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.

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.

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.

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 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.

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 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.

Cortical Plasticity and Olfactory Function in Early Blindness.

Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented "visual" cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

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.

Targeted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea: Six-month results.

OBJECTIVES/HYPOTHESIS: This feasibility study was designed to show the preliminary safety and efficacy of targeted hypoglossal neurostimulation (THN), and to identify baseline predictors of successful therapy. STUDY DESIGN: Open-label, prospective, multicenter, single-arm cohort study, conducted at seven centers in the U.S.A. and Europe. METHODS: Forty-six participants with moderate to severe obstructive sleep apnea (OSA), failing or intolerant of continuous positive airway pressure, were implanted. Primary (Apnea-Hypopnea Index [AHI], Oxygen Desaturation Index [ODI]) and secondary (Arousal Index, Epworth Sleepiness Scale Index, Sleep Apnea Quality of Life Index) outcomes were measured at baseline and compared at 6 months. Data were analyzed to identify participant characteristics that would predict success with therapy. RESULTS: Sixty-seven adverse events (AEs) were observed among 36 participants; most of the AEs were related to the implant procedure and resolved without sequelae; one device replacement was necessary. Forty-three participants showed significant (P < .01) decreases in both AHI and ODI at 6 months; 35% (15 of 43) met criteria for AHI responders and 40% (17 of 43) for ODI responders. Significant improvement was observed in all the secondary endpoints. Predictors-of-success selection criteria were identified as baseline AHI < 65/hr, baseline apnea index ≤ 30, baseline body mass index < 35, and <15 events/hr of SpO2 decrease > 10%. Seven participants met these criteria; 86% (6 of 7) were AHI responders and 86% (6 of 7) were ODI responders, indicating that THN therapy can be efficacious in a carefully selected population of OSA patients. CONCLUSIONS: This feasibility study suggests that THN therapy is likely to be safe and effective in selected patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:2618-2623, 2016.

Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma.

The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time.

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.

Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a very frequent affliction that affects about 1-5% of the adult population in its severe form. Continuous positive airway pressure (CPAP) is the most commonly used treatment and is highly effective, but its use is limited by low long-term adherence rates and overall poor acceptance among the patients. Therefore, there is a need for developing alternative approaches to OSA treatment, including a more 'natural' concept of maintaining an open airway through neuromodulation. Here we review the concept, scientific rationale, and technical details of hypoglossal nerve stimulation. We also review results of published clinical studies with several hypoglossal stimulation devices that are being investigated today. Hypoglossal nerve stimulation appears to be a very promising treatment for patients with moderate-to-severe OSA. If its efficacy is confirmed, it will probably be complementary with CPAP therapy and initially aimed at patients unable or unwilling to use CPAP. Once it becomes a standard therapy, its advantages might prove sufficient to challenge CPAP as the first-line therapy.

Unirhinal Olfactory Testing for the Diagnostic Workup of Mild Cognitive Impairment.

BACKGROUND: Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage. OBJECTIVES: Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI). METHODS: Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls. RESULTS: As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups. CONCLUSION: MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

Volume of olfactory bulb and depth of olfactory sulcus in 378 consecutive patients with olfactory loss.

The aim of this study was to investigate the olfactory bulb (OB) and sulcus (OS) in a large group of patients who have been well-characterized in terms of olfactory function, with a specific focus on the comparison between patients with olfactory loss due to chronic rhinosinusitis, head trauma, or acute infections. A retrospective study of 378 patients with olfactory loss was performed. Orthonasal olfactory function was assessed with the"Sniffin' Sticks" test kit, including tests for odor threshold, odor discrimination, and odor identification. Magnetic resonance imaging analyses were focused on OB volume and OS depth. Major results of the present study included the (1) demonstration of a correlation between olfactory function and OB volume across the various pathologies in a very large group of subjects; (2) the three functional tests exhibited a similar degree of correlation with OB volume. (3) The right, but not the left OS correlated with olfactory function; in addition, (4) OS was negatively correlated with age. In contrast to OS, (5) no side differences were found for the OB. Finally, (6) the three different causes of olfactory loss exhibited different patterns of results for the three olfactory tests. The present data suggest that the morphological assessment of the OB volume and OS depth produces useful clinical indicators of olfactory dysfunction.

Altered top-down cognitive control and auditory processing in tinnitus: evidences from auditory and visual spatial stroop.

PURPOSE: Tinnitus is the perception of a sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. Here, we hypothesize that these brain alterations affect top-down cognitive control mechanisms that play a role in the regulation of sensations, emotions and attention resources. METHODS: The efficiency of the executive control as well as simple reaction speed and processing speed were evaluated in tinnitus participants (TP) and matched control subjects (CS) in both the auditory and the visual modalities using a spatial Stroop paradigm. RESULTS: TP were slower and less accurate than CS during both the auditory and the visual spatial Stroop tasks, while simple reaction speed and stimulus processing speed were affected in TP in the auditory modality only. CONCLUSIONS: Tinnitus is associated both with modality-specific deficits along the auditory processing system and an impairment of cognitive control mechanisms that are involved both in vision and audition (i.e. that are supra-modal). We postulate that this deficit in the top-down cognitive control is a key-factor in the development and maintenance of tinnitus and may also explain some of the cognitive difficulties reported by tinnitus sufferers.