Naohiro Yoshida

Clinical efficacy of anti-IgE therapy for eosinophilic otitis media.

Objective Eosinophilic otitis media (EOM) is an intractable otitis media characterized by a highly viscous effusion containing eosinophils, and high levels of immunoglobulin (Ig) E are detected in the middle ear effusion (MEE). We carried out a pilot study to determine whether anti-IgE therapy is efficacious in the treatment of EOM. Study Design Prospective study. Setting Tertiary referral center. Patients and Methods Eight patients with EOM received the anti-IgE agent omalizumab for at least 3 months, in addition to ordinary treatments for EOM. They were evaluated by a questionnaire for ear and respiratory symptoms, clinical scores, surrogate markers in the blood, and hearing acuity before and after the anti-IgE therapy. Nine EOM patients without anti-IgE therapy were included as controls. Results The ear symptom scores and clinical scores gradually decreased during the therapy. In particular, 5 patients who were treated for more than 1 year showed improvement of their clinical scores with resolution of the MEE. The total serum IgE level was significantly elevated after 3 months of therapy (p < 0.01). Deterioration of the bone conduction hearing levels was more frequently found in the control group than in the omalizumab group. Conclusion This pilot study provides new evidence establishing that long-term anti-IgE therapy improved the clinical ear symptoms of EOM and bone conduction hearing levels were mostly preserved. Therefore, long-term anti-IgE therapy can be effective for EOM to inhibit eosinophilic inflammation in the middle ear.

Audiometry with nasally presented masking noise: novel diagnostic method for patulous eustachian tube.

Objective: Nasal-noise masking audiometry was developed to assess the acoustic transfer function from the nasopharyngeal cavity to the middle ear via patulous eustachian tube (ET). Study Design: Prospective. Setting: Tertiary referral center. Patients: Twenty-seven ears of 18 patients with patulous ET and 20 ears of 10 healthy subjects with no history of ear disease or complaints of aural symptoms. Main Outcome Measures: Audiometric measurement was conducted with and without masking noise presented in the nasal cavity. Results: The masking effect of nasally presented noise caused elevation of the threshold for the tone presented in the external auditory canal. This threshold elevation was significantly greater, particularly in the lower-frequency region, in ears with patulous ET and was decreased to the normal range after obstructive treatment of the patulous ET. Conclusion: Nasal-noise masking audiometry is a simple and effective way to identify patulous ET.

Differences in middle ear ventilation disorders between pars flaccida and pars tensa cholesteatoma in sonotubometry and patterns of tympanic and mastoid pneumatization.

Objective To investigate differences in middle ear ventilation mechanisms between pars flaccida and pars tensa cholesteatoma. Study Design Retrospective case review. Setting A referral hospital otolaryngology department. Patients Sixty-six ears with pars flaccida cholesteatoma (mean age, 45.7 yr) and 19 ears with pars tensa cholesteatoma (mean age, 58.8 yr) were included. Patients with totally adhesive tympanic membranes or mixed-type cholesteatoma were excluded. Interventions Patients underwent canal wall down tympanoplasty with canal reconstruction. The canal wall was reconstructed with tragal or conchal cartilage and cortical bone grafts. Main Outcome Measures Habitual sniffing, preoperative sonotubometry results, mastoid pneumatization (maturation), and postoperative aeration around the stapes were investigated. Preoperative mastoid pneumatization and postoperative aeration around the stapes were measured on computed tomography scans. Results Ten (15.4%) of 65 patients with pars flaccida cholesteatoma and 3 (15.7%) of 19 patients with pars tensa cholesteatoma were habitual sniffers (p = 0.5). Preoperative sonotubometry indicated that a patulous pattern was more common in ears with pars flaccida than pars tensa cholesteatoma (42.8% versus 7.1%, p < 0.05), and a stenotic pattern was more common in ears with pars tensa than pars flaccida cholesteatoma (85.8% versus 42.8%, p < 0.01). Preoperative mastoid pneumatization and postoperative aeration around the stapes were significantly better in ears with pars flaccida than pars tensa cholesteatoma (p < 0.01 and p < 0.05, respectively). Conclusion Significantly different tubal function and mastoid pneumatization patterns suggest differences in ventilation disorders and cause between ears with pars flaccida and pars tensa cholesteatoma.

Reversible cochlear function with ANCA-associated vasculitis initially diagnosed by otologic symptoms.

