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Objectives: Olfactory habituation is a transient decrease in olfactory sensitivity caused by prolonged odor exposure, aiding in the discernment of new olfactory stimuli against the background. We explored the impact of subclinical olfactory impairment on odor habituation using age as a proxy., Methods: Before the actual experiment, the individual olfactory threshold for the rose-like odorant phenylethyl alcohol (PEA) was assessed separately for the left and right nostril using the "Sniffin' Sticks" test, and ratings for odor intensity and pleasantness were collected. After applying a nasal clip continuously delivering PEA odor to one nostril for 10 min and 2 h, respectively, threshold, intensity, and pleasantness were reassessed immediately after clip removal., Results: In the group of 80 participants (younger adults-mean age 27.7 ± 4.5 years; older adults-mean age 61.5 ± 4.7 years), olfactory thresholds were already significantly elevated after just 10 min, and this habituation was even more pronounced after 2 h. This effect could be observed bilaterally even though significantly more distinct on the exposed side. Older participants generally exhibited a more pronounced habituation on the exposed side after 2 h compared to the younger participants., Conclusion: The results indicate that older people experience more notable habituation after extended exposure to odors. This is most likely due to the compromised olfactory function in age. Although older and younger subjects scored in the normosmic range when tested with standardized olfactory tests, the stress on the system after exposure to an odor clearly revealed the lower functionality of the aging sense of smell., Level of Evidence: 3 Laryngoscope, 134:3765-3768, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: This study aimed to determine the characteristics of patients with qualitative olfactory dysfunction (qualOD) and whether individuals with parosmia exhibit increased olfactory sensitivity to previously reported odorous triggers of parosmia., Methods: This study included individuals aged ≥18 years, divided into quantitative OD only, parosmia, and phantosmia groups. Data collected included: clinical-demographic data, "Sniffin' Sticks" scores, questionnaires (depression scale, importance of olfaction), and information about parosmia and phantosmia. A proportion of patients underwent trigger odor threshold testing for 2-Furfurylthiol [FFT] found in coffee and 2,6-nonadienal [Nonadienal] found in cucumber., Results: Those with parosmia were typically younger women, with shorter OD duration due to post-viral OD (PVOD), hyposmic/normosmic, and experienced parosmia more severely. Parosmia was 3.5 times more likely in PVOD. Those with phantosmia were older, with longer OD duration due to idiopathic OD, hyposmic/anosmic, and experienced phantosmia less severely. There were no significant differences between FFT and Nonadienal threshold scores in patients with parosmia, phantosmia, or only quantitative OD, but all groups had significantly increased olfactory sensitivity for trigger odors compared to phenyl ethyl alcohol (PEA)., Conclusion: Parosmia and phantosmia patients have distinct characteristics. This may provide clinicians with a better understanding of possible olfactory outcomes in these patients. The higher olfactory sensitivity of all groups to trigger odors compared to PEA raises interesting points about parosmia triggers and odors in the context of warning for danger, in relation to the pathophysiology of parosmia that may be worth exploring in future studies., Level of Evidence: 3 Laryngoscope, 134:3277-3285, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The aim of this study was to generate normative data of retronasal olfactory threshold values for normosmic and hyposmic individuals and to test the validity of that data by determining the discriminative power for normosmic/hyposmic differentiation., Study Design: Prospective, descriptive and methodological study., Methods: The orthonasal olfactory function of 20 normosmic and 20 hyposmic cases was evaluated using the Sniffin' Sticks Olfactory test. Sniffin' Sticks odor threshold, odor discrimination, and odor identification values and threshold discrimination identification (TDI) scores were recorded. A 13-item test battery previously prepared in our Rhinology Laboratory for retronasal olfactory threshold test that consisted of concentrated solutions prepared from 2:1 diluted 99% phenylethyl alcohol (PEA) and water was used. Each concentration was evaluated with water control, and if not answered correctly, the same process was continued by moving to a higher concentration series. Four consecutive correct answers were determined as the patient's retronasal olfactory threshold., Results: A strong correlation was found between Sniffin' Sticks TDI scores and retronasal odor threshold values in the normosmic group (P < .001, r:0.67). A very strong correlation was found between Sniffin' Sticks TDI scores and retronasal olfactory threshold values in the hyposmic group (P < .001, r:0.81). Furthermore, receiver operating characteristic (ROC) analysis revealed that the sensitivity and the specificity of normosmic/hyposmic differentiation of retronasal olfactory threshold test was 95% and 100%, respectively. The diagnostic cutoff value was 8.5., Conclusions: This study shows that the retronasal olfactory test, a psychophysical odor test performed using an orally presented stimulus, can be used to differentiate normosmic and hyposmic cases., Level of Evidence: 3 Laryngoscope, 131:1608-1614, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective/hypothesis: With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease., Study Design: Prospective cohort study., Methods: A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities., Results: There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction., Conclusions: Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function., Level of Evidence: 3 Laryngoscope, 131:1095-1100, 2021., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective/hypothesis: This study aims to determine the association between parosmia and clinically relevant recovery of olfactory function in patients with post-infectious olfactory dysfunction (PIOD) receiving olfactory training., Study Design: Retrospective cohort study., Methods: This was a retrospective cohort study of patients with PIOD that received olfactory training. Adult patients with the major complaint of quantitative smell loss were recruited and treated at several ENT clinics in German between 2008 and 2018. The outcome was based on the association between smell-loss related factors (including parosmia and phantosmia) and clinically relevant changes in overall and subdimension olfactory function of threshold, discrimination, and identification using binary logistic regression analysis., Results: A total of 153 participants with PIOD were included. Clinically relevant improvements in overall olfactory function were more likely in those that had lower baseline olfactory function. Relevant improvements in discrimination function were more likely in those that had lower baseline olfactory function and those that had parosmia at the initial visit. Similarly, relevant improvements in odor identification were more likely in those that had a lower baseline olfactory function and in those who had parosmia at the first visit. Clinically significant improvements in odor threshold were more likely in those who were older in age., Conclusions: This study demonstrated that the presence of parosmia is associated with clinically relevant recovery in olfactory discrimination and identification function in patients with PIOD receiving olfactory training., Level of Evidence: 4 Laryngoscope, 131:618-623, 2021., (© 2020 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives/hypothesis: The aim of the study was to develop a test for the assessment of retronasal olfaction in healthy participants and patients with olfactory disorders using "tasteless" powders., Study Design: Prospective case-control series., Methods: A total of 150 participants (110 women, 40 men, mean age = 40 ± 16 years) were recruited for this study; 100 were healthy controls and 50 were patients with olfactory loss due to infections of the upper respiratory tract (n = 25), idiopathic causes (n = 12), sinonasal disease (n = 7), and head trauma (n = 6). Orthonasal olfactory function was evaluated using the Sniffin' Sticks test battery, and retronasal olfaction was evaluated using powders lacking distinctive tastes administered to the oral cavity. To establish test-retest reliability, healthy participants had their orthonasal and retronasal function tested twice., Results: The validity analyses revealed that the selected 16 stimuli differentiated between normosmic participants and patients with olfactory loss, and that retronasal and orthonasal olfaction were highly correlated., Conclusions: The results of the present study indicate that patients with olfactory loss and controls can be clearly separated using a reliable test of retronasal olfaction based on 16 retronasal stimuli., Level of Evidence: 2b Laryngoscope, 131:E324-E330, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Quality of life related to olfactory disorder (OD) depends on the perceived impairment. It is not known why some patients with OD report smell and flavor loss while others report smell loss only. In order to understand this, we compared the two clinical presentation forms in terms of demographics, clinical features, and orthonasal olfaction test results., Study Design: Observational, analytic, cross-sectional study., Methods: A total of 401 patients with measured orthonasal OD presenting at a tertiary referral center were divided in 2 groups according to their subjective reports (smell loss only = 129 patients vs. smell and flavor loss = 272 patients). Groups were compared in terms of demographic (age, sex), clinical features (duration of disease, type of onset, etiology, degree of impairment due to the disorder) and test results (taste and orthonasal olfaction)., Results: Groups did not differ in terms of age, sex distribution, orthonasal olfactory, or taste function. Patients reporting smell and flavor loss were characterized by a mainly sudden onset of the disorder and a predominance of postinfectious olfactory loss. They also have a shorter disease duration and a higher disease impairment. For patients reporting smell loss only, disease duration is longer, they feel less impaired, the onset of the disorder is to a higher degree protracted and the main cause is idiopathic., Conclusions: Patients with orthonasal OD reporting smell and flavor loss feel more impaired and present significant different clinical features compared to patients reporting smell loss only. Future studies measuring retronasal olfaction are necessary to fully understand flavor perception in OD., Level of Evidence: 4 Laryngoscope, 130:2869-2873, 2020., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives: Many patients complain about olfactory fluctuation (OF), which is a symptom commonly attributed to sinonasal disease. Data-based evidence for its association with sinonasal disease is scarce. The aim of the study is to identify explanatory variables associated with OF and to analyze its predictive value regarding sinonasal disease., Study Design: We performed a retrospective study based on patients with olfactory dysfunction., Methods: We analyzed data from 482 patients attending the smell and taste outpatient clinic with full psychophysical workup and structured questions regarding their symptoms. The questionnaire included items on OF and chronic nasal symptoms. Clinical investigators filled out the second part of this questionnaire that included information about nasal endoscopy, psychophysical tests of orthonasal olfaction (Sniffin' Sticks), retronasal olfaction, and putative etiology of olfactory dysfunction., Results: OF was more prevalent in sinonasal disease (42.4%) compared to other putative etiologies of olfactory dysfunction such as postinfectious (28%) or posttraumatic (11.7%) (X2 [5, n = 440] = 24.98; P < .0001). OF was strongly associated with Sniffin' Sticks score categories (anosmia, hyposmia, normosmia) (X2 [2, n = 424] = 39.21; P < .0001; Cramer's V = 0.30; P < .0001) and presence of "chronic nasal symptoms" (X2 [1, n = 437] = 22.71; P < .0001; Cramer's V = 0.23; P < .0001). The accuracy in predicting putative sinonasal disease etiology when OF was present depended strongly on the clinical context., Conclusion: Olfactory fluctuation is a symptom mostly but not exclusively associated with sinonasal disease, elevated Sniffin' Sticks test scores, and is frequently accompanied by other nasal complaints. Its presence is valuable information for clinicians to be integrated into the clinical context when doing patients' workup., Level of Evidence: 4 Laryngoscope, 130:2442-2447, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Self-ratings seem to be the most effortless strategy for assessment of patients' chemical senses. Notably, although flavor perception strongly relies on olfaction, the relationship between self-reported flavor perception and orthonasal olfactory tests have hitherto not been considered. The aim of this study was to investigate the relationship between self-perceived olfactory function (SO), taste (ST), and flavor perception (SF) and smell test results in patients with olfactory dysfunction (OD)., Methods: We included 203 patients with quantitative OD. Group comparison, bivariate correlation, and ordinal logistic regression were employed to quantify the relationships between predictor variables (age, gender, reason for OD, and orthonasal olfaction-summed scores of threshold, discrimination, and identification [TDI]) and outcomes of SO and SF ("impaired," "average," or "good")., Results: Group comparison revealed significant differences between SO and SF (P < .001). Stronger correlations were found between SO and TDI (r = 0.64), compared to SF and TDI (r = 0.27). No relevant correlation was found between ST and TDI (r = 0.10). Higher TDI was associated with odds of higher SO in univariate (odds ratio = 1.25) and multivariable analyses (adjusted odds ratio = 1.23), and both models showed good fit of data. Conversely, regression models on the associations between TDI and changes in SF did not meet the assumption of goodness of fit., Conclusion: We found that higher orthonasal olfactory performance was associated with odds of higher SO in patients with OD, even after controlling for olfactory-relevant factors. To the contrary, similar models based on flavor perception failed to describe these relationships. This indicates for SF and ST to be less represented by the TDI compared to SO., Level of Evidence: 4 Laryngoscope, 130:2213-2219, 2020., (© 2020 The Authors. The Laryngoscope published by Wiley Periodicals, Inc. on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The human sense of smell constitutes the main part of flavor perception. Typically, patients with loss of olfactory function complain of diminished perception during eating and drinking. However, some patients with smell loss still report normal enjoyment of foods. The aim of the present study was to compare orthonasal and retronasal olfactory function in patients with non-sinonasal smell loss and subjectively normal flavor perception., Methods: Nineteen patients (mean age [range] 52.0 [8-83 years]) with self-reported olfactory impairment but subjective normal flavor perception were included. Olfactory performance was assessed using the Sniffin' Sticks (TDI) for orthonasal and the Candy Smell Test (CST) for retronasal function. Visual analogue scales were used for self-assessment of odor (SOP), taste (STP), and flavor perception (SFP), ranging from 0 (no perception) to 10 (excellent perception)., Results: Mean (SD) SFP was 8.0 (1.8). Mean (SD) orthonasal TDI-score of all patients was 14.4 (5.3, range 6-25.3) with 11 patients classified as anosmic and eight as hyposmic. Mean/SD retronasal CST-score was 8.8 (2.7, range 3-13) within the range of anosmia/hyposmia. No correlation was found between SFP and the CST (P = .62)., Conclusion: The present results showed that despite claiming normal flavor perception, our patients were ortho- and retronasally dysosmic using standard tests for olfactory function. Although other explanations could be possible, we suggest that this subjective flavor perception might be due to unconscious memory recall from previously experienced cross-modal sensory interactions., Level of Evidence: 4 Laryngoscope, 130:1629-1633, 2020., (© 2019 The Authors. The Laryngoscope published by Wiley Periodicals, Inc. on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging technique widely used in olfactory research. During a typical fMRI olfactory block-design, one functional "run" refers to a combination of multiple blocks with continuous brain image acquisition. The current study investigated the length of functional runs on odor-induced brain response signals (blood oxygen level dependent [BLOD]) within the primary and key secondary olfactory areas., Methods: Twenty-five female adults (age range 19 to 30 years, mean age 25 years) underwent a block-design fMRI measurement with odor stimulation. Twelve participants received the odor stimuli within a short run paradigm (six blocks in each 4-minute run, eight runs in total), and 13 participants received the odor stimulation with a long-run paradigm (12 blocks in each 8-minute run, four runs in total). For each paradigm, two odors (peach and rose) were alternatingly presented between runs. Participants rated odor intensity and pleasantness at the end of each run. Ratings and fMRI data were analyzed for different subsections and compared between groups., Results: There was a higher level of brain activation in the insula and orbitofrontal cortex during the short-run paradigm as compared to the long-run paradigm. However, there was no difference for odor intensity or pleasantness ratings., Conclusion: The current study suggested the employment of short runs with multiple repetitions for odor stimulation during fMRI research., Level of Evidence: 3 Laryngoscope, 130:1110-1115, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The goals of this study were to assess retronasal olfaction in patients with chronic rhinosinusitis (CRS) and describe clinical factors that influence retronasal olfaction. This study sought to investigate the influence of retronasal olfaction on patient-perceived outcomes and examine the relationship between retronasal and orthonasal olfaction., Methods: Retronasal olfactory function was tested using odorized powders in the oral cavity, whereas Sniffin' Sticks test (Burghart Instruments, Wedel, Germany) were used to assess orthonasal function prospectively in 69 adult CRS patients. Endoscopic evaluation of the olfactory cleft was scored using the Olfactory Cleft Endoscopy Scale (OCES). Several quality-of-life (QOL) instruments relating to sinonasal, olfactory, and chemosensory