Higher Prevalence and Severity of Eosinophilic Otitis Media in Patients with Asthma-COPD Overlap Compared with Asthma Alone.

INTRODUCTION: Eosinophilic otitis media (EOM) is well-known to frequently co-exist with adult-onset asthma. Both diseases are similar type 2 inflammation and are considered to have a "one airway, one disease" relationship. Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO), characterized by airway obstruction caused by airway wall thickening (AWT), is a severe condition with a higher incidence of mortality compared to asthma alone or COPD alone. Based on the "one airway, one disease" concept, we hypothesized that the inflammatory pathophysiology of EOM differs depending on its comorbidity with ACO or with asthma alone. METHODS: A total of 77 chronic rhinosinusitis (CRS) patients with asthma were enrolled in this study. The subjects were divided into 2 groups: a group with comorbid asthma alone (asthma group; 46 patients), and a group with comorbid ACO (ACO group; 31 patients). The 2 groups were compared and assessed with regard to various factors, including the patients' clinical characteristics, prevalence rate of EOM, EOM severity, EOMs relationships with smoking and AWT, and the eosinophil and neutrophil cell counts in the middle ear effusion (MEE). RESULTS: The ACO group included significantly more males (p < 0.05), was significantly older (p < 0.05), and showed significantly lower lung function values (FEV1 [L], FEV1 [%pred]) (p < 0.01) compared with the asthma group. The ACO group also had a significant history of smoking as shown by the Brinkman index (p < 0.01) and greater AWT as assessed by high-resolution computed tomography (p < 0.05). The EOM prevalence rate was significantly higher in the ACO group (p < 0.05), especially with increased ACO severity (p < 0.05). The EOM severity was also significantly higher in the ACO group (p < 0.05) and also correlated with the ACO severity (p < 0.05). The pretreatment ear clinical characteristics score and the average air conduction hearing level were significantly higher in the ACO group (p < 0.05). The eosinophil percentage in the MEE/otorrhea was significantly lower in the ACO group (25.3%) than in the asthma group (54.7%) (p < 0.05). Conversely, the neutrophil percentage was significantly higher in the ACO group (75.7% vs. 41.9%) (p < 0.05). CONCLUSIONS: Our findings suggest that, in CRS patients with asthma, comorbidity with ACO may be a clinical factor leading to increased EOM prevalence and severity, as well as a higher neutrophil infiltration percentage in the middle ear. Cessation of smoking and early therapeutic intervention for ACO may mitigate progression of bronchial remodeling (i.e., reduce AWT) and help reduce the prevalence and severity of EOM.

Increased Expression of Activation-Induced Cytidine Deaminase in Sinus Mucosa from IgG4-Related Disease Patients with Comorbid Chronic Rhinosinusitis.

OBJECTIVE: IgG4-related disease (IgG4-RD) is a systemic condition characterized by an elevated serum IgG4 level, localized infiltration of IgG4-positive plasma cells, and lesions in various organs. IgG4-RD also shows high rates of complication with allergic diseases and is often accompanied by elevated serum IgE levels. Reports in recent years have also shown high rates of complication with chronic rhinosinusitis (CRS) and its characteristic nasal manifestations. Accordingly, we speculate that there may be a distinct form of CRS that, as an IgG4-RD, differs from other CRS. Here, we investigated whether the elevated levels of factors that are thought to be important in the pathogenesis of IgG4-RD are also seen in the sinus mucosa of IgG4-RD-associated CRS patients. METHODS: Ethmoid sinus mucosa specimens from 9 IgG4-RD (6 Mikulicz disease and 3 Küttner's tumor) patients with elevated serum IgG4 and IgE and from 22 control CRS patients were examined immunohistochemically for Treg cytokines (IL-10 and TGF-ß), activation-induced cytidine deaminase (AID), and immunocompetent cells. The 22 control CRS patients were divided into 3 subgroups based on the serological findings for IgG4 and IgE. Quantitative real-time PCR was performed to examine the expression of AID. RESULTS: The ethmoid sinus mucosa from patients with IgG4-RD-associated CRS showed, in comparison with the 3 CRS control subgroups, significantly elevated AID production. Their mucosa also showed significantly increased infiltration of CD-20-positive immunocompetent cells compared with the controls. On the other hand, immunohistochemical examination found no significant differences in the number of IL-10- or TGF-ß-positive cells. CONCLUSION: Ethmoid sinus mucosa from IgG4-RD-associated CRS patients showed clearly increased AID production, suggesting AID involvement in class-switching to IgG4 in those local sites. This implies the existence of a distinct form of CRS that is an IgG4-RD.

