Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers.

BACKGROUND: Eosinophilic Esophagitis (EoE) is a chronic inflammatory condition of the esophagus triggered by food and aeroallergens. There is a need for noninvasive biomarkers that reliably detect EoE in patients with cardinal symptoms and predict treatment response to reduce endoscopic evaluations. STUDY: Nonasthmatic patients 18 years or above with suspected or diagnosed EoE, gastroesophageal reflux disease (GERD), and control individuals with indication for endoscopy were enrolled prospectively between November 2020 and May 2022. Participants underwent body plethysmography with fractionated exhaled nitric oxide (FeNO) level measurement. Besides, serum and fecal biomarkers were measured by ELISA. A follow-up examination was scheduled after treatment initiation in patients with active EoE. RESULTS: The median FeNO level in active EoE (20 ppb) was higher compared with GERD (15 ppb, P=0.038) and control individuals (14 ppb, P=0.046). Median FeNO did not significantly differ in EoE patients who underwent follow-up assessment after treatment response (20 ppb vs. 18 ppb, P=0.771). Serum EDN, ECP, and the absolute eosinophil blood count (AEC) were elevated in active EoE compared with control individuals but not compared with GERD except for AEC. Serum EDN, ECP and AEC decreased in EoE in remission at follow-up assessment. None of the fecal biomarkers was elevated in active EoE or during treatment. CONCLUSIONS: Assessment of FeNO may have diagnostic value in differentiating patients with active EoE from non-EoE patients but is not a suitable marker for monitoring disease activity. Serum EDN, ECP, TARC, and AEC levels are emerging as potential candidates for monitoring disease activity in EoE.

Taste Alteration in External Auditory Canal Cholesteatoma: Indicator of Impending N VII Affection.

INTRODUCTION: External auditory canal cholesteatoma (EACC) is a rare disease, with an estimated incidence of approximately 1:1,000 adult and 1.6:1,000 pediatric otologic patients. Systematic studies of chronic ear disease and taste alteration prior to surgery are rare; in fact, there are no such studies for EACCs. Therefore, we describe chorda tympani nerve (CTN) dysfunction and the related clinical consequences in EACC patients. METHODS/STUDY DESIGN: Between 1992 and 2021, we retrospectively analyzed the symptoms, signs, and radiological and intraoperative descriptions of CTN involvement in 73 patients. Liquid taste tests and, since 2009, Taste StripsTM as well as an olfactory screening test (Smell DiskettesTM) have been performed for all symptomatic patients and, when feasible, all other EACC patients. RESULTS: Ten of 73 patients complained subjectively of dysfunction, and 8 showed abnormal taste test results. Four patients complained of olfactory dysfunction (3 cases with pathological taste tests). Gustatory dysfunction was most frequent in radiogenic EACC cases (n = 4), followed by postoperative EACC (n = 3). Two postoperative patients were asymptomatic despite abnormal test results. Rarely, patients with idiopathic (n = 2) and posttraumatic (n = 1) EACC showed acute taste dysfunction that was confirmed in each with abnormal test results. DISCUSSION/CONCLUSION: CTN dysfunction often developed asymptomatically in chronic ears, except for idiopathic and posttraumatic EACCs under previous healthy middle ear conditions. Taste disturbance is not a cardinal symptom of EACC, but objective testing suggests that up to one out of 10 EACC patients with advanced disease may experience regional gustatory dysfunction prior to surgery. Especially in context of a new and acute presentation, regional taste dysfunction may alert the clinician of potential progressive EACC invasion and danger to the facial nerve.

Apparently Minor Head Trauma Can Lead to Anosmia: A Case Report.

We report the case of a 49-year-old female patient who suffered from anosmia following an apparently mild head trauma when bumping into a door at her home. She reported no other accompanying symptoms after the injury that day. Olfactory function was completely lost, which was noted the day after the trauma. Gustatory function remained normal. Magnetic resonance imaging indicated lesions/bleeding in the right frontal lobe and in the area of the olfactory sulcus/bulb. The present case indicates that in case of apparently mild head trauma with anosmia, an MRI scan of the head should be performed because of suspect brain damage. This case also points to the deeper question how to gauge severity of head trauma.

Gustatory function and taste perception in patients with oral lichen planus and tongue involvement.

