Characterization of the Sniff Magnitude Test

ORIGINAL ARTICLE Characterization of the Sniff Magnitude Test

Robert A. Frank, PhD; Robert C. Gesteland, PhD; Jason Bailie, BS; Konstantin Rybalsky, BS; Allen Seiden, MD; Mario F. Dulay, PhD

Objective: To evaluate the potential utility of the Sniff Results: The SMT generally showed good agreement with Magnitude Test (SMT) as a clinical measure of olfactory UPSIT diagnostic categories, although SMT scores were function. only modestly elevated in the mild and modest hyposmia range of the UPSIT. Age-related decline in olfac- Design: Between-subject designs were used to com- tory ability was evident on the UPSIT at younger ages than pare the SMT and University of Pennsylvania Smell Iden- that seen with the SMT. As predicted, otolaryngology pa- tification Test (UPSIT) in study participants from a broad tients with olfactory complaints were found to be im- range of ages. paired on both the UPSIT and SMT.

Subjects: A total of 361 individuals from retirement com- Conclusions: The SMT provides a novel method for munities and an urban university and patients from an evaluating the sense of smell that shows good general otolaryngology clinic. agreement with the UPSIT. Its minimal dependence on language and cognitive abilities provides some advan- Intervention: Study participants completed the SMT and UPSIT using standard procedures. tages over odor identification tests. There is some indi- cation that the UPSIT may be more sensitive to olfac- Main Outcome Measures: The UPSIT was scored us- tory (and/or nonolfactory) deficits. We conclude that ing standard procedures to calculate the number of cor- sniffing behavior can be exploited for the clinical evalu- rectly identified odors; a score that can range from 0 to ation of olfaction. A comparison of performance on odor 40 correct. The measure of olfactory function generated identification and sniffing tests may provide novel in- by the SMT is the “sniff magnitude ratio,” defined as sight into the nature of olfactory problems in a variety the mean sniff magnitude generated by the odor stimuli of patient populations. divided by the mean sniff magnitude to nonodorized air blanks. Arch Otolaryngol Head Neck Surg. 2006;132:532-536

T IS ESTIMATED THAT SOME FORM available,1 so accurate assessment is of olfactory disorder afflicts at needed. least 1% of the general adult The most common clinical methods of population and 50% or more of olfactory evaluation are based on odor de- people older than 65 years.1 Ol- tection and identification.8-11 These meth- factoryI disorders can be traced to a di- ods have been used productively to char- verse set of causes that include upper res- acterize olfactory disorders in a variety of piratory tract infections, nasal and sinus patient populations, but they have some disease, developmental disorders, endo- drawbacks. Odor detection thresholds are crine problems, head trauma, and neuro- only moderately reliable, are time consum- psychiatric diseases.1-3 Anosmia (loss of the ing, involve complex series of odor presen- sense of smell) and hyposmia (a dimin- tation, and demand focused attention to an ished sense of smell) have been noted as ephemeral stimulus. Odor identification Author Affiliations: early symptoms of Alzheimer disease and tests require patients to sniff odorant CompuSniff, LLC (Drs Frank idiopathic Parkinson disease.4,5 These facts samples and then identify or label them. The and Gesteland), and support the routine testing of olfactory interpretation of these tests can become Departments of Psychology abilities in older adults, especially in light problematic when evaluating children, (Drs Frank and Dulay and of the finding that people are poor judges people with impaired cognitive function, Messrs Bailie and Rybalsky), 6,7 Cell Biology (Dr Gesteland), of their own olfactory abilities. In addi- and individuals from diverse cultural and 12-14 and Otolaryngology tion, effective treatments for conductive linguistic backgrounds. (Dr Seiden), University of olfactory loss (ie, loss associated with poor The Sniff Magnitude Test (SMT) (Com- Cincinnati, Cincinnati, Ohio. airflow to the olfactory epithelium) are puSniff, LLC, Cincinnati, Ohio) was de-