Sialorrhea Successfully Treated by the Combined Use of Selective M1 and M3 Muscarinic Acetylcholine Receptor Antagonists.

Sialorrhea is often treated with anticholinergic agents, but they can have undesirable side effects such as drowsiness, sedation, and constipation. Effective medication that acts selectively on the salivary glands is needed. We report the case of a patient with sialorrhea who was successfully treated by the combined use of pirenzepine and solifenacin (M1 and M3 muscarinic receptor antagonists, respectively). The patient was a 51-year-old man with mean unstimulated and stimulated salivary flow rates per 10 min of 6.1 mL and 41.7 mL, respectively (both were measured three times). 99mTcO4- salivary gland scintigraphy revealed characteristic spontaneous saliva secretion without stimulation. He was treated with Scopolia extract, escitalopram, solifenacin succinate, and the combined administration of solifenacin succinate and pirenzepine. A statistically significant decrease was observed from the pre-medication unstimulated and stimulated salivary flow rates only following the combined administration of solifenacin and pirenzepine. The major muscarinic receptor subtype expressed in the salivary glands is M3; however, M1 is also present. A study using knockout mice demonstrated that the presence of either M1 or M3 receptors was sufficient for salivation. Thus, the combined use of selective M1 and M3 antagonists could provide a good treatment option for sialorrhea.

Tonsillectomy plus steroid pulse therapy is the most effective treatment in adult patients with C-Grade I IgA nephropathy, and the weight of the extracted palatine tonsils and Yamamoto scale have no significant correlation with the effects of this treatment.

OBJECTIVE: We studied patients who underwent tonsillectomy plus steroid pulse therapy (TSP) for immunoglobulin A nephropathy (IgAN), in order to investigate the clinical factors associated with a positive response to this treatment. METHODS: We analyzed 118 IgAN patients who underwent TSP. We collected patients' data retrospectively, including age, sex, blood pressure, onset of IgAN, pathological findings of a renal biopsy, serum concentration of creatinine, estimated glomerular filtration rate, serum concentration of protein, urinary protein, hematuria, past history of tonsillitis, the Yamamoto scale, the weight and pathological findings of the extracted palatine tonsils, and the presence or absence of anti-platelet drugs and renin-angiotensin system inhibitors (RAS-I) usage. This study included participants who were over 18 years of age, had undergone tonsillectomy within three months of steroid pulse therapy administered thrice, in whom renal biopsy was performed within a year before treatment, and with follow-up period of over 3 years. Clinical remission (CR) of urinary abnormalities was defined as remission of both proteinuria and hematuria: three consecutive negative results over a 6-month period, with a urinary sediment red blood cell count of <5/HPF, and a proteinuria qualitative reaction of (-) to (±). RESULTS: The CR rate of all cases was 56.8% and statistical significance was observed with respect to the C-Grade (P = 0.0003, P = 0.028) using both univariate and multivariate analysis. The CR rate of C-Grade І (73.4%) patients was significantly higher than that of C-Grade II patients (39.0%; P = 0.0004) and C-Grade III patients (30.8%; P = 0.003). We analyzed clinical factors in each C-Grade patient. No statistical significance was observed with respect to any of the factors using univariate analysis in C-Grade I patients. The weight of the extracted palatine tonsils and Yamamoto scale showed no statistical significance in every analysis. Fibrosis or hyalinization of the stroma of the palatine tonsils showed statistical significance (P = 0.026) only in the univariate analysis of C-Grade III patients. However, the patient number of C-Grade III was small. CONCLUSION: Our results indicate that TSP is mostly effective in patients with of C-Grade I IgAN and that the C-Grade reflects the clinical indication for TSP. The weight of the extracted palatine tonsils and Yamamoto scale did not show obvious correlations with the clinical effect of TSP.

