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A 35-year-old female presented with headache, photophobia and developed sudden loss of vision after having undergone right-side ophthalmectomy and radiochemotherapy for retinoblastoma in infancy. A neoplastic lesion was found in the left middle cranial fossa and was surgically removed. The diagnosis was radiation-induced osteosarcoma with RB1 gene alteration. Although she received chemotherapy for the residual tumor, it progressed 17 months later. Maximal surgical resection with craniofacial reconstruction was required. We utilized two three-dimensional models for surgical planning. She was discharged without neurological deficits other than loss of light perception subsequent to left ophthalmectomy. In cases where retinoblastoma is treated with radiotherapy, long-term follow-up is necessary to monitor for radiation-induced tumor development.

DOI： 10.18926/AMO/64367

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A patient complained of acute right vision loss and headache. A computed tomography scan revealed ethmoidal sinus mucocele in the right ethmoid sinus that was compressing the optic nerve and emergency endoscopic sinus surgery was performed.

DOI： 10.1002/ccr3.6696

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Language：English   Publishing type：Research paper (scientific journal)  

A 44-year-old Japanese man presented with fever and sore throat. He had a history of refractory chronic sinusitis that did not respond to several years of pharmacotherapy, and underwent endoscopic sinus surgery (ESS) 5 months prior to his presentation, but his symptoms persisted. A biopsy specimen was taken from the right nasal cavity, and extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) was diagnosed. Two years after complete remission was achieved by chemoradiation therapy, he developed hemophagocytic lymphohistiocytosis (HLH) without recurrence of ENKTL. Epstein-Barr virus (EBV)-DNA copy number was relatively high and EBV-infected lymphocytes (CD8 + T cells) were detected in the peripheral blood. Pathological review of the biopsy specimens taken during ESS showed that CD8 + T cells with slightly atypia infiltrating the stroma were EBV positive. These findings suggested that the patient had underlying chronic active EBV infection (CAEBV) that caused the refractory chronic sinusitis, eventually developed into ENKTL, and also caused HLH. Clinicians should consider adult-onset CAEBV in the differential diagnosis of patients with refractory chronic sinusitis.

DOI： 10.1007/s12185-022-03306-y

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OBJECTIVE: Combination intranasal drugs with a corticosteroid and antihistamine are available in several countries with better effect than treatments with single agents. However, it remains unclear whether this effect is also seen in Japanese cedar pollinosis (JCP), the most prevalent seasonal allergic rhinitis in Japan. We investigated the effect of an add-on intranasal antihistamine with an intranasal corticosteroid in JCP during the pollen dispersal period. (UMIN000025508) METHODS: We performed a double-blinded, randomized, placebo-controlled trial from March 1 to 14, 2017. Patients (n = 20 per group) received either a mometasone furoate nasal spray (MFNS) plus a levocabastine nasal spray (levocabastine group) or MFNS plus a placebo nasal spray (placebo group). The primary endpoint was the difference in the total nasal symptom score (TNSS) after treatment between the two groups. Differences in the total ocular symptom score, total symptom score, total medication score, total symptom-medication score, and five individual symptoms as well as safety were the secondary endpoints. RESULTS: The change in the TNSS from baseline was significantly greater in the levocabastine group than in the placebo group. A significant reduction in the TNSS was observed more than 6 days earlier in the levocabastine group than in the placebo group. Such add-on effects were also seen in the secondary endpoints. Both treatments were well-tolerated. CONCLUSION: The intranasal antihistamine provided better control of not only nasal symptoms, but also of ocular symptoms, and decreased the need for rescue medications when added to intranasal corticosteroid treatment in JCP patients.

DOI： 10.1016/j.anl.2022.05.007

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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BACKGROUND: The total naso-ocular symptom score (TSS) is widely used as an endpoint to evaluate the severity of seasonal allergic rhinitis. However, it is not a generic preference-based measure. We sought to develop an algorithm for mapping between the TSS and health utility in Japanese cedar pollinosis (JCP). We also performed a cost-utility analysis of sublingual immunotherapy (SLIT) for JCP by using this algorithm. METHODS: Patients with JCP filled out the TSS questionnaire and EQ-5D-5L simultaneously during the pollen season in 2019 and in 2020. We estimated a direct utility mapping model by regressing responses to individual TSS questions directly onto utility. The incremental cost-effectiveness ratio (ICER) of active SLIT to a placebo was determined by examining the drug expense and the estimated quality-adjusted life year (QALY) using a dataset from a double-blind placebo-controlled clinical trial. RESULTS: A total of 238 records were included for analysis. The estimated utility decreased with increasing severity of rhinitis. Patients with comorbid asthma showed lower utility. A negative and significant correlation was seen between the TSS and utility in both 2019 and 2020. The estimated equations were: Y(utility) = -0.0161∗X(TSS) + 1.005 in non-asthmatic JCP patients. The ICER of active SLIT to the placebo was estimated to be 4,049,720 and 6,011,218 JPY/QALY in the first and second year, respectively. CONCLUSIONS: It is possible to reasonably predict utility from the total naso-ocular symptom score by using regression models. In the estimated algorithm, pre-seasonal SLIT for JCP is cost-effective.