functions were used to assess the interactions between patient-reported outcome measures and retronasal olfaction., Results: There was strong correlation between retronasal and total orthonasal olfaction scores (r = 0.77, P < 0.001) as well as retronasal scores with orthonasal subscores. Retronasal scores were worse in patients with nasal polyposis (P = 0.002), asthma (P = 0.04), and aspirin-exacerbated respiratory disease (AERD) (P = 0.02), whereas OCES was the only independent predictor of retronasal olfaction (r = -0.42, P < 0.001). Significant correlation existed between retronasal olfaction and olfactory-specific QOL and chemosensory smell scores., Conclusion: Few studies have examined retronasal olfaction in CRS patients. In this cohort, CRS patients demonstrated deficits in retronasal olfaction, with worse scores in patients with nasal polyposis, asthma, and AERD. Retronasal olfaction scores correlate with degree of inflammation of the olfactory cleft. Retronasal olfaction correlated strongly with orthonasal olfaction and patient-reported smell and taste metrics, although orthonasal olfaction may have a stronger correlation with these metrics., Level of Evidence: NA. Laryngoscope, 2437-2442, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Olfactory dysfunction is common among the general population, with chronic rhinosinusitis (CRS) as one of the leading causes. Patients affected by CRS often report changes in taste sensations; however, quantitative measurements have not been performed to date. Therefore, the present study aimed to investigate gustatory and olfactory function in CRS patients prior to and after multimodal treatment., Study Design: Prospective cohort study., Methods: Twenty-one patients suffering from CRS with nasal polyps (14 male, seven female) with a mean age of 48 ± 15 years were included in the study. Chemosensory function was assessed prior to and approximately 190 days after multimodal treatment, which included endoscopic sinus surgery, oral antibiotics for 5 days, oral steroids for 12 days, and at least 6 weeks of topical nasal steroids. Olfactory function was tested with the Sniffin' Sticks test battery, whereas gustatory function was measured with taste strips. A clinically relevant change in olfactory function was defined as a change of ≥5 points in the threshold, discrimination, and identification scores., Results: Compared to normative data, patients baseline gustatory and olfactory function was impaired. After multimodal treatment, improvements were seen in olfactory function for eight patients (42%), remained stable in 10 patients (53%), and deteriorated in one patient (5%). Taste function remained unchanged following sinus surgery., Conclusions: Patients suffering from CRS with polyps exhibit olfactory and taste dysfunctions. Multimodal treatment leads to an improvement in olfactory, but not gustatory functionality., Level of Evidence: 4. Laryngoscope, 128:E86-E90, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Others have reported olfactory disturbances following endoscopic approaches to the skull base. However, there is a lack of consensus on the extent and duration of dysfunction. This study aimed to compare our results with previously published work and to validate the olfactory strip-sparing approach., Study Design: Prospective study to assess olfaction in 50 patients scheduled to undergo resection of skull base tumors via extended endoscopic approaches., Methods: Patients were divided into two groups. Group I had a nasoseptal flap (NSF), and group II included patients in whom rescue flaps were performed bilaterally. Olfactory outcomes were assessed using repeated University of Pennsylvania Smell Identification Test at baseline, 6 weeks, 3 months, and 6 months following surgery., Results: Ultimately, 42 patients (seven group I and 35 group II) were available for assessment. Scores for group I were lower than at baseline at 6 weeks postoperatively (30.71 ± 5.5 vs. 24.5 ± 5.4; P = .05). However, by the third postoperative month the scores had improved to a level that was not significantly different from baseline (29.0 ± 3.7; P = .5). At 6 months, the score was 30.0 ± 3.9. Patients in group II showed no difference between their baseline and 6-week scores (31.5 ± 5.3 vs. 29.7 ± 5.9; P = .16). Six months postoperatively, the score was significantly higher (33.78 ± 3.6; P = .04)., Conclusions: Expanded endoscopic approaches to skull base tumors involving reconstruction with an NSF are associated with a short-term negative impact on olfaction. Olfaction does not seem to be affected by the surgical resection of pituitary adenomas associated with rescue flaps. Identification of the olfactory epithelium and meticulous harvesting of the NSF are critical to preserve olfaction., Level of Evidence: 4. Laryngoscope, 127:1970-1975, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To measure odor detection thresholds and associated nasal and behavioral factors in an older adult population., Study Design: Cross-sectional cohort study., Methods: Odor detection thresholds were obtained using an automated olfactometer on 832 participants, aged 68 to 99 (mean age = 77) years in the 21-year (2013-2016) follow-up visit of the Epidemiology of Hearing Loss Study., Results: The mean odor detection threshold (ODT) score was 8.2 (range = 1-13; standard deviation = 2.54), corresponding to an n-butanol concentration of slightly less than 0.03%. Older participants were significantly more likely to have lower (worse) ODT scores than younger participants (P < .001). There were no significant differences in mean ODT scores between men and women. Older age was significantly associated with worse performance in multivariable regression models, and exercising at least once per week was associated with reduced odds of having a low (≤5) ODT score. Cognitive impairment was also associated with poor performance, whereas a history of allergies or a deviated septum was associated with better performance., Conclusions: Odor detection threshold scores were worse in older age groups but similar between men and women in this large population of older adults. Regular exercise was associated with better odor detection thresholds, adding to the evidence that decline in olfactory function with age may be partly preventable., Level of Evidence: 3b. Laryngoscope, 127:1257-1262, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Trigeminal nerve mediates the perception of nasal airflow. This study examines whether impaired intranasal trigeminal function is a part of the paradoxical nasal obstruction sensation in patients with empty nose syndrome (ENS)., Study Design: Prospective case-control study in a tertiary hospital., Methods: Three groups were examined: 1) ENS patients with previous bilateral near total inferior turbinectomy, 2) patients who underwent near total inferior turbinate removal (ITR) without ENS symptoms, and 3) control participants. All participants examined with active anterior rhinomanometry, olfactory testing (extended Sniffin' Sticks test), and trigeminal testing (lateralization task using menthol and odorless solvent)., Results: Seventy-one participants were included (21 ENS patients, 18 ITR patients, and 31 controls). Analyses revealed that ENS patients had significantly lower scores on trigeminal lateralization testing than the ITR group and controls. The ENS group had also significantly lower scores in olfactory testing than controls. No statistical differences were found in rhinomanometry between groups. The gender factor was not associated with the chemosensory testing; however, this was not the case with the age factor, as trigeminal test results were negatively correlated., Conclusions: This study demonstrates significantly impaired intranasal trigeminal function in ENS patients when compared with ITR patients and controls. Further prospective studies are needed to clarify the role of preoperative trigeminal function of these patients and the contribution of surgery to this impairment., Level of Evidence: 3b. Laryngoscope, 127:1263-1267, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Reports about fluctuating olfactory deficits are rare, as are reports of unilateral olfactory loss. We present a case of unilateral anosmia with contralateral normosmia, presenting as rapidly fluctuating anosmia. The olfactory fluctuation occurred in sync with the average nasal cycle duration. Examination after nasal decongestion, formal smell testing, and imaging revealed unilateral, left-sided anosmia of sinonasal cause, with right-sided normosmia. We hypothesize that the nasal cycle induced transient anosmia when blocking the normosmic side. Fluctuating olfactory deficits might hide a unilateral olfactory loss and require additional unilateral testing and thorough workup., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Patients with olfactory dysfunction benefit from repeated exposure to odors, so-called olfactory training (OT). This does not mean occasional smelling but the structured sniffing of a defined set of odors, twice daily, for a period of 4 months or longer. In this prospective study, we investigated whether the effect of OT might increase through the use of more odors and extension of the training period., Study Design and Methods: This study shows OT results when performed with four or 12 odors for 36 weeks in patients with postinfectious olfactory dysfunction. A total of 85 subjects participated (mean age 45.6 ± 10.5 years, range 24-68 years). Three groups were formed: 1) In the modified olfactory training (MOT) group, patients used three sets of four different odors sequentially. 2) Participants in the classical odor training (COT) group used four odors. 3) Participants in the control group did not perform OT. All groups were matched for age and sex distribution of participants., Results: Both participants in the COT and MOT groups reached better scores than controls in terms of odor discrimination and odor identification. Continuing OT with four different odors after the 12th and 24th weeks produced better results in terms of odor discrimination and odor identification scores as compared to using the same four odors throughout the entire study., Conclusion: This study confirmed the effectiveness of OT. Increasing the duration of OT and changing the odors enhances the success rate of this therapy., Level of Evidence: 2b. Laryngoscope, 125:1763-1766, 2015., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The aim of this study is to identify predictors for olfactory outcomes in patients with nasal polyposis (NP) after surgery on the ethmoidal labyrinths, either with or without resection of the polyps of the olfactory cleft (OC)., Study Design: Prospective study., Methods: Ninety-six patients endoscopically operated on for NP were enrolled in this study. Olfactory measurements were performed 1 day prior to surgery and 6 weeks after surgery, using odor thresholds and identification tests of the Sniffin' Sticks kit and a 0- to 10-point visual analog scale. The multivariate logistic regression model was also used to assess independent predictors for olfactory outcomes after surgery., Results: Twenty-seven patients with preoperative normosmia demonstrated normal olfactory function 6 weeks after surgery. Out of 69 patients with preoperative hypo-anosmia, 33 patients (47.83%) improved their olfactory function after surgery on the basis of the Sniffin' Sticks results. History of previous sinus surgery was reported by 77.78% of patients without olfactory improvement and by 51.52% with olfactory improvement (P = .022). By multivariate analysis, history of previous sinus surgery for NP remained a strong predictor of poor olfactory outcomes after surgery (adjusted odds ratio = 4.14, 95% confidence interval: 1.29-13.32, P = .017). Histopathological types of lesions inside the OC as well as the resection of moderate/big lesions in the OC were not predictors of olfactory outcomes., Conclusions: The more previous sinus surgeries, the smaller the chance for patients to recover their olfactory function after each surgical revision., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To evaluate the effectiveness of crenotherapy on the olfactory performance of elderly patients with chronic rhinosinusitis (CRS)., Study Design: A longitudinal case-control study of a cohort of elderly patients affected by CRS and olfactory dysfunction assessed with the Sniffin' Sticks (Burghart Medical Technology, Wedel, Germany) (SS) olfactory test., Methods: One hundred and thirty-seven elderly subjects with CRS were divided into two groups. The investigational arm (n = 69) underwent crenotherapy with hyperthermal water, rich in mineral salts, and the control group (n = 68) underwent NaCl 0.9% both for 12 days. At baseline and at 1 and 6 months after treatment, both groups underwent ear nose and throat assessment and SS. Self-report questionnaires were administered at baseline to evaluate the patients' own olfactory response, and after treatment to evaluate their degree tolerability. Olfactory performance was then evaluated in elderly subjects with hyposmia without CRS (n = 40) and in younger subjects with both hyposmia and CRS (n = 40)., Results: No adverse reactions were reported after crenotherapy. The SS total score showed that crenotherapy induced a statistically significant improvement in the olfactory function of both the elderly and the younger subjects with hyposmia and CRS. By contrast, no improvement was observed in the control arm and in the elderly with hyposmia without CRS. All subjects showed a good degree of tolerability., Conclusions: We demonstrated that crenotherapy effectively improves olfactory function in elderly patients with CRS. Finally, our study suggests that crenotherapy represents a safe therapeutic strategy for the treatment of CRS and olfactory dysfunction in the elderly., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Olfactory dysfunction is deemed to be a significant contributor to poor quality of life in chronic rhinosinusitis (CRS)., Objective: To assess and to compare the effectiveness of three modalities of corticosteroids administration in patients with CRS., Study Design: A prospective randomized controlled study, Methods: Thirty patients with CRS were randomized in three groups depending on the route of corticosteroids administration: 16 days by oral route (Medrol (Pfizer, Belgique), 32 mg/8 days -16 mg/4 days-8 mg/4 days); nasal spray (Rhinocort (AstraZeneca, Belgique), 2 × 2 × 64 µg/nostril); or sonic nebulization (Pulmicort (AstraZeneca, Belgique), 2 × 1 mg/4 mL) (Sonic nebulizer, AOHBOX-NL11SN, DTF, France). Olfactory function was assessed using orthonasal threshold discrimination identification and retronasal psychophysical olfactory tests (RNT) before and after the treatment. Same intranasal modalities were previously tested for in vitro airways scintigraphic deposition., Results: In vitro differences in drug deposition pattern between both intranasal modalities were demonstrated. Threshold discrimination identification and RNT were similar between three groups at baseline. Threshold discrimination identification improved by 5.5, 5.8, and -1.1 for sonic nebulization, oral, and nasal spray groups, respectively (P = 0.010). This improvement was clinically relevant for oral and nebulized administration. It was similar between oral and nebulized administration but significantly higher than nasal spray administration. Retronasal psychophysical olfactory tests improved similarly for the three groups (P = 0.231) CONCLUSION: Effectiveness of sonic nebulized and oral administration is demonstrated on orthonasal olfactory. The clinical benefit is better than with nasal spray., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The increased number of endoscopic endonasal transsphenoidal approaches (EETSA) has been associated with sinonasal complications such as olfactory dysfunction. Current studies have compared preoperative and postoperative olfactory function according to surgical type and age., Study Design: Retrospective review of medical records at a tertiary referral center., Methods: Patients were divided into two groups according to surgical type and into four groups according to age. The two surgical groups were defined based on the bilateral nasoseptal flap technique (group A: right conventional nasoseptal flap and left modified nasoseptal rescure flap; group B: bilateral modified nasoseptal rescue flap). The four age groups were ≤ 30, 31-45, 46-60, and ≥ 61 years. Patients underwent preoperative olfactory function evaluation using a visual analogue scale (VAS), the Connecticut Chemosensory Clinical Research Center Test (CCCRC), and the Cross-Cultural Smell Identification Test (CCSIT). Repeat testing was performed 6-months postoperatively., Results: A total of 226 patients who underwent binostril four-hand EETSA were included in this study. In both groups A and B, the olfactory function was significantly decreased according to CCCRC and CCSIT scores (P < 0.05). The VAS scores were significantly decreased in both groups (P < 0.05). The symptom scores and olfactory test results were significantly changed in >30-year-old patients who had undergone EETSA., Conclusion: EETSA might contribute to olfactory dysfunction independent of surgery type. In addition, age may affect the restoration of olfaction after EETSA. Patients who plan to undergo EETSA must be informed that their olfaction may be impaired., Level of Evidence: 4., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Olfactory deficits that develop after viral upper respiratory infection (URI) may have different effects on patient depression index compared to chronic sinusitis with olfactory loss. However, there have been no controlled trials to evaluate the different effects of chronic sinusitis and URI on depression index., Study Design: Prospective study of 25 subjects in two groups., Methods: This study enrolled 25 participants who were diagnosed with post-URI olfactory loss as the study group and 25 patients with chronic sinusitis and olfactory loss as a control group. Control group participants were matched for age, sex, and degree of olfactory loss (threshold, discrimination, and identification [TDI]). We compared the Beck Depression Inventory (BDI) scores of each group and analyzed the correlation between TDI and BDI., Results: The mean BDI score of the post-URI group was significantly higher than that of the control group (14.52 ± 6.59 vs. 9.32 ± 5.23; P=.002). Age, sex, and TDI score did not affect BDI score in the post-URI olfactory loss group. However, BDI score in the sinusitis group was inversely correlated with TDI score (R=-0.423; P=.035), and the BDI score of female subjects (11.00 ± 5.13) was significantly higher than that of male subjects (5.00 ± 2.16; P = .047)., Conclusions: Post-URI olfactory loss affected patient mood more severely than chronic sinusitis with a similar degree of olfactory loss. This influence was not affected by sex, age, or TDI score in the post-URI olfactory loss group., Level of Evidence: 3b., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Associations between olfactory