Objective To present 8 cases with hearing loss as an initial symptom of antineural cytoplasmic antibody (ANCA)–associated vasculitis (AAV) involving granulomatosis with polyangiitis (GPA) and to discuss the treatment and mechanisms of hearing outcomes after immunosuppressive therapy. Study Design Retrospective case review. Setting Tertiary referral center. Patients Eight patients were referred to our university hospital between 2004 and 2012 for intractable otitis media with acute progressive mixed (conductive and sensorineural) hearing loss and facial palsy. Intervention(s) Diagnostics and treatment. Main Outcome Measures Otologic symptoms as initial manifestations of otitis media with AAV and cochlear function after treatment. Results Eight cases (6 female and 2 male subjects; aged 54–73 yr; 6 MPO [myeloperoxidase]–ANCA-positive and 2 PR3 [proteinase 3]–ANCA-positive cases) were included. Progressive hearing loss was present in all patients, and facial palsy was present in 5 of 8 patients total. Patients with hearing levels better than 95 dB improved with good speech discrimination after immunosuppressive therapy, but the completely deaf could not be recovered. All patients have been successfully controlled for 1 to 8 years without any systemic disorders. Conclusion This study showed the difficulty of diagnosing localized AAV and the effectiveness of immunosuppressive therapy for hearing loss in the early stage. Based on these results, early-stage AAV would influence the stria vascularis in the cochlea. Otitis media with ANCA-associated vasculitis is a new entity among the causes of intractable otitis media and progressive hearing loss.

Relationship between postoperative aeration around the stapes and postoperative hearing outcome after canal wall down tympanoplasty with canal reconstruction for cholesteatoma.

Objectives: To evaluate the correlation between postoperative aeration around the stapes and hearing outcome after canal wall down tympanoplasty with canal reconstruction for cholesteatoma. Study Design: Retrospective case review. Setting: University hospital otolaryngology department. Patients: Seventy ears of 65 patients with middle ear cholesteatoma were included. Patients who had fixed or poorly mobile ossicular chain was excluded. Interventions: They were underwent canal wall down tympanoplasty with canal reconstruction. Canal wall was reconstructed with the tragal or conchal cartilage and the cortical bone plate. Main Outcome Measures: We measured aeration around the stapes on coronal and axial computed tomographic sections at 1 year after ossiculoplasty and investigated the correlation between postoperative aeration around the stapes and postoperative air-bone gap (using the mean of 0.5-, 1-, and 2-kHz threshold values) at 1 year after ossiculoplasty. We also investigated it for each of Wullstein type and for each of 0.25-, 0.5-, 1-, 2-, and 4-kHz thresholds. Results: Aeration around the stapes was negatively correlated with postoperative air-bone gap (correlation coefficient, -0.53; p < 0.05). Types I and IV tympanoplasty had a higher correlation with postoperative air-bone gap than type III tympanoplasty. The 0.5-KHz frequency had a higher correlation with postoperative air bone gap than other frequencies. Conclusion: Measurement of postoperative aeration around the stapes is an effective method for evaluating the importance of middle ear aeration. Aeration around the stapes contributes to better hearing outcome.

Effects of heat stress on Young's modulus of outer hair cells in mice.

Intense sound exposure causes permanent hearing loss due to hair cell and cochlear damage. Prior conditioning with sublethal stressors, such as nontraumatic sound, heat stress and restraint protects the ear from acoustic injury. However, the mechanisms underlying conditioning-related cochlear protection remain unknown. In this paper, Youngs modulus and the amount of filamentous actin (F-actin) of outer hair cells (OHCs) with/without heat stress were investigated by atomic force microscopy and confocal laser scanning microscopy, respectively. Conditioning with heat stress resulted in a statistically significant increase in Youngs modulus of OHCs at 3-6 h after application, and such modulus then began to decrease by 12 h and returned to pre-conditioning level at 48 h after heat stress. The amount of F-actin began to increase by 3 h after heat stress and peaked at 12 h. It then began to decrease by 24 h and returned to the pre-conditioning level by 48-96 h after heat stress. These time courses are consistent with a previous report in which heat stress was shown to suppress permanent threshold shift (PTS). In addition, distortion product otoacoustic emissions (DPOAEs) were confirmed to be enhanced by heat stress. These results suggest that conditioning with heat stress structurally modifies OHCs so that they become stiffer due to an increase in the amount of F-actin. As a consequence, OHCs possibly experience less strain when they are exposed to loud noise, resulting in protection of mammalian hearing from traumatic noise exposure.

Effect of omalizumab on biomarkers in middle ear effusion in patients with eosinophilic otitis media

Abstract Conclusions: Eosinophil cationic protein (ECP) concentrations in middle ear effusion (MEE) in patients with eosinophilic otitis media (EOM) were significantly decreased at 3 months after the administration of omalizumab from the baseline level (p < 0.05). This study provides new evidence that omalizumab reduces eosinophilic inflammation in the middle ear and that the reduction of ECP may not be caused by suppression of interleukin (IL)-5 production in the middle ear mucosa. Objective: EOM is an intractable otitis media characterized by a highly viscous effusion containing eosinophils. We recently reported that anti-IgE therapy using omalizumab was efficacious in the treatment of EOM. To clarify the underlying mechanism, we determined changes in biomarkers in MEE related to eosinophilic inflammation after therapy. Methods: Nine patients with EOM received the anti-IgE agent omalizumab for 3 months. Among them, five patients continued anti-IgE therapy for longer than 1 year. Eight EOM patients without administration of omalizumab were also included in the study as controls. The concentrations of eosinophilic inflammatory markers such as ECP, IgE, IL-4, and IL-5 in MEE were measured before and after the administration of omalizumab. Results: After 3 months of omalizumab therapy, the ECP concentration in MEE was significantly reduced from the baseline level (p < 0.05), while no significant change of ECP in the serum was observed. The concentrations of IL-4 and IL-5 in MEE showed no significant change before and after the therapy in EOM patients treated with omalizumab.

