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1.
Int Arch Allergy Immunol ; 184(11): 1116-1125, 2023.
Article in English | MEDLINE | ID: mdl-37619543

ABSTRACT

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.


Subject(s)
Asthma , Otitis Media , Pulmonary Disease, Chronic Obstructive , Male , Adult , Humans , Prevalence , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , Asthma/complications , Asthma/epidemiology , Otitis Media/complications , Otitis Media/epidemiology , Otitis Media/drug therapy , Chronic Disease
2.
ORL J Otorhinolaryngol Relat Spec ; 83(4): 286-294, 2021.
Article in English | MEDLINE | ID: mdl-34077941

ABSTRACT

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.


Subject(s)
Immunoglobulin G4-Related Disease , Rhinitis , Sialadenitis , Sinusitis , Chronic Disease , Cytidine Deaminase , Humans , Immunoglobulin G4-Related Disease/complications , Rhinitis/complications , Sinusitis/complications
3.
Pulm Pharmacol Ther ; 68: 102032, 2021 06.
Article in English | MEDLINE | ID: mdl-33862220

ABSTRACT

BACKGROUND: Omalizumab, an anti-IgE antibody, has been widely used in many countries, including Japan. However, some patients do not respond to omalizumab, and the cause of treatment failure has not been fully elucidated. OBJECTIVE: This study aimed to evaluate the characteristics of adult asthma patients who failed to achieve disease control with omalizumab in a real-world setting. METHODS: We retrospectively reviewed the medical records of patients in Tokyo Women's Medical University Hospital between March 2009 and May 2016. The patient characteristics and factors for treatment failure with omalizumab were evaluated, as were treatment alternatives after discontinuation of omalizumab. RESULTS: In total, 59 patients were included in this study. The omalizumab-ineffective group had a significantly higher number of patients with eosinophilic sinusitis (P = 0.001) and eosinophilic otitis media (P = 0.023) than the omalizumab-effective group. A multivariate analysis revealed that both eosinophilic chronic rhinosinusitis (odds ratio: 23.4; P = 0.011) and eosinophilic otitis media (odds ratio: 6.71; P = 0.039) were associated with treatment failure with omalizumab. Most patients with eosinophilic comorbidities of the ear, nose, and throat (ENT) in the omalizumab-ineffective group received mepolizumab or benralizumab as alternative therapy, following which disease control was achieved. CONCLUSION: Eosinophilic comorbidities of the ENT may affect treatment failure with omalizumab in patients with severe asthma. Anti-interleukin-5 antibody or anti-interleukin-5Rα antibody rather than anti-IgE antibody should be considered as an additional therapy for patients with severe asthma who have eosinophilic comorbidities of the ENT.


Subject(s)
Anti-Asthmatic Agents , Asthma , Adult , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Female , Humans , Omalizumab/therapeutic use , Retrospective Studies , Treatment Failure
4.
Intern Med ; 60(16): 2683-2686, 2021 Aug 15.
Article in English | MEDLINE | ID: mdl-33678746

ABSTRACT

We herein report a 73-year-old man who experienced cerebral infarction caused by infection with a Mucromycocetes species. A delay in anti-fungal treatment might result in a lethal clinical outcome. We were unable to establish an accurate diagnosis based on histological findings and cerebrospinal fluid culture. Therefore, we performed polymerase chain reaction (PCR) using paraffin-embedded specimens, and based on the findings, successfully started administering anti-fungal treatment. We suggest that PCR using sinus specimens be applied when mucormycosis is suspected as an etiology of cerebral infarction and a confirmative diagnosis cannot be established based on the results of pathological examinations or cerebrospinal fluid culture.