Patients Over 60 Years of Age Have Poor Prognosis in Facial Nerve Decompression Surgery with Preserved Ossicular Chain.

OBJECTIVE: We report our retrospective study of the recovery rate of auditory ossicles preserved facial nerve decompression surgery via the transmastoid approach in cases of both an electroneurography score of < 10% and a Yanagihara score of ≤8 in Bell's palsy and Ramsay Hunt syndrome. MATERIALS AND METHODS: We retrospectively reviewed 47 patients who we were able to follow-up for more than 6 months following the onset of palsy. The recovery rate was defined by the Japan Society for Facial Nerve Research or the Yanagihara score. RESULTS: Twelve months after palsy onset, the recovery rate was 48.8% (20/41) for all patients, 65.2% (15/23) for patients with Bell's palsy, and 27.8% (5/18) for patients with Ramsay Hunt syndrome. Comparing the clinical efficacy of surgical treatment at 12 months after palsy onset, we observed a statistically significant effect of age. Comparing the Yanagihara scores of patients aged < 60 years with those of patients aged ≥60 years revealed that patients aged ≥60 years had significant poor prognosis, particularly in patients with Ramsay Hunt syndrome, which showed a very low recovery rate (14.3%). We also analyzed six other factors, but none showed statistical significance. CONCLUSION: The clinical efficacy of surgical treatment of Ramsay Hunt syndrome was inferior to that of Bell's palsy, which is consistent with previous reports. There was a statistically significant difference in the Yanagihara score between patients aged < 60 years and those aged ≥60 years. Particularly, patients with Ramsay Hunt syndrome aged ≥60 years have a very low recovery rate.

Optimal control of asthma improved eosinophilic otitis media.

BACKGROUND: Eosinophilic otitis media (EOM) is often associated with comorbid asthma. The middle ear cavity is part of the upper airway. Therefore, EOM and asthma can be considered to be a crucial part of the "one airway, one disease" phenomenon. Based on the concept of one airway, one disease in the context of allergic rhinitis and asthma, optimal level of inhalation therapy for better asthma control leads to improvement in allergic rhinitis. OBJECTIVE: We conducted a pilot study to determine whether appropriate strengthening of inhalation therapy for asthma is effective for EOM. METHODS: Fifteen patients with EOM and comorbid asthma were enrolled in this study. Eight patients were randomly selected and administered appropriately strengthened inhalation therapy for asthma (strengthened group). The effect of the therapy on EOM was assessed by comparing a questionnaire for ear symptoms, clinical characteristic score, pure tone audiometry, blood tests and temporal bone computed tomography (CT) examination before and after the therapy. Seven other EOM + asthma patients without the above mentioned therapy were included as controls. RESULTS: In the strengthened group, the score of ear symptoms, clinical characteristics score, peripheral blood eosinophil count, CT score, and air conduction hearing level improved significantly after strengthening the inhalation therapy, but not in the control group. The lung function tests (forced vital capacity [%predicted], forced expiratory volume in 1 second [FEV1] [L], and FEV1 [%predicted]) significantly increased in the strengthened group after the therapy, but not in the control group. CONCLUSION: In this study we demonstrated that EOM improved along with improved lung function when appropriately optimal inhalation therapy was implemented in patients with EOM and asthma. Administration of optimizing therapy for asthma might be effective for concomitant EOM.

Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis: The minor axis of the sialolith is a regulative factor for the removal of sialoliths in the hilum of the submandibular gland using sialendoscopy alone.

OBJECTIVE: To assess the general guidelines for the removal of sialoliths for submandibular gland sialolithiasis using sialendoscopy alone. METHODS: We analyzed 61 sialoliths treated using sialendoscopy in 42 patients with submandibular gland sialolithiasis. We evaluated the submandibular gland sialoliths and divided each case based upon the location: the Wharton's duct or the hilum. We measured the major and minor axes of the sialoliths using a soft tissue computed-tomography (CT) scan and evaluated the removal rate of the sialoliths using sialendoscopy alone. RESULTS: The removal rate of the sialoliths in the Wharton's duct (52.6%) was significantly higher than that in the hilum of the submandibular gland (26.1%) (P=0.042). The minor axis was significantly correlated to the treatment outcome of sialendoscopy alone for all cases (P=0.030). A significant correlation was observed for cases involving the hilum of the submandibular gland and the measurement of the minor axes of the sialoliths for the treatment outcome of sialendoscopy alone (P=0.009). The major axis showed no correlation with the treatment outcomes of sialendoscopy alone. CONCLUSION: The measurement of the minor axes of the sialoliths with a soft tissue CT scan was correlated with treatment outcome of sialendoscopy alone for all cases, particularly sialoliths in the hilum. The easurement of the major axis showed no correlation with outcomes of sialendoscopy alone.

