Clin Exp Otorhinolaryngol.  2020 Aug;13(3):274-284. 10.21053/ceo.2020.00864.

Development of a Korean Culture-Friendly Olfactory Function Test and Optimization of a Diagnostic Cutoff Value

• Ha JG
• Kim J
• Nam JS
• Park JJ
• Cho HJ
• Yoon JH
• Kim CH

• KMID: 2504923
• DOI: http://doi.org/10.21053/ceo.2020.00864

Abstract

Objectives
. Cultural familiarity and safety must be considered when assessing olfactory ability. The YSK olfactory function (YOF) test is a new olfactory function test using culturally familiar odorants to Koreans.
Methods
. The YOF test comprises three subtests for threshold (T), discrimination (D), and identification (I). The identification test included eight universal and four Korean culture-friendly odorants, which were selected considering eight major functional groups. Data were obtained from 1,127 subjects over 19 years old. Subjects were classified as having normosmia (n=542), hyposmia (n=472), and anosmia (n=113) by self-reported olfactory function. The YOF test and the Korean version of the Sniffin’ stick test (KVSS-II) were performed on the same day in random order. Diagnostic cutoffs for anosmia and hyposmia were calculated using the Youden index (J).
Results
. The mean values for each T/D/I subtest and the total TDI score were as follows: normosmia (T, 4.6±2.3; D, 8.6±2.1; I, 11.1±1.7; TDI score, 24.2±4.5); hyposmia (T, 3.3±2.2; D, 7.1±2.5; I, 9.2±3.1; TDI score, 19.5±6.4); and anosmia (T, 1.7±1.2; D, 5.1±2.5; I, 5.0±3.2; TDI score, 11.8±5.6). The correlation coefficients between the YOF test and KVSS-II were 0.57, 0.65, 0.80, and 0.86 for T, D, I, and the TDI score, respectively (P<0.001). The diagnostic cutoffs were a TDI score ≤14.5 (J=0.67) for anosmia and 14.5(TDI score ≤21.0 (J=0.38) for hyposmia. The diagnostic efficacy of the YOF test (area under the curve [AUC], 0.88) was equivalent to that of the KVSS-II (AUC, 0.88; P=0.843; DeLong method).
Conclusion
. The YOF test is a new olfactory test using safe and Korean culture-friendly odorants. It showed equivalent validity with the conventional olfactory function test. Furthermore, the YOF test provides information on the major functional groups of odorants, potentially enabling a more comprehensive interpretation for patients with olfactory disorders.

Keyword

Smell; Olfactory Perception; Culture; Odorants

Figure

• 

  Fig. 1. The YSK olfactory function test is composed of three subtests of threshold, discrimination, and identification, which each have 12-point scales.

• 

  Fig. 2. Score distributions and scatter plot by age of the total TDI score and each T/D/I subtest. The results of the YSK olfactory function (YOF) test of the normosmia group showed grossly normal distributions (A, B, D) except for the identification test (C, intentionally skewed to the right). The horizontal scale of the threshold graph (A) is expressed in units of 1 point for simple visualization. For total TDI score and all results of each T/D/I subtest, olfactory function significantly decreased with increasing age of the subjects (E-H; P<0.001, respectively). T, threshold; D, discrimination; I, identification.

• 

  Fig. 3. The receiver operating characteristic (ROC) curve for the total TDI scores of the YSK olfactory function (YOF) test and Korean version of the Sniffin’ stick test (KVSS-II) to predict anosmia (A) and hyposmia (B). The diagnostic cutoffs of the YOF test calculated through the Youden index were as follows: anosmia (TDI score ≤14.5: AUC, 0.88; P<0.001; Youden J score: 0.67; sensitivity, 79.8%; specificity, 87.2%) and hyposmia (14.5

• 

  Fig. 4. Correlations between the YSK olfactory function (YOF) test and the Korean version of Sniffin’ stick test (KVSS-II). (A) Threshold test, (B) discrimination test, (C) identification test, (D) total TDI score. The correlation coefficients for the YOF test and KVSS-II were 0.57 for T, 0.65 for D, 0.80 for I, and 0.86 for the TDI score (P<0.001, respectively). T, threshold; D, discrimination; I, identification.