function to quality-of-life (QOL) and disease severity in patients with rhinosinusitis is poorly understood. We sought to evaluate and compare olfactory function between subgroups of patients with rhinosinusitis using the Brief Smell Identification Test (B-SIT)., Study Design: Cross-sectional evaluation of a multicenter cohort., Methods: Patients with recurrent acute sinusitis and chronic rhinosinusitis with and without nasal polyposis were prospectively enrolled from three academic tertiary care sites. Each subject completed the B-SIT, in addition to measures of disease-specific QOL. Patient demographics, comorbidities, and clinical measures of disease severity were compared between patients with normal (BSIT≥9) and abnormal (BSIT<9) olfaction scores. Regression modeling was used to identify potential risk factors associated with olfactory impairment., Results: Patients with rhinosinusitis (n=445) were found to suffer olfactory dysfunction as measured by the B-SIT (28.3%). Subgroups of rhinosinusitis differed in the degree of olfactory dysfunction reported. Worse disease severity, measured by computed tomography and nasal endoscopy, correlated to worse olfaction. Olfactory scores did not consistently correlate with the Rhinosinusitis Disability Index or Sinonasal Outcome Test scores. Regression models demonstrated nasal polyposis was the strongest predictor of olfactory dysfunction. Recalcitrant disease and aspirin intolerance were strongly predictive of worse olfactory function., Conclusions: Olfactory dysfunction is a complex, multifactorial process found to be differentially expressed within subgroups of rhinosinusitis. Olfaction was associated with disease severity as measured by imaging and endoscopy, with only weak associations to disease-specific QOL measures., Level of Evidence: 2b., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The aim of this study was to evaluate the effects of olfactory training (OT) on olfactory function in patients with persistent postinfectious olfactory dysfunction (PIOD)., Study Design: Randomized, single-blind, controlled, multicenter crossover study., Methods: Twelve tertiary university medical centers participated. Investigations were performed at three visits (baseline, after 18 weeks, and after 36 weeks), including only subjects with PIOD of <24-months duration. At each visit, participants received detailed assessment of olfactory function. Seventy subjects trained with high concentrations of four odors for 18 weeks; the other half (n = 74) trained with low concentrations of odors. For the following 18 weeks this regimen was switched., Results: After 18 weeks, olfactory function improved in the high-training group in 18 of 70 participants (26%), whereas only 11/74 improved in the low-training group (15%). In subjects with a duration of olfactory dysfunction of <12 months, olfactory function improved in 15/24 participants (63%) of the high-training group and in 6/31 participants (19%) of the low-training group (P = .03)., Conclusions: OT improves PIOD, and the use of odors at higher concentrations is beneficial to improvement. OT is a safe procedure and appears to be particularly useful in patients who start OT within 12 months after the onset of the disorder. OT is the first successful therapy regime in patients with PIOD., Level of Evidence: 1b., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: There is evidence that the olfactory system can be modulated by repeated exposure to odors, a procedure called olfactory training. The aim of this study was to assess the effectiveness of olfactory training in patients with postinfectious and post-traumatic olfactory dysfunction., Study Design: Prospective study of 119 patients with postinfectious and post-traumatic olfactory dysfunction., Methods: Two groups of patients (postinfectious and post-traumatic) performed the olfactory training (n = 49 and n = 23, respectively) over a period of 16 weeks and were compared with two control groups of the same etiology (n = 32 and n = 15). Patients with sinunasal, neurologic, or idiopathic disease were excluded. Training was performed twice daily with the use of four odors (phenyl ethyl alcohol [rose], eucalyptol [eucalyptus], citronellal [lemon], and eugenol [cloves]). Olfactory testing was performed by means of the Sniffin' Sticks test battery (threshold, discrimination, identification) at the time of diagnosis, and 8 and 16 weeks later. All patients evaluated their olfactory function by means of a visual analogue scale (0-100)., Results: Compared to controls, training patients in both groups presented significantly higher scores of olfactory function as measured by the Sniffin' Sticks test. This increase was measured in 67.8% of postinfectious and 33.2% of post-traumatic patients. Subjective ratings were in accordance with the olfactory test results. Subset analysis showed that olfactory function mainly increased olfactory identification followed by discrimination in both training groups., Conclusions: The present study suggests that a 16-week short-term exposure to specific odors may increase olfactory sensitivity in patients with postinfectious and post-traumatic olfactory dysfunction., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To explore quality of life (QoL) improvement after treatment of patients with chronic olfactory disorders; and to correlate QoL with olfactory rehabilitation and evaluate olfactory improvement values over which QoL outcomes are significantly recovered., Study Design: Prospective clinical study., Methods: Eighty-nine patients following endoscopic sinus surgery for chronic rhinosinusitis (CRS) and immunotherapy for allergic rhinitis (AR) were studied. Olfactory function was evaluated using Sniffin' Sticks test pre-and 12 months after treatment. All patients completed six validated QoL questionnaires either specific for olfaction (Questionnaire of Olfactory Deficits-QOD) and for assessing mental health (Zung Anxiety Scale, State-Trait Anxiety Inventory, Zung Depression Scale, Beck Depression Inventory), or generic one (Short Form-36)., Results: Significant improvement (all P < 0.001) of olfactory function by 27.4% in total cohort (AR: 10.4%, P = 0.004; CRS: 39.9%, P < 0.001), expressed by the combined Threshold-Discrimination-Identification (TDI) score-and of all QoL questionnaires scores (all P < 0.01) as well, was observed after treatment. There was a positive correlation between olfactory recovery and improvement of patients' QoL. ROC analysis revealed that an increase in the TDI score by 3.50 points in AR and 4.75 points in CRS was necessary for a clinically significant improvement in all QoL questionnaires results., Conclusions: QoL and mental health of patients suffering from chronic sinonasal diseases are totally recovered after treatment, presenting a direct positive relationship with smell improvement. An increase of olfactory function by 3.50 points for AR and 4.75 points for CRS might be considered the cutoff point for patients' QoL significant recovery., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Nasal nitric oxide (NO) and olfactory function are decreased in patients with chronic inflammatory sinonasal disease, suggesting a link between these two parameters. The aim of the study was to investigate nasal NO levels in patients with olfactory dysfunction due to different causes., Study Design: Prospective study in a university clinic setting (tertiary referral center)., Methods: Posttraumatic (n = 11), idiopathic (n = 13), and sinonasal-related olfactory-impaired patients (n = 55) were compared with healthy subjects (n = 11). Nasal NO levels, olfactory testing (Sniffin' Sticks), and rhinosinusitis questionnaires (Short-Form 36, Sinonasal Outcome Test 22, Rhinosinusitis Disability Index) were obtained., Results: No significant difference in nasal NO levels were found between the different olfactory dysfunction causes. Nasal NO correlated negatively with age and positively with overall olfactory function, olfactory discrimination, and identification but not with olfactory thresholds. The more nasal symptoms prevailed in the Rhinosinusitis Disability Index, the lower the nasal NO., Conclusions: Nasal NO levels do not allow for discrimination between olfactory loss due to various etiologies based on the present data. Nasal NO production seems to decrease with age and also seems to be associated to overall olfactory function and in particular to central nervous system tasks such as olfactory discrimination and identification but not to olfactory thresholds. These findings raise questions about the link and interaction between olfactory function and nasal NO., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: In this study we investigated the effectiveness of vitamin A in postinfectious and posttraumatic smell disorders. A possible effect of vitamin A is likely due to the stimulation of regeneration and repair of the peripheral olfactory system., Study Design: Double-blind, randomized, placebo-controlled clinical trial., Methods: A total of 52 patients (age range, 20-70 years; mean age, 52 years) participated, 26 of whom received placebo (7 male, 19 female) and another 26 verum (8 male, 18 female). A standardized history was obtained in each patient. Olfactory function was measured by means of the Sniffin' Sticks test kit, a validated technique to investigate odor thresholds, odor discrimination, and odor identification. Vitamin A was prescribed at a dose of 10,000 IU per day for 3 months. Follow-up testing was performed on average 5 months after the first investigation., Results: Forty-four percent of all patients reported recovery of their sense of smell; 29% of the participants exhibited significant improvement in measured olfactory function. However, there was no significant difference between the outcome of patients receiving verum or placebo., Conclusions: The systemic application of vitamin A at a dose of 10,000 IU per day for 3 months does not appear to be useful in the treatment of postinfectious or posttraumatic olfactory loss., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: The objectives of this study were to investigate correlations, before and after surgery, between olfactory function self-ratings and measurements, and self-ratings of nasal obstruction and smell; and to establish cutoff points of self-rating scores for smell reduction in patients with nasal polyposis (NP)., Study Design: Prospective study., Methods: A total of 80 patients with NP (36 women, 44 men; aged 49 ± 4 years) were enrolled. Self-ratings (0- to 10-point scale) and measurements of olfactory function with standardized Sniffin' Sticks odor threshold and identification tests were assessed 1 day before surgery, and at 6 weeks (26-78 days) and 7 months (132-318 days) after surgery. Relationships were studied with Spearman correlation coefficients. Cutoff points of self-rating scores for olfactory deficit were established using the receiver operating characteristic curve., Results: Overall, olfactory function self-ratings and measurements correlated strongly preoperatively (r = -0.66, P < .0001) and postoperatively (r = -0.67 at 6 weeks and -0.66 at 7 months, P < .0001). This relationship was better in patients with previous surgery. The correlation was weaker before surgery (r = -0.35, P = .01) than after in hyposmic/anosmic patients (r = -0.74, P < .0001 at 6 weeks and r = -0.73, P = .0002 at 7 months) and was not found in normosmic patients. Self-ratings of nasal patency and smell were not correlated when two complaints were dissociated. Cutoff points of self-rating scores for smell reduction were nine units preoperatively and five units postoperatively., Conclusions: Self-ratings and measurements of olfactory function correlated well before and after surgery in NP patients with olfactory deficits. Self-ratings were not reliable pre- and postoperatively in normosmic patients., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Oral corticosteroids may restore conductive olfactory dysfunction that has been defined as steroid-dependent olfactory loss, but the effect may be temporary. This study was designed to evaluate whether applying topical corticosteroids with a squirt system was more effective than using a nasal spray to maintain olfactory improvement following oral corticosteroids., Study Design: Prospective randomized trial enrolling 32 patients., Methods: Patients were enrolled if they had suffered from olfactory dysfunction for more than 3 months, and if their composite scores of odor threshold, discrimination, and identification scores in Sniffin' Sticks olfactory tests increased by more than six points after 1 week of oral corticosteroid treatment. A total of 32 patients were enrolled and randomized into two groups. All patients were treated with topical corticosteroids for 2 months using either the spray or squirt system, respectively., Results: Both measured and self-rated olfactory functions after 1 and 2 months of topical corticosteroid treatment were better in the squirt group than in the spray group. However, 2 months of topical corticosteroid treatment with the squirt system only partially maintained olfactory improvement., Conclusions: The application of topical corticosteroids with a squirt system was more effective than with a spray in maintaining olfactory improvement with oral corticosteroid treatment. Nevertheless, it only partially maintained the improvement so that topical corticosteroid treatment using a squirt system needs to be combined with intervals of short-term oral corticosteroids to treat steroid-dependent olfactory loss while avoiding the side effects of long-term oral corticosteroid use., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: Despite the significant health impact of olfactory loss in chronic rhinosinusitis (CRS), the underlying pathophysiology is incompletely understood. A transgenic mouse model of olfactory inflammation induced by tumor necrosis factor-alpha (TNF-α) has provided new insights into the cellular and molecular basis of inflammatory olfactory loss. Here, we utilize systemic corticosteroids to suppress downstream cytokine expression, in order to study the direct role of TNF-α in CRS-associated olfactory dysfunction., Methods: Transgenic mice were induced to express TNF-α in the olfactory epithelium for 6 weeks. In a subset of mice, 1 mg/kg prednisolone was administered concurrently to inhibit downstream inflammatory responses. The olfactory epithelium (OE) was analyzed by histology and electro-olfactogram (EOG) recordings., Results: Treatment with prednisolone successfully prevented inflammatory infiltration over significant regions of the OE. In areas where significant subepithelial inflammation was present, a corresponding loss of olfactory neurons was observed. In contrast, areas without major inflammatory changes had normal olfactory neuron layers, despite chronic local expression of TNF-α. Prednisolone partially reversed the complete loss of olfaction in the mouse model, preserving odorant responses that were significantly diminished compared to controls, but not absent., Conclusions: The addition of prednisolone to the transgenic model of olfactory inflammation isolates the direct effects of induced TNF-α expression on the OE. The finding that prednisolone treatment prevents neuronal loss in some regions of the OE suggests that TNF-α does not directly cause neuronal apoptosis--rather, that subepithelial inflammation or other downstream mediators may be responsible. At the same time, EOG results imply that TNF-α directly causes physiologic dysfunction of olfactory neurons, independent of the inflammatory state. An understanding of the role of TNF-α and other inflammatory cytokines may suggest novel therapeutic strategies for CRS-associated olfactory loss., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Empty nose syndrome (ENS) patients have a persistent sense of impaired nasal patency despite radical resection of nasal turbinates. The aim of this study was to elucidate differences in cerebral activation during free breathing and after inhalation of a fragrance (lemonene) and a pseudodecongestant (menthol) over a nasofacial mask. Our hypothesis was that menthol would be perceived as beneficial and that cerebral activation would show differences in areas corresponding to emotional suffering and air hunger in ENS patients., Study Design: Prospective, controlled intervention with lemonene and menthol during functional magnetic resonance imaging (f-MRI) experiment., Methods: Ten right-handed ENS patients were compared to 15 controls using f-MRI and fully automated data analysis with SPM software. Nasal patency was measured with rhinomanometry and rated on a four-point scale., Results: Despite similar objective nasal flow, ENS patients rated nasal patency significantly worse than did controls. Menthol was perceived to increase nasal patency. In patients, f-MRI data showed different activation of temporal cortex areas after inhalation of menthol. The comparison of patients and controls showed ENS-specific activation of temporal and cerebellar areas and amygdala during the rating task itself., Conclusions: Our experiments showed different cerebral processing of the feeling of nasal patency in ENS patients with prominent activation of areas belonging to the limbic system. The beneficial effect of menthol seems to correspond to activation differences in the temporal pole. These results demonstrate a neuronal substrate for both symptoms and their relief in ENS patients., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: The aim of the present study was to evaluate the course of olfactory dysfunction in patients with olfactory loss following infections of the upper respiratory tract., Study Design: Prospective cohort., Methods: A total of 27 patients were included; each patient was evaluated twice. Psychophysical testing of olfactory function was performed with the Sniffin' Sticks test and chemosensory functions with event-related potential (ERP)., Results: At T1, 15 patients were considered hyposmic, 12 as anosmic. Accordingly, nine and 27 patients demonstrated olfactory ERP. At T2, 16 and 11 patients were considered as hyposmic and anosmic, and 11 demonstrated olfactory ERP. Analysis of variance did not show significant differences for any parameters between T1 and T2: threshold, discrimination, identification (TDI) scores at the Sniffin' Sticks and amplitudes and latencies of N1 and P2 in the ERP. However, seven patients demonstrated an increase of more or equal to six points at the TDI score, indicating significant improvement. Four of the seven patients had olfactory ERP at T1 (57%); of those patients who did not show improvement, five of 20 (25%) exhibited olfactory ERP. Thus, the presence of olfactory ERP predicts a positive evolution of olfactory function with a relatively high specificity of 83%., Conclusions: The current findings clearly confirm earlier results on recovery rate of postinfectious olfactory loss. The new finding is that the presence of olfactory ERP at the first consultation is also a positive predictive factor of a favorable outcome in this disease.