Diagnostic and treatment effects of sialendoscopy for patients with swelling of the parotid gland when sialoliths are undetected with computed tomography.

Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct. Balloon expansion of the duct was performed in these 2 patients and a steroid drug was injected into the duct in one patient. Complete remission was archived in one patient treated with sialendoscopy. Three patients had sialolithiasis. Microsialoliths and/or white floating matter was observed and removed using sialendoscopy. All patients experienced complete remission. In cases of Sjögren syndrome and recurrent parotitis, sialendoscopic surgery was performed, but the symptoms showed no improvement. For patients with microsialoliths, sialendoscopy may be most useful for diagnosis and treatment when the sialoliths are not detected with CT imaging. At present, sialendoscopic surgery have limitation in the treatment of Stensen's duct stenosis and may similarly have limitation in the treatment of Sjögren's syndrome and recurrent parotitis.

The landmark for removal of sialoliths using sialendoscopy alone in parotid gland sialolithiasis.

OBJECTIVE: To assess the general guidelines for removal of sialoliths in parotid gland sialolithiasis using sialendoscopy alone. METHODS: We analyzed 34 sialoliths treated using sialendoscopy in 26 patients with parotid gland sialolithiasis. We divided the Stensen's duct and parotid gland into for parts using computed tomography findings: (A) front of the masseter, (B) anterior and lateral to the center (anterolateral) of the masseter, (C) posterior and lateral to the center (posterolateral) of the masseter, (D) behind of the masseter. The location and size of each sialolith was assessed. RESULTS: The removal rates of sialoliths in the different locations by sialendoscopy alone were as follows: front of the masseter, 68.8%; anterolateral of the masseter, 60.0%; posterolateral of the masseter, 0%; and behind of the masseter, 33.3%. The removal rate using sialendoscopy alone was significantly higher in the sections anterior to the center of the masseter than in those posterior to the center of the masseter (66.7% [14/21] vs. 20.0% [2/10]; P=0.019). The size of the sialolith was not correlated to the removal rate by sialendoscopy alone. CONCLUSION: Sialoliths of the parotid gland located in positions anterior to the center of the masseter are significantly easier to remove by sialendoscopy alone. The center of the masseter is a general landmark for removal of sialoliths from the parotid gland using sialendoscopy alone. The size of the sialolith is not correlated with removal, except rare huge sialoliths.

Basophils are increased and express increased levels of interleukin-4 in the parotid lesions of Kimura disease.

BACKGROUND: Kimura disease (KD) is a systemic soft-tissue disease that leads to formation of painless masses in lymph nodes, with the highest predilection for the head and neck and especially the parotid gland. KD lesions are characterized by marked eosinophil infiltration, production of IgE and increased expression of T-helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, etc.). Skewing to a Th2 inflammation is also demonstrated in the peripheral blood, with elevated eosinophils and high IgE levels. It is thought that basophils may play important roles in orchestrating this Th2 inflammation via IL-4 production leading to the induction of IgE synthesis as well as eosinophil infiltration. However, there are no reports as yet on the role of basophils in KD. OBJECTIVE: The present study was performed to investigate the potential role of basophils in the pathogenesis of KD. In this context we also examined the expression of IL-4 in basophils in the KD lesions. METHODS: By immunohistochemistry using a monoclonal antibody against a basophil marker ProMBP1 we investigated the number and distribution of basophils in the KD lesions. By double immunohistochemistry we analyzed the colocalization of IL-4 in basophils. RESULTS: There was an increased number of basophils infiltrating the KD parotid gland lesions as compared to that in normal control parotid tissue. By double-immunofluorescence we found that approximately 7% of IL-4-positive cells in KD patients' parotid glands were basophils. CONCLUSION: Basophils may also play a role in the pathogenesis of KD, leading to the induction of IgE synthesis and eosinophil infiltration.