DOI： 10.1016/j.alit.2021.11.002

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

1日2回の生理食塩水洗浄と抗菌薬の保存的加療により、人工内耳植え込み術後の局所感染を制御できた小児の1例(1歳11ヵ月男児)について報告した。本症例で術後創部感染の保存的加療が可能であった要因として、「起炎菌がMRSAなどではなく、MSSAであったこと」「鼓膜所見や起炎菌から、中耳からの感染ではなく、皮膚からの感染であったため」「当院では、人工内耳植え込み術の際、minimum invasive surgeryを行っていること」が考えられた。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J07545&link_issn=&doc_id=20220120310010&doc_link_id=%2Ffm9areka%2F2021%2F000103%2F010%2F0177-0180%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffm9areka%2F2021%2F000103%2F010%2F0177-0180%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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BACKGROUND: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To assess the efficacy and safety of benralizumab in patients with ECRS. METHODS: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. RESULTS: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. CONCLUSION: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

DOI： 10.1177/19458924211009429

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DOI： 10.1111/all.14858

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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DOI： 10.1016/j.alit.2020.12.003

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BACKGROUND: Hyaluronan is one of the major extracellular matrixes in chronic rhinosinusitis (CRS) associated with tissue remodeling. Prostaglandin D2 (PGD2) is also associated with the pathogenesis of CRS. However, little is known about whether PGD2 regulates hyaluronan production by human airway fibroblasts. OBJECTIVE: We sought to determine the effect of PGD2 on the mRNA expression of three isoforms of membrane-bound hyaluronic acid synthase (HAS1, HAS2 and HAS3) in fibroblasts, the major source of hyaluronan production, derived from CRS patients. METHODS: Nasal polyp-derived fibroblasts (NPDF) and uncinate tissue-derived fibroblasts (UTDF) were established from CRS patients with nasal polyps and those without, respectively. These fibroblasts were stimulated with PGD2 or PGD2 receptor (DP/CRTH2)-selective agonists in the presence or absence of receptor-selective antagonists. mRNA levels for HAS1, HAS2 and HAS3 were determined by real-time quantitative PCR. RESULTS: PGD2 (1 µM) significantly enhanced HAS1 but not HAS2 or HAS3 mRNA expression by NPDF. Enhanced HAS1 mRNA expression was also obtained by stimulation with a DP receptor-selective agonist, but not with a CRTH2 receptor-selective agonist. In addition, PGD2-induced HAS1 mRNA expression was significantly inhibited by pre-treatment with DP receptor-selective antagonists. Similar induction of PGD2-induced HAS1 mRNA expression was seen in UTDF. CONCLUSION: PGD2 selectively stimulates HAS1 mRNA expression in local fibroblasts in CRS via DP, but not CRTH2, receptors.

DOI： 10.1177/1945892420932781

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A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.

DOI： 10.1016/j.mmcr.2020.09.004

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BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.

DOI： 10.1016/j.alit.2019.12.004

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HYPOTHESIS: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. BACKGROUND: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. METHODS: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. RESULTS: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. CONCLUSION: Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media.

DOI： 10.1097/MAO.0000000000002537

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.amjoto.2019.102315

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BACKGROUND: A remarkable relationship between upper airway conditions and lung diseases has been reported. At the same time, sinonasal findings in chronic cough patients have not been fully examined. OBJECTIVE: The purpose of this study is to show paranasal sinus findings and lung function in chronic cough patients without asthma and chest X-ray abnormalities. METHODS: A total of 1412 patients with persistent cough were enrolled in this study. Of these patients, 376 patients were evaluated for further examination, as the patients with asthma and/or chest X-ray abnormality were excluded from the study. Normal control subjects without any chronic respiratory symptoms were also recruited. Pulmonary function was examined by spirometry. A bronchial obstruction reversibility test was applied. The Lund-Mackay computed tomography (CT) score, peripheral blood eosinophil count, and immunoglobulin E concentration in serum samples were examined. The Sino-Nasal Outcome Test was used to determine the severity of clinical symptoms. RESULTS: The patients with an abnormal soft tissue shadow in the paranasal sinus had significant obstructive lung function. The percent predicted forced expiratory volume in 1 second (FEV1.0) and the FEV1.0/forced vital capacity ratio negatively correlated with Lund-Mackay CT scores both before and after bronchodilator inhalation. There was a statistically significant correlation between pulmonary function and eosinophil count. CONCLUSION: The patients with chronic cough frequently had paranasal sinus abnormalities. The Lund-Mackay CT score may be useful for assessing the condition of the lower airway in chronic cough patients. Upper airway examinations should play a part in the management of chronic cough.

DOI： 10.1177/1945892418825094

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BACKGROUND: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). METHODS: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. RESULTS: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. CONCLUSIONS: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.

