The genomic landscape of Ménière's disease: a path to endolymphatic hydrops.

BACKGROUND: Ménière's disease (MD) is a disorder of the inner ear that causes episodic bouts of severe dizziness, roaring tinnitus, and fluctuating hearing loss. To date, no targeted therapy exists. As such, we have undertaken a large whole genome sequencing study on carefully phenotyped unilateral MD patients with the goal of gene/pathway discovery and a move towards targeted intervention. This study was a retrospective review of patients with a history of Ménière's disease. Genomic DNA, acquired from saliva samples, was purified and subjected to whole genome sequencing. RESULTS: Stringent variant calling, performed on 511 samples passing quality checks, followed by gene-based filtering by recurrence and proximity in molecular interaction networks, led to 481 high priority MD genes. These high priority genes, including MPHOSPH8, MYO18A, TRIOBP, OTOGL, TNC, and MYO6, were previously implicated in hearing loss, balance, and cochlear function, and were significantly enriched in common variant studies of hearing loss. Validation in an independent MD cohort confirmed 82 recurrent genes. Pathway analysis pointed to cell-cell adhesion, extracellular matrix, and cellular energy maintenance as key mediators of MD. Furthermore, the MD-prioritized genes were highly expressed in human inner ear hair cells and dark/vestibular cells, and were differentially expressed in a mouse model of hearing loss. CONCLUSION: By enabling the development of model systems that may lead to targeted therapies and MD screening panels, the genes and variants identified in this study will inform diagnosis and treatment of MD.

Burden of allergic rhinitis: allergies in America, Latin America, and Asia-Pacific adult surveys.

Allergic rhinitis (AR; also nasal allergies or "hay fever") is a chronic upper airway inflammatory disease that affects ∼60 million adults and children in the United States. The duration and severity of AR symptoms contribute to a substantial burden on patients' quality of life (QoL), sleep, work productivity, and activity. This study was designed to examine symptoms, QoL, productivity, comorbidities, disease management, and pharmacologic treatment of AR in United States and ex-U.S. sufferers. Allergies in America was a comprehensive telephone-based survey of 2500 adults with AR. These data are compared and contrasted with findings from the Pediatric Allergies in America, Allergies in Latin America, and Allergies in Asia-Pacific telephone surveys. The prevalence of physician-diagnosed AR was 14% in U.S. adults, 7% in Latin America adults, and 9% in Asia-Pacific adults. Nasal congestion is the most common and bothersome symptom for adults. Approximately two-thirds of adults rely on medication to relieve intolerable AR symptoms. Incomplete relief, slow onset, <24-hour relief, and reduced efficacy with sustained use were commonly reported with AR medications, including intranasal corticosteroids. One in seven U.S. adults reported achieving little to no relief with AR medications. Bothersome adverse effects of AR medications included drowsiness, a drying feeling, medication dripping down the throat, and bad taste. Perception of inadequate efficacy was the leading cause of medication discontinuation or change and contributed to treatment dissatisfaction. These findings support the assertion that AR burden has been substantially underestimated and identify several important challenges to successful management of AR.

Is there a role for aerosol nasal sprays in the treatment of allergic rhinitis: a white paper.

This White Paper presents the Consensus Statements derived from a Special Issues Board (SIB) held in Chicago, IL, in October 2010. The SIB was convened to address the question of whether there is a need for both aerosol and aqueous intranasal steroids (INSs) in the treatment of allergic rhinitis (AR). The faculty reviewed the published record of efficacy and safety of aerosol and aqueous INSs, as well as patient and physician satisfaction and preferences for currently available INSs, and burden of disease. Agreement on unmet needs also included the practice experience of the faculty and their colleagues. The body of evidence indicates that INSs are equally effective and well tolerated for most patients. However, differences exist among current aqueous formulations as well as between these products and their aerosol antecedents, based on the properties of the nasal spray. Aerosol formulations, although no longer available, may be preferred for some patients with specific pathophysiology and may be preferred by some patients based on sensory perception. There are good reasons to expand the currently available options of INSs by having both aerosol and aqueous formulations.

