Discussion
Olfactory dysfunction has become one of the common symptoms associated with many cases of corona virus 11-13. During the response to odorants, there is a simultaneous increase in cyclic adenosine monophosphate and calcium cations. The cyclic adenosine monophosphate is produced by activation of adenylate cyclase and the increase in calcium cations is due to influx via cyclic nucleotide channels. Therefore, it is hypothesized that decreasing intranasal free calcium cations may reduce feedback inhibition and lead to improved receptor response and olfactory function 14.
This prospective randomized controlled trial tested the topical application of DTPA for the treatment of anosmia post COVID-19 infection. DTPA is a chelating agent that can strongly sequester divalent and trivalent cations and form a strong metal complex product. DTPA wraps around a metal ion forming up to eight bonds. At pH 8, DTPA selectively forms a calcium-DTPA complex even in the presence of sodium, potassium or magnesium cations. This reaction mechanism leads to a decrease in calcium cation in the nasal secretions. The described results confirm that the reduction of calcium cations in by DTPA improves the olfactory performance.
The ”Sniffin’ Sticks” test is a widely used olfactory performance assessment tool consisting of three subtests: odor threshold, odor discrimination and odor identification. It was introduced over 20 years ago and its test-retest reliability and validity have been demonstrated. The calculated scores of the odor test confirmed that topical application of DTPA produces significant improvement in odor performance15,16.
Quantitative analysis of calcium cations provides an indication of the increase or decrease in calcium cations. This approach is based on the design of a carbon paste ion-selective electrode. Carbon paste electrodes are considered as an important type of ion-selective electrodes due to their advantages of chemical inertness, robustness, stable response, no need for internal solution and suitability for a variety of sensing and detection applications. Also, it can be used with a small volume of nasal secretion 10. Using the developed electrode, it was possible to determine the calcium cation concentration before and after the described treatment. The results obtained showed a sharp decrease in calcium cation concentration in the patients treated with topical DTPA. This can be explained by the chelation of the calcium cation and the formation of the calcium DTPA complex product.
This paper introduced an evidence for a relationship between lowering calcium cation concentration in the nasal secretions by DTPA and the improvement in the olfactory performance.