DOI： 10.1016/j.alit.2018.09.002

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: Prophylactic treatment with intranasal corticosteroids is effective for pollen-induced seasonal allergic rhinitis. However, the appropriate time to start this treatment remains unclear. We performed a double-blinded, randomized, placebo-controlled trial. Starting on February 1, 2014, patients with Japanese cedar pollinosis received either fluticasone furoate nasal spray (FFNS) for 8 weeks (Group A: n = 24), placebo nasal spray for 2 weeks followed by FFNS for 6 weeks (Group B: n = 23), or placebo for 4 weeks followed by FFNS for 4 weeks (Group C: n = 23). The primary endpoint was comparison of the total naso-ocular symptom score (TSS). Secondary endpoints including the increment cost effective ratio (ICER) were also determined. Continuous pollen dispersion began on the 24th of February. Therefore, Group A and Group B received 3-weeks and 1-week of prophylactic treatment, respectively, whereas Group C received post-onset treatment. During the peak pollen-dispersal period, significant differences in TSS were seen between the groups, particularly between Group A and C. The ICER of Group B vs. Group C was lower than that of Group A vs. Group C. These results suggest that long-term prophylactic treatment with FFNS is clinically the most potent treatment, whereas short-term prophylactic treatment is cost effective for pollen-induced allergic rhinitis.

DOI： 10.3390/medsci7010011

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BACKGROUND: The development of methods to predict the clinical effectiveness of sublingual immunotherapy (SLIT) for allergic diseases is a crucial matter. We sought to determine whether whole saliva, which is the first body component that contacts allergen extracts during SLIT, is associated with the clinical effectiveness of SLIT in Japanese cedar pollinosis. METHODS: Blood monocytes or monocytic THP-1 cells were cultured in the presence or absence of either whole saliva or pure saliva with or without treatments including filtration and blockade of TLR2 and/or TLR4 signaling. IL-10 levels in the supernatants were then measured. Whole saliva-induced IL-10 production by THP-1 cells was compared between asymptomatic and disease-onset patients during peak pollen dispersal after SLIT. RESULTS: Both monocytes and THP-1 cells produced substantial amounts of IL-10 in response to whole saliva. IL-10 production was significantly reduced in response to pure saliva and 0.2 μm-filtered saliva. Simultaneous treatment with polymyxin B and TL2.1, a neutralizing antibody against TLR2, also reduced IL-10 production. IL-10 levels produced by THP-1 cells in response to whole saliva collected prior to SLIT were significantly higher in asymptomatic patients determined by symptom-medication scores than disease-onset patients following SLIT. Such differences were not seen in saliva collected 3 months after the initiation of SLIT or saliva collected during peak pollen dispersal. CONCLUSIONS: Our results provide a basis for why the sublingual route is effective and preferable in allergen immunotherapy. Saliva-induced IL-10 levels produced by THP-1 cells may be a predictive marker for clinical remission after SLIT.

DOI： 10.1016/j.alit.2018.07.008

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BACKGROUND: The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a critical molecule mediating interleukin-1β (IL-1β) responses. However, the role of the NLRP3 inflammasome in otitis media has not been fully examined. AIMS/OBJECTIVES: The purpose of this study is to assess the expression of NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in lipopolysaccharide-induced otitis media. MATERIALS AND METHODS: BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 h after injection. Concentrations of IL-1β, NLRP3, ASC, and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. RESULTS: The transtympanic injection of lipopolysaccharide significantly upregulated levels of IL-1β, NLRP3, ASC, and caspase-1 in the middle ear as compared with the control mice. The proteins of NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear cavity. CONCLUSIONS AND SIGNIFICANCE: Lipopolysaccharide induces NLRP3 inflammasome components in the middle ear. The NLRP3 inflammasome may play an important role in the pathogenesis of otitis media. Modulation of inflammasome-mediated inflammation may be a novel therapeutic strategy for otitis media.

DOI： 10.1080/00016489.2018.1515499

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BACKGROUND: IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). METHODS: Dispersed nasal polyp (NP) cells and uncinate tissue (UT) cells were prepared from patients with CRS with and without NP, respectively. Cells were incubated with SEB, and then the levels of IL-10 in the cell supernatants were determined. The effect of neutralizing IL-10 on SEB-induced IL-5, IL-13, IFN-γ, and IL-17A production was examined. Expression of IL-10 in NPs was also determined. RESULTS: IL-10 was expressed in infiltrating inflammatory cells in NPs. NP cells, especially non-adherent NP cells, produced substantial amounts of IL-10 in response to SEB. Although baseline production of IL-10 was significantly higher in NP cells than UT cells, the degree of IL-10 response to SEB was not significantly different between the cell types. The degree of IL-10 production was negatively correlated with the degree of eosinophilia both in tissues and peripheral blood whereas positively correlated with the 1-s forced expiratory volume/forced vital capacity ratio. Patients with severe ECRS displayed a significant decrease in IL-10 production compared with those with non-ECRS. IL-10 neutralization significantly augmented SEB-induced IL-13 and IFN-γ production by NP cells. CONCLUSIONS: Impaired IL-10 production in response to SEB in NP may exacerbate the pathophysiology of ECRS including eosinophilia and lower airway obstruction.