Allergy, Immunotherapy, and Alternative Treatments for Dizziness.

Allergic reactions may result in central symptoms of dizziness, including nonspecific chronic imbalance, Meniere's disease, and autoimmune inner ear disease. Excepting first-generation antihistamines, and short-term use of steroids, most pharmacotherapies used to treat allergic rhinitis have limited benefit in treating allergically induced or related dizziness. Allergy immunotherapy and/or an elimination diet for diagnosed food allergies have been found to be effective treatments. Individuals diagnosed with autoimmune inner ear disease remain challenging to treat and may require high-dose, long-term steroid treatment, biologics, or immunomodulators for symptom control.

Otologic Manifestations After COVID-19 Vaccination: The House Ear Clinic Experience.

OBJECTIVE: With the increasing numbers of COVID-19 vaccinations available there are some reports of new onset of otologic symptoms. We present our experience in recently vaccinated patients over a 30-day time frame. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary otology ambulatory practice. PATIENTS: All patients with available diagnostic codes, COVID-19 questionnaires and clinical notes. INTERVENTIONS: Observational recordings. MAIN OUTCOME MEASURES: Within the same 30-day time period in 2019, 2020, and 2021, 1.6, 2.4, and 3.8% respectively, of all office visits were for patients with the diagnosis of new onset idiopathic sensorineural hearing loss (SNHL) without other underlying otologic diagnoses. In this time frame in 2021, 30 patients out of the 1,325 clinical visits had new or significantly exacerbated otologic symptoms that began shortly after COVID-19 vaccination. Specifically, 18 patients received Moderna and 12 patients received Pfizer vaccine. Their mean age was 60.9±13.8 years old; 11 were women and 19 men. The mean onset of symptoms was 10.18 ±â€Š9 days post-vaccination. Symptoms included 25 patients (83.3%) with hearing loss, 15 (50%) with tinnitus, eight (26.7%) with dizziness, and five (16.7%) with vertigo. Eleven patients had previous otologic diagnoses, including six patients with Menière's disease, two with autoimmune inner ear disease (AIED), and three having both. CONCLUSIONS: There are no definite correlations to the COVID-19 pandemic or vaccination and new or worsened otologic symptoms. Vaccinated patients with new or exacerbated otologic symptoms should be promptly referred for evaluation. Suspected cases of post-vaccination otologic symptoms should be reported to the Center for Disease Control (CDC) vaccine adverse event reporting system (VAERS).

Burden of allergic rhinitis: results from the Pediatric Allergies in America survey.

Allergic rhinitis (AR), a chronic inflammatory disease of the upper airway, is one of the most common chronic diseases in the United States and is estimated to affect up to 60 million people. Pediatric Allergies in America is the largest and most comprehensive survey to date of pediatric patients and parents of patients with allergy, as well as health care providers (HCPs), regarding AR in children and its treatment. The goals of the survey were to determine the prevalence of AR in the US pediatric population and to collect information on what effect the condition has on patients in terms of symptom burden, quality of life, productivity, disease management, and pharmacologic treatment. This national survey screened 35,757 households to identify 500 children with HCP-diagnosed nasal allergies and 504 children without nasal allergies who were between the ages of 4 and 17 years. Parents of young children, as well as children 10 to 17 years of age, were questioned about the condition and its treatment. In parallel, 501 HCPs were interviewed. This survey has captured previously unavailable data on the prevalence of nasal allergies and their most common and most bothersome symptoms, on the effect of nasal allergies on the quality of life of children, and on medication use, including both over-the-counter and prescription medications, and has identified factors affecting satisfaction with treatment. The Pediatric Allergies in America survey also identifies distinct areas for improvement in the management of AR in children. In fact, based on the results of this survey, it appears that HCPs overestimate patients' and parents' satisfaction with disease management and the benefit of medications used for the treatment of nasal allergies in children. Findings from this national survey have identified important challenges to the management of AR, suggesting that its burden on children in the United States has been significantly underestimated.

