(Invited) Breath Analysis in Lung and Systemic Diseases
Authors: Dweik Raed 
Published: May 2020

Introduction

As the headspace of the blood, our exhaled breath contains a vast array of substances and molecules that hold great promise for monitoring our health and for the diagnosis and management of various lung and systemic diseases. This includes substances we produce endogenously as part of our normal (or disease-related) metabolism whether this is local in the lung or systemic in origin. Since we are constantly inhaling air from our environment as we breathe in the ambient air, exhaled breath can also reflect our environmental exposure(s). Furthermore, our breath contains volatile compounds produced by our “internal environment”: the bacteria in our gut and mouth. Add to all of those volatile byproducts generated from our diet, medications, drugs, or toxins that we are exposed to and you get a very rich matrix that has great potential to revolutionize and personalize medicine.

Recent Advances in Breath Analysis

With continued advances in technology, essentially anything in the blood that is potentially volatile or has a volatile metabolite can be measured in exhaled breath. Sensor array (electronic nose) devices can be trained to recognize patterns or “smell-prints” in exhaled breath that allow identification of certain diseases or disorders. However, this technology is not well-suited to identify the specific compounds that contribute to a recognized pattern. The mass spectrometry approach to breath analysis on the other hand, allows the identification of specific individual compounds in the breath, but it is not well-suited to recognize patterns commonly seen in disease.

Methods

In our group, we have used both approaches to analyze breath and have come to recognize the strengths a weaknesses of both approaches. More recently we started to use an approach that combines the strengths of both methods. By approaching each compound (or peak) on the mass spectrometry output as its own sensor, we are able to recognize patterns or “breath-prints” in mass spectrometry data in a way similar to how the sensor arrays recognize “smell-prints”. Unlike pattern recognition by the sensor array based systems, the major strength of our approach is that we are able to identify the single components that contribute to each pattern we recognize.

Results and Conclusions

With this best-of-both-worlds approach, we are able to identify unique “breath-prints” in patients with liver disease (fetor hepaticus) as well as heart and kidney disease. We are further able to analyze these patterns to identify single molecules in the breath of these patients and link them to the underlying pathobiology of the disease.

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