DOI： 10.1016/j.alit.2018.02.001

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OBJECTIVE: In 2013, the Japanese Rhinologic Society proposed a simple classification for endoscopic sinus surgery (ESS). This classification consists of five procedures (type I, fenestration of the ostiomeatal complex, with uncinectomy and widening of the natural ostium; type II, single-sinus procedure, with manipulating the inside of the sinus; type III, polysinus procedure; type IV, pansinus procedure; type V, extended procedure beyond the sinus wall). The clinical relevance of this classification in chronic rhinosinusitis (CRS) and paranasal sinus cyst was evaluated. STUDY DESIGN: A retrospective validation study. METHODS: A total of 122 patients (195 sinuses) who underwent ESS in Okayama University Hospital in 2012 were enrolled. The relationships between the ESS classification and the clinical course, including the operation time, bleeding amounts during surgery and postoperative changes of olfaction, the computed tomography (CT) score, and nasal airway resistance were analyzed. RESULTS: A total of 195 ESS procedures were classified into type I (n = 3), type II (n = 17), type III (n = 91), type IV (n = 82), and type V (n = 2). The major phenotypes of type II, III, and IV ESS were paranasal sinus cyst (68%), CRS without nasal polyps (77%), and CRS with nasal polyps (55%), respectively, and the difference was significant. The degree of ESS based on this classification was positively and significantly correlated with the operation time and bleeding amounts. As a whole, olfaction, CT score, and nasal airway resistance were significantly improved after surgery. The degree of improvement was similar between type III and type IV ESS. CONCLUSION: This simple classification for ESS reflected the perioperative burden of the disease.

DOI： 10.2500/ar.2017.8.0208

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CONCLUSIONS: Chronic rhinosinusitis diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012, not by computed tomography alone, is one of the prognostic factors affecting long-term survival in patients with lung transplantation. Endoscopic sinus surgery might play a beneficial role in the management of lung transplantation recipients with chronic rhinosinusitis. OBJECTIVE: To show the effect of paranasal sinus infection on post-lung transplantation survival. METHOD: Lung transplantation recipients were included in this study. Computed tomography was performed before and after lung transplantation. The severity of chronic rhinosinusitis was evaluated by Lund-Mackay scoring system. The survival rate was calculated by the Kaplan-Meier method. RESULTS: One hundred and forty-eight patients received lung transplantation for various indications. Chronic rhinosinusitis was found in 18.9% (28/148) of the lung transplantation recipients. Of 28 patients with chronic rhinosinusitis, seven patients underwent endoscopic sinus surgery due to persistent post-nasal drip. The recipients with chronic rhinosinusitis who did not receive endoscopic sinus surgery (n = 21) showed a significantly lower survival rate as compared to the patients without chronic rhinosinusitis. There was no statistically significant difference in the survival rate between the recipients with (n = 50) and without (n = 98) paranasal sinus abnormality on computed tomography.

DOI： 10.1080/00016489.2016.1247497

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BACKGROUND: IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined. RESULTS: IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs. CONCLUSIONS: These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.

DOI： 10.1016/j.alit.2016.04.017

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BACKGROUND: Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. METHODS: We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. RESULTS: In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. CONCLUSIONS: These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

DOI： 10.1016/j.alit.2015.12.007

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BACKGROUND: Toll-like receptor 3 (TLR3) is expressed in upper airways, however, little is known regarding whether Toll-like receptor 3 (TLR3) signals exert a regulatory effect on the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), especially on eosinophilic inflammation. We sought to investigate the effect of Poly(IC), the ligand for TLR3, on cytokine production by dispersed nasal polyp cells (DNPCs). METHODS: DNPCs were pretreated with or without Poly(IC), and were then cultured in the presence or absence of staphylococcal enterotoxin B (SEB), following which the levels of IL-5, IL-10, IL-13, IL-17A and interferon (IFN)-γ in the supernatant were measured. To determine the involvement of IL-10 and cyclooxygenase in Poly(IC)-mediated signaling, DNPCs were treated with anti-IL-10 monoclonal antibody and diclofenac, the cyclooxygenase inhibitor, respectively. Poly(IC)-induced prostaglandin E2 (PGE2) production was also determined. RESULTS: Exposure to Poly(IC) induced a significant production of IL-10, but not of IL-5, IL-13, IL-17A or IFN-γ by DNPCs. Pretreatment with Poly(IC) dose-dependently inhibited SEB-induced IL-5, IL-13 and IL-17A, but not IFN-γ production. Neutralization of IL-10 significantly abrogated the inhibitory effect of Poly(IC). Treatment with diclofenac also abrogated the inhibitory effect of Poly(IC) on SEB-induced IL-5 and IL-13 production. However, unlike exposure of diclofenac-treated DNPCs to lipopolysaccharide, the ligand for TLR4, exposure of these cells to Poly(IC) did not enhance IL-5 or IL-13 production. Poly(IC) did not significantly increase PGE2 production by DNPCs. CONCLUSIONS: These results suggest that TLR3 signaling regulates eosinophilia-associated cytokine production in CRSwNP, at least in part, via IL-10 production.

