Biochemical and immunological indicators of human sensitivity to odors in model olfactometric studies

Introduction. Dynamic olfactometry, with participation of a team of human panelists as sensors, was developed to quantify odor concentrations in samples of atmospheric air and model mixtures.

The aim of the work is to evaluate the informativity of a number of salivary biochemical and immunological parameters as possible markers of human olfactory acuity in model olfactometric study of emissions from food industry enterprises.

Materials and methods. Experimental study is based on the use of ECOMA T08 olfactometer, three food odorants with odors of orange, cognac and coffee, 10 panelists tested with n-butanol, standard methods for assessing cytokines IL-1β, IL-6, IL-8, sIgA, NAG, α-amylase, intensity of luminol-enchanced chemiluminescence in the samples of mixed saliva of the participants

Results. An algorithm has been developed for the preprocessing of olfactometric data, optimal for their correlation analysis with saliva molecular parameters. Among 7 saliva markers under study, there is shown only one to be associated with human olfactory acuity in Spearman’s correlation test – IL-8 content (R= −0.392; p=0.032 with odor thresholds and close to reliable positive associations with perceived odor intensity in combined data matriх, N=30). Peculiarities of the scatterplot «odor thresholds/IL-8» suggest healthy persons with a sharper sense of smell to have more flexible mechanisms for releasing IL-8 in response to provoking changes in oral microbes, and this chemotactic signal, in turn, leads to timely attraction of blood neutrophils, reducing bacterial colonization and thickness of supraepithelial mucus, and so to more efficient binding of odorant molecules with olfactory receptors.

Limitations. Small sample sizes, although they correspond to the practical purposes of the European standard EN 13725.

Conclusion. The data obtained indicate that dynamic olfactometry, created as a practical tool for assessing odor concentrations in atmospheric air, can also be used to study the molecular mechanisms of olfaction.

Compliance with ethical standards. The consent of the Local Ethics Committee of the Centre for Strategic Planning of the Federal medical and biological agency of Russia was obtained for conducting of the research involving human participants (Protocol No. 3 of 08/17/2020). All participants gave informed voluntary written consent to participate in the study.

Contributions:
Khripach L.V. – research concept and design, biochemical and ELISA assays, writing the article;
Knyazeva T.D. – biochemical and ELISA assays;
Andryushin I.B. – olfactometry;
Budarina O.V. – research concept and design, editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: October 16, 2025 / Revised: November 11, 2025 / Accepted: December 2, 2025 / Published: January 15, 2026

1. Moskowitz H.R., Dravnieks A., Klarman L.A. Odor intensity and pleasantness for a diverse set of odorants. Percept. Psychophys. 1976; 19(2): 122–8. https://doi.org/10.3758/BF03204218

2. Distel H., Ayabe-Kanamura S., Martínez-Gómez M., Schicker I., Kobayakawa T., Saito S., et al. Perception of everyday odors – correlation between intensity, familiarity and strength of hedonic judgement. Chem. Senses. 1999; 24(2): 191–9. https://doi.org/10.1093/chemse/24.2.191

3. de Lichtenberg Broge E.H., Wendin K., Rasmussen M.A., Bredie W.L. Familiarity and identification of everyday food odors in older adults and their influence on hedonic liking. Food Qual. Prefer. 2023; 103: 104715. https://doi.org/10.1016/j.foodqual.2022.104715

4. Hosoya K., Komachi T., Maeda Y., Akazawa H., Ogino E., Yoshida A., et al. Evaluation of odor recognition threshold measurement methods in T&T olfactometry: A survey study. Auris Nasus Larynx. 2024; 51(1): 61–8. https://doi.org/10.1016/j.anl.2023.07.009

5. Miwa T., Ikeda K., Ishibashi T., Kobayashi M., Kondo K., Matsuwaki Y., et al. Clinical practice guidelines for the management of olfactory dysfunction – secondary publication. Auris Nasus Larynx. 2019; 46(5): 653–62. https://doi.org/10.1016/j.anl.2023.07.009

6. Lopatin A.S., ed. Olfactory Dysfunction. Russian Society of Rhinologists. Practical Recommendations [Ol’faktornaya disfunktsiya. Rossiiskoe obshchestvo rinologov. Prakticheskie rekomendatsii]. Moscow; 2024. (in Russian)

7. Vakhrushev S.G., Smbatyan A.S. Diagnostic value of different olfactometry methods. Rossiiskaya otorinolaringologiya. 2016; (3): 48–53. https://doi.org/10.18692/1810-4800-2016-3-48-53 https://elibrary.ru/waacuf (in Russian)

