Retronasal odor perception interacts with taste and other sensory modalities during flavor perception. However, the influence of sweet taste on retronasal odor identification, and its modulation by age, remains poorly understood. Here, we investigated the effects of gymnemic acid (GA)-induced sweet taste suppression on retronasal odor identification in younger (n = 83) and older adults (n = 41). Using a mixed factorial design, participants completed the ThreeT test under normal and sweet taste suppression conditions, with subjective taste ratings, odor identification accuracy, and reaction times recorded. Results showed that oral rinsing with GA significantly reduced perceived sweetness intensity, confirming effective sweet taste suppression. At the behavioral level, sweet taste suppression affected retronasal odor identification in an age-dependent manner, as indicated by a significant age group × condition interaction. Follow-up analyses indicated that odor identification performance decreased in older adults under sweet taste suppression (p = 0.003), whereas no significant change was observed in younger adults (p = 0.330). Reaction times showed a similar reduction under sweet taste suppression across age groups. These findings suggest that the contribution of sweet taste to retronasal odor identification is age-dependent, with older adults showing greater reliance on gustatory input for successful odor identification. The results provide new insights into gustatory–olfactory interactions and highlight the importance of multisensory integration mechanisms in chemosensory aging, with potential implications for understanding flavor perception under reduced-sugar conditions across the lifespan.
BACKGROUND:Mucus overlies the nasal mucosa in the respiratory and olfactory regions, which perform distinct physiological functions. However, proteomic differences between respiratory mucosa (RM) and olfactory cleft (OC) mucus remain unclear. METHODS:Mucus samples were collected from the RM and OCs of 25 healthy participants (mean age: 24.8 years [SD 4.16]; 12 women, 13 men) using cotton and viscose strips. Proteomic profiling was performed using nano liquid chromatography-electrospray ionization tandem mass spectrometry (nanoLC-MS/MS), and enriched proteins were analyzed for functional associations. Olfactory testing was performed using the Sniffin' Sticks odor identification test. RESULTS:RM mucus contained a greater number of enriched proteins, including complement components (e.g., C3, C4), neutrophil antimicrobial proteins (e.g., myeloperoxidase, neutrophil elastase, S100 proteins), and coagulation-related/proteolytic proteins (e.g., fibrinogen, plasminogen, vitronectin, alpha-2-macroglobulin). These proteins were associated with immune defense, coagulation, and regulatory pathways. OC mucus contained fewer enriched proteins, including aldehyde dehydrogenase family 3 member B1, chloride intracellular channel protein 6, long-chain fatty acid transport protein 2, and stromelysin-2, supporting epithelial maintenance, ionic homeostasis, and odorant metabolism. Overrepresented processes in OC mucus were linked to ciliary structure/motility and epithelial maintenance. CONCLUSIONS:Proteomic profiles reflect regional specialization: RM mucus is optimized for immune response, whereas OC mucus maintains a microenvironment conducive to sensory function and epithelial integrity. Collectively, the results highlight how regional mucus proteomic differences parallel the distinct physiological roles of the respiratory and olfactory epithelia and provide a foundation for investigating proteomic changes in olfactory dysfunction or nasal inflammatory disease.
The significance of olfaction in human behavior is well recognized, yet there is a lack of standardized measurement tools applicable to all age groups. Particularly, children and the elderly currently lack specific standardized assessment instruments. This study included 454 healthy participants (154 children, 150 young adults, and 150 older adults). After three rounds of item screening and confirmatory factor analysis, we developed a 12-item questionnaire encompassing four dimensions: "Food," "Hazards," "Interpersonal Relationships," and "Spatial Orientation." The results demonstrate that the questionnaire exhibits good test-retest reliability and structural validity. Our findings indicate a positive correlation between the perceived importance of olfaction and age across a wide age range, but this trend does not reach statistical significance within any specific age group. Children scored significantly lower than both young adults and seniors, with no significant difference between the latter two groups. Additionally, trends were observed regarding gender differences in olfactory behaviors and variations across different olfactory activities. The present questionnaire is a reliable and validated self-report measurement of an individual's significance of olfaction for people over 10 years old.