Objectives: Olfactory function is known to be modulated by repeated exposure to odors. The aim of this investigation was whether patients with olfactory loss would benefit from "Training" with odors in terms of an improvement of their general olfactory function. It was hypothesized that olfactory Training should produce both an improved sensitivity towards the odors used in the Training process and an overall increase of olfactory function., Study Design: The prospective study was performed in patients with olfactory dysfunction., Methods: One group of patients performed the Training (n = 40), whereas another part did not (n = 16). Exclusion criteria for patients were sinunasal disease. Olfactory training was performed over a period of 12 weeks. Patients exposed themselves twice daily to four intense odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the "Sniffin' Sticks" (thresholds for phenyl ethyl alcohol, tests for odor discrimination and odor identification) in addition to threshold tests for the odors used in the training process., Results: Compared to baseline, training patients experienced an increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. In contrast, olfactory function was unchanged in patients who did not perform olfactory training. The present results indicate that the structured, short-term exposure to selected odors may increase olfactory sensitivity.

Objectives/hypothesis: A degree of smell disturbance has been found in seasonal and perennial allergic rhinitis, but alterations in olfaction in patients with persistent allergic rhinitis (PER) have not yet been evaluated. The aims of the study were to evaluate the impact of PER on the sense of smell, and to characterize this impact based on self-reported hyposmia (SRH) and PER severity., Study Design/methods: A prospective controlled study was performed on 49 consecutive patients with PER. PER patients were subclassified depending on severity and the presence of SRH. Olfactory function was evaluated by the Barcelona Smell Test-24 (BAST-24) olfactometry for smell detection, identification, and forced choice for first and fifth cranial nerve (CN) dependent odors in comparison to a group of 60 healthy volunteers. In patients with SRH, obstruction was evaluated by peak nasal inspiratory flow (PNIF) and acoustic rhinometry; and nasal inflammation was evaluated by nasal nitric oxide (nNO)., Results: Most patients with PER (67%) presented SRH. Moderate/severe PER (84.8%) predominated among patients with SRH, while mild PER (75%) predominated among patients without SRH. Smell detection, identification, and forced choice tests were significantly worse in PER patients (P < .05) than in healthy controls for the odors related to the first and fifth CN. Among subgroups, patients with moderate/severe PER and/or with SRH presented a significant reduction in smell detection (P < .05) compared to healthy controls. Nasal NO correlated (R: 0.4; P < .05) with loss of smell., Conclusions: Patients with PER have a moderate loss of smell (BAST-24) with a higher impairment in those with self-reported hyposmia and moderate-to-severe PER. These results suggest that the sense of smell should be further investigated in all patients with allergic rhinitis, both in a clinical setting and in clinical trials.

