Abstract
Background
It is important to use odor threshold and odor identification (OI) tests to evaluate children's olfactory function. However, there is a lack of Chinese normative data obtained in a large sample for these tests.
Objective
The purpose of this study was to provide normative data for Chinese children regarding olfactory threshold (OT) and OI tests, as well as combined scores, which help clinicians distinguish between normosmia and dysfunction in clinical diagnosis.
Methods
Olfactory testing was conducted using the “Sniffin’ Sticks” OT test and the 12-item “U-Sniff” OI test; TI score was calculated as the sum of OT and OI scores. The data were collected from 450 children between the age of 5 and 17 years. In line with previous studies, participants were divided into subgroups regarding their age: (1) 5-8 years, (2) 9-11 years, and (3) 12-17 years.
Results
Normative data for OT, OI, and TI score were established across different age groups. Age was found to have a significant impact on OT, OI, and TI performance. Elder children achieved higher scores compared to younger children (P < 0.001 for all).
Conclusion
This study offers normative data for evaluating the sense of smell in Chinese children using both the OT and OI tests. These tests can help differentiate between a normal sense of smell and dysfunction. Combining these two tests can provide a comprehensive evaluation of the olfactory function in children.
Introduction
It is estimated that around 20% of people have a reduced sense of smell, while 5% suffer from functional anosmia. 1 However, there is a lack of reliable data on the incidence of olfactory dysfunction in children, possibly due to difficulties in performing olfactory tests on children. Anosmia in children can be congenital, either as an isolated disorder or in association with syndromes such as Kallmann syndrome. 2 Alternatively, it can be acquired secondarily, for example, due to head trauma, rhinosinusitis, adenoid hypertrophy, or upper respiratory infections, including COVID-19 infection.3,4
Children with olfactory dysfunction experience an increased frequency of hazardous events, such as food poisoning or failure to detect smoke, and have an overall decreased daily diet and poor nutrition which is important for the growth and development of children. This creates an increasing need for a standardized assessment of olfactory function in children. However, the clinical diagnostics of olfactory dysfunction turns out to be challenging due to low attention span, linguistic development, and lack of odor experience. Several olfactory tests have been developed to address these challenges, mainly focusing on odor identification (OI) abilities. The “U-Sniff” test is a widely used test that can measure OI abilities in children as young as 3 years old. This test can differentiate between normosmia and a reduced sense of smell with high accuracy. 5 It is also important to consider cultural differences as OI scores may vary across different countries. However, there is limited information available about the normative data of OI among Chinese children aged 6-8 years, and the sample size in the studies is small, with older children not included. 6
Some research indicate that a composite score may be better suited for the clinical assessment of olfactory dysfunction than an isolated measure of olfactory performance such as OI. 7 To overcome the issue of limited verbal ability in children, a threshold test specifically designed for children has been developed. The “Sniffin’ Sticks” olfactory threshold (OT) test could reflect validly the olfactory sensitivity of children and is particularly sensitive for the assessment of peripheral olfactory dysfunction. The OT measurement is suitable and reliable for children starting at an age of 5 years in its standard three-alternative-forced choice paradigm.8,9 The non-verbal olfactory test of odor thresholds might be appropriate in patients without cognitive deficits, which appears to produce results of more reliability and comprehensiveness combining with OI test. However, the data for the OT is not sufficiently reported, and it is lacking of normal data for Chinese children.
The “Sniffin’ Sticks” OT test as well as the “U-Sniff” test, as a supra-threshold test, are routinely used in our clinic for evaluation of olfactory function in children. However, previous research reporting normative data for olfactory tests in children included only a small sample or single OI test which related to the cognitive and verbal development. It is necessary for a routine clinical test to have normative data for both olfactory measurements based on a large population. Therefore, the aim of this study was to provide normative data for Chinese children using the “Sniffin’ Sticks” OT, the “U-Sniff” OI test and combined score, and to provide the cut-off standard between normosmia and dysfunction in clinical diagnosis.