Subject(s)
Carotid Artery Thrombosis , Mucormycosis , Aged , Cerebral Infarction/diagnosis , Humans , Male , Mucormycosis/complications , Mucormycosis/diagnosis , Paraffin Embedding , Polymerase Chain Reaction
5.
Curr Opin Allergy Clin Immunol ; 20(1): 9-13, 2020 02.
Article in English | MEDLINE | ID: mdl-31524656

ABSTRACT

PURPOSE OF REVIEW: Eosinophilic otitis media (EOM) is an intractable otitis media characterized by numerous eosinophils infiltrating the middle ear cavity, which is part of the upper airway. EOM shows a high rate of comorbidity with asthma. They are considered to have a 'one airway, one disease' relationship. Here, we summarize our current knowledge regarding the characteristics of EOM, EOM's relationship with asthma and the efficacy of optimal treatments for EOM. RECENT FINDINGS: The greater the severity of asthma, the more pronounced the development of EOM. Asthma control is usually inadequate in asthmatics who develop EOM, and appropriate strengthening of asthma inhalation therapy leads to improvement in the EOM. EOM severity can be divided into mild, moderate, and severe. Intratympanic infusion therapy using a topical steroid such as triamcinolone acetone is effective for mild EOM, whereas moderate EOM requires a systemic steroid in addition to triamcinolone acetone, and severe EOM forms granulation tissue that requires surgical removal. Recently, the effectiveness of molecularly targeted drugs is being reported, but more data need to be accumulated. SUMMARY: EOM and asthma are closely related. Optimal asthma treatment is important for treating EOM. Treatments commensurate with the severity of EOM are being developed.


Subject(s)
Asthma/immunology , Eosinophils/immunology , Eustachian Tube/immunology , Otitis Media/immunology , Asthma/drug therapy , Asthma/epidemiology , Comorbidity , Eosinophilia , Humans , Injection, Intratympanic , Molecular Targeted Therapy , Otitis Media/drug therapy , Otitis Media/epidemiology , Triamcinolone Acetonide/therapeutic use
6.
J Nippon Med Sch ; 86(2): 117-121, 2019.
Article in English | MEDLINE | ID: mdl-31130562

ABSTRACT

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.


Subject(s)
Muscarinic Antagonists/administration & dosage , Pirenzepine/administration & dosage , Receptor, Muscarinic M1/antagonists & inhibitors , Receptor, Muscarinic M3/antagonists & inhibitors , Sialorrhea/drug therapy , Solifenacin Succinate/administration & dosage , Animals , Drug Therapy, Combination , Humans , Male , Mice, Knockout , Middle Aged , Radionuclide Imaging , Receptor, Muscarinic M1/physiology , Receptor, Muscarinic M3/physiology , Salivary Glands/diagnostic imaging , Salivary Glands/physiopathology , Salivation , Sialorrhea/diagnostic imaging , Sialorrhea/physiopathology , Treatment Outcome
7.
Auris Nasus Larynx ; 46(5): 764-771, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30665673

ABSTRACT

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.


Subject(s)
Glomerulonephritis, IGA/therapy , Glucocorticoids/administration & dosage , Palatine Tonsil/surgery , Prednisolone/administration & dosage , Tonsillectomy/methods , Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Female , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/urine , Hematuria , Humans , Hyalin , Male , Middle Aged , Multivariate Analysis , Organ Size , Palatine Tonsil/pathology , Platelet Aggregation Inhibitors/therapeutic use , Prognosis , Proteinuria , Pulse Therapy, Drug , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Young Adult
8.
J Int Adv Otol ; 14(1): 77-84, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29764779

ABSTRACT

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.


Subject(s)
Decompression, Surgical/methods , Ear Ossicles/surgery , Facial Nerve/surgery , Facial Paralysis/surgery , Myoclonic Cerebellar Dyssynergia/surgery , Adult , Aged , Facial Paralysis/diagnosis , Facial Paralysis/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myoclonic Cerebellar Dyssynergia/diagnosis , Myoclonic Cerebellar Dyssynergia/epidemiology , Postoperative Complications , Prognosis , Recovery of Function/physiology , Retrospective Studies
10.
Asia Pac Allergy ; 8(1): e5, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29423372

ABSTRACT

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.

11.
Auris Nasus Larynx ; 45(4): 772-776, 2018 Aug.
Article in English | MEDLINE | ID: mdl-28935124

ABSTRACT

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.