Optimization of intranasal corticosteroid formulations for the treatment of allergic rhinitis.

Intranasal corticosteroids (INCSs) provide safe and effective treatment of allergic rhinitis (AR). Currently available INCSs differ in terms of the components included in each formulation that may influence efficacy, tolerability, and patient preference for treatment. Patient preference for a specific INCS is largely attributable to the sensory attributes that are dependent on characteristics of the formulation. Preservatives and additives can irritate and dry the mucosal membranes, or they can confer an unpleasant odor or taste to an INCS formulation. Spray volume also may affect patients' sensory perceptions of INCS formulations. Relative osmotic pressure or tonicity may affect nasal absorption and retention of an INCS and potentially affect clinical efficacy. A hypotonic suspension is a new formulation option for INCSs that may improve sensory attributes and has the potential to improve patient satisfaction and treatment outcomes in patients with AR. Optimization of INCS formulations may improve efficacy and tolerability and influence patient preference for treatment.

Patient and healthcare-provider perspectives on the burden of allergic rhinitis.

Allergic rhinitis (AR) is a chronic inflammatory disease characterized by nasal itching, sneezing, rhinorrhea, and nasal obstruction. Although the incidence of AR has been increasing, the reported prevalence of AR differs among surveys. Allergies in America was a comprehensive national survey that included 2500 adults diagnosed with AR and 400 healthcare practitioners who treat AR. Participants were interviewed about the burden of AR and comorbid conditions and the effect of AR on productivity and quality of life. Approximately 43% of nasal allergy sufferers reported that their nasal allergies were seasonal, and 56% indicated that their allergies were persistent throughout the year. Seasonal allergies were worse during the spring and fall, as reported by 56 and 45% of sufferers, respectively. Nasal congestion was ranked as the most common symptom experienced by patients daily or on most days during the worst month for nasal allergies. Patients and healthcare providers indicated that nasal congestion was the most bothersome symptom of AR. Asthma was diagnosed in 20% of patients with AR. Nasal allergy sufferers and healthcare providers indicated that nasal allergies affected productivity, led to missed workdays, and had a negative effect on patient quality of life. Patients and healthcare professionals report that symptoms of AR are bothersome. Effective treatment options for nasal symptoms of AR may decrease the burden of illness and improve patient productivity and quality of life.

Meniere's disease: prevalence of contralateral ear involvement.

OBJECTIVE: Determine the prevalence and time interval for conversion from unilateral to bilateral involvement in Meniere's disease and cochlear hydrops. STUDY DESIGN AND SETTING: Retrospective chart review in a tertiary otologic referral center. PATIENTS: 232 patients diagnosed with Meniere's Disease (n=186) or cochlear hydrops (n=46) between 1959 and 2001, who visited the clinic over a five-year period between 1997-2001 and have at least 2 audiograms more than 12 months apart. MAIN OUTCOME MEASURES: Prevalence of cochlear hydrops relative to Meniere's Disease, rate of progression from unilateral to bilateral involvement; interval between unilateral onset of symptoms and bilateral involvement; and rate of progression from cochlear hydrops to Meniere's disease. RESULTS: Initial diagnosis was Meniere's disease in 71% and cochlear hydrops in 29% of all 950 hydropic patients presenting between 1997 and 2001. In the study sample, Meniere's disease was bilateral at presentation in 11%; an additional 12% (14% of unilaterals) became bilateral during the follow-up period. At presentation, 6.5% of cochlear hydrops patients were bilateral, with another 26% becoming bilateral. Conversion from cochlear hydrops to Meniere's disease occurred in 33% and some of these are included among the bilateral. The average time interval for conversion from unilateral to bilateral Meniere's was 7.6 years (SD=7.0 years). CONCLUSION: Most otologists are aware of the potential for contralateral ear involvement and conversion from cochlear hydrops to Meniere's disease after diagnosis. These changes are significant, require long-term follow-up for detection, and may necessitate further treatment. Patients should be counseled regarding this potential when interventions are considered, especially with respect to ablative treatments.