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tion tests by overcoming some of the limitations of the High Sniff to Air Only more traditional tests. The SMT is based on a well- Sniff to Odor established reduction in sniff magnitude that normally occurs in response to an odor. A number of studies have demonstrated that sniff vigor and duration play an important role in modulating odor perception.15,16 Laing17 reported that sniff volume is reduced as odorant concen- Sniff Pressure

tration increases, an observation subsequently verified by Low investigators from several laboratories.18-21 Given the simple, rapid nature of the sniff response, it may be buffered from 0 variations in age, language, culture, and cognitive ability. 0 1.0 2.0 If odorant-induced modulation of sniffing can be used as Time, s a measure of the early events in olfactory processing, its combination with tests that rely on cognitive abilities (eg, Figure 1. Depiction of hypothetical sniff pressure measurements to odor identification tests) may provide a powerful ap- nonodorized air (solid line) and an odor stimulus (dotted line). Note that proach to differentiating between olfactory deficits caused sniffs produce negative pressure so that high pressure refers to high by loss of primary sensory input into the olfactory system negative pressure. and dysfunction of higher-order processing associated with troposmia, phantosmia, or olfactory agnosia. OLFACTORY TESTS The SMT is based on the reduction in sniffing that normally occurs when an odor is encountered. Sniffs to University of Pennsylvania Smell Identification Test stimuli composed of nothing but nonodorized air are longer and more vigorous compared with sniffs to odor- The UPSIT10 is the most widely used olfactory test in the world, ized air, and this difference can be used as an indicator having been administered to nearly 100 000 persons in the last of smell function (Figure 1). When a patient’s sense of decade. In this test, the patient is required to identify, in a 4-al- smell is impaired, this normal, odor-induced decrease in ternative multiple-choice format, each of 40 odorants pre- sniffing is reduced or eliminated. sented on microencapsulated “scratch and sniff” labels. The de- Initial studies demonstrated the feasibility of the SMT pendent measure is the number of items correctly answered. and some of its advantages. For example, it was shown The UPSIT was completed in the presence of a research assis- that the odor-induced sniff suppression is not affected tant who answered questions and offered help as requested. The by deficits in memory or attention in older adults and UPSIT was scored using standard procedures to calculate the that the SMT scores of children (who do poorly on odor number of correctly identified odors, this being a score that can identification tests) did not differ from those of adults.14,22,23 range from 0 to 40 correct. The present investigation had 2 main goals. One was to Sniff Magnitude Test more fully characterize the SMT in a sample of people that was diverse by age and olfactory abilities. The Uni- The SMT was administered as described previously.14 The SMT versity of Pennsylvania Smell Identification Test (UPSIT) device and a photograph of a person prepared to sniff are shown also was administered to allow for a comparison with the in Figure 2. The odor canisters contain either no odor (ie, they SMT. Good general agreement between the SMT and serve as nonodorized air blanks) or they contain 5.0 mL of an UPSIT was expected for the adults tested in this study. odor stimulus diluted in mineral oil. During testing, the par- The second goal was to demonstrate that a sample of pa- ticipant wears a bilateral nasal cannula of the type used to pro- tients with olfactory complaints would produce abnor- vide oxygen to patients with limited respiratory capacity (as mal results on the SMT. shown in Figure 2). A participant’s sniff creates a negative pressure that is sensed by a pressure transducer connected to the cannula and an analog-to-digital processing board located within METHOD a controller device. The digitized output signal of the board is sent to a laptop computer. Within milliseconds of detecting a SUBJECTS sniff, the computer opens the lid of the testing canister, thereby exposing the participant to any odor stimulus within the can- A sample of 361 individuals with a range of olfactory abilities ister. This all occurs very rapidly (within 15 milliseconds) once was recruited. Recruitment sites included local retirement com- a sufficient sniff pressure is achieved, and sniff pressure mea- munities, students and employees at the University of Cincin- surements are recorded by the computer every 10 millisec- nati (Cincinnati, Ohio), and patients from an otolaryngology onds until the transducer detects a return to ambient air pres- clinic in Cincinnati. Participants were recruited through ad- sure. Thus, data from a single sniff are recorded on each trial. vertisements in local newspapers and bulletin boards and Four stimulus canisters were used in the present study: 1 through physician referrals. The ears, nose, and throat (ENT) was a no-odor stimulus (air blank); 1 contained 5.0 mL of a patients included individuals with specific olfactory com- mixture composed of 1.0 mL of liquid methylthiobutyrate (MTB, plaints as well as other patients with problems such as chronic also known as S-methylthiobutanoate, 98% purity) in 99 mL sinusitis, rhinitis, nasal polyps, and other conditions rou- of mineral oil (1.0% vol/vol); 1 contained 5.0 mL of a mixture tinely encountered by an ENT physician. Written informed con- composed of 3.0 mL of liquid MTB in 97 mL of mineral oil (3.0% sent was obtained from all study participants, and the re- vol/vol); and 1 contained 5.0 mL of a mixture composed of 1.0 search was approved by the internal review board of the mL of ethyl 3-mercaptoproprionate (EMP, 99% purity) in 99 University of Cincinnati. mL of mineral oil (1.0% vol/vol). The odorized air that is cre-