OBJECTIVES: The aim of the study was to evaluate if patients with oral lichen planus (OLP) and tongue involvement have impaired taste function and if there is an association to the perception of pain. MATERIAL AND METHODS: The test group included patients with OLP and involvement of the tongue without treatment (n = 20). Control subjects had no mucosal or systemic disease affecting taste function and were matched for age and gender (n = 20). Patients' intraoral pain and subjective perception of taste were recorded on a visual analog scale. Taste function was assessed by means of the "taste strips." RESULTS: Measured taste function was slightly but significantly decreased in OLP patients compared to control subjects (p = 0.01). Self-rated taste perception did not differ in both groups (p = 0.8). Post hoc analysis showed that particularly the taste quality "sour" was most affected by the OLP status (p = 0.01). There were no correlations between pain and subjective/objective taste perception. CONCLUSION: Untreated OLP subjects have lower gustatory function, which they are not aware of. CLINICAL RELEVANCE: Impaired gustatory function in patients with OLP may affect patient's quality of life. Further studies on larger samples sizes are requested.

[Conservative and surgical management of chronic Rhinosinustitis]. / Konservative und operative Behandlung der chronischen Rhinosinusitis.

Chronic rhinosinusitis is a common complex medical condition associated with high therapy costs and quality of life impairment. The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012 delineates the current standard of management of the patient with chronic rhinosinusitis for both defined disease forms: with and without polyps. Medical history and endoscopic or CT findings are needed for the correct diagnosis. Therapy of chronic rhinosinusitis aims at achieving a local disease control and reducing patients' symptoms. The center point of conservative therapy of both forms is the topical application of steroids together with nasal saline irrigations. In case of persistence of symptoms or in severe chronic rhinosinusitis with polyps, different local application methods of steroids or short systemic steroid cures should be considered. In case of insufficient disease control with conservative treatment, functional endoscopic sinus surgery is the accepted as "gold standard". Purpose of the surgical management is opening of the sinus ostia in order to improve sinus ventilation and mucociliary clearance as well as to facilitate a wide distribution of topical drugs. Due to technical advances, endoscopic sinus has been reported to be a safe and effective procedure.

Localization of odors can be learned.

Chemicals selectively stimulating the olfactory nerve typically cannot be localized in a lateralization task. Purpose of this study was to investigate whether the ability of subjects to localize an olfactory stimulus delivered passively to 1 of the 2 nostrils would improve under training. Fifty-two young, normosmic women divided in 2 groups participated. One group performed olfactory lateralization training, whereas the other group performed cognitive tasks. Results showed that only subjects performing lateralization training significantly improved in their ability to lateralize olfactory stimuli compared with subjects who did not undergo such training.

Reduced olfactory bulb volume in adults with a history of childhood maltreatment.

The human olfactory bulb (OB) is the first relay station of the olfactory pathway and may have the potential for postnatal neurogenesis in early childhood. In animals, chronic stress affects the OB and olfactory functioning. For humans, it has been shown that major depressive disorder is accompanied by reduced OB volume and reduced olfactory function. However, it is not clear if major stress in childhood development also affects olfactory functioning and OB volume in humans. OB volume was measured and olfactory function was tested in 17 depressive patients with and 10 without a history of severe childhood maltreatment (CM). CM patients exhibited a significantly reduced olfactory threshold and identification ability. The OB volume of the CM patients was significantly reduced to 80% of the non-CM patients. In conclusion, postnatal neurogenesis might be by reduced in CM, which may affect olfactory function of the brain in later life. Alternatively, a reduced OB volume may enhance psychological vulnerability in the presence of adverse childhood conditions although other areas not analyzed in this study may also be involved.

Intrinsic chemosensory signal recorded from the human nasal mucosa in patients with smell loss.

Physiological investigation of olfactory receptor function in hyposmic or anosmic patients is rare. Pioneers examined the electro-olfactogram in patients with olfactory disturbance. Although the electro-olfactogram is an established method to record olfactory responses from human olfactory epithelium, the response is only measured at specific sites of the olfactory mucosa. In contrast to that the response of the olfactory epithelium to chemosensory stimuli can be studied in a specific nasal area by means of intrinsic optical signal recording. Five functionally anosmic patients were included in the present study. In all patients, responses could be obtained following trigeminal stimulation with CO2. In some patients, responses could be obtained after olfactory stimulation with H2S and PEA. The present data show that in the studied patients trigeminal function seems to be preserved, while it appears that in some patients olfactory function is preserved to a certain degree.

Impaired Taste Perception in Lichen Planus Patients with Tongue Involvement.