Olfactory performance and nasal microbial composition are shaped by complex interactions among biological, environmental, and lifestyle factors. Further, emerging research suggests that traditional environments may support both sensory function and microbial health, but empirical evidence remains limited. Here, we assessed olfactory and microbial health in a West Papuan population with an additional focus on environmental context (varying degrees of modernization) and subsistence practices (hunter status). Participants from Dani tribe of West Papua from three locations (town outskirts, village, jungle) completed olfactory testing and provided nasal microbiome samples. Alpha and beta diversity analyses did not reach statistical significance for any of the tested variables, suggesting that overall community richness, evenness, and structure were broadly conserved across groups. In contrast, within-population analyses revealed some lifestyle-associated patterns: hunters exhibited higher nasal bacterial abundance and slightly higher odor identification scores than non-hunters. Olfactory performance did not differ significantly by place of residence. Across all three sites, participants exhibited broadly comparable and markedly low odor threshold and identification score. Our findings underscore the complexity of olfactory-microbiome relationships and contribute to a better understanding of factors contributing to microbial and sensory health. The absence of statistically significant differences in alpha and beta diversity across tested variables suggests relative stability of overall nasal microbial community structure; however, limited sample size or inter-individual variability may have reduced power to detect small or localized effects.
Postinfectious olfactory dysfunction (PIOD) is common in COVID-19 patients. This 2-arm double-blinded randomized controlled trial (RCT) aimed to establish proof-of-concept for vitamin A versus placebo as a treatment modality for patients with PIOD. This study compared 9,000 IU daily self-administered vitamin A intranasal drops versus peanut oil drops over 12 wk in COVID-19 patients with PIOD. Outcome measures included: olfactory bulb volume (OBV), olfactory sulcus depth, cerebral functional MRI blood oxygen level dependent (BOLD) signal, Sniffin' Sticks TDI score, SSParoT, olfactory disorder questionnaire (ODQ) score, and brain-derived neurotropic factor (BDNF) levels were collected from participants at baseline and after trial intervention at 12 wk. Fifty-seven PIOD were recruited in the trial and allocated to vitamin A or placebo arm at a 2:1 ratio. After withdrawals and exclusions, 30 participants in the vitamin A arm and 15 in the placebo arm were analyzed. There was no significant difference in the change in OBV between both groups. Aside from an improvement in the quality-of-life component of ODQ questionnaire scores (P = 0.01), there were no significant differences in any of the other secondary outcome measures. This proof-of-concept trial has demonstrated no significant effect of intranasal vitamin A on olfactory function in COVID-19 PIOD patients. Further work is required to identify other therapeutic agents in the management of PIOD or evaluate a different PIOD cohort with non-COVID etiology.
OBJECTIVE:Are paired chemosensory stimuli with very short interstimulus-intervals (ISIs) more often perceived as distinct events when delivered synchronously with inspiration than when delivered asynchronously? METHODS:Twin stimuli (H2S, phenylethyl alcohol [PEA], CO2) were repeatedly administered intranasally to 40 participants using a constant-flow olfactometer, synchronized with inspiration, at varying ISIs. In the first part of the study, participants indicated whether they perceived one or two stimuli. In the second part, event-related potentials (CSERP) were recorded from 20 participants using only H2S stimuli with very short ISIs (0.6-1.6 s). The CSERPs were then qualitatively and quantitatively evaluated based on whether stimuli were perceived or not. RESULTS:The perception rate of twin stimuli increased with increasing ISI. A plateau in the discrimination of separate twin stimuli, averaging 90%, was observed with CO2 or H2S stimulation at ISIs between 1.6 and 3.0 s, respectively, up to 9.0 s. For PEA stimulation, a plateau of approximately 70% was observed between 3.0 and 9.0 s. CSERP detection rates were 100% for both perceived first and second twin stimuli, while non-perceived second stimuli showed a 70% rate. The latencies of the CSERPs did not differ across the three conditions. The amplitudes were larger for non-perceived second stimuli than for perceived first and second stimuli. CONCLUSION:Predominantly inspiration-synchronous stimulation allows higher detection of responses at both psychophysical and electrophysiological levels, even at very short ISIs. These findings may help to reduce the duration of clinical experiments and electrophysiological assessments of olfactory function. LEVEL OF EVIDENCE: 4:
Background Despite the high prevalence of smell disorders, there are only a few centres specialising in the evaluation and treatment of patients with smell and taste disorders. While the comprehensive evaluation at centres requires considerable coordination, basic management techniques can be implemented with minimal effort. Summary This manuscript provides guidance on implementing these steps to provide a meaningful workup in patients with smell and taste disorders. Patients can be evaluated using a stepwise process to assess self-reported smell function. Key messages The impact of olfactory dysfunction should be documented using validated, disease-specific quality-of-life questionnaires. Nasal endoscopy is mandatory to rule out sinonasal inflammation, one of the most frequent underlying etiologies of smell disorders. Further comprehensive evaluation must include a thorough patient history and psychophysical tests of odour identification and gustatory function.