8. Alekseeva N.S., Ponomareva T.A. Diagnostics of olfactory disorders in the patients with Parkinson’s disease and Polypous sinusitis with the use of the Sniffin’ Sticks test. Vestnik otorinolaringologii. 2014; (1): 37–40. https://elibrary.ru/rwaosd (in Russian)

9. Rumeau C., Nguyen D.T., Jankowski R. How to assess olfactory performance with the Sniffin’ Sticks test. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 2016; 133(3): 203–6. https://doi.org/10.1016/j.anorl.2015.08.004

10. Dobretsov K.G., Kashirskiy D.V. Study of olfactory threshold using Russian version of Sniffin’ Sticks test. Rossiiskaya rinologiya. 2024; 32(1): 6–10. https://doi.org/10.17116/rosrino2024320116 https://elibrary.ru/jaydqc (in Russian)

11. Sipos L., Galambosi Z., Bozóki S., Szadoczki Z. Statistical overview of the Sniffin’ sticks olfactory test from the perspectives of anosmia and hyposmia. Sci. Rep. 2025; 15(1): 8984. https://doi.org/10.1038/s41598-025-93380-z

12. Ministry of the Environment Government of Japan. Office of Odor, Noise and Vibration Environmental Management Bureau. Odor Index Regulation and Triangular Odor Bag Method. Available at: https://www.env.go.jp/en/air/odor/regulation/index.html

13. Nagata Y., Takeuchi N. Measurement of odor threshold by triangle odor bag method. Odor Measurement Review. 2003; 118: 118–27.

14. Wang Y., Shao L., Kang X., Zhang H., Lü F., He P. A critical review on odor measurement and prediction. J. Environ. Manag. 2023; 336: 117651. https://doi.org/10.1016/j.jenvman.2023.117651

15. Xu Y., Liang W., Hu Y. Methodological assessment of screening methods and minimum panel member requirements for odor assessments. Build. Environ. 2023; 237: 110326.

16. ASTM E679-91. Standard Practice for Determination of Odor and Taste Threshold By a Forced-Choice Ascending Concentration Series Method of Limits. American Society for Testing and Materials. Philadelphia, PA; 2004.

17. GOST R ISO 16000-8–2015. Indoor Air. Part 28. Determination of odor emission from building materials using test chambers. Moscow; 2015. (in Russian)

18. GOST R 58578–2019. Rules for establishing standards and monitoring odor emissions into the atmosphere. Moscow; 2019. (in Russian)

19. Yatsenko-Khmelevskaya M.A., Tsibul’skii V.V., Khitrina N.G., Korolenko L.I. Olfactometric investigations of odor emissions by industrial enterprises in Russia. Biosfera. 2013; 5(3): 303–10. https://elibrary.ru/rdcisl (in Russian)

20. Budarina O.V., Sabirova Z.F., Andryushin I.B., Shipulina Z.V. Hygienic justification for the classification of the danger of sources of emissions of substances having an olfactorial action. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2023; 102(9): 888–95. https://doi.org/10.47470/0016-9900-2023-102-9-888-895 https://elibrary.ru/uyfatq (in Russian)

21. Kuzmin S.V., Budarina O.V., Rakhmanin Yu.A., Pinigin M.A., Dodina N.S., Skovronskaya S.A. Prospects of the development and harmonization of hygienic standardization taking into account the risk of odour in the ambient air. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2024; 103(2): 96–103. https://doi.org/10.47470/0016-9900-2024-103-2-96-103 https://elibrary.ru/bvtxvx (in Russian)

22. European committee for standardisation. Air quality. Determination of odour concentration by dynamic olfactometry. European standard EN 13725:2003.

23. Harreveld A.P., Heeres P., Harssema H. A review of 20 years of standardization of odor concentration measurement by dynamic olfactometry in Europe. J. Air Waste Manag. Associat. 1999; 49(6): 705–15. https://doi.org/10.1080/10473289.1999.11499900

24. Harreveld A.P. Update on the revised EN 13725:2021. Chem. Engin. Transact. 2021; 85: 115–20. https://doi.org/10.3303/CET2185020

25. Mahin T. Measurement and regulation of odors in the USA. Odor Measurement Review. 2003; 62–8.

26. Department of Environmental Protection. Odour Methodology Guideline. Perth (Western Australia); 2002.

27. Leonardos G. Selection of panelists. J. Air Pollut. Control. Associat. 1980; 30(12): 1297–8.

28. Dravnieks A., Jarke F. Odor threshold measurement by dynamic olfactometry: significant operational variables. J. Air Pollut. Control. Associat. 1980; 30(12): 1284–9. https://doi.org/10.1080/00022470.1980.10465182

29. Clanton C.J., Schmidt D.R., Nicolai R.E., Goodrich P.R., Jacobson L.D., Janni K.A., et al. Dynamic olfactometry variability in determining odor dilutions-to-threshold. Transactions of the ASAE. 1999; 42(4): 1103–12.