Prognostic implications of and audiometric evidence for hearing fluctuation in Meniere's disease.

OBJECTIVES/HYPOTHESIS: 1) To establish criteria for significant hearing fluctuation by assessing the range and occurrence of hearing fluctuations over the course of Meniere's disease; 2) to determine if audiometric evidence exists to support the notion that Meniere's disease is a pathophysiologic process involving the whole cochlea; and 3) to suggest prognostic implications for initial hearing fluctuation in patients with Meniere's disease. STUDY DESIGN: Retrospective case series review. METHODS: A total of 488 patients diagnosed by 1995 American Academy of Otolaryngology-Head and Neck Surgery Meniere's disease criteria for whom audiometric data were prospectively collected (2 cohorts: 341 and 146 patients initially seen between April 2002 to July 2003 and between January to December 2010, respectively). Based on several definitions for significant hearing fluctuation, change in hearing was categorized as "same," "worse," or "better" between any two consecutive evaluations. The relationship of initial hearing fluctuation to future hearing fluctuation and future hearing loss was evaluated. RESULTS: Hearing fluctuation was evident in Meniere's disease patients with heterogeneous audiometric follow-up; and the characteristics of these hearing fluctuations, including the mean incidence, is described. Audiometric data suggests that there is a high congruence in Meniere's disease between changes in low- and high-frequency thresholds. Initial hearing fluctuation is associated with the occurrence of future and more frequent hearing fluctuations. CONCLUSION: Understanding the range of hearing fluctuations establishes a basis for determining audiometric thresholds used in evaluating future therapeutic trials aimed at the prevention of hearing loss in Meniere's disease. This knowledge will also inform the counseling directed toward patients diagnosed with Meniere's disease.

Prevalence of heat shock protein in patients with Meniere's disease and allergy.

OBJECTIVE: The study purpose was to investigate the prevalence of elevated heat shock protein 70 (HSP-70) in patients with Meniere's disease who have milk allergy compared with those who are not allergic to milk. METHODS: Fifty-five patients with Meniere's disease and allergy in whom milk allergy had been confirmed by intradermal progressive dilutional food testing or skin testing to milk antigen were included. Blood serum was tested for HSP-70 elevation with a Western blot assay using bovine renal extract. The 29 women and 26 men ranged in age from 29 to 76 years (mean age 52.8 years). Forty percent of the patients had bilateral Meniere's disease. RESULTS: Overall prevalence of HSP-70 elevation was 29.1%. This was higher in bilateral patients (50%) than unilateral patients (15%) (P

Randomized double-blinded, placebo-controlled clinical trial of famciclovir for reduction of Ménière's disease symptoms.

OBJECTIVE: To conduct a clinical trial of famciclovir for symptom control in Meniere's disease. STUDY DESIGN AND SETTING: Randomized, double-blinded placebo-controlled clinical trial in a tertiary referral center, with 12 subjects in the active treatment arm and 11 subjects in the placebo arm. RESULTS: There were no serious adverse events. Twenty-five percent of the famciclovir group and 18% of the placebo group showed a reduction in number of vertigo spells, the primary efficacy endpoint. This difference was not statistically significant. All subjects improved in dizziness and health-related quality of life. There was a trend for the famciclovir arm to have less fluctuation in hearing relative to the placebo arm. CONCLUSION: No dramatic effects of famciclovir were found on vertigo or dizziness. Some promising effects on reduction of the fluctuation in hearing were observed. SIGNIFICANCE: Famciclovir may suppress the fluctuation of hearing in Meniere's disease, but had a minimal effect on vertigo or dizziness symptoms in this study. The probable multifactorial etiology in Meniere's disease requires that further studies be conducted to determine the effects of antiviral medications. EBM RATING: A.