DOI： 10.1016/j.alit.2015.08.005

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CONCLUSIONS: The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the pathogenesis of middle ear diseases. Modulation of inflammasome-mediated inflammation may be a novel therapeutic strategy for cholesteatoma and chronic otitis media. OBJECTIVE: NLRP3 inflammasome is a critical molecule mediating interleukin (IL)-1β responses. However, the expression of NLRP3 in the pathogenesis of cholesteatoma and chronic otitis media has not been fully examined. This study sought to assess the expression of NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in middle ear tissues in patients with cholesteatoma or chronic otitis media. METHODS: Middle ear tissue samples were obtained from patients with cholesteatoma or chronic otitis media. Control middle ear samples were collected during cochlear implant surgery of patients without middle ear inflammation. The expression of NLRP3, ASC, and caspase-1 were examined by reverse transcription polymerase chain reaction (RT-PCR) assay and immunohistochemical study. RESULTS: The levels of mRNA of NLRP3, ASC, and caspase-1 were significantly elevated in cholesteatoma and chronic otitis media as compared with that of normal controls. The proteins of NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells in cholesteatoma and chronic otitis media.

DOI： 10.3109/00016489.2015.1093171

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Language：Japanese   Publisher：Japan Rhinologic Society  

DOI： 10.7248/jjrhi.55.121

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Other Link： http://search.jamas.or.jp/link/ui/2017039132

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BACKGROUND: A close relationship between upper and lower respiratory tract diseases has been reported. The purpose of this study was to evaluate lung function in patients with chronic rhinosinusitis (CRS) who have never smoked. METHODS: A total of 208 patients with CRS were enrolled in this study. Of these subjects, 96 patients were ever smokers and 112 patients were never smokers. CRS patients with lower pulmonary diseases including chronic obstructive pulmonary disease (COPD) and asthma were excluded from this study. Age-matched normal control subjects (n = 55) who were never smokers were also recruited. Pulmonary function testing was performed using spirometry. Lund-Mackay computed tomography (CT) score, peripheral blood eosinophil count, and immunoglobulin E (IgE) level in serum samples were examined. Nasal obstruction was evaluated by active anterior rhinomanometry. RESULTS: CRS patients who were ever smokers have decreased lung function. Never-smoking patients with CRS also showed significant obstructive lung function changes as compared with normal controls. No significant correlation was detected between the clinical parameters (CT score, eosinophil count, IgE level, and nasal resistance) and lung function. CONCLUSION: Asymptomatic obstructive lung function changes were observed in never-smoking patients with CRS. Our findings suggest that patients with CRS should be followed carefully in order to detect lung diseases.

DOI： 10.1002/alr.21628

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BACKGROUND: Recent studies have revealed that Staphylococcus aureus and its components participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyps. OBJECTIVE: We sought to determine whether staphylococcal protein A (SpA) from S aureus regulated cellular responses in nasal polyps, especially when coupled to immunoglobulins in immune complexes (ICs). METHODS: Dispersed nasal polyp cells (DNPCs) or peripheral blood monocytes were cultured in vitro with SpA in the presence or absence of IgG, and IL-5, IL-13, IFN-γ, IL-17A, and IL-10 levels were measured in the supernatants. The effect of SpA exposure on staphylococcal enterotoxin B-induced cytokine production by DNPCs in the presence and absence of IgG, IgA, and autologous serum was also examined. RESULTS: Exposure to SpA induced DNPCs to produce significantly higher IL-10, IL-13, and IL-17A levels than DNPCs without SpA, although the magnitude of the IL-17A increase was less than that of IL-10 and IL-13. SpA induced IL-10 production mainly from adherent DNPCs, and this was significantly enhanced in the presence of IgG; similar results were observed in peripheral blood monocytes. IC formation between SpA and IgG (SpA-IgG ICs) was confirmed by using native polyacrylamide gel electrophoresis. SpA-IgG ICs, but not SpA alone, almost completely suppressed staphylococcal enterotoxin B-induced IL-5, IL-13, IFN-γ, and IL-17A production by DNPCs; similar inhibition was observed in DNPCs treated with SpA in the presence of either IgA or autologous serum. CONCLUSIONS: Our results suggest that SpA can regulate the pathogenesis of enterotoxin-induced inflammation in patients with chronic rhinosinusitis with nasal polyps through coupling to immunoglobulins.