Subject(s)
Salivary Duct Calculi/surgery , Salivary Ducts/surgery , Salivary Gland Calculi/surgery , Submandibular Gland Diseases/surgery , Adolescent , Adult , Aged , Endoscopy , Female , Humans , Male , Middle Aged , Otorhinolaryngologic Surgical Procedures/methods , Salivary Duct Calculi/diagnostic imaging , Salivary Ducts/diagnostic imaging , Salivary Gland Calculi/diagnostic imaging , Submandibular Gland Diseases/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
12.
Auris Nasus Larynx ; 45(4): 880-884, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29217121

ABSTRACT

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.


Subject(s)
Edema/surgery , Parotid Diseases/surgery , Parotid Gland/surgery , Salivary Gland Calculi/surgery , Adult , Aged , Constriction, Pathologic , Edema/diagnostic imaging , Endoscopy , Female , Humans , Male , Middle Aged , Otorhinolaryngologic Surgical Procedures , Parotid Diseases/diagnostic imaging , Parotid Gland/diagnostic imaging , Parotitis/diagnosis , Parotitis/surgery , Retrospective Studies , Salivary Ducts/diagnostic imaging , Salivary Ducts/surgery , Salivary Gland Calculi/diagnostic imaging , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/surgery , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
13.
Auris Nasus Larynx ; 45(2): 306-310, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28651858

ABSTRACT

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.


Subject(s)
Anatomic Landmarks , Masseter Muscle/diagnostic imaging , Parotid Diseases/surgery , Salivary Duct Calculi/surgery , Adult , Aged , Endoscopy , Female , Humans , Male , Middle Aged , Parotid Diseases/diagnostic imaging , Salivary Duct Calculi/diagnostic imaging , Salivary Ducts/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
14.
Asia Pac Allergy ; 7(4): 221-226, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29094020

ABSTRACT

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.

15.
Article in English | MEDLINE | ID: mdl-25676453

ABSTRACT

OBJECTIVE: The objective of this study was to investigate the expression of thymic stromal lymphopoietin (TSLP) and TSLP receptor (TSLPR) in Kimura's disease (KD). METHODS: Using parotid gland tissues from KD patients and control subjects, we quantified the expression levels of mRNA for TSLP, interleukin (IL)-25, IL-33, and their receptors by massively parallel sequencing. We also performed immunohistochemical analysis of TSLP and TSLPR, and counted cells immunoreactive for these proteins by the polymer immunocomplex and double immunofluorescence methods. RESULTS: The levels of mRNA for TSLP, TSLPR, and IL-25R, but not IL-25, IL-33, or IL-33R, were significantly elevated in parotid gland tissues from the KD group as compared to the control group. Immunohistochemical analysis revealed that TSLP- and TSLPR-positive cells were significantly increased in number in parotid gland tissues from KD patients. Double immunofluorescence staining showed that TSLP and TSLPR were localized mainly in CD68-positive macrophages and tryptase-positive mast cells, respectively. CONCLUSIONS: Overexpression of TSLP and TSLPR might contribute to the pathogenesis of KD through interactions between macrophages and mast cells. Regulation of TSLP/TSLPR signaling may be a potential therapeutic approach for KD.


Subject(s)
Angiolymphoid Hyperplasia with Eosinophilia/metabolism , Cytokines/metabolism , Interleukin-17/metabolism , Interleukin-33/metabolism , Parotid Gland/metabolism , Receptors, Cytokine/metabolism , Adolescent , Adult , Aged , Angiolymphoid Hyperplasia with Eosinophilia/etiology , Angiolymphoid Hyperplasia with Eosinophilia/pathology , Case-Control Studies , Cytokines/genetics , Female , Humans , Interleukin-17/genetics , Interleukin-33/genetics , Male , Middle Aged , RNA, Messenger/metabolism , Receptors, Cytokine/genetics , Young Adult , Thymic Stromal Lymphopoietin
16.
Article in English | MEDLINE | ID: mdl-25633710