Taste dysfunction affects quality of life, yet its biological development remains poorly understood. We investigated clinical and biochemical differences between 50 patients with idiopathic dysgeusia and 102 healthy controls (110 women, 42 men; mean age 46.4 ± 1.4 years). Each participants underwent a clinical anamnesis, a taste test, and a blood analysis. Patients were older (61 vs. 39 years; p < 0.001) and more often female (86
OBJECTIVES:Retinoic acid, a metabolite of Vitamin A, and has been shown in animal work to support olfactory receptor neuron regeneration. A limited amount of clinical research has also demonstrated potential therapeutic benefit in patients with olfactory dysfunction (OD). We therefore performed, to our knowledge, the first prospective study investigating whether the intranasal vitamin A containing 'Coldatsop' is beneficial in treating patients with non-sinonasal OD. METHODS:A non-blinded prospective comparative study was performed, in patients with OD due to post-infectious, post-traumatic and idiopathic aetiologies. Patients were treated with olfactory training (OT) alone, OT plus intranasal Vitamin A (Coldastop, OT+VA) or OT plus intranasal steroids (mometasone furoate, OT+S) for 12 weeks. Full psychophysical olfactory testing was performed before and after treatment using the "Sniffin' Sticks" test battery (with results for odour threshold, discrimination, identification, and composite 'TDI'). RESULTS:144 patients completed the study: 52 OT, 42 OT+S, 50 OT+VA. The majority of patients had PIOD. There were no significant differences between groups in age/sex. There were statistically significant improvements in each subtest (T/D/I) and composite scores (TDI) within each treatment regimen. Across groups, there was a significant interaction between treatment and time (controlling for baseline characteristics) for odour threshold, F(2, 139)=3.2, P=0.044, with the largest improvement being seen in the OT+VA group. Further, the greatest proportion of patients reached clinically significant improvement within the OT+VA group (T/D/I/TDI), but this did not reach statistical significance Conclusion: Intranasal Vitamin A may be of benefit in treating OD. Further large-scale randomised trials are required.
Abstract Background Olfactory dysfunction (OD) affects approximately 22% of the general population, yet children account for only around 2% of specialist olfactory clinic attendees — a striking disparity that likely reflects systematic under-detection rather than lower disease prevalence. There are currently no internationally endorsed clinical guidelines governing the assessment of children with suspected OD. A recent international survey of 167 paediatric otolaryngologists across 36 countries found that more than half never perform psychophysical olfactory testing, a majority routinely order neuroimaging, and that multidisciplinary collaboration is largely lacking - findings that collectively motivate this consensus effort. Materials and Methods This is a prospectively registered, multi-round modified Delphi consensus study. A steering committee of seven international experts spanning paediatric otorhinolaryngology, chemosensory science, neuropaediatrics, and research methodology will generate an initial set of candidate consensus statements across 12 pre-defined clinical domains, derived from a structured narrative evidence review and practice-gap data. A panel of 15-25 international experts will vote anonymously over two to three sequential rounds using a 9-point Likert scale. Consensus is defined a priori as a median score ≥7 with ≥75% of panellists rating 7–9 and an IQR of ≤2. A post-Delphi virtual ratification meeting will follow voting rounds. Patient and Public Involvement (PPI) is embedded throughout: a family advisory group of 4-6 parents, caregivers, and young people with lived experience of paediatric OD, recruited in partnership with anosmie.org, will review candidate statements before Round 1, and PPI findings will inform statement framing before expert voting begins. This study was assessed using the Health Research Authority (HRA) online decision tool for England and found not to require NHS Research Ethics Committee (REC) review. The study will be conducted in accordance with the Research Governance Framework for Health and Social Care (2nd Edition). Discussion The final consensus statements and supporting methodology will be submitted for peer-reviewed publication. The study will be reported in compliance with the ACCORD and DELPHISTAR reporting standards for consensus methods. The protocol has been pre-registered prospectively on the Open Science Framework (OSF) prior to data collection.