DOI： 10.1016/j.jaci.2014.10.058

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HYPOTHESIS: Macrophage migration inhibitory factor plays an important role in noise-induced hearing loss. BACKGROUND: Macrophage migration inhibitory factor is an essential factor in axis formation and neural development. Macrophage migration inhibitory factor is expressed in the inner ear, but its function remains to be elucidated. METHODS: Macrophage migration inhibitory factor-deficient mice (MIF(-/-) mice) were used in this study. Wild-type and MIF(-/-) mice received noise exposure composed of octave band noise. Auditory brainstem response thresholds were examined before (control) and at 0, 12, and 24 hours and 2 weeks after the intense noise exposure. Morphological findings of cochlear hair cells were investigated using scanning electron microscopy. Histopathological examination with hematoxylin and eosin staining and TUNEL assay were also performed. RESULTS: In both the wild-type and MIF(-/-) mice, acoustic overstimulation induced significant hearing loss compared with the control level. Two weeks after the intense noise exposure, the MIF(-/-) mice had an increased hearing threshold compared with the wild-type mice. Scanning electron microscopy demonstrated that the outer hair cells in the MIF(-/-) mice were affected 2 weeks after noise exposure compared with the wild-type mice. TUNEL-positive cells were identified in the organ of Corti of the MIF(-/-) mice. CONCLUSION: The MIF(-/-) mice had prolonged hearing loss and significant loss of cochlear hair cells after intense noise exposure. Macrophage migration inhibitory factor may play an important role in recovery from acoustic trauma. Management of macrophage migration inhibitory factor may be a novel therapeutic option for noise-induced hearing loss.

DOI： 10.1097/MAO.0000000000000755

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BACKGROUND: In contrast to Staphylococcus aureus-derived superantigenic exotoxins, the role of non-superantigenic exotoxins in the pathogenesis of eosinophilic airway diseases remains obscure. We sought to characterize S. aureus alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Dispersed nasal polyp cells and uncinate tissue cells were prepared from patients with CRS with and without nasal polyps, respectively. Cells were incubated with various concentrations of alpha-toxin or staphylococcal enterotoxin B and then the levels of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in the cell supernatants were determined. The pathophysiological significance of alpha-toxin-induced cytokine production was also determined including radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum total IgE level, and 1-s forced expiratory volume/forced vital capacity ratio (FEV1/FVC). RESULTS: Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production was higher in nasal polyp cells than in uncinate tissue cells. The potency of alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to that of enterotoxin. Alpha-toxin-induced IFN-γ, IL-17A, and IL-10 production significantly and negatively correlated with the degree of eosinophil infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-γ and IL-10 production significantly and positively correlated with FEV1/FVC. IL-10 production was significantly lower in asthmatic patients compared to non-asthmatics CONCLUSIONS: S. aureus-derived alpha-toxin can provoke cellular responses in nasal polyps. These responses, especially failure to synthesize IL-10, may play a role in the pathophysiology of CRSwNP.

DOI： 10.2332/allergolint.14-OA-0703

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BACKGROUND: The relationship between upper and lower airway diseases has been reported. However, the pulmonary function of patients with chronic rhinosinusitis (CRS) has not been fully examined. METHODS: Pulmonary function was measured in 273 patients with CRS and 100 age-matched normal control subjects. No patients with chronic obstructive pulmonary disease (COPD) were included in this study. The patients with CRS were divided into 8 subgroups based on the presence of asthma, sensitization to common inhaled antigens, and nasal polyposis. The relationships between pulmonary function and clinical parameters, including radiographic severity of CRS according to the Lund-Mackay computed tomography (CT) staging system, eosinophil count in the peripheral blood, and serum total immunoglobulin E (IgE) levels, were assessed. RESULTS: In pulmonary function testing, the CRS patients had affected pulmonary function. The CRS patients without asthma showed latent obstructive pulmonary function changes when compared to normal controls. No significant correlations were observed between pulmonary function and any clinical parameters (Lund-Mackay CT staging score, eosinophil count in the peripheral blood, and serum total IgE levels). CONCLUSION: CRS patients had significant obstructive lung function changes regardless of the presence of asthma. The patients with CRS who had not been clinically diagnosed as having lower respiratory tract diseases might have had subclinical lower airway diseases. Therefore, clinicians should be aware of pulmonary function and lower lung diseases in patients with CRS.

DOI： 10.1002/alr.21370

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.neuroscience.2014.08.042

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Interleukin (IL)-17A is a major cytokine produced by Th17 cells, which are associated with chronic inflammations. The local expression of IL-17A in allergic rhinitis (AR) remains to be characterized. We sought to determine the role of IL-17A expression in human inferior turbinate mucosa in the pathophysiology of AR. Inferior turbinate mucosa was sampled from medical treatment-resistant, surgery-required patients with perennial AR (PAR, n = 21), nonallergic rhinitis with eosinophilia syndrome (NARES, n = 7), and nonallergic hypertrophic rhinitis (HR, n = 13). IL-17A expression was determined with immunohistochemical staining. The mean number of IL-17A(+) cells and eosinophils per field were counted. Total serum immunoglobulin E (IgE) levels, blood eosinophil count, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio were also examined in each patient. IL-17A was primarily expressed in infiltrating inflammatory cells. The number of IL-17A(+) cells in nasal mucosa was significantly higher in the PAR group compared with HR (p = 0.002) and NARES (p = 0.021) groups. There was a significant and positive correlation between the number of IL-17A(+) cells and total nasal symptom score (rho = 0.403; p = 0.011), especially sneezing score (rho = 0.471; p = 0.003). The number of IL-17A(+) cells was significantly and positively correlated with the degree of eosinophil infiltration (rho = 0.623; p < 0.001), but not with total serum IgE levels (rho = 0.284; p = 0.098), blood eosinophil counts (rho = 0.302; p = 0.056), or FEV1/FVC ratio (rho = 0.092; p = 0.569). The present study provides evidence that IL-17A expression in the nasal mucosa is associated with the pathophysiology of AR, including disease severity and nasal eosinophilia.

