Breath vs Skin VOCs: What’s the Difference?

Published on: 12 Aug 2024

What are VOCs?

Recently, volatile organic compounds (VOCs) have become an exciting prospect as potential biomarkers. VOCs are carbon-based compounds that are gaseous at room temperature and can be naturally produced by the body as a product of various metabolic processes.

Several factors make VOCs favorable as biomarkers for clinical research and practice. Because some VOCs are a product of metabolic processes, their abundance can accurately reflect the status of these processes to help indicate an individual’s state of health. In many diseases, alterations in metabolic processes can occur in the early stages, causing VOC profiles to change. VOC biomarkers could therefore detect metabolic changes earlier than cell/blood-based biomarkers, which usually require more time and more advanced changes to indicate a diseased state. Because VOCs are gaseous at room temperature, they are continuously emitted from the body from different sources. These include exhaled breath, sweat, and urine. A key advantage of this is that VOCs can therefore be collected relatively non-invasively, as opposed to a tissue biopsy or blood sample. Additionally, this characteristic enables the real-time monitoring of VOC biomarkers. This is especially useful for monitoring disease progression and treatment response. As a result, research focusing on VOCs as biomarkers has been increasing.

Currently, VOC analysis in the breath is the most characterized, with 1488 breath VOCs being identified, as compared to 379 in blood, 623 in skin, and 444 in urine (1). Gases in the breath have shown strong correlations with different diseases in many areas. For example, OMED has developed breath kits that analyze hydrogen and methane in breath samples to detect small intestine bacterial overgrowth and carbohydrate malabsorption (2). Breath VOCs have also shown strong correlations with lung, gastrointestinal, and liver cancer, bacterial and viral infectious diseases, and other conditions (3). Owlstone Medical have recently published a paper highlighting the current landscape of the applications of breath VOCs in various disease areas.

Breath VOCs research shows promising results, what about skin VOCs?

Skin VOCs have also been extensively studied and have shown promising results. Research has shown differences in VOCs emitted from chronic leg wounds and normal skin arising from differences in bacteria and ingested medications (4). Other skin VOCs have been correlated with certain diseases, including aldehydes in adenocarcinomas, carboxylic acids in melanomas, and infection (5), and fatty acyls in stress (6). Interestingly, there are common VOCs associated with certain diseases found in both the breath and skin, such as acetone in diabetes (7,8). Ketone and alcohol VOCs emitted by humans have even been used to develop portable sensors for search and rescue operations (9). Compared to breath VOCs, skin VOCs analysis is less invasive and has the potential for wearables that can continuously measure emitted VOCs. Despite all these benefits, why is our current understanding of skin VOCs so limited?

What are some difficulties in analyzing VOCs from the skin?

Because the skin is highly exposed to the external environment, there are many confounding variables that can make collecting VOCs from the skin challenging. This includes skin photochemistry – especially in response to sunlight, traffic pollutants, personal care products, and perfumes (5). This continuous environmental exposure makes it more difficult to differentiate between endogenously and exogenously produced skin VOCs. For example, phenol can be found in high levels in urban areas due to traffic emissions (10), benzoic acid from food preservatives, and undecanal from food flavorings (5). Although similar issues are faced in the analysis of breath VOCs, it is relatively easier to remove these environmental contaminants due to the development of breath collection technologies. In breath VOC analysis, the use of a clean air supply, such as the CASPER® Portable Air Supply, can standardize the inhaled air of breath test participants to remove potential contaminants.