Techniques of intranasal steroid use.

OBJECTIVE: The effectiveness of topical intranasal steroids (INS) sprays for the treatment of allergic and nonallergic rhinitis may be limited by lack of instruction in the optimal spray technique. To determine whether the technique used affects the efficacy and safety of the product, this review of evidence had the goal of identifying and establishing a preferred method of applying INS sprays. STUDY DESIGN: A MEDLINE search of pertinent literature on 7 INS and 1 intranasal antihistamine spray preparations conducted with the use of appropriate search terms, yielded an initial 121 articles, 29 of which were identified as appropriate for review and grading for quality of evidence. RESULTS: The analysis provided no definitive evidence regarding how best to instruct patients to use INS or antihistamine spray devices. CONCLUSIONS: On the basis of a lack of clear evidence regarding instructions to maximize efficacy and safety of these drugs, the panel recommended a 7-step standard technique.

Allergy and the contemporary otologist.

Allergy may affect the outer, the middle, or the inner ear. Although the otologic manifestations of allergy are not by themselves diagnostic, the history, including family history and associated symptoms in other target organs, will often help lead to the correct diagnosis and institution of therapy. Patients with significant and chronic symptoms, including those with labyrinthine symptoms of allergy, respond well to specific immunotherapy or dietary elimination.

An open label study to evaluate the safety and efficacy of intratympanic golimumab therapy in patients with autoimmune inner ear disease.

OBJECTIVE: To evaluate the safety and efficacy of intratympanically injected golimumab (GLM), a TNF-α inhibitor, as a steroid-sparing agent for patients with steroid-dependent autoimmune inner ear disease (AIED). STUDY DESIGN: Open label. SETTING: Tertiary referral center. PATIENTS: Ten patients with steroid-dependent AIED were enrolled in Stage 2. The average patient age at enrollment was 59, with an average of 12.5 years from the start of bilateral hearing loss symptoms. The average dose of daily prednisone at the start of injections was 18 mg. INTERVENTION: Intratympanic injection of GLM. MAIN OUTCOME MEASURE: Hearing loss progression (treatment failure) was defined as either an increase in pure-tone thresholds by frequency or a decrease in word recognition score. RESULTS: There were no serious adverse events. Five of seven per-protocol subjects experienced stable pure-tone thresholds in the injected ear, whereas 4 had stable word recognition scores. Two subjects experienced an improvement in word recognition scores. The results support the hypothesis that GLM may be a promising treatment. CONCLUSIONS: The TNF-α inhibitor GLM stabilized hearing in 3 of 7 per-protocol subjects with AIED and allowed a complete tapering off of prednisone in those 7 subjects. Studies with larger samples sizes are warranted.

New horizons: Current and potential future self-treatments for acute upper respiratory tract conditions.

Acute upper respiratory tract conditions (URTCs), including the common cold, allergic rhinitis (AR), and acute sinusitis, are among the most common afflictions worldwide, affecting millions of individuals annually in the United States alone. A common theme among these conditions is that they share similar symptomatology and are often inadequately treated. These conditions typically cause mild, albeit bothersome, symptoms for a typical duration of 7 to 10 days in the case of the common cold, ≥ 2 weeks for AR exacerbations, and > 4 weeks for acute sinusitis. The common cold and AR elicit localized (upper airway) and systemic inflammatory cascades responsible for symptoms such as cough, nasal congestion, rhinorrhea, watery eyes, sneezing, headache, and general malaise. Acute sinusitis typically occurs because of a secondary bacterial or fungal infection of mucus-clogged nasal and sinus cavities and has symptoms similar to those previously listed, with the addition of increased facial and ear pressure/pain. Acute URTC symptoms are frequently managed with over-the-counter (OTC) products. Currently available OTC options can have limited efficacy in treating the broad array of symptoms associated with acute URTCs, and some have unwanted side effects. There is an unmet need for OTC therapies that have broad clinical activity, can reduce the severity and duration of illness when taken at the first sign of symptoms, and/or provide prophylaxis. This review article examines the available evidence supporting emerging and potentially new OTC pharmacologic, nutraceutical, and nonpharmacologic therapies on the horizon for the treatment of acute URTCs. This review is not intended to be a comprehensive evaluation of all potential URTC therapies, and the approvability of many of the agents discussed for OTC use in the United States may be subject to debate.