DOI： 10.2500/ar.2014.5.0078

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cambridge University Press (CUP)  

<title>Abstract</title><sec id="S0022215114000450_sec1"><title>Background:</title>A close relationship between upper and lower respiratory tract diseases has been reported. However, little is known about pulmonary function in patients with upper respiratory tract diseases.

</sec><sec id="S0022215114000450_sec2"><title>Methods:</title>Pulmonary function was measured in: 68 patients with chronic rhinosinusitis without nasal polyps, 135 patients with chronic rhinosinusitis with nasal polyps, 89 patients with allergic rhinitis and 100 normal control subjects. The relationships between pulmonary function and clinical parameters were assessed. These parameters included radiographic severity of chronic rhinosinusitis, serum total immunoglobulin E levels, concentrations of cytokines in nasal secretions and exhaled nitric oxide levels.

</sec><sec id="S0022215114000450_sec3"><title>Results:</title>The pulmonary function of patients with chronic rhinosinusitis was significantly affected. The level of interleukin-5 in nasal secretions was significantly correlated with pulmonary function in patients with chronic rhinosinusitis.

</sec><sec id="S0022215114000450_sec4"><title>Conclusion:</title>The findings indicated latent obstructive lung function changes in chronic rhinosinusitis patients. The cytokines in nasal secretions might be related to obstructive lung function changes in chronic rhinosinusitis.

</sec>

DOI： 10.1017/s0022215114000450

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BACKGROUND: Statistically significant results of medical intervention trials are not always clinically meaningful. We sought to estimate the minimal clinically important difference (MCID) (the smallest change in a given endpoint that is meaningful to a patient) during seasonal alteration of Japanese cedar/cypress pollinosis (JCCP). METHODS: Results of a double-blinded, placebo-controlled trial of JCCP patients conducted between 2008 and 2010 were analyzed using an anchor-based method in which a face scale for Japanese rhinoconjunctivitis quality-of-life questionnaire (JRQLQ) was set as an anchor. MICDs were calculated as changes of average scores, including those for naso-ocular symptoms with 5 items in diary cards (T5SS), naso-ocular symptoms with 6 items (T6SS) and QOL with 17 items on the JRQLQ when face scale scores either improved or deteriorated by one point. RESULTS: In 2009 and 2010, 3,698 and 374, respectively, grains/cm(2) of pollens were dispersed. The MCIDs for T5SS in 2009 and 2010 were 1.426 (0.285 per item) and 1.441 (0.288), respectively. The MCIDs for T6SS were 4.115 (0.686) and 3.183 (0.531) in 2009 and 2010, respectively. The MCIDs for QOL were 10.469 (0.616) and 6.026 (0.354) in 2009 and 2010, respectively. CONCLUSIONS: For T5SS in the diary, T6SS and QOL in JRQLQ, unit differences of 1.5 (0.3 per item), 3.6 (0.6) and 8.2 (0.5), respectively, were considered clinically meaningful by JCCP patients. The MCID for symptoms recorded in the diary was stable irrespective of the dispersed pollen level.

DOI： 10.2332/allergolint.13-OA-0570

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OBJECTIVES/HYPOTHESIS: Granulocyte/macrophage colony-stimulating factor is important in the pathogenesis of acute and chronic inflammatory disease. We hypothesized that granulocyte/macrophage colony-stimulating factor plays a pivotal role in middle ear inflammation and that neutralization of granulocyte/macrophage colony-stimulating factor would inhibit neutrophil migration into the middle ear and production of inflammatory mediators. STUDY DESIGN: Animal experiment. METHODS: We used transtympanic administration of lipopolysaccharide, a major component of gram-negative bacteria, into mice to induce an experimental otitis media. Control mice received injection of phosphate-buffered saline into the middle ear cavity. Mice were systemically treated with granulocyte/macrophage colony-stimulating factor neutralizing antibody or control immunoglobulin G via intraperitoneal injection 2 hours before transtympanic injection of lipopolysaccharide or phosphate-buffered saline. Middle ear effusions were collected. Concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in middle ear effusions were measured by enzyme-linked immunosorbent assay. Histologic examination of the middle ear was also performed. RESULTS: Transtympanic injection of lipopolysaccharide upregulated levels of granulocyte/macrophage colony-stimulating factor, IL-1β, TNF-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in the middle ear. Concentrations of cytokines and chemokines were significantly decreased in mice injected with granulocyte/macrophage colony-stimulating factor neutralizing antibody. Infiltration of inflammatory cells into the middle ear cavity induced by lipopolysaccharide was also significantly reduced by neutralization of granulocyte/macrophage colony-stimulating factor. CONCLUSIONS: Systemic injection of granulocyte/macrophage colony-stimulating factor neutralizing antibody inhibits the middle ear inflammation induced by lipopolysaccharide in mice. Our findings suggest that granulocyte/macrophage colony-stimulating factor may offer a novel therapeutic target for the management of intractable otitis media.

