Breath diagnostics

Breath diagnostics involves the analysis of a sample of human breath to monitor, diagnose, and detect diseases and conditions. Besides its primary constituents – nitrogen, oxygen, carbon dioxide and water vapour – exhaled human breath contains over one thousand other compounds at trace levels.[1] Many of these species are formed as the by-products of metabolic processes and can be indicative of a number of different diseases and conditions. Examples of such biomarkers are outlined below:

Breath diagnostics
Purposeanalysis of breath to detect diseases

Acetone - Diabetes mellitus[1] Ammonia - Renal Disease[2] Hydrogen Sulfide - Liver Cirrhosis[3] Methane - Colonic Fermentation[4]

Breath Acetone for Diabetes Diagnosis

Diabetes mellitus is a serious chronic illness that affects how the body uses food, and is a life-threatening human disease if left untreated. It affects more than 171 million people worldwide.[5]

Diabetes mellitus can be subdivided into; type I diabetes, where the body does not produce insulin, the hormone which facilitates the uptake of glucose by cells; and type II diabetes, where the body becomes resistant to insulin, thus inhibiting the extent of glucose usage. In each case, the ineffective use of glucose as a source of energy leads to the subsequent breakdown of fatty acids to compensate. This consumption of fatty acids by ketosis, produces acetone which is excreted into the blood, before equilibrating with air in the lungs. Diabetes may therefore be characterised by elevated breath acetone levels.[6] There are several new technologies being developed to diagnose and monitor diabetes by means of an acetone breath test. It is hoped that the breath test will one day supersede the use of finger-prick blood tests and provide non-invasive diabetes monitoring.[7] These technologies include Cavity Enhanced Absorption Spectroscopy (CEAS) and Plasma Emission Spectroscopy (PES).

Volatile Organic compound mixture for early diagnosis, phenotyping, and therapy response prediction

The current state of the art of breath diagnostics is the use of an Electronic nose to detect the complete mixture of Volatile organic compound (VOCs) in the human breath. Breathomix BV is providing the latest advancement: BreathBase®,[8] that is able to diagnose lung cancer up to two years earlier than standard clinical care.[9] It can tell doctors who will respond to immunotherapy and it is able to distinguish different subtypes of disease in asthma and COPD.[10] Therefore, treatment of asthma / COPD will be easier and tailored to the individual patient bringing us a step closer to personalized medicine / precision medicine.

Breath aerosol analysis

Breath aerosol analysis consists in the sampling and analysis of particles emitted in the respiratory tract and present in exhaled breath.[11] This is a relatively new field that holds great promise for direct diagnostics of pathogens, such as Influenza, and for in-vivo monitoring of the respiratory lining fluid (Respiratory epithelium) components, such as proteins and phospholipids.[12] Various methods are used for sampling exhaled breath aerosols, such as filters, impactors, impingement filter, or electrostatic precipitators.[13][14] This latter field is related to that of Bioaerosol sampling and analysis.

References
  1. Wang et al. (2009). "Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits" Sensors 2009, 9(10) doi:10.3390/s91008230
  2. Thorpe et al. (2008). "Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis" Optics Express, 16(4) doi:10.1364/OE.16.002387
  3. Modugno et al. (1998). "Detection of H2S at the ppm level using a telecommunication diode laser" Optics Communications, 145(1-6) doi:10.1016/S0030-4018(97)00461-6
  4. Marchand et al. (2006). "Breath hydrogen and methane in populations at different risk for colon cancer" International Journal of Cancer, 55(6) doi:10.1002/ijc.2910550603
  5. Wild et al. (2004). "Global prevalence of diabetes: estimates for 2000 and projections for 2030" Diabetes Care, 27(5) doi:10.2337/diacare.27.5.1047
  6. Turner et al. (2009) "Breath acetone concentration decreases with blood glucose concentration in type I diabetes mellitus patients during hypoglycaemic clamps" Journal of Breath Research, 3(4) doi:10.1088/1752-7155/3/4/046004
  7. "Diabetes breath test 'on way'". Telegraph. 2007-09-25. Retrieved 2011-12-31.
  8. "BreathBase® Solution | Breathomix". www.breathomix.com. Archived from the original on 2020-02-06.
  9. de Vries, R.; van den Heuvel, J.m.; Dagelet, Y.w.f.; Dijkers, E.; Fabius, T.; de Jongh, F.h.c.; Jak, P.m.c.; Haarman, E.g.; Kester, S.; Bekkers, M.; van den Heuvel, M.m.; Baas, P.; in t Veen, J.c.c.m.; Maitland-van der Zee, A.h.; Sterk, P.j. (1 May 2019). "Prospective Early Detection of Lung Cancer in COPD Patients by Electronic Nose Analysis of Exhaled Breath". C110. The Future of Lung Cancer Biomarkers: Where Should We Look?. C110. The Future of Lung Cancer Biomarkers: Where Should We Look?. American Thoracic Society. pp. A7451. doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a7451. S2CID 202804944.
  10. de Vries, Rianne; Dagelet, Yennece W.F.; Spoor, Pien; Snoey, Erik; Jak, Patrick M.C.; Brinkman, Paul; Dijkers, Erica; Bootsma, Simon K.; Elskamp, Fred; de Jongh, Frans H.C.; Haarman, Eric G.; in ‘t Veen, Johannes C.C.M.; Maitland-van der Zee, Anke-Hilse; Sterk, Peter J. (January 2018). "Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label". European Respiratory Journal. 51 (1): 1701817. doi:10.1183/13993003.01817-2017. ISSN 0903-1936. PMID 29326334.
  11. Almstrand A-C, Bake B, Ljungstrom E, Larsson P, Bredberg A, Mirgorodskaya E, et al. Effect of airway opening on production of exhaled particles. J Appl Physiol. 2010;108(3):584–8.
  12. Almstrand A-C, Ljungström E, Lausmaa J, Bake B, Sjövall P, Olin A-C. Airway Monitoring by Collection and Mass Spectrometric Analysis of Exhaled Particles. Anal Chem. 2009 Jan 15;81(2):662–8.
  13. Pardon, Gaspard; Ladhani, Laila; Sandström, Niklas; Ettori, Maxime; Lobov, Gleb; van der Wijngaart, Wouter (2015). "Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface". Sensors and Actuators B: Chemical. 212: 344–352. doi:10.1016/j.snb.2015.02.008. ISSN 0925-4005.
  14. Ladhani, Laila; Pardon, Gaspard; Moons, Pieter; Goossens, Herman; van der Wijngaart, Wouter (2020). "Electrostatic Sampling of Patient Breath for Pathogen Detection: A Pilot Study". Frontiers in Mechanical Engineering. 6. doi:10.3389/fmech.2020.00040. ISSN 2297-3079.
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