Objective nasal airflow measures in relation to subjective nasal obstruction, trigeminal function, and olfaction in patients with chronic rhinosinusitis.

BACKGROUND: This study aimed to determine how nasal airflow measures and trigeminal function vary among patients with chronic rhinosinusitis (CRS) versus healthy controls and whether these measures are correlated with subjective nasal obstruction (SNO), olfactory function, and CRS control. METHODOLOGY: Participants included CRS patients and healthy controls. After a structured medical history, nasal airflow (peak nasal inspiratory flow [PNIF]; active anterior rhinomanometry [AAR]), trigeminal function (trigeminal lateralization test, CO2 sensitivity), and olfactory ("Sniffin' Sticks" odor identification test) tests were performed. SNO ratings were also obtained. RESULTS: Sixty-nine participants were included (37 men, 32 women, mean age 51 years). There was no significant difference for objective nasal airflow between patients and controls, but CRS patients had worse SNO, trigeminal function, and olfaction compared to controls. SNO, but not objective nasal airflow tests, was negatively correlated with CO2 sensitivity and odor identification. CONCLUSION: The perception of nasal obstruction does not only depend on nasal airflow, but may also be modulated by trigeminal function and other factors. Thus, the role of objective nasal airflow measures as a sole method of functional nasal obstruction assessment in CRS remains limited.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Olfactory stimulation may modulate the sensation of nasal patency.

BACKGROUND: The sensation of nasal patency can be induced by inhaling menthol, which predominantly produces trigeminal stimulation. It remains unclear whether olfactory stimulation can also induce or modulate the sensation of nasal patency. METHODOLOGY: A total of 118 participants (normosmia: n=67, olfactory dysfunction: n=51) were exposed to four odors in a randomized order: 1) phenylethanol (PEA), 2) menthol, 3) a mixture of PEA and menthol, 4) nearly odorless propylene glycol. The odors were presented by nasal clips. After the nasal clip had been removed, the participants rated relative nasal patency (RNP) from - 50 to +50, and their peak nasal inspiratory flow (PNIF) was measured. Repeated measures analysis of variance was used to examine the difference of RNP and PNIF among the four conditions and the influence of olfactory function. RESULTS: The RNPs, other than PNIFs, differed between the four conditions. Menthol induced the highest RNP, followed by the mixed solution, PEA and the odorless condition. Normosmic participants, but not those with olfactory dysfunction, responded to PEA significantly higher than odorless condition with regard to RNP. The correlation analysis showed that the better the subjective or measured olfactory performance, the greater the PEA-induced sensation of nasal patency. CONCLUSIONS: A specific olfactory stimulant that selectively induces olfactory perception can also evoke and modulate the sensation of nasal patency. Hence, patients might benefit from exposing themselves to odors in order to relieve the annoying nasal obstruction.

Smell, taste and trigeminal function: similarities and differences between results from home tests and examinations in the clinic.

BACKGROUND: This study aimed to examine an easy-to-conduct home chemosensory test as a screening tool prior to clinical testing and to investigate the associations between home and clinical tests. METHODS: We examined 200 participants who performed a chemosensory test including subjective ratings as well as psychophysical smell, taste and trigeminal function tests at their homes. Following that, they were invited to the clinic for standardized testing using the Sniffin sticks test for assessment of olfactory function, taste sprays and strips for taste function, and a lateralization test for trigeminal function. RESULTS: The home smell test correlated well with the Sniffin sticks test. The home test had acceptable sensitivity for detecting smell loss (sensitivity of 67% at a specificity of 92%). The home test could distinguish between patients with olfactory loss and healthy controls. In contrast, the home tests for taste and trigeminal function did not provide valid results. When comparing home and clinical smell and taste tests older age and olfactory loss were the most influencing confounders in various models, while participants who had olfactory loss and admitted to drink alcohol regularly were more likely to have consistency between home and clinical smell measurements. CONCLUSIONS: Although the standardized psychophysical tests are valid and reliable and should be recommended, simple methods used at home could reflect the patients' information to some degree and provide useful data prior to clinical testing. The present home chemosensory test allows motivated individuals to screen their olfactory function in a simple way at home. Results from smell tests, but not from tests of taste or trigeminal function, obtained at home correlate with tests obtained at the clinic. Moreover, tests conducted at home or in the clinic have confounders that should be considered by researchers and clinicians.