Oral steroid treatment for hearing improvement in Ménière's disease and endolymphatic hydrops.

OBJECTIVE: To determine the effect of oral steroid treatment on hearing in unilateral Ménière's disease and endolymphatic hydrops patients. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: All patients presenting during the 2010 calendar year with confirmed unilateral Ménière's disease or endolymphatic hydrops. Those with a first visit and second visit audiogram (n = 58) were included in the analysis of oral steroid treatment effect. INTERVENTION: Steroid treatment for hearing loss. MAIN OUTCOME MEASURE: Change in hearing, as defined by change in affected ear threshold values or speech discrimination score from pretreatment visit to posttreatment visit. RESULTS: Hearing (threshold, speech discrimination score) in patients' affected ear did not significantly change from first visit to second visit after treatment with steroids relative to patients who did not receive steroid treatment. CONCLUSION: The results of this and other studies would indicate that a Ménière's disease or endolymphatic hydrops patient is unlikely to experience an improvement in hearing from a short course of oral steroid. Clinically observed temporary improvement did not sustain over several months. Further work to elucidate the mechanisms underlying hearing loss in hydrops, perhaps focusing on the dendrite damage noted in animal models of hydrops, is warranted.

Comorbidities and allergic rhinitis: not just a runny nose.

Allergic rhinitis is rarely found in isolation and should be considered in the context of upper and lower airway disease. People with AR are at greater risk of suffering asthma, rhinosinusitis, and other related upper airway conditions. Most people with both nasal allergies and asthma report that their asthma gets better when their nasal allergies are under control. People with AR are more than twice as likely to suffer problems sleeping due to their nasal allergy symptoms.

Facing the music: pre- and postconcert assessment of hearing in teenagers.

OBJECTIVE: Determine the effect of exposure to a single rock/pop concert on pure-tone hearing thresholds and outer hair cell function in teenagers. STUDY DESIGN: Repeated measures pre- and postconcert assessment of hearing. SETTING: Mobile hearing conservation test vehicle and large indoor concert venue. SUBJECTS: Twenty-nine normal-hearing teenagers and young adults ages 13 to 20 years. INTERVENTION: Attendance at a public rock/pop concert. MAIN OUTCOME MEASURES: Pre- and postconcert pure-tone thresholds in both ears from 500 Hz to 8 kHz, pure-tone average (PTA) for 2, 3, and 4 kHz, distortion product otoacoustic emissions (DPOAEs), proportion of subjects experiencing a PTA change of 10 dB or greater. RESULTS: Concert sound levels at the subjects' position averaged 98.5 dBA. Only 3 subjects used the hearing protection provided. Thresholds for 2 to 6 kHz increased significantly from pre- to postconcert (p ≤ 0.001). The increase in PTA (2, 3, and 4 kHz) between test intervals averaged 6.3 and 6.5 dB for the right and left ears, respectively, and 33.3% of subjects had a threshold shift of 10 dB or greater in the PTA in at least 1 ear (p ≤ 0.001). The number of subjects experiencing a reduction in DPOAE amplitude (17/25) and the change in mean amplitude were statistically significant (p ≤ 0.001 and p ≤ 0.004, respectively). CONCLUSION: Exposure to a single live-music rock/pop concert can produce a threshold shift and decrease in otoacoustic emissions amplitude indicating impact on outer hair cell function. Results clearly indicate a need for research on this public health issue regarding "safe" listening levels, especially in younger people with more years for accrual of damage.