Materials and Methods
Participants
The data were collected from 450 participants (221 females, 229 males) between the age of 5 and 17 years (mean age 9.65 ± 3.36 years) who were from 15 different provinces (5 southern provinces, 6 northern provinces, 4 western provinces). According to previous studies participants were divided into three age groups: (a) 5-8 years, (b) 9-11 years, and (c) 12-17 years.10,11 All participants were thoroughly interviewed（including their parents）and medically investigated to confirm that none of the participants had a history of olfactory dysfunction. Furthermore, other possible causes of anosmia, such as traumatic brain injury, upper respiratory tract infection, sinonasal or brain disease, drug or toxic exposure, or any other factors, were ruled out. Additionally, nasal endoscopy/anterior rhinoscopy were conducted to exclude any inflammatory disease related to the nasal area. Participants were recruited from the Physical Examination Center, and written informed consent was obtained from each participant's parents or legal guardians. Appropriate IRB approval from Capital Center for Children's Health was obtained for this study (IRB. SHERLL2023031), and the study has been registered for clinical trials in China (NO.ChiCTR2400085571).
Olfactory Testing
The OT of the “Sniffin’ Sticks” test and the OI test—“U-Sniff” test were used (“Sniffin’ Sticks,” Burghart GmbH, Wedel, Germany). Standard administration was performed according to the manufacturer's instructions for the Sniffin’ Sticks test and U-Sniff test.8,12
Olfactory Threshold
The participants in the study were blindfolded and received no feedback during the task. The researchers used a staircase procedure to assess the OT for phenylethylalcohol, which involved 16 dilution steps of phenylethylalcohol, starting from the highest dilution of 4%. Each staircase was made up of three “Sniffin’ Sticks,” one containing a dilution of phenylethylalcohol and two containing only propylene glycol. The participants’ task was to identify the odor-containing “Sniffin’ Stick” within the triplet in a three-alternative-forced choice method. The triplets were presented at intervals of approximately 20 s. Testing continued until seven reversal points were obtained. The individual OT was calculated as the average of the last four reversal points and could range from one to 16 points. 8
Odor Identification
The ability to identify odors was assessed using 12 odors in a four-alternative-forced choice procedure. The test consisted of 12 different odors, including apple, banana, butter, coffee, cut grass, fish, flower, lemon, onion, orange, peach, and strawberry. Each odor was presented separately using the “Sniffin’ Sticks” with an interval of about 20 s. The participants were asked to identify the odor of each “Sniffin’ Stick” by choosing from four descriptors presented as pictures and in writing. The sum of correct answers was considered the OI score, which ranged from zero to 12 points. All subjects underwent olfactory testing in a quiet, well-ventilated room with relatively constant temperature and humidity.
Statistical Analyses
All analyses were performed using SPSS 17.0. The significance level was set at 0.05. TI score was the sum of OT and OI scores. OT and OI and TI scores results were expressed as mean ± standard deviation. An ANOVA with age and an independent sample t-test sex were performed. The test was designed as a clinical screening test, meaning it had to distinguish between normal olfactory function and olfactory dysfunction. Therefore, the 10th percentile was used as a cut-off based on existing tests. 1
Results
Olfactory Test Results
We performed three separate linear mixed models for OT and OI and TI scores. Within each model, we included participants’ sex (229 males vs 221 females) and age groups ((1) 181 subjects, (2) 133 subjects, (3) 136 subjects). A total of 450 participants completed the examination. For an overview and details about the test results, please see Table 1.
Normative Data of the Sniffin'Sticks and U-Sniff Tests for Children.
Olfactory Threshold
The OT score of participants ranges from 3 to 13.75 points. The youngest age group (1) scored 6.61 ± 2.04 points, ranging from 3.25 to 13 points, while the second age group (2) reached 7.35 ± 2.23 points, ranging from 3 to 13.75 points. Children between an age of 12 and 17 years achieved a mean of 7.74 ± 2.22 points for OT, ranging from 3.5 to 13 points.
Odor Identification
The OI score of participants ranges from 3 to 12 points. The youngest age group (1) scored 9.11 ± 1.65 points for OI, ranging from 3 to 12 points, while the second age group (2) reached 10.03 ± 1.61 points, ranging from 3 to 12 points. Children older than 12 years achieved a mean of 10.40 ± 1.18 points for OI, ranging from 8 to 12 points.