Omega-3 supplementation in postviral olfactory dysfunction: a pilot study.

BACKGROUND: This study aimed to examine whether omega-3 supplementation would support olfactory recovery among postviral olfactory dysfunction patients. METHODOLOGY: Patients with postviral olfactory dysfunction were included in this non-blinded, prospective pilot study. Structured medical history was taken from the patients, including the following: age, sex, history of COVID-19 infection, and duration of symptoms. Patients were randomly assigned to receive olfactory training only (control group) versus olfactory training with omega-3 supplementation (treatment group). All patients exposed themselves twice a day to four odours (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon], and eugenol [cloves]). Olfactory function was measured before and after training using 'Sniffin' Sticks', comprised of tests for odour threshold, discrimination, and identification. The average interval between olfactory tests was 3 months. RESULTS: Fifty-eight patients were included in the study, 25 men and 33 women. Generally, an improvement in olfactory scores was observed. Compared to the control group, the improvement in odour thresholds was more pronounced in the omega-3 group. Age, sex, and duration of symptoms had no effect on olfactory scores among both control and treatment groups. CONCLUSION: Overall, the present results indicate that omega-3 supplementation may be an option for adjunct therapy with olfactory training in patients with postviral olfactory dysfunction.

Reliability and validity of a brief version of the Questionnaire of Olfactory Disorders (brief QOD) in patients with olfactory dysfunction.

BACKGROUND: The aim of this study was to determine the reliability and validity of the brief version of Questionnaire of Olfactory Disorders (brief QOD). METHODS: A total of 372 patients participated in this study. Olfactory function was examined using the Sniffin' Sticks test. The brief version of QOD, including 4 items concerning parosmia (QOD-P), 7 items concerning quality of life (QOD-QOL), and 3 visual analog scales to rate disease burden, awareness of the disorder and issues related to professional life (QOD-VAS), was used to assess subjective information on olfactory dysfunction. We evaluated the split-half reliability, internal consistency and validity of the brief QOD. RESULTS: The split-half reliability was 0.60 (QOD-P), 0.87 (QOD-QOL), and 0.66 (QOD-VAS), respectively. The Cronbach's coefficient was 0.63 (QOD-P), 0.87 (QOD-QOL), and 0.71 (QOD-VAS), respectively. Olfactory function was found to be associated with QOD-P, QOD-QOL and QOD-VAS. CONCLUSIONS: The brief QOD is a suitable scale for the assessment of subjective severity of olfactory dysfunction for purposes such as treatment counseling, disability assessment, treatment control, and research in patients with olfactory disorder.

Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients.

OBJECTIVES: We have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. We also aimed to determine whether sodium citrate is beneficial in treating qualitative olfactory dysfunction. METHODS: We performed a prospective, controlled study. Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The left nasal cavity was untreated and, therefore, acted as an internal control. Monorhinal olfactory function was assessed using the "Sniffin' Sticks" composite 'TDI' score, before and after treatment. The presence of parosmia and phantosmia was also assessed. RESULTS: Overall, there was a significant increase in TDI after treatment (using the best of right and left sides). Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. The proportion of patients reporting parosmia did not change significantly after treatment. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. CONCLUSIONS: Treatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. It may, however, be beneficial in treating phantosmia, which should be further addressed in future work.

Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

Faster olfactory adaptation in patients with olfactory deficits: an analysis of results from odor threshold testing.

BACKGROUND: Patients with olfactory deficits often report rapid and lasting olfactory adaptation compared to the time when they had normal olfactory function. However, this phenomenon receives little scientific attention. This retrospective study aimed to compare the patterns of olfactory adaptation in normosmic controls and patients with olfactory impairment by analyzing the trajectory of turning points in odor threshold tests based on the staircase technique. METHODS: 4120 subjects (1684 hyposmia, 1742 anosmia and 694 normosmic controls) were included in this study. Their odor threshold, odor discrimination and odor identification ability were assessed using the Sniffin’ Sticks. We analyzed the trajectory of turning points in the odor threshold test. RESULTS: Current results suggested that patients with hyposmia needed significantly more trials to reach the final threshold scores than controls and anosmic group, and controls needed more trials than anosmic group. The difference between the first turning point and final threshold scores in the anosmic group was significantly larger than in the hyposmia group and in controls. CONCLUSION: People with poor olfaction seem to adapt faster to olfactory stimuli. The trajectory of turning points in odor threshold test may serve as an indicator of olfactory adaptation and function of olfactory receptors. Olfactory adaptation may provide a new tool in the assessment of subtle olfactory loss.