Reference

1. Blomqvist EH, Bramerson A, Stjarne P, Nordin S. Consequences of olfactory loss and adopted coping strategies. Rhinology. 2004; Dec. 42(4):189–94.

2. Asahina K, Pavlenkovich V, Vosshall LB. The survival advantage of olfaction in a competitive environment. Curr Biol. 2008; Aug. 18(15):1153–5.

3. Berendse HW, Ponsen MM. Detection of preclinical Parkinson’s disease along the olfactory trac(t). J Neural Transm Suppl. 2006; (70):321–5.

4. Jung HJ, Shin IS, Lee JE. Olfactory function in mild cognitive impairment and Alzheimer’s disease: a meta-analysis. Laryngoscope. 2019; Feb. 129(2):362–9.

5. Pause BM, Miranda A, Goder R, Aldenhoff JB, Ferstl R. Reduced olfactory performance in patients with major depression. J Psychiatr Res. 2001; Sep-Oct. 35(5):271–7.

6. Hedner M, Larsson M, Arnold N, Zucco GM, Hummel T. Cognitive factors in odor detection, odor discrimination, and odor identification tasks. J Clin Exp Neuropsychol. 2010; Dec. 32(10):1062–7.

7. Hsieh JW, Keller A, Wong M, Jiang RS, Vosshall LB. SMELL-S and SMELL-R: olfactory tests not influenced by odor-specific insensitivity or prior olfactory experience. Proc Natl Acad Sci U S A. 2017; Oct. 114(43):11275–84.

8. Hummel T, Whitcroft KL, Andrews P, Altundag A, Cinghi C, Costanzo RM, et al. Position paper on olfactory dysfunction. Rhinology. 2016; Jan. 56(1):1–30.

9. Doty RL, Brugger WE, Jurs PC, Orndorff MA, Snyder PJ, Lowry LD. Intranasal trigeminal stimulation from odorous volatiles: psychometric responses from anosmic and normal humans. Physiol Behav. 1978; Feb. 20(2):175–85.

10. Doty RL, Smith R, McKeown DA, Raj J. Tests of human olfactory function: principal components analysis suggests that most measure a common source of variance. Percept Psychophys. 1994; Dec. 56(6):701–7.

11. Rospars JP. Interactions of odorants with olfactory receptors and other preprocessing mechanisms: how complex and difficult to predict? Chem Senses. 2013; May. 38(4):283–7.

12. Hong SC, Yoo YS, Kim ES, Kim SC, Park SH, Kim JK, et al. Development of KVSS test (Korean version of Sniffin’ Sticks Test). Korean J Otolaryngol-Head Neck Surg. 1999; Jul. 42(7):855–60.

13. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses. 1997; Feb. 22(1):39–52.

14. Hong SM, Park IH, Kim KM, Shin JM, Lee HM. Relationship between the Korean version of the Sniffin’ Stick Test and the T&T Olfactometer in the Korean population. Clin Exp Otorhinolaryngol. 2011; Dec. 4(4):184–7.

15. Cho JH, Jeong YS, Lee YJ, Hong SC, Yoon JH, Kim JK. The Korean version of the Sniffin’ stick (KVSS) test and its validity in comparison with the cross-cultural smell identification test (CC-SIT). Auris Nasus Larynx. 2009; Jun. 36(3):280–6.

16. Youden WJ. Index for rating diagnostic tests. Cancer. 1950; Jan. 3(1):32–5.

17. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988; Sep. 44(3):837–45.

18. Hackett PL, Brown MG, Buschbom RL, Clark ML, Miller RA, Music RL, et al. Teratogenic study of ethylene and propylene oxide and nbutyl acetate. Richland (WA): Battelle Pacific Northwest Laboratories;1982.

19. David RM, Tyler TR, Ouellette R, Faber WD, Banton MI. Evaluation of subchronic toxicity of n-butyl acetate vapor. Food Chem Toxicol. 2001; Aug. 39(8):877–86.