TI Score
The TI score of Participants ranges from 8.5 to 25.75 points. The youngest age group (1) scored 15.83 ± 2.66 points, ranging from 8.5 to 22.5 points, while the second age group (2) reached 17.40 ± 2.59 points for TI, ranging from 10.25 to 25.75 points. Children between the age of 12 and 17 years achieved a mean of 18.14 ± 2.61 points for TI, ranging from 13 to 25 points.
Factors Influencing Olfactory Threshold and Odor Identification
A significant difference in OT and OI including TI score was observed among the different age groups (OT: F = 10.615, P < 0.001; OI: F = 30.953, P < 0.001; TI score: F = 29.902, P < 0.001). The results of OT, OI, and TI scores indicated an increase with age (P for trend < 0.001 for all). A fully factorial model revealed no significant effect of sex on OT and OI and TI scores (OT: males 7.02 ± 2.19 points vs females 7.42 ± 2.22 points, t = −1.870, P = 0.062; OI: males 9.72 ± 1.63 points vs females 9.80 ± 1.58 points, t = −0.521, P = 0.603; TI: males 16.61 ± 2.76 points vs females 17.10 ± 2.51 points, t = −1.825, P = 0.069). For an overview, see Figure 1.
(A) Olfactory threshold score increases with age. (B) Odor identification score increases with age. (C) TI score increases with age. Displayed are the OT,OI and TI scores for each of the three age groups (mean + SD).
Normative Data and Percentile Ranges
The 10th percentile is commonly used to define the cut-off between normal olfactory function and a reduced sense of smell. 13 The following scores were defined for the three age groups: (1) 5-8 years) OT 4 points, OI 7 points, TI 13 points; (2) 9-11years) OT 5 points, OI 8 points, TI 14 points; (3) 12-17years) OT 5 points, OI 9 points, TI 15 points. Table 1 shows a graphical display of the percentile ranges.
Discussion
Our research study has provided normative data for the OT and OI tests, along with the total score TI, using the “Sniffin’ Sticks” and “U-Sniff” tests. This data could help clinicians distinguish between normosmia and dysfunction in children aged 5-17 years. Furthermore, it was observed that OT and OI performance, as well as the combined TI scores, increased with age but showed no difference in sex. The combination of OT and OI scores was valuable and comprehensive in evaluating the olfactory function of children.
Our study presents the normal OT data of Chinese children at different age stages. We found that OT differed among the three age groups, but not between boys and girls. This suggests that olfactory sensitivity increases with the growth and development of children, but is not related to gender. OT is an important test to evaluate the olfactory sensitivity of children and is particularly sensitive for the assessment of peripheral olfactory dysfunction. OT testing is little influenced by cognitive factors and less dependent on verbal abilities. 14 It was usually found in the clinic that the patients with allergic rhinitis had reduced OT but normal OI due to inflammation-induced nasal obstruction and mucosal edema. Previous studies have also shown the feasibility of the “Sniffin’ Sticks” OT test in children starting at age 5 years.15,16 However, the data is not sufficiently reported. Hummel et al collected OT data of 25 girls scoring on average 6.59 ± 2.23 points and 17 boys achieving 7.22 ± 2.59 points between age 5 and 15 years. 13 Strauss who assessed sensitivity to phenylethyl alcohol with the Elsberg injection technique, found OT to increase progressively from children 8-10 years old, to adolescents 16-18 years old, to adults 21-39 years old. 17 It is likely that young children perform worse than adults or older children initially because they have less experience and bring less semantic information to the task. Both common and novel odors are more novel to younger children. 18 Some results show that the school grade level has an influence on OT scores. The authors suggest that the increase in OT scores with age can be attributed to a higher ability to concentrate and an improving short-term memory. 19
Our study firstly reported the normal data of OI in 450 Chinese children aged 5 to 17 years. The results indicated that OI scores increased with age, but was not related to sex. The “U-Sniff” is a widespread international identification test, and it has been proved to be feasible for children starting at age 3 years.5,20 This study showed older children performing better than younger children, which was in agreement with previous work reporting an increase in OI performance with age in children, especially before adolescence.5,7,12 U-Sniff are age dependent with older children performing better than younger children. The factors contributing to this age dependent increase in OI performance may include linguistic development and odor familiarity.12,21,22 Especially odor learning, which takes place during the development of children, as well as verbal development seems to be associated with olfactory identification ability. 19
The current study provided normative data for the U-Sniff test for Chinese children between age 5 to 17 years. The results showed that the mean OI score was 9.76 ± 1.60 points, which is similar to the results from the previous studies (9.86 ± 1.87 points) that included children aged 6 to 8 years from 19 different countries, but did not include China. 12 The U-Sniff test scores differed significantly across different countries in the previous studies, which might be due to various cultural backgrounds. In the only report including 50 Chinese children aged 6 to 8 years, the mean OI score was 10.60 ± 1.13 points (range 8-12), which was slightly higher than the result of this study (9.11 ± 1.65 points for OI at 5 to 8 years). 6 These might be due to differences in the age of the examined population. Furthermore, the study found that there was an age difference in the U-Sniff test scores. This is consistent with the majority of previous studies, which showed that OI abilities increase with age in children.5–7,12
In this study, a few children had lower scores on the OI test. Entry errors and non-real data were first ruled out. The possible reasons are, firstly, the younger age of the subjects, and their limited comprehension and lower cooperation during testing may have affected results. Secondly, cultural differences or varying life experiences played a role. Some children are unfamiliar with certain test odors (for example, some young children have never encountered the smell of coffee), making correct choices difficult.