Olfactory training changes electrophysiological responses at the level of the olfactory epithelium.

BACKGROUND: Olfactory training (OT) has been shown to increase olfactory performance in healthy subjects and patients with post-traumatic or post-infectious olfactory loss. Morphological correlates such as olfactory bulb volume increase and gray matter changes suggest central changes in olfactory brain areas following olfactory exposure. Some evidence from animal studies indicates peripheral changes upon OT whereas no such data exist in humans. This study explores the question whether changes in olfaction following OT are associated with alterations of the electro-olfactogram (EOG) derived from the olfactory epithelium. METHODOLOGY: We compared electrophysiological EOG responses to a pleasant, rose-like odor (phenylethyl alcohol, PEA) and to an unpleasant odor (rotten eggs, H2S) in patients and controls. EOG were recorded in smell impaired patients before and after OT for a period of 4-6 months. RESULTS: EOG recordings following PEA and H2S stimulation were significantly more often obtained in controls than in patients. OT was associated with a significantly higher number of EOG recordings. CONCLUSIONS: OT is associated with an increase in EOG responses implicating stimulus-induced plasticity to start at the level of the olfactory epithelium.

Mutation in Nav 1.7 causes high olfactory sensitivity.

Mutations in the sodium-channel Nav 1.7, encoded by the gene SCN9A, are known to cause pain disorders. In particular, gain-of-function missense mutations in Nav 1.7 have been shown to be causal in primary erythromelalgia. We present a patient with erythromelalgia, pain attacks and hyperosmia with a mutation within the sodium-channel gene SCN9A. A 50-year-old woman presented with burning pain in both feet and abdominal pain attacks developed over the course of 10 years. Furthermore, this patient experienced a hypersensitivity for odours. Clinical investigation as well as serum/cerebrospinal fluid laboratory findings and electrophysiological testing were unremarkable. Olfactory testing showed high olfactory acuity for all screened modalities and good intranasal sensitivity. Furthermore, quantitative sensory testing within the trigeminal area revealed very low thresholds for thermal, tactile and pain detection. In addition, quantitative sensory testing at the lower legs showed hyperalgesia and, as the disease progresses, thermal sensory function loss. Skin biopsies of the proximal and distal lower limbs revealed reduced epidermal nerve fibre density indicating small fibre neuropathy. Genetic analysis of the SCN9A gene demonstrated a heterozygous mutation in Exon 20 - c.3734A>G (p.N1245S). Treatment with clinically available sodium-channel inhibitors did not result in significant pain relief. Local application of the sodium-channel blocker ambroxol however, reduced pain intensity. Continuous odour exposure stabilised mood and induced a short-term pain relief. This clinical note illustrates the course of middle-age onset erythromelalgia and points to clinical findings related to a likely pathogenic missense mutation affecting the sodium-channel Nav 1.7. SIGNIFICANCE: This case report illustrates the course of middle-age onset erythromelalgia with presumed gain-of-function in olfactory and pain sensation associated with a Nav1.7 channel mutation.

Correlation among olfactory function, motors' symptoms, cognitive impairment, apathy, and fatigue in patients with Parkinson's disease.

Although Parkinson's disease (PD) is usually considered as a movement disorder, it is strongly associated with non-motor symptoms (NMS), including smell and taste dysfunctions, cognitive impairment, apathy, fatigue, and autonomic dysregulation. Olfactory deficit is considered the most common NMS in PD preceding the motor symptoms for years. The aim of this study was to investigate olfactory function, cognitive impairment, apathy, and fatigue in patients with PD in comparison with healthy controls, and subsequently to analyse the correlations between these NMS and motor symptoms severity in subjects with PD. One hundred and forty-seven participants were enrolled (96 PD patients, mean age in years 67.5, SD 7.2; 51 healthy controls; mean age 65.1, SD 11.8). Olfactory function was evaluated using the Sniffin' Sticks test (odor detection threshold, discrimination and identification). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment. Apathy was examined by the self-report version of Starkstein Apathy Scale and fatigue was evaluated with the Parkinson's Disease Fatigue Scale. PD patients showed severe impairment in odor detection threshold, discrimination, and identification compared to healthy controls. Moreover, in PD patients, apathy and fatigue scores were significantly increased, while MoCA scores were decreased in comparison with controls. Multivariate linear regression analyses showed that both apathy and Unified PD Rating Scale (UPDRS) were associated with odor identification, discrimination and Threshold-Discrimination-Identification (TDI) score. In conclusion, our results reported changes in apathy and motor disability as significant predictors in alterations of odor identification, discrimination and TDI score. Furthermore, these data suggest that olfactory dysfunction might progress in tight relation with motor impairment UPDRS but also with non-motor symptoms such as apathy.

