Unilateral Choanal Atresia: Indications of Long-Term Olfactory Deficits and Volumetric Brain Changes Postsurgically.

BACKGROUND: Very few studies have investigated whether unilateral choanal atresia is associated with permanent olfactory deficits. OBJECTIVE: This study aimed to evaluate the olfactory performance of patients with unilateral choanal atresia postsurgically. METHODS: Three patients with unilateral atresia were examined in terms of olfactory performance with the Sniffin' Sticks test (odor identification, threshold, and discrimination), size of the olfactory bulb, and volumetric brain changes. RESULTS: All patients demonstrated significantly lower olfactory performance in terms of odor threshold on the same side with the choanal atresia. Grey matter reductions were found ipsilaterally in the hippocampus. CONCLUSIONS: This pilot study indicates that persistent olfactory deficits and volumetric brain changes are present in patients with unilateral choanal atresia.

Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction.

BACKGROUND: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). OBJECTIVE: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. METHODS: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. RESULTS: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. CONCLUSIONS: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.

Tackling nasal symptoms in athletes: Moving towards personalized medicine.

Adequate nasal breathing is indispensable for athletes, and nasal symptoms have been shown to interfere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease, and therefore, adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symptoms are more prevalent in athletes compared to the general population and certain sports environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on unmet needs for the management and prevention of these symptoms in athletes within the concept of precision medicine.

Clinical efficacy of intranasal drug delivery by nebulization in chronic rhinosinusitis: a systematic review.

BACKGROUND: Treatment of chronic rhinosinusitis (CRS) aims to treat the underlying inflammation or infection. Although the optimal modality of administration remains controversial, inhalation route is usually preferred. The aim of this systematic review was to summarize the efficacy of intranasal corticoisteroids or antibiotics delivery by nebulization on symptoms, histology, endoscopy scores, nasal obstruction, clinical outcomes and quality of life in CRS. METHOD: This systematic review followed the PRISMA guidelines. Randomized controlled, comparative and cohort studies evaluating effects of treatment by nebulization in sinusitis were identified and reviewed from two databases (PubMed and Scopus). Two reviewers independently assessed study quality and reviewed the selected studies. RESULTS: 600 references were retrieved and 12 studies evaluating 377 patients were included in the systematic review. Different devices were used. Efficacy of nasal delivery by nebulization was systematically observed on symptoms and size of polyps and frequently on inflammatory parameters in all studies. The presence of polyps improved the efficacy of the nebulization. This way of delivery appears not convincing regarding antibiotics. Few side effects were noted in the retrieved studies and only for nebulized antibiotics. CONCLUSIONS: This systematic review highlighted that based on the present literature nebulization is not better than nasal spray to the delivery of corticosteroids due to the positive results on symptoms, endoscopic appearance and histological outcomes. For antibiotics delivery, the nebulization is not of added value.

Chronic maxillary atelectasis and silent sinus syndrome: two faces of the same clinical entity.

Chronic maxillary atelectasis (CMA) and silent sinus syndrome (SSS) are rare clinical entities characterized by an implosion of the maxillary sinus that may or may not be associated with sinonasal symptoms, and are complicated by ipsilateral enophthalmos. The objective of this article is to discuss the definitions, physiopathology, clinical and radiographic characteristics, and surgical management of these entities. We retrospectively reviewed 18 patients (7 women, 11 men, aged 12-70 years) diagnosed and treated in the ear, nose, and throat departments of four Belgian teaching hospitals between 2000 and 2015. Nine patients had a history of sinus disease. In all cases, a computed tomography scan showed downward displacement of the orbital floor, increased orbital volume, and maxillary sinus contraction. Five patients met the criteria for grade II CMA and 13 for grade III CMA. Four patients met the criteria for SSS. All patients underwent wide endoscopic middle maxillary antrostomy. There were no orbital complications and all patients experienced resolution or a dramatic reduction of their symptomatology. Only one patient asked for an orbital floor reconstruction to correct a persisting cosmetic deformity. Although CMA and SSS are usually regarded as different entities in the literature, we believe that they lie on the same clinical spectrum. Treatment for both conditions is similar, i.e., middle meatal antrostomy to halt or even reverse the pathological evolution and reconstruction of the orbital floor in the event of persistent cosmetic deformity.

Olfaction in Chronic Rhinosinusitis.

Olfactory dysfunction is a frequent complaint in chronic rhinosinusitis patients and has a significant impact on quality of life. Therefore, it is essential that clinicians are aware of the importance of olfactory dysfunction in chronic rhinosinusitis (CRS) patients and know how to deal with it. Notably, the evaluation of olfactory function (i.e., using psychophysical testing) and imagery of olfactory bulb play an important role in the evaluation of patients and give essential information about the "baseline" olfactory function. Because the high impact of olfactory function on quality of life and medical and/or surgical treatment should be proposed to patients. However, it remains difficult to predict the outcome of treatment as well as long-term efficacy. The first section of this review is dedicated to the assessment of olfactory function. Secondly, we will discuss the etiopathology of olfactory dysfunction in CRS with and without nasal polyps. Finally, we will review literature findings about the efficacy of different treatments on olfactory function.