30. Bhuker A., Maurya N.K. Selection and performance of sensory panelists: A comprehensive review of factors influencing sensory evaluation outcomes. J. Nutr. Food Process. 2024; 7(15). https://doi.org/0.31579/2637-8914/278

31. Khripach L.V., Knyazeva T.D., Zheleznyak E.V., Makovetskaya A.K., Koganova Z.I., Budarina O.V., et al. Screening and post-screening of air pollution markers in mixed saliva of preschool children. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2020; 99(6): 610–17. https://elibrary.ru/tuzauq (in Russian)

32. Khripach L.V., Budarina O.V., Knyazeva T.D., Makovetskaya A.K., Koganova Z.I., Andryushin I.B. Biochemical and immunological markers of the adaptive response in olfacto-odorimetric studies. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2022; 101(7): 741–8. https://doi.org/10.47470/0016-9900-2022-101-7-741-748 https://elibrary.ru/diuxzm (in Russian)

33. Pokrovskii A.A., Kravchenko L.V., Tutel’yan V.A. Effect of aflatoxin and mitomycin C on the activity of lysosomal enzymes. Biokhimiya. 1971; 36(4): 690–6. (in Russian)

34. Khripach L.V. Application of free radical methods to assess the effect of polychlorinated dioxins and furans on the health status of the population. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2002; (2): 72–6. (in Russian)

35. Sultan B., May L.A., Lane A.P. The role of TNF-α in inflammatory olfactory loss. Laryngoscope. 2011; 121(11): 2481–6. https://doi.org/10.1002/lary.22190

36. Henkin R.I., Schmidt L., Velicu I. Interleukin 6 in hyposmia. JAMA Otolaryngol. Head Neck Surg. 2013; 139(7): 728–34. https://doi.org/10.1001/jamaoto.2013.3392

37. Aboelenin A.Y., Elsawy M.F., Hassan A.A., Qotb M.M., Hegab A., Aboelmaaty A.R. Correlation between Interleukin-6 serum level and olfactory dysfunction severity in COVID-19 patients in Egypt. Int. J. Med. Arts. 2024; 6(1): 4069–76.

38. Schlosser R.J., Mulligan J.K., Hyer J.M., Karnezis T.T., Gudis D.A., Soler Z.M. Mucous cytokine levels in chronic rhinosinusitis-associated olfactory loss. JAMA Otolaryngol. Head Neck Surg. 2016; 142(8): 731–7.

39. Wang H., Jaen C., Yoshikawa K., Haneoka M., Saito N., Nakamura J., et al. Cytokine profile in human olfactory cleft mucus and associated changes in olfactory function. BioRxiv. 2018; 332395.

40. Wu J., Chandra R.K., Li P., Hull B.P., Turner J.H. Olfactory and middle meatal cytokine levels correlate with olfactory function in chronic rhinosinusitis. Laryngoscope. 2018; 128(9): E304–10. https://doi.org/10.1002/lary.27112

41. Darnell E.P., Wroblewski K.E., Pagel K.L., Kern D.W., McClintock M.K., Pinto J.M. IL-1Rahigh-IL-4low-IL-13low: A novel plasma cytokine signature associated with olfactory dysfunction in older US adults. Chem. Senses. 2020; 45(5): 407–14. https://doi.org/10.1093/chemse/bjaa029

42. Ekström I., Vetrano D.L., Papenberg G., Laukka E.J. Serum C-reactive protein is negatively associated with olfactory identification ability in older adults. i-Perception. 2021; 12(2): 20416695211009928. https://doi.org/10.1177/20416695211009928

43. Chapman S., Kondo K., Ihara S., Ijichi C., SatoK., Touhara K. Fibronectin in the olfactory mucus increases sensitivity of olfactory receptor response to odorants. Sci. Adv. 2025; 11(20): eadu7271. https://doi.org/10.1126/sciadv.adu7271

44. Cavaliere C., Incorvaia C., Frati F., Messineo D., Ciotti M., Greco A., et al. Recovery of smell sense loss by mepolizumab in a patient allergic to dermatophagoides and affected by chronic rhinosinusitis with nasal polyps. Clin. Mol. Allergy. 2019; 17: 3. https://doi.org/10.1186/s12948-019-0106-2

45. Byrne M.L., O’Brien-Simpson N.M., Reynolds E.C., Walsh K.A., Laughton K., Waloszek J.M., et al. Acute phase protein and cytokine levels in serum and saliva: a comparison of detectable levels and correlations in a depressed and healthy adolescent sample. Brain Behav. Immun. Health. 2013; 34: 164–75. https://doi.org/10.1016/j.bbi.2013.08.010