Some VOCs are produced by the body at very low concentrations. The method of collection is therefore crucial in ensuring sufficient signal-to-noise for adequate detection sensitivity. Our current understanding of an optimal collection methodology for skin VOCs is limited. Experiments usually either analyze gas directly adjacent to the skin, indirectly capture VOCs on to an absorbent material placed near the skin surface or analyze VOCs within an enclosed chamber containing the subject or area (5). An optimal sampling site is also missing, with differences in skin VOCs detectable based on whether collection is undertaken on the hand, forearm, back, wrist, etc. (5). Because the skin is denser than alveoli, and different skin regions have different perfusion, there are further difficulties in standardizing results from different areas. Similar sampling issues are faced in the analysis of breath VOCs, but new technologies are being developed to address them. For example, devices such as the ReCIVA® Breath Sampler directly captures and pre-concentrates VOCs onto multiple sorbent tubes for a practical and precise method of collecting VOCs. In conclusion, although the potential applications of skin VOCs are attractive, limitations in their sampling methods are currently holding back their development.

The current landscape of skin VOC analysis is constantly developing, with new advances unlocking new disease areas and applications of these compounds. However, until the shortfalls in collection and analysis methods are addressed, it will be difficult to unlock the potential of skin VOCs. For now, the collection of VOCs from the breath offers a promising alternative non-invasive collection platform, with established methods and technologies allowing for their accurate analysis and utilization in research.

References
  1. Drabińska N, Flynn C, Ratcliffe N, Belluomo I, Myridakis A, Gould O, et al. A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome. J Breath Res. 2021 Apr;15(3):034001. doi: 10.1088/1752-7163/abf1d0
  2. Tansel A, Levinthal DJ. Understanding Our Tests: Hydrogen-Methane Breath Testing to Diagnose Small Intestinal Bacterial Overgrowth. Clin Transl Gastroenterol. 2023 Apr 1;14(4):e00567. doi: 10.14309/ctg.0000000000000567
  3. Chou H, Godbeer L, Allsworth M, Boyle B, Ball ML. Progress and challenges of developing volatile metabolites from exhaled breath as a biomarker platform. Metabolomics. 2024 Jul 8;20(4):72. doi: 10.1007/s11306-024-02142-x
  4. Thomas AN, Riazanskaia S, Cheung W, Xu Y, Goodacre R, Thomas CLP, et al. Novel noninvasive identification of biomarkers by analytical profiling of chronic wounds using volatile organic compounds. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2010;18(4):391–400. doi: 10.1111/j.1524-475X.2010.00592.x
  5. Mitra A, Choi S, Boshier PR, Razumovskaya-Hough A, Belluomo I, Spanel P, et al. The Human Skin Volatolome: A Systematic Review of Untargeted Mass Spectrometry Analysis. Metabolites. 2022 Sep 1;12(9):824. doi: 10.3390/metabo12090824
  6. Lucchi G, Crépin M, Chambaron S, Peltier C, Gilbert L, Guéré C, et al. Effects of psychological stress on the emission of volatile organic compounds from the skin. Sci Rep. 2024 Mar 27;14(1):7238. doi: 10.1038/s41598-024-57967-2
  7. Yamane N, Tsuda T, Nose K, Yamamoto A, Ishiguro H, Kondo T. Relationship between skin acetone and blood beta-hydroxybutyrate concentrations in diabetes. Clin Chim Acta Int J Clin Chem. 2006 Mar;365(1–2):325–9. doi: 10.1016/j.cca.2005.09.016
  8. Sha MS, Maurya MR, Shafath S, Cabibihan JJ, Al-Ali A, Malik RA, et al. Breath Analysis for the In Vivo Detection of Diabetic Ketoacidosis. ACS Omega. 2022 Jan 24;7(5):4257–66. doi: 10.1021/acsomega.1c05948
  9. Ruzsanyi V, Wiesenhofer H, Ager C, Herbig J, Aumayr G, Fischer M, et al. A portable sensor system for the detection of human volatile compounds against transnational crime. Sens Actuators B Chem. 2021 Feb 1;328:129036. doi: 10.1016/j.snb.2020.129036
  10. Lu C, Wang X, Dong S, Zhang J, Li J, Zhao Y, et al. Emissions of fine particulate nitrated phenols from various on-road vehicles in China. Environ Res. 2019 Dec;179(Pt A):108709. doi: 10.1016/j.envres.2019.108709