Chemosensory Dysfunction in Alcohol-Related Disorders: A Joint Exploration of Olfaction and Taste.

Chemosensory (olfaction-taste) dysfunctions are considered as reliable biomarkers in many neurological and psychiatric states. However, experimental measures of chemosensory abilities are lacking in alcohol-dependence (AD) and Korsakoff Syndrome (KS, a neurological complication of AD), despite the role played by alcohol-related odors and taste in the emergence and maintenance of AD. This study thus investigated chemosensory impairments in AD and KS. Olfactory-gustatory measures were taken among 20 KS, 20 AD, and 20 control participants. Olfaction (odor detection-discrimination-identification) was assessed using the "Sniffin Sticks" battery and taste was measured using the "Taste Strips" task. Impairments were found for high-level olfaction in AD (odor discrimination) and KS (odor discrimination-identification), even after controlling for psychopathological comorbidities. Gustatory deficits were also observed in both groups, indexing a global deficit for chemosensory perception. Finally, the gradient of impairment between the successive disease stages for odor identification suggests that the hypothesis of a continuum between AD and KS regarding cognitive deficits can be generalized to chemosensory perception. AD and KS are thus characterized by deficits in chemosensory abilities, which could constitute a marker of the AD-KS transition. In view of its deleterious influence on everyday life, chemosensory dysfunction should also be taken into account in clinical settings.

Retronasal testing of olfactory function: an investigation and comparison in seven countries.

Flavor perception is to a large extent determined by olfaction, and persons who lost their sense of smell consequently complain about strongly reduced enjoyment of food. The retronasal olfactory function is especially important for flavor appreciation. The aim of this study was to compare retronasal function across different cultures and to develop a test that is applicable across cultures. Identification of 39 retronasal applied odor probes was tested in a total of 518 participants of seven countries; 292 of them were healthy, and 226 exhibited a smell disorder. A retest was performed with 224 of the healthy participants. Furthermore, all participants were tested for orthonasal threshold, identification, and discrimination ability. Significant cultural differences in identification ability were found in 92% of the probes. The 20 probes that could be identified above chance in healthy participants of all countries and that could differentiate between patients and controls were selected for the final retronasal test. This test was well able to differentiate between controls and patients in different countries and showed a good coherence with the orthonasal test (r = 0.80) and a good retest-reliability (r = 0.76). Furthermore, it is age-independent. The strong cultural differences observed in retronasal identification underline the necessity to develop a culturally independent instrument. This retronasal test is easy to apply and can be used across different countries for diagnostics and clinical research.

Targeted hypoglossal neurostimulation for obstructive sleep apnoea: a 1-year pilot study.

Continuous positive airway pressure (CPAP) is an effective but cumbersome treatment for obstructive sleep apnoea (OSA). Noncompliant patients need alternative therapies. We studied a tongue neurostimulation approach: targeted hypoglossal neurostimulation (THN) therapy with the aura6000™ System. A multi-contact electrode positioned around the main trunk of the twelfth nerve connected to an implanted pulse generator stimulates segments of the nerve, activating dilator muscles. The primary objective was to improve the polysomnographically determined apnoea/hypopnoea index (AHI) at 3 months, and maintain the improvement after 12 months of treatment. 13 out of 14 operated patients were successfully implanted. At 12 months, the AHI decreased from 45±18 to 21±17, a 53% reduction (p<0.001). The 4% oxygen desaturation index fell from 29±20 to 15±16 and the arousal index from 37±13 to 25±14, both p<0.001. The Epworth sleepiness scale decreased from 11±7 to 8±4 (p=0.09). THN was neither painful nor awakened patients, who all complied with therapy. There were two transient tongue paresis. The present study represents the longest study of any hypoglossal neurostimulation reported to date. We conclude that THN is safe and effective to treat OSA in patients not compliant with CPAP.

Plasticity of the human olfactory system: the olfactory bulb.

In the last years, an increasing interest has been paid to the olfactory system, particularly to its abilities of plasticity and its potential continuous neurogenesis throughout adult life. Although mechanisms underlying adult neurogenesis have been largely investigated in animals, to some degree they remain unclear in humans. Based on human research findings, the present review will focus on the olfactory bulb as an evidence of the astonishing plasticity of the human olfactory system.

Chronic Rhinosinusitis Outcome Registry (CHRINOSOR): Establishment of an International Outcome Registry Driven by mHealth Technology.

BACKGROUND: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics. OBJECTIVE: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology. METHODOLOGY: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion. RESULTS: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included. CONCLUSIONS: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE.

The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?