PURPOSE: To analyse the taste function in a pool of untreated patients with oral lichen planus (OLP) with tongue lesions (n = 35) and without tongue lesions (n = 36) and to compare it to healthy subjects (n = 36). MATERIALS AND METHODS: Firstly, the subjective overall taste ability and impairment of the sensations of 'sweet', 'sour', 'salty' and 'bitter' were recorded in all three groups. Secondly, taste function was tested in all included subjects using the standardised 'Taste Strips' test. RESULTS: Data showed a statistically statistically significant difference in overall taste perception between OLP patients with tongue lesions and control subjects (p = 0.027) for the tested taste function. The sensation of 'sour' showed the most pronounced difference (p = 0.08). The subjective taste perception and that of individual taste qualities did not differ statistically significantly between the three groups, and the correlation between subjective and objective taste perception was low. There was also a low correlation between taste scores and the presence of lesions on different areas of the tongue. CONCLUSION: For patients with OLP experiencing a loss in appetite, a formal taste examination and subsequent counselling should be considered.

Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view.

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects.

Odors enhance visual attention to congruent objects.

Although it is well known that visual stimuli affect olfactory performance, little is known about the reverse case: the influence of odor on visual performance. This study aimed to determine whether odors can enhance attention towards visually presented objects congruent with the odors. Sixty healthy participants were presented with four odors (orange, lavender, coffee, and liquorice) before and during the presentation of photographic slides containing one congruent and three incongruent objects with the presented odors. The participants' visual attention was assessed as the total number and time of eye fixations by using an eye tracking system. When the participants smelled an odor, they looked more frequently and longer at a corresponding object as compared to the odorless condition. In conclusion, our findings demonstrate for the first time an olfactory priming effect on visual selective attention: odor can increase attention towards a congruent visual object as compared to a non-odor condition.

Individual significance of olfaction: development of a questionnaire.

Clinical experience shows that the individual significance of olfactory function varies between subjects. In order to estimate these individual differences we developed a questionnaire to study the subjective importance of the sense of smell. Questions were arranged within three subscales: association with olfactory sensations, application of the sense of smell, and the readiness to draw consequences from the olfactory perception. The questionnaire was shown to be time efficient, suitable for normosmic subjects and patients with hyposmia or anosmia. It exhibited a good internal reliability (Cronbach's Alpha = 0.77). First results in 123 subjects indicate that the subjective importance of the sense of smell stays at the same level throughout life-span despite of a decreased olfactory sensitivity. Furthermore, women reported a higher importance of olfaction. It is hoped that this questionnaire will contribute to clarify, for example, cross-cultural differences in the perception of odours.

Challenges in topical therapy of chronic rhinosinusitis: The case of nasal drops application - A systematic review.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a common health issue associated with a significant life quality impairment. Intranasal glucocorticoid is the treatment of choice both as initial therapy as well as after surgery. In contrast to nasal spray, liquid glucocorticoids in form of nasal drops have the advantage of reaching the middle and upper meatus. The efficiency of the glucocorticoid nasal drops is nevertheless strictly dependent on the head position they are being applied in. Several head positions have been described in the literature but no clear recommendation towards the best suited position exist to date. METHODS: A systematic review was completed using the PubMed database. Journal articles assessing the effect of head position on intranasal drop fluid distribution, clinical effectiveness, or factors affecting patient compliance were included. RESULTS: In total 15 publications meeting the inclusion criteria have been found, out of which 9 cover the effect of head position as a primary outcome using quantitative measures. CONCLUSIONS: The positions Lying Head Back, Lateral Head Low, and variations of those can be recommended equally at the moment. Evidence speaks against the use of the classic Head Back position because of poor clinical outcome, and against the position Head Down and Forward as initial therapeutic approach because of high discomfort. For the olfactory cleft, a new head position has been described (Kaiteki), although no comparisons to other positions exist to date.

Characteristics of Olfactory Disorder With and Without Reported Flavor Loss.

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.

Multisensory environmental sensitivity in patients with chronic tinnitus.