99mTcO4- accumulation in scintigraphy and expression of Na+/I- symporter in salivary gland tumors.

OBJECTIVE: Warthin's tumors and oncocytomas show exceptionally good (99m)TcO4(-) (Tc) accumulation images in Tc scintigraphy. However, the mechanism of Tc accumulation in these tumors remains unclear. Sodium-iodide symporter (NIS) is a plasma membrane protein expressed in the thyroid, lactating breast, stomach and salivary glands; it facilitates uptake of I(-) and Tc. We hypothesized that Warthin's tumor cells and oncocytomas may also express NIS, which would promote uptake of Tc. We examined NIS localization and the mechanism of Tc accumulation in various salivary gland tissues. METHODS: Immunohistological localization of NIS was performed for 19 tumors from 18 patients who underwent preoperative Tc scintigraphy. Expression of mRNA for NIS in the normal salivary gland, Warthin's tumors and pleomorphic adenomas was analyzed by real-time PCR. RESULTS: In normal salivary glands, striated duct cells were strongly immunostained by anti-NIS antibodies. In Warthin's tumors, eosinophilic epithelial cells exhibited positive immunostaining, but their staining was varied among the cases. Furthermore, all Tc-positive specimens were NIS-positive, and all Tc-negative specimens were NIS-negative. Real-time PCR showed that NIS mRNA expression was detectable in normal salivary glands and Warthin's tumor cells. The expression was significantly higher in normal salivary glands compared with Warthin's tumor cells and pleomorphic adenoma. CONCLUSION: Tc-positive salivary glands expressed NIS. Our findings suggest that Tc accumulation in Warthin's tumors and oncocytomas is due to poorer Tc excretory function compared with normal salivary gland tissues, in addition to active uptake of (99m)TcO4(-) via NIS.

Improvement of eosinophilic otitis media by optimized asthma treatment.

Eosinophilic otitis media (EOM) shows a very high rate of association with asthma, and intractable otitis media involves marked eosinophil infiltration into the middle ear. The middle ear space is connected to the nasopharynx by the Eustachian tube, and it is considered a part of the upper respiratory tract. Allergic rhinitis and asthma often coexist as chronic inflammatory diseases of the upper and lower airways, respectively, and have an impact on each other. In fact, inhaled corticosteroids reduce seasonal eosinophilia systemically in the circulation and locally in the nasal mucosa, as well as attenuate seasonal nasal symptoms. We report a case of EOM associated with adult-onset asthma that improved following optimal asthma therapy after changing the treatment from inhaled fluticasone propionate (FP) (200 µg b.i.d.) to a combination of FP/salmeterol (250/50 µg b.i.d.). This result supports the hypothesis that EOM and asthma are closely linked, presenting as different manifestations of a similar disease syndrome.

Neuromuscular junctions of the posterior cricoarytenoid muscle in multiple system atrophy: a case study.

CONCLUSION: The present study showed a variety of stages of neurogenic degeneration of the muscle fibers and the neuromuscular junctions (NMJs) of the posterior cricoarytenoid (PCA) muscle in multiple system atrophy (MSA). These findings coincide with abductor paralysis of vocal cords. Ultrastructural features of the NMJs of the PCA muscle in MSA were different from those of previous studies on experimental resection of recurrent nerve and amyotrophic lateral sclerosis (ALS). OBJECTIVES: MSA may influence various respiratory functions. Upper airway tracts including larynx are affected without exception during its clinical course. Morphological changes of NMJs of the intrinsic laryngeal muscle in MSA were examined ultrastructurally. PATIENT AND METHODS: The patient was a 68-year-old male complaining of recurrent aspiration pneumonia, dysphagia, respiratory disturbance, and abductor paralysis of vocal cords. The motor nerve terminals of the PCA muscle in a patient with MSA were investigated electron microscopically. RESULTS: The NMJs showed varying degrees of ultrastructural changes by motor nerve degeneration. They were seen in the pre- and post-synaptic regions. Muscle fibers losing nerve terminals showed severe damage in their cytoplasm.