Chronic upper airway inflammation is amongst the most prevalent chronic disease entities in the Western world with prevalence around 30% (rhinitis) and 11% (rhinosinusitis). Chronic rhinitis and rhinosinusitis may severely impair the quality of life, leading to a significant socio-economic burden. It becomes more and more clear that the respiratory mucosa which forms a physiological as well as chemical barrier for inhaled particles, plays a key role in maintaining homeostasis and driving disease. In a healthy state, the mucosal immune system provides protection against pathogens as well as maintains a tolerance toward non-harmful commensal microbes and benign environmental substances such as allergens. One of the most important players of the mucosal immune system is immunoglobulin (Ig) A, which is well-studied in gut research where it has emerged as a key factor in creating tolerance to potential food allergens and maintaining a healthy microbiome. Although, it is very likely that IgA plays a similar role at the level of the respiratory epithelium, very little research has been performed on the role of this protein in the airways, especially in chronic upper airway diseases. This review summarizes what is known about IgA in upper airway homeostasis, as well as in rhinitis and rhinosinusitis, including current and possible new treatments that may interfere with the IgA system. By doing so, we identify unmet needs in exploring the different roles of IgA in the upper airways required to find new biomarkers or therapeutic options for treating chronic rhinitis and rhinosinusitis.

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.

Auditory Neuropathy Spectrum Disorders: From Diagnosis to Treatment: Literature Review and Case Reports.

Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by deteriorated speech perception, despite relatively preserved pure-tone detection thresholds. Affected individuals usually present with abnormal auditory brainstem responses (ABRs), but normal otoacoustic emissions (OAEs). These electrophysiological characteristics have led to the hypothesis that ANSD may be caused by various dysfunctions at the cochlear inner hair cell (IHC) and spiral ganglion neuron (SGN) levels, while the activity of outer hair cells (OHCs) is preserved, resulting in discrepancies between pure-tone and speech comprehension thresholds. The exact prevalence of ANSD remains unknown; clinical findings show a large variability among subjects with hearing impairment ranging from mild to profound hearing loss. A wide range of prenatal and postnatal etiologies have been proposed. The study of genetics and of the implicated sites of lesion correlated with clinical findings have also led to a better understanding of the molecular mechanisms underlying the various forms of ANSD, and may guide clinicians in better screening, assessment and treatment of ANSD patients. Besides OAEs and ABRs, audiological assessment includes stapedial reflex measurements, supraliminal psychoacoustic tests, electrocochleography (ECochG), auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs). Hearing aids are indicated in the treatment of ANSD with mild to moderate hearing loss, whereas cochlear implantation is the first choice of treatment in case of profound hearing loss, especially in case of IHC presynaptic disorders, or in case of poor auditory outcomes with conventional hearing aids.

Mechanisms Linking Olfactory Impairment and Risk of Mortality.

Olfaction is a sense involved in a complex set of tasks, influencing eating behavior, increasing awareness of environmental hazards and affecting social communication. Surprisingly, smell disorders are very frequent, especially in the elderly population. Several recent studies conducted mostly in older subjects have demonstrated a strong association between olfactory impairment and overall mortality risk, with anosmia being even more predictive of 5 years mortality risk than cardiovascular disease. Presently, the underlying pathophysiology linking olfactory impairment to mortality remains unknown and only putative mechanisms are suggested. This review aims to examine the link between olfactory impairment and mortality and to discuss existing ideas on underlying existing mechanisms including, (1) the effect of olfactory loss on nutrition, life-threatening situations and social interactions, (2) associated neurodegenerative diseases, (3) accelerated brain aging, and (4) reflection of general health status being reflected in olfactory function.

Neuropsychological profiles of children with vestibular loss.

BACKGROUND: The impact of vestibular loss (VL) on cognition has been previously studied in experimental animal, human and adult patient studies showing links between VL, and cognitive impairments in space orientation, working memory, mental rotation and selective attention. However, few studies have been conducted on children with VL. OBJECTIVE: We investigated for the first time, the impact of a VL on children's cognition. METHODS: 13 children with VL (10 years, 5 months) and 60 average-age matched controls performed a neuropsychological assessment consisting of visuospatial working memory, selective visual attention, mental rotation and space orientation tasks. RESULTS: Children with VL recalled smaller sequences for both forward and backward memory subtasks (mean±SD = 6.3±1.9 and 5.3±2.6) than controls (8.2±2.3 and 7.3±2.0), have less accurate mental rotation scores (25.4±6 versus 30.8±5.1) and greater additional distance travelled in the maze task (96.4±66.6 versus 60.4±66.3); all corrected p-values <0.05. Selective visual attention measures do not show significant differences. CONCLUSIONS: Children with VL show similar cognitive difficulties that adults with VL, in tasks involving dynamic cognitive processes (higher attentional load) that in tasks requiring static cognitive processes such as visual attention task.

Clinical significance of olfactory event-related potentials related to orthonasal and retronasal olfactory testing.

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.

Olfactory function and olfactory bulb volume in patients with postinfectious olfactory loss.

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.

Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell.

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.