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1 0.9

0.8

5 2 0.7

Sniff Magnitude Ratio 0.6

4 3 0.5 Normosmia Mild Moderate Severe Anosmia (34-40) Hyposmia Hyposmia Hyposmia (1-18) (30-33) (26-29) (19-25) UPSIT Diagnostic Group

B Figure 3. Mean sniff magnitude ratios as a function of University of Pennsylvania Smell Test (UPSIT) diagnostic categories. The score range of each UPSIT diagnostic group is given in parentheses. The bars depict 1 SEM.

canisters was being used prior to taking a sniff. Each test started with 3 trials using the nonodorized air (blank) canister. This established a no-odor sniffing baseline. The next 3 trials ex- posed the participant to 1.0% MTB. If the sniff magnitude ratio comparing 1.0% MTB and the no-odor trials was 0.75 or greater (ie, 25% suppression to Յ1.0% MTB), 6 additional trials were run. The first 3 used 3.0% MTB, and the second 3 used 1.0% EMP. These additional trials were included to verify the sniff pattern for individuals with unusually low levels of sniff suppression. The measure “sniff magnitude” was generated from the SMT Figure 2. Photographs of the Sniff Magnitude Test device components (1, data and consisted of the sum of the negative pressure values laptop computer; 2, controller box; 3, nasal cannula; 4, odor canister base; generated across the duration of the single sniff that occurs on and 5, odor canister) (A), and an individual being tested with the nasal each trial. This measure is proportional to the area under the cannula and odor canister in place (B). sniff pressure-time curve. The measure of olfactory function generated by the SMT is the “sniff magnitude ratio,” defined ated in the headspace of the canister for these odor stimuli is as the mean sniff magnitude generated by the odor stimuli di- moderately intense and easily detected by a person with a nor- vided by the mean sniff magnitude to nonodorized air blanks. mal sense of smell. The MTB and EMP stimuli are flavor and fragrance additives described as having a fecal, ripe cheese odor and a burnt, skunky odor, respectively, at the concentrations RESULTS used in the test. Previous research and pilot studies done in our laboratory demonstrated that the MTB and EMP stimuli Of the 361 people tested, 137 were recruited from the produce no nasal irritation as demonstrated by the inability to retirement communities, 89 from the ENT clinic, and 135 localize the stimuli in a 2-nostril localization test. from the University of Cincinnati community. The mean Once informed consent was obtained, participants com- age of the participants was 53.4 years (range, 18-94 years), pleted a short health and demographics questionnaire. Next they and the sample was 74% female. completed the UPSIT and the SMT. For the SMT, the nasal can- The relationship between UPSIT diagnostic catego- nula was fitted into place, and the participant was told that several different canisters would be provided for sniffing and that ries and sniff magnitude ratios is depicted in Figure 3. his or her task was to report whether an odor was present. The As sniff magnitude ratios increase (indicating less odor- test administrator placed the canister approximately 2.0 cm di- induced sniff suppression and a poorer sense of smell), rectly beneath the nose, and once in position, the participant one would expect UPSIT scores to decrease (indicating was instructed to “sniff until you smell something.” It was em- fewer correctly identified odors). This pattern of results phasized that a single, natural sniff was appropriate, such as was observed. Statistical analyses revealed that the SMT would be taken when sampling a perfume or food. Several prac- scores of participants who scored in the UPSIT norm- tice trials were completed prior to data collection. Once an ad- osmic range were significantly different from the scores equate pressure was generated by a sniff, the lid of the canister of the other UPSIT groups except for the mild hyposmia remained open until the participant’s sniff ended (ie, the nega- Ͻ group (F4,356=22.4, P .001; Tukey HSD (Honestly Sig- tive pressure produced by the inspiration was no longer de- Ͻ tected by the transducer). nificant Difference) post hoc test, P .05 [SPSS 12.0 for Once a sniff trial ended, the test administrator connected Windows; SPSS Inc, Chicago, Ill]). the canister needed for the next trial and repeated the testing The relationships between age and scores on the ol- procedure. The testing protocol was designed so that partici- factory tests are shown in Figure 4. The mean UPSIT pants were not able to detect which of the 4 identical stimulus scores of participants in their teens, twenties, and thir-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 ties did not differ from each other but were significantly higher than the mean UPSIT scores for people 40 years A Ͻ and older (F8,352=10.47, P .001; Tukey HSD post hoc 1.0 test, PϽ.05 [SPSS 12.0 for Windows]). Sniff magnitude 0.9 ratios increased significantly with age, but the SMT measure was not significantly elevated from the levels of people 0.8

