Sense of smell and olfactory disorder in humans

By Shiyi Liang

    The sense of smell is vital to the daily lives of animals and humans, helping in the recognition of specific danger like fire or rotten food, as well as being a sense of attraction between creatures. Odours are recognized by the olfactory epithelium in the nasal cavity and the brain. There are three types of cells in olfactory epithelium: olfactory receptor cells, supporting cells, and basal cells. Olfactory receptor cells (ORCs) are neurons, with axons to reach into the central nervous system. (Bear, Connors, and Paradiso, n.d.). Odorant receptors on the olfactory receptor cells are G-protein coupled receptors which vary in their amino acid sequence to detect different odorants (Gonzalez-Kristeller, do Nascimento, Galante and Malnic, 2015). Resembling taste receptor cells, olfactory receptor cells have a short life span with new receptor cells forming from basal cells. Odorants will dissolve in the mucus produced by supporting cells before binding to the cilia of ORCs. Olfactory receptor proteins, specific transport G-proteins, are used to induce membrane depolarization, propagating an action potential along the axons into the olfactory bulbs. Each glomerulus in the olfactory bulb assembles axons from one type of receptor cell in the olfactory epithelium, meaning that the site of activation of the olfactory bulb changes as the type of odorant changes. The targets of the action potential are the olfactory cortex, a region of the cerebral cortex in the brain, and some of its surrounding regions, where the information is analysed (Bear, Connors and Paradiso, n.d.).

Multiple methods have been developed to measure olfactory performance quantitatively and qualitatively, including the University of Pennsylvania Smell Identification Test (UPSIT), the Connecticut Chemosensory Clinical Research Center test (CCCRC), and The Sniffin’ Sticks test ®. UPSIT uses a booklet with multiple-choice tests and encapsulated fragments under a brown stripe. Subjects should scratch and smell the fragment to choose the best fit smell for the multiple-choice question. The CCCRC is similar to the UPSIT but involves an additional threshold test (Cain and Rabin, 1989, Doty, Shaman, Kimmelman and Dann, 1984). The Sniffin’ Sticks test ® is comprised of three subtests, a T threshold test, an I identification test, and a D odour discrimination test. These three tests produce three scores, the sum of which is the TDI score. (Rumeau, Nguyen, and Jankowski, 2016).

There are two main categories of olfactory dysfunction: quantitative and qualitative. Quantitative olfactory dysfunction can be measured by checking the loss of olfaction. This includes hyposmia and anosmia, a partial or complete loss of the sense of smell. Qualitative olfactory dysfunction is a distortion or alteration of smell and includes troposmia and phantosmia. Patients with troposmia sense a smell differently as remembered, whilst phantosmia is referred to smelling an odour when there is no odorant around (Leopold, 2002). 

There are several underlying reasons for olfactory dysfunction, including aging, sinonasal diseases, head trauma, post-viral infection, toxin, and drugs. But the pathophysiological theories based on olfactory dysfunction are still yet to be discovered.

Aging and age-related diseases like Alzheimer’s disease can be a significant cause of olfactory dysfunction. Patients may discover both gustatory and olfactory dysfunction which impair their quality of life (Kondo et al., 2020). The experiment of Hummel et al studied the effect of age on the trigeminal mediated response, which is thought to be related to olfactory loss, and suggested a decrease of intranasal trigeminal sensitivity in older subjects (Hummel, Futschik, Frasnelli and Hüttenbrink, 2003). Another experiment of Hummel et al used “Sniffin Sticks” method to compare the TDI score of more than 3000 subjects in different age groups and showed that a decrease in odour threshold can be largely related to age (Hummel, Kobal, Gudziol and Mackay-Sim, 2006). 

Furthermore, viruses can cause post viral olfactory dysfunction. It is common that viruses infect the upper respiratory and cause this loss, but it remains unknown which virus has the closest relationship with olfactory dysfunction (Suzuki et al., 2007). Some animal studies showed that viruses can cause damage to olfactory nerve pathways and related areas of the brain, as well as the olfactory epithelium (Seiden, 2004).

In a study of olfactory dysfunction in COVID-19 patients, 86 patients were tested with 61.4% self-reporting a loss in smell (Lechien et al., 2020). For SARS-CoV-2, the possible cause of anosmia is that the virus binds to sustentacular cells around the olfactory neurons since they express the ACE2 receptor, rather than binding directly to olfactory receptor cells. The virus may enter nasopharynx there and lead to an inflammatory response and disruption of the epithelium, leading to a loss of smell (Rebholz et al., 2020).