To compare the efficacy of WeChat-guided olfactory training (WG-OT) versus text-based olfactory training (TB-OT) in improving odor identification and enhancing adherence in patients with persistent olfactory dysfunction (OD), and to evaluate the mediating role of adherence and psychological outcomes. A prospective cohort study was conducted from March 2024 to June 2025. A total of 113 adults with moderate-to-severe OD were randomized to WG-OT (n = 50) or TB-OT (n = 63). Both groups performed twice-daily exposure to four odorants for 12 weeks. Primary outcomes were changes in odor threshold (T) and identification (I) measured by Sniffin’ Sticks. Secondary outcomes included adherence rates, PHQ-9 depression scores, QOD (Questionnaire of Olfactory Disorders), and endoscopic scores (OCES). WG-OT demonstrated significantly higher adherence (89.4
BACKGROUND:Olfactory training (OT) is an established, behaviourally effective intervention for post-viral and idiopathic olfactory dysfunction, yet the temporal dynamics of its neural mechanisms remain insufficiently understood. Most neuroimaging studies rely on standard hemodynamic models that capture activation amplitude but overlook the timing and shape of the blood-oxygen-level-dependent (BOLD) response. Hence, we re-examined previous results on the effects of OT in patients with olfactory loss and healthy controls. METHODS:Using a novel multi-model fMRI framework, we systematically mapped temporal tuning profiles of olfactory network responses in patients with olfactory dysfunction (PAT; n = 20) and matched healthy controls (CON; n = 19) before and after a 12-week OT program. For each subject, we generated a family of first-level models with systematically shifted hemodynamic onsets, allowing the estimation of region-specific response amplitude, latency, and waveform properties. Analyses focused on three key regions of interest (ROIs): the right insula, amygdala, and orbitofrontal cortex (OFC)-nodes critically implicated in olfactory perception and emotional-evaluative processing. RESULTS:Before training, patients exhibited absent or weak BOLD responses across all ROIs. After training, they showed clear activation recovery ("gain-of-function"), characterized by delayed and broadened hemodynamic peaks relative to controls-indicative of slower but re-emerging network synchrony. In contrast, healthy controls displayed adaptive neural refinement, evidenced by amygdala habituation and a biphasic-like response in the OFC, reflecting efficient temporal reorganization of olfactory processing. CONCLUSION:Olfactory training induces state-dependent neural plasticity. In patients, recovery appears to involve broader and delayed engagement of olfactory networks, suggesting compensatory recruitment during sensory restoration. In contrast, healthy individuals show more precise and efficient neural responses after training. Together, these findings highlight different patterns of functional adaptation in the human olfactory system during recovery and learning.
The Sniffin’ Sticks test is among the most commonly used methods of olfactory assessment and has been successfully adapted across various countries. However, to date, no study has examined cultural changes over time, within the same country. The present research is the first to explore the adaptation of odor labels to contemporary contexts. A total of 83 normosmic participants (57 women) aged 18 to 75 years (y) (M = 35.2 y, SD = 13.7) were enrolled in four studies in which we replaced the unfamiliar odor labels with more familiar ones and balanced the frequency of labels used in the entire set of odor labels. Lastly, forty additional healthy participants (28 women) aged from 18 to 61 y (M = 32.8 y, SD = 11.4) were recruited to assess the test–retest reliability of the newly developed version of SS-OIT labeling within a period ranging from 1 to 57 days (M = 14.8 days, SD = 13.2). We aimed to increase the number of labels that are known by the present population, and hence, we modified 31
Chronic rhinosinusitis (CRS) with and without nasal polyps has a prevalence of around 10%, being one of the most common chronic diseases in Europe. It is characterized by a wide range of symptoms leading to a high individual, clinical and socioeconomic burden due to loss of productivity of individual patients and challenging therapeutic processes. This study aimed to investigate the effects of functional endoscopic sinus surgery (FESS) on olfactory function and associated quality of life of CRS patients, particularly regarding postoperative differences in neuronal processes. Using psychophysical and electrophysiological tools, the goal was to quantify postoperative changes to predict the neuronal functions related to olfactory improvements after FESS and ultimately provide better therapeutic recommendations in the future. Twenty-five CRS patients with nasal polyps aged from 30 to 64 years (CRS group) and 20 healthy controls aged from 23 to 54 years (control group) participated in this study. Both groups were tested twice (interval 3 to 6 months), with the first examination of the patients taking place a few days before surgery. Testing included questionnaires (medical history including self-ratings of olfactory function and nasal breathing, SNOT-20 questionnaire), psychophysical methods (Sniffin Sticks for olfactory function [TDI score], Peak Nasal Inspiratory Flow) and electrophysiological methods (olfactory and trigeminal event-related potentials). CRS group patients were also subjected to preoperative clinical examination and preoperative CT-scans. While the CRS group improved in terms of self-ratings of the sense of smell and TDI scores, as well as nasal breathing and quality of life, the control group did not show major longitudinal differences. In addition, electrophysiological measures suggested that trigeminal sensitivity decreased after surgery. CRS patients showed benefits from surgery in terms of olfaction, nasal breathing and quality of life, at least 3-6 months after the intervention. Interestingly, electrophysiological measurements suggested a postoperative decrease of trigeminal sensitivity.
