(Invited) Breath Analysis in Lung and Systemic Diseases

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. References 1. Dweik RA (Guest Editor), Amann A. Exhaled breath analysis: the new frontier in medical testing. Journal of Breath Research (JBR). 2008; 2 (030301):1-3. 2. Hunter GW, Dweik RA. Applied Breath Analysis: An Overview of the Challenges and Opportunities in Developing and Testing Sensor Technology for Human Health Monitoring in Aerospace and Clinical Applications. Journal of Breath Research (JBR). 2008; 2 (037020):1-7. 3. Mashir A and Dweik RA. Exhaled Breath Analysis: the New Interface between Medicine and Engineering. Advanced Powder Technology. 2009; 20: 420–25. 4. Paschke KM, Mashir A, Dweik RA. Clinical applications of breath testing. F1000 medicine reports 2010;2:56. 5. Mondal SP, Dutta PK, Hunter GW, Ward BJ, Laskowski D, Dweik RA. Development of High Sensitivity Potentiometric NOx Sensor and its Application to Breath Analysis. Sensors & Actuators:. 2011;158: 292– 298. 6. Hunter GW, Xu JC, Biaggi-Labiosa A, Laskowski D, Dutta PK, Mondal S, Ward BJ, Makel DB, Liu CC , Chang CW, Dweik RA. Smart Sensors Systems for Human Health Breath Monitoring Applications. J Breath Res. 2011; 5(3). 7. Dweik RA. The great challenge for exhaled breath analysis: embracing complexity, delivering simplicity. J Breath Res. 2011; 5(3):030201. 8. Cikach Jr, FS and Dweik RA. Cardiovascular Biomarkers In Exhaled Breath. Progress in Cardiovascular Disease. 2012; 55:34-43. 9. Braun PX, Gmachl GF, Dweik RA. Bridging the Collaborative Gap: Realizing the Clinical Potential of Breath Analysis for Disease Diagnosis and Monitoring. IEEE sensors. 2012; 12: 3258-3270. 10. Samara MA, Tang WHW, Cikach F, Gul Z, Tranchito L, Paschke KM, Viterna J, Wu Y, Dweik RA. Single Exhaled Breath Metabolomic Analysis Identifies Unique Breathprint in Patients with Acute Decompensated Heart Failure. J Am Coll Cardiol. 2013; 61: 1463-4 11. Hanouneh IA, Zein NN, Cikach F, Dababneh L, Grove D, Alkhouri N, Lopez R, Dweik RA. The breathprints in patients with liver disease identify novel breath biomarkers in alcoholic hepatitis. Clin Gastroenterol Hepatol. 2014 Mar; 12(3):516-23.