Smell and lung cancer

Exhaled biomarkers have been studied in cancer for many years(1,2).

Breath testing is a fast, non-invasive method that is based on the presence of specific volatile organic compounds (VOCs) in exhaled breath:

• human breath contains more than three thousand different compounds including large number of volatile organic compounds (VOCs)
  • exhaled VOCs may originate from two main sources: exogenous volatiles that are present in sampling material or inhaled (or absorbed through the skin) and then exhaled and those endogenously produced by different biochemical processes including those that are released during cancer cell metabolism
  • there are several lines of evidence showing that metabolic pathways in cancer cells produce different volatile compounds (or at least a different pattern of them) than in noncancerous tissue. These effects have been observed in a variety of different cancer types including lung, breast and malignant melanomas.
    • the wide variety of confounding sources makes the application of standardised breath sampling and analysis critically important (1,2)
  • application of system biology and the use of pattern recognition to define distinct phenotype handprints is a recently developed method that focuses on patterns rather than individual constituents and has been suggested to be an important and valid approach for cancer research (3)
    • artificial olfaction systems (also called electronic noses) are based on pattern recognition as they discriminate complex 'smellprints' without identifying individual components. Like the human olfactory system, the electronic one also generates a 'smellprint' that can be compared to previously stored ones
      • publications have demonstrated that breath samples from patients with lung cancer and those from healthy subjects can be distinguished by electronic nose technology
        • use of an electronic nose for sensing cancer offers several advantages, but it also has disadvantages. Strengths include high sensitivity, ease of administration of the test and portability of the detector
        • limitations include loss of sensitivity in the presence of water vapour or high concentrations of a single component; sensor drift and the inability to provide absolute calibration; relatively short life of some sensors; necessity to do considerable method development work for each specific application; and the inability to obtain quantitative data
    • canine based sensing of 'smellprints' have also been applied
      • dogs had an accuracy of 99% in discriminating between smells from exhaled breath of patients with lung cancer and controls. The stage of cancer, age of patients, smoking habit or the most recently eaten meal did not influence the dog’s diagnostic performance (4)
      • a further study evaluated the abilities of specifically trained dogs to distinguish samples derived from lung cancer patients of various tumor stages from matched healthy controls (5)
        • using a combination of urine and breath samples, the dog correctly predicted 40 out of 41 cancer samples, corresponding to an overall detection rate of cancer samples of 97.6% (95% CI [87.1, 99.9%]).
          • using urine samples only the dog achieved a detection rate of 87.8% (95% CI [73.8, 95.9%])
          • with breath samples, the dog correctly identified cancer in 32 of 41 samples, resulting in a detection rate of 78% (95% CI [62.4, 89.4%])
        • study authors concluded:
          • known from current literature that breath and urine samples carry VOCs pointing to cancer growth
          • olfactory detection of lung cancer by specifically trained dogs is highly suggestive to be a simple and non-invasive tool to detect lung cancer

Reference:

• (1) Horváth I, Lázár Z, Gyulai N, Kollai M, Losonczy G. Exhaled biomarkers in lung cancer. Eur Respir J 2009;34:261-75.
• (2) Szulejko JE, McCulloch M, Jackson J, McKee DL, Walker JC, Solouki T. Evidence for cancer biomarkers in exhaled breath. IEEE Sensors J 2010;10:185-210.
• (3) Wolkenhauer O, Auffray C, Baltrusch S, Blüthgen N, Byrne H, Cascante M, et al. Systems biologists seek fuller integration of systems biology approaches in new cancer research programs. Cancer Res 2010;70:12-3.
• (4) Editorial. Lung cancer. Lung Cancer 2010;68: 127-128.
• (5) Feil C, Staib F, Berger MR, Stein T, Schmidtmann I, Forster A, Schimanski CC. Sniffer dogs can identify lung cancer patients from breath and urine samples. BMC Cancer. 2021 Aug 13;21(1):917.