Objectives/hypothesis: The use of steroids either systemically or topically is known as a common therapy in patients with anosmia. Nevertheless, investigations giving proof for the benefit of a topical therapy are very rare, and no prognostic factors are known. In our study, we for the first time evaluated the additional effect of a topical therapy not only with steroids but also with antibiotics after conventional pretreatment with oral steroids and propose the steroid-responsiveness of an anosmia as a prognostic factor., Study Design: Retrospective design., Methods: We analyzed the data of 299 patients with olfactory dysfunction. Eighty-nine underwent initial pretreatment with systemic steroids and presented data over a sufficient follow-up time. In a second step all these patients were given a topical treatment in a head down forward position, namely either budesonid alone or in combination with neomycin. Primary outcome parameter was the threshold, discrimination and identification (TDI) score., Results: Initial therapy with oral steroids changed the TDI from 15.5 to 18.7 in the means (P < .001). In general, leaving away systemic steroids while applying local therapy did not led to a reduction of the TDI (P < .001). Dividing up the patients into those suffering from a steroid-responsive anosmia (SRA) and those without benefit from initial systemic steroids (non-SRA), the topical treatment led to a significant difference between the two groups with benefit toward the non-SRA group (P < .001). Regarding only the nonchronic rhinosinusitis anosmics, these findings became even more apparent. Furthermore, in non-SRA patients we found even better results with steroids in combination with neomycin as a topical therapy. In this group, the combined topical therapy elevated the TDI for +2.1 points whereas topical steroids alone raised it only for +1.0 point., Conclusions: The steroid-responsiveness of anosmia seems to be a relevant prognostic indicator for a significant benefit of a topical therapy in general. Within all patients, the effect of an initial systemic therapy could be maintained by the adjacent topical treatment whereas in non-SRA patients a topical therapy has a significant greater impact. Furthermore, antibiotics even seem to have an additional effect in this group. Different reasons, first of all an overwhelmed steroid resistance by additional antiinflammatory effects of antibiotics, e.g., the inhibition of apoptosis might play a role and are discussed.