in their thirties until age reached the sixties (F8,352=8.40, 0.7 PϽ.001; Tukey HSD post hoc test, PϽ.05 [SPSS 12.0 for Windows]). Thus, the UPSIT appears to be more sensi- 0.6

tive to age-related decline in olfactory abilities com- 0.5 pared with the SMT. Sniff Magnitude Ratio A final evaluation of the olfactory tests was per- 0.4

formed for the ENT patients with olfactory complaints. 0.3 There were 14 of these patients evenly divided between men and women with an average age of 52.1 years (range, B 24-67 years). All of these patients were referrals for com- 38 plaints about not being able to taste and/or smell. An evaluation of medical histories and physical examination find- 36

ings produced diagnoses of allergic rhinitis, nasal polyps, 34 post–upper respiratory tract infection anosmia, posttrau- matic injury anosmia, potential anosmia related to toxic 32 chemical exposure, chronic sinusitis, and idiopathic an- 30

osmia. Of the 14 patients, 2 produced normal scores on UPSIT Score

both the UPSIT and SMT on testing. Mean olfactory test 28 scores for 3 groups of study participants are given in the Table. The scores of the patients with olfactory com- 26 plaints were significantly poorer on the UPSIT and SMT 24 compared with the scores of the other 2 groups: (UPSIT, 13-19 20-2930-39 40-49 50-59 60-69 70-79 80-89 90-99 Ͻ Ͻ F2,358=18.1, P .001; Tukey HSD post hoc test, P .05; Age, y Ͻ and SMT, F2,358=3.66, P .05; Tukey HSD post hoc test, PϽ.05 [SPSS 12.0 for Windows]). Figure 4. Mean sniff magnitude ratios (A) and University of Pennsylvania Smell Test (UPSIT) scores (B) as a function of age. The bars depict 1 SEM. COMMENT