Drugs and toxins can be another common cause of the olfactory disorder. Drugs can inactivate receptor function or induce disorder of olfactory receptors and lead to a qualitative or quantitative smell disorder (Henkin, 1994). Furthermore, toxins could cause reversible or irreversible olfactory dysfunction. A study focused on long-term exposure to chemicals including metals, acrylates, styrene, which concluded that exposure to metals like cadmium and chromium affected the olfactory threshold (Gobba, 2006). Long-term alcohol use also leads to Korsakoff’s psychosis, a severe central nervous system damage. (Doty and Bromley, 2004)

Olfaction is an important sense for humans, it allows people to perform in the social and emotional part of life. Moreover, humans can experience being reminded of certain memory by scents; it is suggested that olfactory sensation is associated with memory since the sense of smell is processed in the thalamus, which is also a vital region for memory and learning (Curley, 2020). Recently, the research on the treatment of smell disorders has declined, but a study suggested that Traditional Chinese Acupuncture could have a certain effect on post-viral smell loss after separating 15 patients into two groups and provide one group with Traditional Chinese Acupuncture for 10 weeks and the other with oral vitamin B complex. They also suggest that further investigation with a larger population is needed to confirm (Vent, Wang and Damm, 2010).

References

Bear, Mark, Connors, Barry & Paradiso, Michael A, 2020. Neuroscience 4th ed., Burlington: Jones & Bartlett Learning, LLC.

Gonzalez-Kristeller, D., do Nascimento, J., Galante, P. and Malnic, B., 2015. Identification of agonists for a group of human odorant receptors. Frontiers in Pharmacology, 6. 

Cain, W. and Rabin, M., 1989. Comparability of two tests of olfactory functioning. Chemical Senses, 14(4), pp.479-485.

Doty, R., Shaman, P., Kimmelman, C. and Dann, M., 1984. University of pennsylvania smell identification test: A rapid quantitative olfactory function test for the clinic. The Laryngoscope, 94(2), pp.176-178. 

Rumeau, C., Nguyen, D. and Jankowski, R., 2016. How to assess olfactory performance with the Sniffin’ Sticks test ®. European Annals of Otorhinolaryngology, Head and Neck Diseases, 133(3), pp.203-206. 

Leopold, D., 2002. Distortion of Olfactory Perception: Diagnosis and Treatment. Chemical Senses, 27(7), pp.611-615. 

Kondo, K., Kikuta, S., Ueha, R., Suzukawa, K. and Yamasoba, T., 2020. Age-Related Olfactory Dysfunction: Epidemiology, Pathophysiology, And Clinical Management. 

Hummel, T., Futschik, T., Frasnelli, J. and Hüttenbrink, K., 2003. Effects of olfactory function, age, and gender on trigeminally mediated sensations: a study based on the lateralization of chemosensory stimuli. Toxicology Letters, 140-141, pp.273-280.

Hummel, T., Kobal, G., Gudziol, H. and Mackay-Sim, A., 2006. Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. European Archives of Oto-Rhino-Laryngology, 264(3), pp.237-243.

Suzuki, M., Saito, K., Min, W., Vladau, C., Toida, K., Itoh, H. and Murakami, S., 2007. Identification of Viruses in Patients With Postviral Olfactory Dysfunction. The Laryngoscope, 117(2), pp.272-277. 

Seiden, A., 2004. Postviral olfactory loss. Otolaryngologic Clinics of North America, 37(6), pp.1159-1166. 

Lechien, J., Cabaraux, P., Chiesa‐Estomba, C., Khalife, M., Hans, S., Calvo‐Henriquez, C., Martiny, D., Journe, F., Sowerby, L. and Saussez, S., 2020. Objective olfactory evaluation of self‐reported loss of smell in a case series of 86 COVID ‐19 patients. Head & Neck, 42(7), pp.1583-1590.

Rebholz, H., Braun, R., Ladage, D., Knoll, W., Kleber, C. and Hassel, A., 2020. Loss of Olfactory Function—Early Indicator for Covid-19, Other Viral Infections and Neurodegenerative Disorders. Frontiers in Neurology, 11.

Gobba, F., 2006. Olfactory toxicity: long-term effects of occupational exposures. International Archives of Occupational and Environmental Health, 79(4), pp.322-331.

Henkin, R., 1994. Drug-Induced Taste and Smell Disorders. Drug Safety, 11(5), pp.318-377.

(Curley), A., 2020. Making Sense Of Scents: Smell And The Brain. [online] Brainfacts.org. Available at: <https://www.brainfacts.org/thinking-sensing-and-behaving/smell/2015/making-sense-of-scents-smell-and-the-brain&gt; [Accessed 7 December 2020].

Doty, R. and Bromley, S., 2004. Effects of drugs on olfaction and taste. Otolaryngologic Clinics of North America, 37(6), pp.1229-1254.

Vent, J., Wang, D. and Damm, M., 2010. Effects of traditional Chinese acupuncture in post-viral olfactory dysfunction. Otolaryngology–Head and Neck Surgery, 142(4), pp.505-509.

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