Decreased electrogustometric taste sensitivity in patients with acquired olfactory dysfunction.

BACKGROUND: Cross-modal chemosensory dysfunction between olfaction and gustation is not well known. METHODOLOGY: 180 participants were classified into three groups (60 with olfactory dysfunction, 60 with gustatory dysfunction and 60 healthy controls without chemosensory dysfunction). Olfactory functions were obtained with Sniffin Sticks; gustatory function was measured by suprathreshold gustatory stimuli (taste sprays) and a quasi-threshold measure of taste function (taste strips) for five taste qualities (sweet, salty, sour, bitter and umami). Electric taste threshold was measured using electrogustometry (EGM). In addition, group differences in dietary behaviors were investigated with a specifically designed questionnaire. RESULTS: Patients with olfactory dysfunction had increased electric taste thresholds and decreased scores for the umami taste strip test as compared to healthy controls. Overall there was no major difference between patients with chemosensory dysfunction and healthy controls regarding dietary behaviors, although some patients certainly exhibited dietary problems. Importantly, patients with taste loss, but not patients with smell loss, exhibited a higher degree of depression than controls. CONCLUSION: Patients with olfactory dysfunction showed decreased taste sensitivity which suggested an interaction between the chemical senses taste, trigeminal function, and olfaction. This provides the basis for including both smell and taste psychophysical assessment in clinical practices. In addition, patients with taste loss appeared to suffer most from chemosensory dysfunction.

Effects of analgesics on olfactory function and the perception of intranasal trigeminal stimuli.

BACKGROUND: There is some evidence suggesting that analgesics have an impact on human chemosensory function, especially opioids and cannabinoids are known to interfere with olfactory function. However, largely unknown is the effect of a long-term use of analgesics on the intranasal trigeminal system so far. Here, we investigated olfactory function and the perception of intranasal trigeminal stimuli in pain patients with long-term use of analgesics compared to age-matched healthy controls. METHODS: For this purpose, a psychophysical approach was chosen to measure these sensory functions in 100 chronic pain patients and 95 controls. Olfactory testing was performed using the 'Sniffin' Sticks' test kit, which involves tests for odour threshold, odour discrimination and odour identification. Further, participants were asked to rate the intensity of trigeminal stimuli by using a visual analogue scale. RESULTS: We observed that the chronic use of pain medication was associated with significantly reduced perception of intranasal trigeminal stimuli and olfactory function compared to age-matched controls without intake of analgesics. Results indicate that non-opioid and opioid drugs, or a combination of both did not differ in their effects on chemosensory function. Further, after eliminating the effect of a co-existing depression and the use of co-analgesics, the negative influence of analgesics on olfactory function and trigeminal perception was still evident. CONCLUSION: The observed effect might be mediated due to interaction with opioid receptors in trigeminal ganglia and nuclei or due to trigeminal/olfactory interaction. As a practical consequence, patients should be made aware of a possible impairment of their olfactory and trigeminal function under long-term analgesic treatment. WHAT DOES THIS STUDY ADD?: We observed that the chronic use of pain medication was associated with significantly reduced olfactory function and perception of intranasal trigeminal stimuli compared to age-matched controls without intake of analgesics. Non-opioid and opioid drugs did not differ in their effects on chemosensory function.

Intranasal sodium citrate solution improves olfaction in post-viral hyposmia.