In addition to the influence of age, possible differences between girls and boys regarding olfactory function were analyzed. We found that there was no significant difference between the sexes in terms of OT and OI performance, which is consistent with most studies.13,20,23 Only a few studies have reported that girls perform better than boys in OI abilities. 7 While Hummel et al reported no difference in OT between girls and boys aged 5-15 years. 13 Koelega, on the other hand, found that girls had better OT than boys in only a few odors but not all used odors. 14 It is suggested that differences in development of verbal fluency contribute to this finding.9,19 Based on the current literature, it can be concluded that in cases of sex differences in OI performance girls outperformed boys, but never the other way around. Further research is required to explore the impact of sex on olfaction.
The study conducted a combination of verbal (OI) and non-verbal approaches (OT) to test olfactory performance. The findings suggest that a composite score may be a more suitable assessment of olfactory dysfunction than just relying on a single measure such as OI, as recommended by Kobal and Hummel. 10 The present data suggest that it is beneficial to test olfactory performance by different olfactory tests combinations. That is, when conducting the combined determination of odor thresholds and OI might be appropriate in patients with cognitive deficits or peripheral olfactory dysfunction. However, there is the limitation in this study. This article does not present the data demonstrating the advantages of the TI total score over single test score in clinical diagnosis, which will be the main focus of our future research.
The 10th percentile is commonly used as a separation between olfactory dysfunction and a normal sense of smell in adults. 13 This same criterion was applied in the current study, and the results are reported separately for three different age groups. Sensory function, such as hearing and vision, is routinely monitored and tested in clinical settings to ensure optimal development of children. However, not much is known about the impact of olfactory dysfunction on the development of children, whether it is acquired or congenital. This study provides normative data for olfactory testing in children and comprehensive olfactory testing in the Chinese population. This would lead to early detection and diagnosis of olfactory dysfunction in children, and if possible, early treatment could be initiated.
Conclusions
The study provides normative data for the “Sniffin’ Sticks” OT and the “U-Sniff” OI test for Chinese children aged 5 to 17. The normative data are reported for different age groups separately, considering the neurocognitive and pubertal development of children, and can help to distinguish between normosmia and dysfunction in the clinic. It is recommended to combine the OT and OI tests to comprehensively evaluate the olfactory function of children.
Footnotes
Acknowledgments
We would like to thank professor
Ethical Approval and Consent to Participate
The study was approved by the ethics board of Capital Institute of Pediatrics (NO. SHERLL2023031), and written informed consent was obtained from each participant.
Authorship Contributions
JL collected the data, performed statistical analysis, and prepared the manuscript. YZ contributed equally with JL to this work, who collected the data and performed statistical analysis. XZ collected the samples, did the olfactory tests, and recorded the information. YL collected the samples, did the olfactory tests, and recorded the information. XY performed statistical analysis and reviewed the manuscript. XG collected the samples, did the olfactory tests, and recorded the information. QG designed the study and prepared the manuscript.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Research Foundation of Beijing Municipal Administration of Hospitals Incubating Program (PX2025047) and grant from the Beijing Municipal Natural Science Foundation (7232010).
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.