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Background: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O)., Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus., Results: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies., Conclusion: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further., (© 2022 ARS-AAOA, LLC.)

Objectives: To directly measure the spatial mapping in the olfactory bulb by odor presentation and by direct electrical stimulation., Study Design: Experimental (animal)., Setting: University research laboratory., Subjects and Methods: Odor (n = 8) and electrical stimulation (n = 4) of the olfactory bulb in rats were used to demonstrate the spatial mapping of neural responses in the olfactory bulb. Both multiunit responses to odor stimulation and evoked potential responses to localized electrical stimulation were measured in different regions of the olfactory bulb., Results: Responses that were recorded simultaneously from an array of 32 electrodes positioned at different locations within the olfactory bulb were mapped. Results show different spatial patterns of neural activity for different odors (odor maps). Direct stimulation of the olfactory bulb with electrical current pulses from electrodes positioned at different locations was also effective in generating spatial patterns of neural activity., Conclusion: These data suggest that by programming an array of stimulating electrodes, it should be possible to selectively activate different regions of the olfactory bulb, generating unique patterns of neural activity as seen in normal smell., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objective: To investigate whether a new clinical olfactory test, the Odor Stick Identification Test for Japanese (OSIT-J), can be used to assess olfactory function cross-culturally in a US patient population., Design: Cross-sectional prospective study., Setting: A university medical center otolaryngology clinic., Patients: Fifty US patients presenting with complaints of olfactory dysfunction from December 2004 to January 2006., Interventions: Olfactory testing and patient interview., Main Outcome Measures: Comparison of test results obtained with the OSIT-J, the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory function test, and patients' self-reported level of olfactory function. Patients' opinions regarding the 2 test methods were also recorded., Results: The mean +/- SD time required to administer the OSIT-J (8 +/- 1 minutes) was shorter than that required for the standard CCCRC test (21 +/- 6 minutes). Significant Spearman rank correlations were found between the OSIT-J and CCCRC test scores (r(s) = 0.80, P<.001, n = 50), and patients' self-reported level of olfactory function (r(s) = 0.73, P<.001, n = 50). Although 3 of the 13 odors used in the OSIT-J were not familiar to US subjects, patients reported that the OSIT-J was easier, more interesting, and the odors used more pleasant than the CCCRC test., Conclusions: Olfactory function tests developed in different countries should be evaluated to determine if a cross-cultural bias exists among test odorants. Although a cultural bias was detected for a few odorants, this study demonstrates that a modified version of the OSIT-J can be used to assess olfactory function in US patients.

A new olfactory test, the odor stick identification test for Japanese (OSIT-J), has been developed in Japan. To determine if the OSIT-J would be effective cross-culturally, we administered the test to 52 US and 50 Japanese subjects reporting normal olfactory function. The average composite OSIT-J test score for US subjects was significantly lower (77%) than that for Japanese subjects (94%, P < 0.0001). Both US and Japanese subjects correctly identified eight of the 13 odorants included in the OSIT-J with scores of 80% or higher. However, for five odorants, the US subjects' scores fell below 80% and were consistently lower than Japanese subjects, presumably reflecting cultural differences in odor experience. Most of the US subjects found the OSIT-J to be easy, interesting, pleasant, and short in duration. Although the 13-odorant OSIT-J was found to be suitable for testing US populations, elimination of five test odorants that were unfamiliar to US subjects significantly enhanced the test's effectiveness. Findings from this study emphasize the importance of identifying test odorants that may have a cultural bias, a crucial issue when comparing data obtained from different smell tests used at smell and taste centers around the world.