20. Saillenfait AM, Gallissot F, Sabate JP, Bourges-Abella N, Muller S. Developmental toxic effects of ethylbenzene or toluene alone and in combination with butyl acetate in rats after inhalation exposure. J Appl Toxicol. 2007; Jan-Feb. 27(1):32–42.

21. Bale AS, Lee JS. An overview of butanol-induced developmental neurotoxicity and the potential mechanisms related to these observed effects. Neurotoxicol Teratol. 2016; Jan-Feb. 53:33–40.

22. Segal D, Bale AS, Phillips LJ, Sasso A, Schlosser PM, Starkey C, et al. Issues in assessing the health risks of n-butanol. J Appl Toxicol. 2020; Jan. 40(1):72–86.

23. Scognamiglio J, Jones L, Letizia CS, Api AM. Fragrance material review on phenylethyl alcohol. Food Chem Toxicol. 2012; Sep. 50 Suppl 2:S224–39.

24. Jacquot L, Hidalgo J, Brand G. Just noticeable difference in olfaction is related to trigeminal component of odorants. Rhinology. 2010; Sep. 48(3):281–4.

25. Grabenhorst F, Rolls ET, Margot C, da Silva MA, Velazco MI. How pleasant and unpleasant stimuli combine in different brain regions: odor mixtures. J Neurosci. 2007; Dec. 27(49):13532–40.

26. Bensafi M, Rouby C, Farget V, Bertrand B, Vigouroux M, Holley A. Autonomic nervous system responses to odours: the role of pleasantness and arousal. Chem Senses. 2002; Oct. 27(8):703–9.

27. Albrecht J, Schreder T, Kleemann AM, Schopf V, Kopietz R, Anzinger A, et al. Olfactory detection thresholds and pleasantness of a food-related and a non-food odour in hunger and satiety. Rhinology. 2009; Jun. 47(2):160–5.

28. Doty RL. An examination of relationships between the pleasantness, intensity, and concentration of 10 odorous stimuli. Percept Psychophys. 1975; Sep. 17:492–6.

29. Hong SJ, Li H, Kim ST. Semantic differential evaluation of n-Butanol odor profile: suitability as odor intensity reference. J Odor Indoor Environ. 2019; Jun. 18(2):102–11.

30. Croy I, Lange K, Krone F, Negoias S, Seo HS, Hummel T. Comparison between odor thresholds for phenyl ethyl alcohol and butanol. Chem Senses. 2009; Jul. 34(6):523–7.

31. Zernecke R, Vollmer B, Albrecht J, Kleemann AM, Haegler K, Linn J, et al. Comparison of two different odorants in an olfactory detection threshold test of the Sniffin’ Sticks. Rhinology. 2010; Sep. 48(3):368–73.

32. Zernecke R, Frank T, Haegler K, Albrecht J, Bruckmann H, Wiesmann M. Correlation analyses of detection thresholds of four different odorants. Rhinology. 2011; Aug. 49(3):331–6.

33. Tsukatani T, Miwa T, Furukawa M, Costanzo RM. Detection thresholds for phenyl ethyl alcohol using serial dilutions in different solvents. Chem Senses. 2003; Jan. 28(1):25–32.

34. Kern DW, Schumm LP, Wroblewski KE, Pinto JM, Hummel T, McClintock MK. Olfactory thresholds of the U.S. population of homedwelling older adults: development and validation of a short, reliable measure. PLoS One. 2015; Mar. 10(3):e0118589.

35. Kim JM, Jeong MS, Shin DH, Seol JH, Hong SC, Cho JH, et al. Olfactory identification test using familiar distracters for Koreans. Clin Exp Otorhinolaryngol. 2014; Mar. 7(1):19–23.

36. Poivet E, Tahirova N, Peterlin Z, Xu L, Zou DJ, Acree T, et al. Functional odor classification through a medicinal chemistry approach. Sci Adv. 2018; Feb. 4(2):eaao6086.

37. Malnic B, Hirono J, Sato T, Buck LB. Combinatorial receptor codes for odors. Cell. 1999; Mar. 96(5):713–23.

38. Lotsch J, Reichmann H, Hummel T. Different odor tests contribute differently to the evaluation of olfactory loss. Chem Senses. 2008; Jan. 33(1):17–21.