ABSTRACT

PURPOSE: Eosinophilic otitis media (EOM) is an intractable otitis media characterized by an accumulation of eosinophils in the middle ear and a strong association with asthma. We investigated the relationship between EOM and asthma severity, asthma risk factors, lung function, and airway structural changes assessed by high-resolution computed tomographic (HRCT) scanning. MATERIALS AND METHODS: Forty-one asthma patients with chronic rhinosinusitis (18 men and 23 women; mean age 56 years; age range 25-82 years) were included in this study. EOM was diagnosed according to the published diagnostic criteria. Asthma severity and risk factors for asthma, such as smoking history (Brinkman index, BI), were examined. Airway wall thickness and emphysema were assessed with HRCT scanning by a blinded respiratory specialist using a validated method. Lung function was measured using standard procedures. RESULTS: EOM was diagnosed in 34% of the patients. Asthma severity, BI and airway wall thickness were each statistically greater in patients with EOM than in patients without EOM. CONCLUSION: There was a close relationship between EOM and asthma severity in asthma patients with chronic rhinosinusitis. Cessation of smoking might help prevent EOM by reducing airway wall thickness.


Subject(s)
Asthma/complications , Eosinophilia/etiology , Otitis Media/etiology , Smoking/adverse effects , Adult , Aged , Aged, 80 and over , Asthma/pathology , Case-Control Studies , Chronic Disease , Eosinophilia/diagnosis , Female , Humans , Male , Middle Aged , Otitis Media/diagnosis , Rhinitis/complications , Rhinitis/pathology , Risk Factors , Severity of Illness Index , Sinusitis/complications , Sinusitis/pathology , Smoking/pathology , Spirometry , Tomography, X-Ray Computed
17.
Auris Nasus Larynx ; 41(6): 532-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25199743

ABSTRACT

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.


Subject(s)
Adenolymphoma/diagnostic imaging , Adenoma, Oxyphilic/diagnostic imaging , Adenoma, Pleomorphic/diagnostic imaging , RNA, Messenger/metabolism , Salivary Gland Neoplasms/diagnostic imaging , Salivary Glands/metabolism , Symporters/genetics , Adenolymphoma/genetics , Adenolymphoma/metabolism , Adenoma/diagnostic imaging , Adenoma/genetics , Adenoma/metabolism , Adenoma, Oxyphilic/genetics , Adenoma, Oxyphilic/metabolism , Adenoma, Pleomorphic/genetics , Adenoma, Pleomorphic/metabolism , Carcinoma, Acinar Cell/diagnostic imaging , Carcinoma, Acinar Cell/genetics , Carcinoma, Acinar Cell/metabolism , Carcinoma, Mucoepidermoid/diagnostic imaging , Carcinoma, Mucoepidermoid/genetics , Carcinoma, Mucoepidermoid/metabolism , Humans , Immunohistochemistry , Lymphoma/diagnostic imaging , Lymphoma/genetics , Lymphoma/metabolism , Radionuclide Imaging , Radiopharmaceuticals , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Sodium Pertechnetate Tc 99m , Symporters/metabolism
18.
Auris Nasus Larynx ; 41(4): 384-8, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24406057

ABSTRACT

Kimura's disease is a chronic disease that is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil counts and high serum IgE levels. It is thought to be an IgE-mediated disease. Omalizumab, a monoclonal antibody, has recently been suggested as a potential new systemic treatment for IgE-mediated diseases, based on its efficacy in treating asthma and allergic rhinitis. We report a study of three patients with Kimura's disease who received anti-IgE (omalizumab) treatment. All patients were treated with a fixed schedule of eight cycles of omalizumab 300mg, administered subcutaneously at intervals of 2 weeks. The size of tumorous regions was evaluated by MRI at base line and after 4 months of treatment. Blood samples were taken every month. In each of the patients, the size of tumorous regions and the peripheral blood eosinophil and basophil counts were all decreased after the treatment. These results suggest that omalizumab may be valuable for treatment of Kimura's disease.


Subject(s)
Angiolymphoid Hyperplasia with Eosinophilia/drug therapy , Antibodies, Anti-Idiotypic/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Angiolymphoid Hyperplasia with Eosinophilia/diagnosis , Antibodies, Anti-Idiotypic/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Female , Humans , Injections, Subcutaneous , Magnetic Resonance Imaging , Male , Middle Aged , Omalizumab , Pilot Projects
20.
Allergy Asthma Immunol Res ; 5(3): 175-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23638317

ABSTRACT

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.

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