Objectives: To assess dietary behavior and possible changes in food selection in patients with smell loss., Patients and Methods: A total of 176 patients (114 women and 62 men) age 17 to 86 years were classified into three diagnostic groups (normosmia, n = 12; hyposmia, n = 75; functional anosmia, n = 89) according to their olfactory test scores obtained with "Sniffin' Sticks." Group differences in food intake and dietary behaviors were investigated with a specifically designed questionnaire providing a dietary alterations score (DAS)., Results: Numerous dietary changes were reported, e.g., 29% of all patients reported that they eat less since the onset of olfactory dysfunction, 39% use more spices with their food, 47% go out to eat at restaurants less frequently, 37% eat less sweets, and 48% drink less sweet beverages. Subjects with weight gain or weight loss scored higher on the DAS scale than subjects who did not report changes in weight. Similarly, DAS scale changes were more pronounced in subjects with a gradual onset of olfactory loss compared to subjects with a sudden loss of olfaction. Finally, a change of taste preferences toward savory and salty foods was observed across all patients enrolled in the present study., Conclusions: Patients with olfactory loss report alterations of dietary behaviors. Numerous factors appear to impact the results of olfactory loss in terms of changes in diet.

Objective: The purpose of this study was to evaluate the likelihood of recording olfactory event-related potentials (OERPs) in patients with an olfactory dysfunction and to correlate the electrophysiological responses to orthonasal and retronasal olfactory testing. DESIGN/MATERIALS AND METHODS: This was a prospective study of 65 patients with different origins of their olfactory loss. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test (orthonasal score; maximal score 48) and retronasal olfactory function with odorized powders presented intraorally (retronasal score; maximal score 20). The OERPs were obtained after presentation of 2-phenyl ethyl alcohol, the selected olfactory stimulus. Causes of olfactory dysfunction included postinfectious olfactory loss (n = 15), head trauma (n = 26), nasal polyposis (n = 15), and mixed causes (idiopathic, toxic, drug induced) (n = 9)., Results: Based on orthonasal testing, 32 and 33 patients were diagnosed with anosmia and hyposmia, respectively. Twenty-two patients from the hyposmic group demonstrated reliable OERPs. No OERPs were recorded in the anosmic group. Prevalence of OERPs in a cohort of patients with olfactory dysfunction was 33.8% (22 of 65). Median score (expressed as the percentage of the maximal score that could be obtained theoretically) in which OERPs were recorded was 50% (24 of 48) with orthonasal testing and 80% (16 of 20) with retronasal testing., Conclusions: Patients with olfactory dysfunction usually demonstrate OERPs in one third of the cases. When olfactory dysfunction is in the range that separates normosmic subjects from anosmic patients, patients may have identifiable OERPs. Interpretation of both orthonasal and retronasal psychophysical olfactory testing should be supported by the recording of OERPs in a clinical setting.