Objective: To quantify discrepancies in the diagnosis of olfactory function that might exist when comparing results obtained from centers using different methods of olfactory testing., Study Design: Prospective study of 50 healthy adult volunteers and 25 adult patients with olfactory complaints., Methods: Two test methods, the Connecticut Chemosensory Clinical Research Center (CCCRC) test widely used in the United States, and the Jet Stream Olfactometer (JSO) test used in Japan, were used to measure and categorize the diagnostic level of olfactory function (normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, anosmia). Olfactory function was measured separately for each nostril., Results: There was a significant correlation (rs = 0.788, P < .01, n = 150 nostrils) between diagnostic categories assigned by the CCCRC and JSO test methods. Diagnostic categories were identical for 66.7% of the nostrils tested, and in only 7.3% of the cases did the results differ by more than one category. For the anosmic and normosmic categories, test results were in agreement 91.7% of the time, whereas for the hyposmic categories (mild, moderate, and severe) results were in agreement only 22.2% of the time., Conclusions: Our results demonstrate that when comparing clinical or research data obtained from centers using different olfactory test methods, subjects with diagnoses of anosmia or normosmia may be more reliably compared than those with different levels of hyposmia.

Detection thresholds are typically obtained by presenting a subject with serial dilutions of an odorant. Many factors, including the solvent used to dilute the odorant, can influence the measurement of detection thresholds. Differences have been reported in detection thresholds for phenyl ethyl alcohol (PEA) when different solvents are used. In this study we used gas chromatography (GC) to investigate further the effect of solvent on odor detection thresholds. We used a single ascending method and serial dilutions of PEA in four different solvents--liquid paraffin (LP), mineral oil (MO), propylene glycol (PG) and dipropylene glycol (DPG)--to determine the PEA thresholds for 31 adult subjects. For each solvent, we prepared eight serial log base 10 step dilutions (1-8), with corresponding liquid PEA concentrations of 6.3 x 10(1)-6.3 x 10(-6) (% v/v). We found that the threshold concentrations for PEA in LP (step 6.5) and PEA in MO (step 5.5) were significantly lower (P < 0.05) than for PEA in PG (step 4.0) and DPG (step 4.0) We then used GC to measure both the liquid and gas PEA concentrations for the dilution steps prepared with LP and PG. Although there were large threshold differences in the liquid concentrations of PEA in LP and PG, the headspace gas concentrations of PEA were the same. These results demonstrate the importance of determining the gas concentration of odorant stimuli when performing odor threshold measurements, in particular when comparing odor detection thresholds obtained using different solvents.

Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.

Transection of olfactory nerve fibers leads to deafferentation of olfactory bulbs and a loss of olfactory mediated behavior. Nerve transection studies have shown that during recovery, olfactory nerve fibers can reestablish connections with the olfactory bulbs. Two groups of experimental animals were studied to determine if olfactory mediated behavior returns after recovery. One group (n = 18) received bilateral olfactory nerve transection (BTX), while the second group (n = 4) received a sham surgical procedure. Performance on odor detection and discrimination tasks was measured during recovery periods ranging from 1-120 days. Return of olfactory mediated behavior was first observed 19 days after nerve transection. Performance levels improved with recovery time and by day 40 animals returned to criterion level (> or = 90% correct response). Sham animals maintained a criterion level of performance throughout the recovery period. Horseradish peroxidase (HRP) was used to trace reconnection of olfactory nerve fibers. The absence of HRP label in the bulbs of animals examined one day after BTX, verified the completeness of the nerve transection procedure. After 10 days of recovery, a few HRP labeled axons were observed and the amount of HRP in the bulb increased with recovery time. The results of this study demonstrate that olfactory receptor axons can reestablish functional connections with the deafferented olfactory bulb and these connections are sufficient to restore olfactory mediated behavior.

An olfactory function test developed by the Connecticut Chemosensory Clinical Research Center (CCCRC) was administered to 65 normal subjects to determine its ability to identify normosmic subjects. The CCCRC test categorizes individuals into five distinct levels of olfactory functioning according to composite score ranges derived from odor identification and butanol threshold subtests. These categories are: normosmic (normal); mildly, moderately, and severely hyposmic (impaired functioning); and anosmic (no sensation). Comparing score distributions from CCCRC with ours revealed that a greater percentage of our subjects were categorized as hyposmic because of higher butanol thresholds. The butanol threshold subtest was studied further to determine test-retest reliability and normal day-to-day variability in scores. Norms are the basis for interpreting test scores and are important in diagnosing and treating smell disorders.