BACKGROUND:Retronasal olfaction is essential for aroma perception. Its impairment in individuals with olfactory dysfunction (OD) negatively affects dietary behaviour and quality of life. Regular exposure to odours in a form of olfactory training (OT) is used to rehabilitate the sense of smell. However, retronasal recovery following OT remains insufficiently characterised. OBJECTIVE:To verify whether OT improves retronasal odour identification and whether such improvement is related to orthonasal odour identification recovery. STUDY DESIGN:Prospective, single-arm clinical study. METHODS:Fifty-three patients with OD (predominantly post-COVID-19) completed at least 3 months of OT (conducted bi-daily with four odours). Retronasal function was assessed with the ThreeT test and orthonasal function with the Sniffin' Sticks battery before and after training. RESULTS:OT significantly improved both retronasal (9.40 ± 0.42 vs. 10.85 ± 0.48; p < 0.001) and orthonasal odour identification (8.75 ± 0.50 vs. 10.53 ± 0.50; p < 0.001). Changes in retronasal performance positively, moderately correlated with changes in orthonasal identification (r = 0.38, p = 0.006). Clinically meaningful retronasal improvement was associated with a higher likelihood of orthonasal recovery, χ2(1) = 5.08, p = 0.024; OR = 4.00 (95% CIs: 1.16-13.83). CONCLUSIONS:OT improves retronasal odour identification. The mechanisms of orthonasal and retronasal recovery may be partially overlapping.
OBJECTIVE:Many studies investigated olfactory function following head trauma, but surprisingly few studies looked at smell loss following fractures of the nose. The aim of this study was to examine whether isolated fractures of the nose are associated with olfactory dysfunction. METHODS:A total of 97 participants (49 patients in the fracture group, 48 participants in the control group) were included in this cross-sectional study. The fracture and control groups were matched in terms of gender and age. Time since fracture varied, starting from 28 days to a maximum of 2 years. Olfaction was tested using the "Sniffin Sticks" test battery (odour threshold, discrimination and identification) and further data was collected using a basic questionnaire as well as via ENT examination with nasal endoscopy. RESULTS:Compared to controls the scores for odour discrimination and odour identification were lower in the fracture group (mean odour identification: 11.5 vs. 12.8; mean odour discrimination: 11.2 vs. 12.6; p<0.05). Odour thresholds were also decreased in the trauma group (mean odour thresholds: 6.8 vs. 8.1; p=0.06). General olfactory function scores (TDI score) correlated negatively with the time since fracture (p < 0.001) possibly indicating further decrease of function following trauma. CONCLUSION:Fractures of the nose are associated with a decrease in olfactory function, which is found especially for odour discrimination and odour identification.
Objective:This study aimed to investigate whether electroencephalogram (EEG) data can be used to classify normosmia and anosmia using machine learning approaches and to examine how classification performance varies across single and combined chemical stimulation conditions. Methods:EEG signals were recorded from 66 participants (26 normosmic and 40 anosmic) during olfactory stimulation with phenyl ethyl alcohol (PEA), hydrogen sulfide (H₂S), and carbon dioxide (CO₂), presented to the left and right nostrils. EEG data were averaged for each condition, resulting in six chemosensory event-related potential (CSERP) datasets per participant. Three machine learning models-support vector machine (SVM), random forest (RF), and convolutional neural network (CNN)-were used to classify normosmia and anosmia. Results:Among all single and combined odor conditions, the combination of PEA_Right + H₂S_Left + H₂S_Right achieved the highest performance (ACC = 86.37%, F1 = 0.88, AUC = 0.85). CNN generally outperformed SVM and RF across most conditions. H₂S stimulation consistently provided strong discriminative power, particularly under left-sided presentation. Conclusion:Machine learning applied to EEG-based CSERPs can effectively distinguish olfactory dysfunction, demonstrating the feasibility of this approach for objective evaluation of olfactory processing. Significance:These findings suggest that EEG-based machine learning can serve as an objective framework for assessing olfactory function and may contribute to future development of data-driven diagnostic strategies for smell disorders.