Biochemical Pathways Meggie Hakim,† Yoav Y. Broza,† Orna Barash,† Nir Peled,‡ Michael Phillips, Anton Amann, and Hossam Haick*,† †The Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, TechnionIsrael Institute of Technology, Haifa 32000, Israel ‡The Thoracic Cancer Research and Detection Center, Sheba Medical Center, Tel-Aviv University, Tel-Aviv 52621, Israel Menssana Research, Inc., Fort Lee, New Jersey 07024, United States Breath Research Institute, Austrian Academy of Sciences, 6850 Dornbirn, Austria University-Clinic for Anesthesia, Innsbruck Medical University, 6020 Innsbruck, Austria

Volatile organic compounds of lung cancer and possible biochemical pathways.

Proton-transfer reaction mass spectrometry (PTR-MS) is a technique developed almost exclusively for the detection of gaseous organic compounds in air. Volatile organic compounds (VOCs) in air have both natural and anthropogenic sources. Natural sources include the emission of organic gases by living objects, both plants and animals. A well-known example, which is discussed later in this review, is the emission of a variety of gaseous organic compounds in the breath of animals, which are released from both the digestive system and the lungs. Plants are major sources of organic gases, as is the decay of dead animal and plant matter. Subsequent photochemistry can add further compounds to the mixture. Consequently, even without contributions from humans, ambient air from the Earth’s atmosphere would consist of a complex mixture of VOCs.

Proton-transfer reaction mass spectrometry.

Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilem) Petters discovered acetone in breath in 1857 and Johannes Muller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer, but also during surgery and in intensive care units. The investigation of cell cultures opens up new possibilities for elucidation of the biochemical background of volatile compounds. In future studies, combined investigations of a particular compound with regard to human matrices such as breath, urine, saliva and cell culture investigations will lead to novel scientific progress in the field.

https://iopscience.iop.org/article/10.1088/1752-7155/8/3/034001/pdf

The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva

Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC) disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser spectroscopic techniques and laser sources have driven breath analysis to new heights, moving from laboratory research to commercial reality. Laser spectroscopic detection techniques not only have high-sensitivity and high-selectivity, as equivalently offered by the MS-based techniques, but also have the advantageous features of near real-time response, low instrument costs, and POC function. Of the approximately 35 established breath biomarkers, such as acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species in exhaled human breath have been analyzed by high-sensitivity laser spectroscopic techniques, namely, tunable diode laser absorption spectroscopy (TDLAS), cavity ringdown spectroscopy (CRDS), integrated cavity output spectroscopy (ICOS), cavity enhanced absorption spectroscopy (CEAS), cavity leak-out spectroscopy (CALOS), photoacoustic spectroscopy (PAS), quartz-enhanced photoacoustic spectroscopy (QEPAS), and optical frequency comb cavity-enhanced absorption spectroscopy (OFC-CEAS). Spectral fingerprints of the measured biomarkers span from the UV to the mid-IR spectral regions and the detection limits achieved by the laser techniques range from parts per million to parts per billion levels. Sensors using the laser spectroscopic techniques for a few breath biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available. This review presents an update on the latest developments in laser-based breath analysis.

https://www.mdpi.com/1424-8220/9/10/8230/pdf

Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits

Background
Lung cancer is one of the leading causes of death in Europe and the western world. At present, diagnosis of lung cancer very often happens late in the course of the disease since inexpensive, non-invasive and sufficiently sensitive and specific screening methods are not available. Even though the CT diagnostic methods are good, it must be assured that "screening benefit outweighs risk, across all individuals screened, not only those with lung cancer". An early non-invasive diagnosis of lung cancer would improve prognosis and enlarge treatment options. Analysis of exhaled breath would be an ideal diagnostic method, since it is non-invasive and totally painless.

/pdf/noninvasive-detection-of-lung-cancer-by-analysis-of-exhaled-37la1x5get.pdf

Noninvasive detection of lung cancer by analysis of exhaled breath

Over the last few years, breath analysis for the routine monitoring of metabolic disorders has attracted a considerable amount of scientific interest, especially since breath sampling is a non-invasive technique, totally painless and agreeable to patients. The investigation of human breath samples with various analytical methods has shown a correlation between the concentration patterns of volatile organic compounds (VOCs) and the occurrence of certain diseases. It has been demonstrated that modern analytical instruments allow the determination of many compounds found in human breath both in normal and anomalous concentrations. The composition of exhaled breath in patients with, for example, lung cancer, inflammatory lung disease, hepatic or renal dysfunction and diabetes contains valuable information. Furthermore, the detection and quantification of oxidative stress, and its monitoring during surgery based on composition of exhaled breath, have made considerable progress. This paper gives an overview of the analytical techniques used for sample collection, preconcentration and analysis of human breath composition. The diagnostic potential of different disease-marking substances in human breath for a selection of diseases and the clinical applications of breath analysis are discussed.

Human exhaled air analytics: biomarkers of diseases

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Human exhaled air analytics: biomarkers of diseases