exposition floor and all the talks I want to attend. That said, I really look forward to seeing many of my international colleagues in person.

Every year, Pittcon has quite a good turnout of breath researchers and instrument manufacturers specializing in breath applications.

Not only do we have the two breath-related symposia, there is also a breath networking session, and a scattering of breath-related presentations that I will hunt down.

One of the newest topics is the potential for using breath analysis for detecting marijuana impairment in drivers, like the standard police breathalizer for drunk drivers. Though not something we would get involved with, it sounds like a really important new research area.

What Pittcon Can do for You from AZoNetwork on Vimeo.

What are your future research plans?

In my lab, we are working with a couple of new breath related projects. We are collaborating with NIOSH in their evaluations of firefighters’ protective gear, and we are developing new methods for assessing inflammatory conditions and other responses with human cell lines.

The cell research is especially intriguing in that it allows us to study metabolism, but avoid the expense, infrastructure needs, and ethical issues with using animals or human subjects.

Another project I hope to work on is developing methods for capturing and analysing exhaled aerosols directly. This would be valuable for public health applications where simplicity of sampling in the field is paramount.

Where can readers find more information?

Not surprisingly, the best source of information for all aspects of breath research is the Journal of Breath Research (JBR) published by the Institute of Physics (IoP) in the UK, an organization with roots tracing back to the “Society of Physical Research” established in 1873. JBR has now reached its 10th anniversary and recently published a special issue about cellular respiration. The web site is: http://iopscience.iop.org/journal/1752-7163

About Dr. Joachim PleilJoachim D. Pleil

Joachim Pleil investigates human systems biology of environmental exposures for the U.S. EPAs Office of Research and Development in Research Triangle Park, N.C., and serves as Adjunct Professor of Environmental Sciences and Engineering at the University of North Carolina School of Public Health in Chapel Hill, N.C. He is the editor-in-chief of the Institute of Physics (IOP) Journal of Breath Research (JBR).

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