Background: Birhinal testing of odor identification will not allow the detection of unilateral olfactory loss. The aim of the presented study was to evaluate side differences of odor identification in large groups of healthy subjects and in patients with nasal symptoms., Participants and Method: Self-assessment of olfactory function and evaluation of olfactory function by means of a validated test were performed in 479 healthy subjects, in 765 patients with chronic rhinosinusitis (CRS), and in 53 patients with a tumor. A 12-item odor identification test ("Sniffin' Sticks") was used to evaluate olfactory function separately for each nostril., Results: Fifteen percent of the healthy subjects demonstrated side differences in the identification of at least 3 out of 12 odors. Healthy elderly subjects showed larger side differences in identification of odor than younger ones; a general difference between odor identification with the right or left nostril was not found. Both CRS patients and patients with a tumor had larger side differences than healthy subjects. Only 20% of the patients with a tumor complained about impaired olfactory sensitivity, but more than 75% of them showed deficits in olfactory tests., Conclusion: Side differences of odor identification of 25% or greater should give reason for further investigation. Future studies are needed to investigate whether side differences in healthy subjects are a predicator of a higher risk for general olfactory loss.

Objective: Causative viruses of postviral olfactory dysfunction (PVOD) have not yet been identified. The aim of this study was to investigate causative viruses in patients with PVOD., Study Design and Methods: Nasal discharge was collected from 24 patients with PVOD. We investigated the presence of 10 viruses in nasal discharge and examined the time course, with regard to changes in olfactory dysfunction and nasal obstruction in patients with PVOD, using questionnaires, acoustic rhinometry, and olfactory tests., Results: Rhinoviruses were detected in 10 patients by electrophoresis. Rhinoviruses were also confirmed in four patients by nucleotide sequences. Viral serotypes were identified to be human rhinovirus (HRV)-40, HRV-75, HRV-78, and HRV-80. One of the four patients complained of anosmia, whereas another complained of dysosmia. Olfactory testing did not show significant improvement at 4, 8, 11, and 24 weeks after the first visit in the four patients, although results of acoustic rhinometry significantly improved. Two of the four patients complained of olfactory dysfunction even 6 months after the first visit. Coronavirus and parainfluenza virus were detected in one patient each, and Epstein-Barr viruses were detected in three patients., Conclusions: This study for the first time detected rhinovirus, coronavirus, parainfluenza virus, and Epstein-Barr virus in nasal discharge of patients with PVOD. Furthermore, the present study suggests that rhinoviruses can cause olfactory dysfunction through mechanisms other than nasal obstruction and that rhinoviruses can induce various severities and different time courses of olfactory dysfunction.

Background: Although widely used in healthy subjects and patients with olfactory loss, the significance of changes of scores from validated olfactory tests is unknown., Aim and Methods: The aim of the present study was to relate the self-assigned changes of olfactory function in terms of "better," "unchanged," and "worse" in patients with smell disorders with the results from olfactory testing by means of a validated test set. Olfactory function of 83 anosmic or hyposmic patients (40 women, 43 men; age 12-84 yr) was tested on two occasions (mean interval 136 days, minimum 7 days, maximum 6.7 yr). Olfactory function was assessed using a validated technique ("Sniffin' Sticks"). This test consists of three subtests, one for odor threshold (T), odor discrimination (D), and odor identification (I), with possible results ranging up to 16 points each. From the sum of the results from the three subtests a composite "TDI" score was obtained., Results: Forty-four patients indicated an improvement of olfactory function, whereas 39 patients reported no change. No subject reported deterioration of olfactory sensitivity. Subjects assigned to group BETTER had higher TDI scores in the second olfactory tests than subjects assigned to the group UNCHANGED, both in absolute terms and as compared with the first olfactory test (effect "test occasion" by "self-assessed improvement," P < .001). There was no significant difference between groups with respect to age and sex (P = .99 and .84, respectively). Logistic regression showed that more than 60% of the subjects reported an improvement of olfactory sensitivity when the TDI score increased by 5.5 points., Conclusion: We show that there is a statistically significant relation between measured and perceived improvement of olfactory function in patients who first presented with the diagnosis of anosmia or hyposmia. The results indicate that improved olfactory function in patients with olfactory deficiency is perceived as such in everyday life and is quantitatively related to an improvement in the composite TDI score of the "Sniffin' Sticks" olfactory test battery. This is the basis for the application of a specific therapy for olfactory loss because of a possible gain in quality of life for the patients.