A comparison of patterns of disease extension in keratosis obturans and external auditory canal cholesteatoma.

Objective To investigate the different pathways of progression to the middle ear in keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). Study Design Retrospective case review. Setting Referral hospital otolaryngology department. Patients Patients with KO or EACC and middle ear disease who underwent surgical management were included. Four ears of 4 patients (mean age, 41.25 yr) were the KO group, and 5 ears of 4 patients (mean age, 49.5 yr) were the EACC group. Main Outcome Measures Intraoperative findings of the middle ear cavity were investigated in KO and EACC groups. Results In the KO group, 3 patients had a perforated tympanic membrane and cholesteatoma in the tympanic cavity. The other patient had preoperative right facial palsy. Removal of the keratin plug revealed an adherent tympanic membrane. In intraoperative findings, the tympanic segment of the fallopian canal was found to be eroded because of inflammation. No case initially progressed to the mastoid cavity. Four patients had external auditory canal cholesteatoma with middle ear disease. In EACC group, all patients had initial progression to the mastoid cavity. Conclusion KO tends to progress initially to the tympanic cavity via a diseased tympanic membrane. EACC tends to progress to the mastoid cavity via destruction of the posterior bony canal. This is the first report to investigate differences in pathway of progression to the middle ear cavity in these 2 diseases.

A comparison of preoperative characteristics of chronic otitis media in Down and non-Down syndrome.

Objective To investigate preoperative clinical findings of chronic otitis media (COM) in patients with Down and without (non-Down) syndrome. Study Design Retrospective. Setting Referral hospital, otolaryngology department. Patients Patients with COM who underwent tympanoplasty were included. There were 10 ears of 8 patients (mean age, 14.9 yr) in the Down group and 44 ears of 41 patients (mean age, 14.7 yr) in the non-Down group. Main Outcome Measures Clinical characteristics, including the frequency of preoperative persistent otorrhea, cause of COM, and mastoid pneumatization (maturation), were compared between the 2 groups using clinical records and temporal bone computed tomography (CT). Results Preoperative persistent otorrhea was more frequent in the Down group (60%) than in the non-Down group (27.2%; p < 0.05). Perforation due to tympanostomy tube insertion also occurred more frequently in the Down group (100%) than in the non-Down group (53.3%; p < 0.05). Mastoid pneumatization occurred significantly less in the Down group than in the non-Down group (p < 0.01). There was no significant difference in mastoid pneumatization regardless of the presence or absence of a past history of tympanostomy tube insertion in the Down group (p = 0.3, t test) unlike that in the non-Down group (p < 0.05, t test). All ears attained a dry condition with no perforated eardrums. Conclusion Frequent draining ear and extremely immature mastoid pneumatization, regardless of the presence or absence of a past history of tympanostomy tube insertion, were clinically important characteristics of COM in patients with Down syndrome.

Clinical characteristics and surgical benefits and problems of chronic otitis media and middle ear cholesteatoma in elderly patients older than 70 years.

Objective To investigate the benefits and problems of tympanoplasty in elderly patients older than 70 years. Study Design Retrospective case review. Setting Referral hospital otolaryngology department. Patients Among 1,014 patients who underwent tympanoplasty for chronic otitis media from 2006 to 2011, those aged over 70 years were eligible for inclusion. Main Outcome Measures Clinical characteristics including tympanosclerosis and preoperative severe complications were investigated. In chronic otitis media group, hearing outcomes (air-bone gap at 500-Hz and 1- and 2-kHz frequency) and postoperative ear condition were investigated. In chronic otitis media with cholesteatoma, clinical characteristics including postoperative bone conduction hearing threshold (at 500-Hz and 1- and 2-kHz frequency) were investigated. Results Ninety-seven ears of 83 patients were included. Eighteen ears had obvious findings of tympanosclerosis (18/97 = 18.6%). In chronic otitis media without cholesteatoma (52 ears/47 patients), no preoperative complications were noted. The mean air-bone was 30.8 and 16.1 dB before and after the operation, respectively (p < 0.001). Otorrhea disappeared in 51 ears (98.1%). In chronic otitis media with cholesteatoma (42 ears/33 patients), we noted preoperative severe complications including labyrinthine fistula (7/97 = 7.22%), widely exposed dura (1/97 = 1.03%), and facial palsy 1 (1/97 =1.03%). The mean bone conduction hearing threshold was 39.6 dB and 40.89 dB, respectively (p = 0.7). Three ears of 3 patients had operated ears with open mastoid and underwent canal wall reconstruction tympanoplasty. Conclusion Tympanoplasty in elderly patients older than 70 years seems to be as safe as when performed in younger patients.