BACKGROUND: Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blind trial. METHODOLOGY: Monorhinal olfactory testing for odour identification and threshold was performed in hyposmic patients using Sniffin Sticks, before and after treatment. Treatment consisted of one-off sodium citrate solution application to the olfactory cleft. Sodium chloride solution was applied to the contralateral olfactory cleft, which therefore acted as placebo control. Patients were blinded to the side of sodium citrate application, and side of treatment was randomized between patients. RESULTS: 57 patients participated, aged 22-79. Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal disease (30) and idiopathic (10). Compared with placebo, there was significant improvement in the identification scores of participants with post-viral hyposmia, following sodium citrate treatment. No significant change in olfactory function occurred for either identification or threshold in any other aetiological subgroup. CONCLUSIONS: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Extended version of the "Sniffin' Sticks" identification test: test-retest reliability and validity.

BACKGROUND: The extended, 32-item version of the Sniffin' Sticks identification test was developed in order to create a precise tool enabling repeated, longitudinal testing of individual olfactory subfunctions. NEW METHOD: Odors of the previous test version had to be changed for technical reasons, and the odor identification test needed re-investigation in terms of reliability, validity, and normative values. RESULTS: In our study we investigated olfactory abilities of a group of 100 patients with olfactory dysfunction and 100 controls. We reconfirmed the high test-retest reliability of the extended version of the Sniffin' Sticks identification test and high correlations between the new and the original part of this tool. In addition, we confirmed the validity of the test as it discriminated clearly between controls and patients with olfactory loss. COMPARISON WITH EXISTING METHOD(S): The additional set of 16 odor identification sticks can be either included in the current olfactory test, thus creating a more detailed diagnosis tool, or it can be used separately, enabling to follow olfactory function over time. Additionally, the normative values presented in our paper might provide useful guidelines for interpretation of the extended identification test results. CONCLUSIONS: The revised version of the Sniffin' Sticks 32-item odor identification test is a reliable and valid tool for the assessment of olfactory function.

Lateralized differences in olfactory bulb volume relate to lateralized differences in olfactory function.

The present study aimed to investigate whether side differences in olfactory bulb (OB) volume correlate to respective differences in olfactory function. In a total of 164 healthy volunteers volumetric measures of the OBs were performed plus lateralized measurements of odor thresholds and odor discrimination. Side differences were defined as 10% difference between the left and right OB. In 39 cases volumes on the right side were larger than on the left side, whereas in 29 cases it was the other way around. Subjects with larger right-sided OB volumes were found to be more sensitive to odorous stimulation of the right as compared to the left nostril in terms of odor thresholds and odor detection; higher sensitivity of the left nostrils (decreased odor threshold) was observed in individuals with larger OB volumes on the left side. These data appear to suggest that OB volume may be partly dependent on lateralized influences on the olfactory system, reflecting its lateralized organization.

Responses to olfactory and intranasal trigeminal stimuli: relation to the respiratory cycle.

The aim of the study was to investigate whether the perception of intranasal chemosensory stimuli changes in relation to the respiratory cycle. We investigated 40 healthy subjects with normal olfactory function who participated in four sessions. The first session was used to adapt subjects to the experimental conditions, and, specifically, to train a certain breathing technique (velopharyngeal closure) which prevents intranasal respiratory air-flow. In each of the following three sessions one of three stimulants was tested, namely phenyl ethyl alcohol (PEA), hydrogen sulfide (H(2)S), or the trigeminal stimulant carbon dioxide (CO(2)). The sequence of testing the three stimulants was randomized across all participants. Sessions were separated by at least 1 day. Chemosensory event-related potentials (ERP) were recorded in response to 80 stimuli each. Following each stimulus subjects rated its intensity using a computerized visual analogue scale. Respiration was recorded using a probe in front of the subjects' mouth. While presentation of chemosensory stimuli was performed independent of the respiratory cycle, responses were averaged off-line according to the subjects' respiratory phase when the stimuli had been presented. Intensity of olfactory or trigeminal stimuli did not differ significantly in relation to the respiratory cycle. Olfactory ERP to phenylethyl alcohol were larger when stimuli were presented during inspiration. Similarly, responses to H(2)S tended to be larger when stimuli were presented during inspiratory phases. In addition, responses to CO(2) were larger when stimuli were presented during inspiration. Differences in relation to the respiratory cycle were found specifically for early ERP components. It is important to note that the changes of chemosensory information processing were found in the absence of changes of intranasal airflow. These data indicate on an electrophysiological level that there is priming of both olfactory and trigeminally mediated sensations in relation to the respiratory cycle.