OBJECTIVE: The study aimed at investigating the sensitivity to noise and chemosensory environmental stressors as well as the relation to perceived stress, depression and anxiety in subjects with chronic tinnitus as compared to subjects without tinnitus. METHODS: We included 75 subjects with chronic tinnitus and 75 age and sex-matched subjects without tinnitus. Standardized questionnaires assessing the level of distress and impairment of quality of life caused by tinnitus, perceived level of stress, anxiety and depression, environmental noise and chemosensory sensitivity were used. A subgroup of 27 subjects with chronic tinnitus and 20 age-matched subjects without tinnitus underwent testing of olfactory function with the Sniffin' Sticks test and testing of intranasal trigeminal function using CO2 thresholds. RESULTS: Our data confirmed the increased environmental noise sensitivity (NSS) in patients with tinnitus. Furthermore, we observed an increased environmental chemosensory sensitivity (CSS), but no difference in measured chemosensory function. Subjects with tinnitus showed also significant higher levels of perceived stress, anxiety and depression and those symptoms partially correlated to CSS and NSS. Predictors of both NSS and CSS results were the presence / absence of tinnitus and high anxiety levels while neither stress nor depression were found as predicting variables. CONCLUSIONS: The results suggest that chronic tinnitus is related to a multisensory environmental hypersensitivity. Anxiety seems to be a predictor of this environmental vulnerability.

Separate signals for orthonasal vs. retronasal perception of food but not nonfood odors.

There is a controversy concerning whether smelling via the nose (ortho-nasally) or the mouth (retro-nasally) represent two routes to the same modality or two distinct submodalities. Since olfactory coding is dependent upon experience, and since food odors are experienced retro-nasally, the authors tested the hypothesis that whether an odor represents a food may influence whether sensation via the two routes leads to separable responses. The authors demonstrate that salivary response to food odors decrease with repeated presentation and show that this response rebounds upon presentation of a novel food odor via the same route and upon presentation of the same food odor via a novel route. This finding indicates that the novel odor and the novel route represent distinct sensory signals. This effect is specific, in that it does not depend on differences in odor intensity or pleasantness and is selective, in that it occurs for food odors but not for equally pleasant and intense nonfood odors. These results demonstrate that separable signals are generated for the same food odor depending upon route and support the existence of category-specific processing.

Comparison between odor thresholds for phenyl ethyl alcohol and butanol.

UNLABELLED: Aim of the study was to compare results of odor threshold test using different numbers of dilution steps, separately for butanol and phenyl ethyl alcohol (PEA). METHODS: A total of 116 subjects participated (29 patients with olfactory dysfunction and 87 normosmic subjects). The olfactory threshold for butanol and PEA was examined with 8 (wide step method) and 16 (narrow step method) dilutions. With a delay of about 1 week, all 4 tests were repeated. RESULTS: Test time was shortened by approximately 2 min (25%) for patients when using the wide step method. Butanol and PEA thresholds were not significantly different; in addition, a significant correlation was found between thresholds for the 2 odors (r = 0.60, P < 0.001). Threshold test with both odorants as well as with wide or narrow step method provided satisfying reproducibility (test-retest reliability: r = 0.80-0.84, P < 0.001). Patients with olfactory dysfunction could be clearly separated from normosmic subjects using all 4 different tests. DISCUSSION: The results indicate that threshold testing with PEA is an alternative to butanol. The wide step method provided similar results as the narrow step method but required less time.

Odor-related brain hyper-reactivity in euthymic bipolar disorder: An fMRI and ERP study.

Previous studies on olfactory function in patients with bipolar disorder (BD) are limited and contradictory. The current study aimed to comprehensively analyze the olfactory function of patients with euthymic BD using psychophysical, electrophysiological and neuroimaging techniques. Twenty-one patients with BD in remission and 20 healthy controls were tested with the "Sniffin' Sticks" olfactory test. Block-design fMRI data to a pleasant and an unpleasant stimulus were acquired while recording intensity and hedonic ratings. Olfactory event-related potentials (OERP) to the same stimuli were additionally recorded. Results show no differences between patients and healthy controls in terms of self-rated olfactory function and tested olfactory domains (odor threshold, discrimination or identification) (p>0.05). Compared to healthy controls, patients showed an increased fMRI activation in multiple cortical and subcortical regions as a response to olfactory stimulation, as well as larger amplitudes of OERPs regardless of the hedonic valence of the odor. All in all, patients with euthymic BD showed a stronger central responsiveness to odorous stimuli in fMRI and OERPs despite of normal psychophysical results, indicating the probable existence of an odor-related over-reactive brain network in the remission phase of BD.

Bilateral Ageusia and Tongue Anesthesia Following Unilateral Brainstem Infarct: A Case Report with a Brief Review of the Literature.

We present the case of a 63-year-old male patient who suffered bilateral ageusia following a unilateral left-sided mesencephalon infarct. To the best of our knowledge, this is the first description of a mesencephalon lesion leading to ageusia. We discuss the literature on this rare but important symptom following a stroke.

Lateralized differences in olfactory function.

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.