Table. UPSIT and SMT Scores for ENT Patients The findings of the present study bolster previous re- With Olfactory Complaints Compared With Other search supporting the validity of the SMT as a clinical Study Participants* test of olfaction.14,22 As expected, sniff magnitude ratios indicated more olfactory impairment as people did more No. of poorly on the UPSIT. The well-known deterioration of Sample Patients UPSIT SMR olfactory abilities with age was reflected in elevated SMT Olfactory complaint patients 14 19.6 (2.10) 0.81 (0.075) scores for older adults, and it was shown that the age- Other ENT patients 75 28.6 (1.92) 0.61 (0.068) related effects were not due to aging per se but more likely Other study participants 272 30.8 (1.03) 0.64 (0.037) were indicative of olfactory impairment. Finally, the sniff Abbreviations: ENT, ear, nose, and throat; SMR, sniff magnitude ratio (the magnitude ratios were significantly elevated for a clini- measure of olfactory function generated by the Sniff Magnitude Test [SMT], cal group likely to have olfactory problems, that is, pa- which is the mean sniff magnitude generated by the odor stimuli divided by tients with olfactory complaints. We conclude that sniff- the mean sniff magnitude to nonodorized air blanks); UPSIT, University of Pennsylvania Smell Identification Test. ing behavior can be exploited for the clinical evaluation *Data are given as mean (SEM) score unless otherwise specified. of olfaction. The SMT and UPSIT showed generally good agreement in the present study, but some differences in per- croencapsulated odors used for the UPSIT. Another rea- formance are worthy of note. Study participants identi- son that the UPSIT may be more sensitive to olfactory fied as normosmic and mildly hyposmic on the UPSIT loss is that odor identification tests rely more heavily on were not significantly different on the SMT, and those odor memory and discrimination abilities compared with with moderate UPSIT hyposmia scores had only slightly the SMT. This would make the UPSIT sensitive to a wider elevated sniff magnitude ratios. The UPSIT also showed variety of olfactory problems compared with the SMT. earlier age-related impairment of olfaction compared with A final possibility is that UPSIT performance may par- the SMT. These results may reflect a greater sensitivity tially reflect general (as opposed to olfaction-specific) of the UPSIT to loss of olfactory abilities. One reason for problems with attention and memory. Moderately im- this could be the odor intensity levels used for UPSIT and paired attention and memory are known to correlate with SMT stimuli. The SMT odor stimuli are more intense, and performance on odor identification tests but do not in- therefore may elicit responses more readily that the mi- fluence the SMT.13,23,24 This makes the SMT especially use-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 ful for testing older adults who often experience olfac- 6. Landis BN, Hummel T, Hugentobler M, Giger R, Lacroix JS. Ratings of overall tory losses and declining cognitive abilities, In addition, olfactory function. Chem Senses. 2003;28:691-694. 7. Nordin S, Monsch AU, Murphy C. Unawareness of smell loss in normal aging cultural differences can result in some patients being un- and Alzheimer’s disease: discrepancy between self-reported and diagnosed smell familiar with odorant labels used in the UPSIT, produc- sensitivity. J Gerontol B Psychol Sci Soc Sci. 1995;50:P187-P192. ing poor performance. This would suggest the SMT may 8. Ikeda K, Tabata K, Oshima T, Nishikawa H, Hidaka H, Takasaka T. Unilateral ex- provide a more specific measure of true olfactory loss. amination of olfactory threshold using the Jet Stream Olfactometer. Auris Na- Additional studies are needed to assess the contribution sus Larynx. 1999;26:435-439. of these sensory, perceptual, and cognitive factors to dif- 9. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. “Sniffin’ sticks”: olfactory performance assessed by the combined testing of odor identification, odor discrimi- ferences in performance on the SMT and UPSIT. This in- nation and olfactory threshold. Chem Senses. 1997;22:39-52. formation is important to a more sophisticated under- 10. Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell standing of the causes of olfactory loss in general and may Identification Test: a standardized microencapsulated test of olfactory function. also provide important clues to the etiology of a number Physiol Behav. 1984;32:489-502. of specific disorders that share olfactory dysfunction as 11. Hashimoto Y, Fukazawa K, Fujii M, et al. Usefulness of the Odor Stick Identifi- an early symptom.2,4 cation Test for Japanese patients with olfactory dysfunction. Chem Senses. 2004; 29:565-571. 12. Cain WS, Stevens JC, Nickou CM, Giles A, Johnston I, Garcia-Medina MR. Life- Submitted for Publication: May 2, 2005; final revision span development of odor identification, learning and olfactory sensitivity. received January 4, 2006; accepted January 29, 2006. Perception. 1995;24:1457-1472. Correspondence: Robert A. Frank, PhD, ML 627, The 13. Larsson M, Nilsson L, Olofsson JK, Nordin S. Demographic and cognitive pre- Graduate School, University of Cincinnati, Cincinnati, dictors of cued odor identification: evidence from a population-based study. Chem Senses. 2004;29:547-554. OH 45221-0627 ([email protected]). 14. Frank RA, Dulay MF, Niergarth K, Gesteland RC. A comparison of the Sniff Mag- Financial Disclosure: Drs Gesteland and Frank are co- nitude Test and the University of Pennsylvania Smell Identification Test in chil- owners of CompuSniff, LLC, a small business develop- dren and non-native English speakers. Physiol Behav. 2004;81:475-480. ing the Sniff Magnitude Test. 15. Sobel N, Prabhakaran V, Desmond JE, et al. Sniffing and smelling: separate sub- Funding/Support: The research was supported by Small systems in the human olfactory cortex. Nature. 1998;392:282-286. 16. Sobel N, Khan RM, Hartley CA, Sullivan EV, Gabrieli JDE. Sniffing longer rather Business Innovation Research grant DC04139 from the than stronger to maintain olfactory detection threshold. Chem Senses. 2000; National Institutes of Health, Bethesda, Md, to Com- 25:1-8. puSniff, LLC (Dr Gesteland, principal investigator). 17. Laing DG. Natural sniffing gives optimum odour perception for humans. Perception. 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