Objective: The aims of this study were to evaluate olfactory function with orthonasal and retronasal testing in patients with posttraumatic olfactory loss and to investigate the relation between residual olfactory function and olfactory bulb (OB) volume., Method: A retrospective study of 25 patients with posttraumatic olfactory loss was performed. Orthonasal olfactory function was assessed with the Sniffin' Sticks test kit; retronasal olfactory function was assessed with intraorally applied odors. Magnetic resonance imaging was used to determine OB volume and cortical damage in the frontal and temporal areas., Results: The main outcomes of the present study were the demonstration of a correlation between olfactory function and OB volume, which was more pronounced for retronasal than for orthonasal olfactory function; retronasal olfactory function was most affected in the patients with the most extensive cerebral damage and was least compromised in patients without such damage; OB volumes were smaller in patients with parosmia compared with those without; and the presence of parosmia was clearly associated with the presence of cerebral damage., Conclusion: The data confirm that OB volume is an indicator of olfactory function but, interestingly, in this study, it is largely determined by retronasal olfactory sensitivity. In addition, these results emphasize the role of higher cortical centers in olfactory function, and especially in parosmia, which may, at least in some cases, be related to lesions in the fronto-orbital and anterior temporal cortices. It would be of interest to investigate OB volume further in relation to the prognosis of the disorder.

Leprosy (Hansen's disease) is associated with a high incidence of nasal pathology. Despite this fact, the influence of this disorder on the sense of smell is poorly understood. In this study, we administered a standardized 12-item odor identification test to 77 patients with three types of leprosy: tuberculoid (n = 9), borderline (n = 42), and lepromatous (n = 26). All three types exhibited significantly lower test scores than their respective age-, sex-, and smoking-habit-matched controls. Patients with lepromatous leprosy exhibited significantly lower test scores than those with the other two types. Only patients with lepromatous leprosy exhibited meaningful improvement in smell function after treatment. No association between disease duration, per se, and the severity of the olfactory deficit was present. Overall, 100% of the patients exhibited olfactory dysfunction, suggesting that earlier prevalence estimates based on nonstandardized olfactory testing have underestimated the prevalence of this problem.

Objective: The study aimed to investigate whether the degree of postinfectious olfactory loss is reflected in volume of the olfactory bulb (OB)., Study Design: Retrospective study of 26 patients with postinfectious olfactory loss., Materials and Methods: Olfactory function was assessed with the "Sniffin' Sticks" test kit, and the magnetic resonance imaging study focused on OB volume and the olfactory sulcus., Results: The study revealed that 1) OB volume varies with regard to olfactory function, 2) OB volume decreases with duration of olfactory loss, and 3) patients with parosmia had smaller OB volumes than patients who did not report such smell distortions, although their overall olfactory function was not significantly different from each other., Conclusion: The study emphasizes that OB volume is a gauge of olfactory function.

Objective: Physicians rarely assess smell function, largely because of time considerations. Therefore, there is clinical need for very brief cranial nerve I screening tests. Although a few such tests exist, none have been adequately validated. The goal of this study was to empirically assess the utility of a three-item microencapsulated odor identification test in detecting olfactory dysfunction., Setting: Smell and taste center at a university medical center., Methods: The test was administered to 224 consecutive patients (98 men and 126 women ranging in age from 15-88 years). As part of their overall assessment, the well-validated 40-item University of Pennsylvania Smell Identification Test (UPSIT) was also administered. Sensitivity, specificity, and both negative and positive predictive values of the three-item test were established relative to UPSIT dysfunction categories. Test-retest reliability was determined in a subset of 39 patients., Results: The three-item test was abnormal in 99% (67/68) of patients with anosmia, 85% (35/41) of those with severe microsmia, 76% (31/41) of those with moderate microsmia, and 50% (17/34) of those with mild microsmia. Of the 40 normosmic patients, 62.5% (25/40) correctly identified all odors, 25% (10/40) two odors, and 12.5% (5/40) one odor. None of the normosmic patients missed all three items. Using a cut-off score of 2, the test's sensitivity and specificity were 99% and 40%, respectively, for detecting total anosmia. The corresponding negative and positive predictive values were 98% and 43%. For detecting anosmia and severe microsmia, these values were 93%, 45%, 88%, and 63%. For detecting any olfactory pathology, they were 82%, 63%, 42%, and 91%. The test-retest reliability was 0.87., Conclusion: The brief three-item test used in this study was found to be highly sensitive in identifying olfactory loss in patients with chemosensory complaints, particularly those with severe dysfunction. Although only moderately specific, its high reliability and negative predictive value suggests it may be an appropriate screening test for olfactory loss.

Objectives/hypothesis: Patients with olfactory dysfunction appear repeatedly in ear, nose, and throat practices, but the prevalence of such problems in the general adult population is not known. Therefore, the objectives were to investigate the prevalence of olfactory dysfunction in an adult Swedish population and to relate dysfunction to age, gender, diabetes mellitus, nasal polyps, and smoking habits., Study Design: Cross-sectional, population-based epidemiological study., Methods: A random sample of 1900 adult inhabitants, who were stratified for age and gender, was drawn from the municipal population register of Skövde, Sweden. Subjects were called to clinical visits that included questions about olfaction, diabetes, and smoking habits. Examination was performed with a smell identification test and nasal endoscopy., Results: In all, 1387 volunteers (73% of the sample) were investigated. The overall prevalence of olfactory dysfunction was 19.1%, composed of 13.3% with hyposmia and 5.8% with anosmia. A logistic regression analysis showed a significant relationship between impaired olfaction and aging, male gender, and nasal polyps, but not diabetes or smoking. In an analysis of a group composed entirely of individuals with anosmia, diabetes mellitus and nasal polyps were found to be risk factors, and gender and smoking were not., Conclusion: The sample size of the population-based study was adequate, with a good fit to the entire population, which suggests that it was representative for the Swedish population. Prevalence data for various types of olfactory dysfunction could be given with reasonable precision, and suggested risk factors analyzed. The lack of a statistically significant relationship between olfactory dysfunction and smoking may be controversial.

Objective: To investigate the question of whether there is a difference in retronasal olfactory function between patients suffering from chronic rhinosinusitis with nasal polyposis (NP) and healthy controls. This question was based on the clinical observation that many of these patients present with smell loss without complaining about loss of the appreciation of foods., Study Design: Open prospective study comparing symptomatic patients with healthy controls., Methods: A total of 56 healthy volunteers and 42 NP patients were tested for orthonasal and retronasal odor identification. All subjects received detailed nasal endoscopy; NP was staged according to the Malm classification. Patients rated their olfactory function on visual analogue scales. Orthonasal testing was performed using the "Sniffin' Sticks" test kit. Retronasal testing was evaluated with odorized powders applied to the oral cavity. In both tests, subjects were asked to identify 10 items using a forced choice paradigm., Results: Overall, odor identification was better in controls compared with NP patients (P <.001). Although controls exhibited no difference between orthonasal and retronasal smelling (P =.26), in NP patients, olfactory function was significantly better when odors were applied through the retronasal route (P <.001). Ratings of general olfactory abilities correlated with retronasal and orthonasal olfactory function in NP patients (P <.001) but not in healthy controls (P =.34)., Conclusion: Better retronasal than orthonasal olfactory function seems to be associated with the presence of mechanical obstruction in the anterior portion of the olfactory cleft. In turn, these data indicate that olfactory loss in NP seems to be caused by regional mechanical or inflammatory factors.

The sense of smell has been largely ignored by otorhinolaryngologists, even though 1) its medical stewardship falls within their specialty's purview, 2) olfactory dysfunction is not uncommon in the general population, and 3) disorders of olfaction have significant quality of life, nutritional, and safety consequences. This report provides a succinct overview of the major intranasal neural systems present in humans (namely, cranial nerves O, I, and V, and the nonfunctional accessory [vomeronasal] organ system), along with a summary of notable findings resulting from the application of modern olfactory tests to patient populations, emphasizing diseases of the nose. Such tests have led to the discovery of significant influences of age, gender, smoking, toxic exposure, and genetics on the ability to smell. Within the field of otorhinolaryngology, they have revealed that 1) surgical and medical interventions in patients with rhinosinusitis do not, on average, lead to complete recovery of olfactory function, despite common beliefs to the contrary, and 2) associations are generally lacking between measures of airway patency and olfactory function in such cases. These findings have thrown into question the dogma that olfactory loss in rhinosinusitis is attributable primarily to blockage of airflow to the receptors and have led to histopathological studies demonstrating significant olfactory epithelial compromise in sinonasal syndromes.