DOI： 10.1002/lary.23795

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BACKGROUND: Interleukin-18 (IL-18) is a member of the IL-1 cytokine family that affects chronic inflammation. We sought to characterize IL-18 expression and investigate its release during chronic rhinosinusitis (CRS). METHODS: The expression of IL-18 in nasal polyps (NPs) and uncinate tissues (UTs) from both CRS and non-CRS patients was examined via immunohistochemistry. After culturing dispersed NP cells (DNPCs) with or without various stimulations, IL-18 levels were measured in the culture supernatants. Furthermore, the effect of IL-18 neutralization on staphylococcus enterotoxin B (SEB)-induced cytokine production was also examined. RESULTS: Similar expression of IL-18 in the epithelial layers was observed between the NPs and UTs. However, there was a significantly higher number of IL-18(+) cells in the lamina propria from NPs compared to UTs without CRS. This increased number was significantly correlated with the radiological severity of sinusitis and local eosinophilia. After the dispersion, IL-18 was spontaneously released by NP cells in a phase-dependent manner. While SEB, fungal antigens, and TLR agonists did not enhance the release, exposure to protease or one cycle of a freeze-and-thaw treatment did induce release of IL-18 from rested DNPCs. In addition, neutralization of IL-18 significantly suppressed SEB-induced IL-5, IL-13, and IFN-γ, but not IL-17A production. CONCLUSIONS: These results suggest that the pro-inflammatory effect of IL-18 released by danger signals may be involved in the pathogenesis of CRS, which includes eosinophilic inflammation and NP formation, via the augmentation of both Th2- and Th1-associated cytokine production.

DOI： 10.1159/000341668

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BACKGROUND: The usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. OBJECTIVES: To study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. METHODS: We designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. RESULTS: The placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P < .01) and POT (3.9; P = .03) groups. All patients in the placebo and POT groups were classified as having persistent rhinitis, whereas 80% of the EIT group met the ARIA classification criteria (P = .03). The quality-of-life score and nasal eosinophil cationic protein levels were lower in the EIT and POT groups compared with the placebo group. Daytime sleepiness, smell disturbance, and the mean dose of loratadine taken as the rescue medication were similar. Treatment with mometasone was well tolerated. CONCLUSION: EIT with INSs is superior to POT in controlling pollinosis.

DOI： 10.1016/j.anai.2012.08.016

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DOI： 10.1111/j.1365-2222.2012.04015.x

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BACKGROUND: Little is known about the safety and effectiveness of early interventional treatment (EIT) with intranasal corticosteroids for seasonal allergic rhinitis. We designed a double-blinded, randomized, placebo-controlled 12-week trial of EIT with mometasone furoate nasal spray (MFNS) for Japanese cedar/cypress pollinosis (JCCP). METHODS: A total of 50 JCCP patients received MFNS (200μg once daily: n = 25) or placebo (n = 25) starting on February 1, 2010. Treatments continued until the end of April. The primary endpoint was the comparison of the total nasal symptom score (TNSS) between the MFNS and placebo groups. The secondary endpoints included comparisons of QOL, daytime sleepiness, nasal ECP levels, and safety. RESULTS: Continuous dispersion of Japanese cedar pollen began on February 22. Although the placebo group showed a significant worsening of symptoms after the start of the continuous dispersion, no worsening occurred in the MFNS group. A significant difference in the TNSS between the two groups was seen starting at 4 weeks after the treatment. Similar results were seen for QOL and sleepiness. Nasal ECP levels in March were significantly lower in the MFNS group. A total of 56% of the MFNS group progressed to a persistent allergic rhinitis state in accordance with the ARIA classification, as opposed to 84% of the placebo group. MFNS was well tolerated, and the plasma cortisol concentrations were similar between the two groups. CONCLUSIONS: EIT with MFNS for JCCP is both safe and effective. This treatment can potentially lessen symptoms and help pollinosis patients remain in the intermittent state.

DOI： 10.2332/allergolint.11-OA-0382

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Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

DOI： 10.1111/j.1365-2249.2010.04292.x

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DOI： 10.1016/j.jaci.2010.09.029

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DOI： 10.1016/j.jaci.2010.05.014

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BACKGROUND: Recent investigations have revealed that staphylococcal enterotoxins (SEs), COX metabolism, or both might participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyposis. OBJECTIVE: We sought to determine whether COX metabolism, especially prostaglandin (PG) E(2), plays a significant role in SE-induced cellular responses in nasal polyps. METHODS: Dispersed nasal polyp cells (DNPCs) were prepared from nasal polyps by means of enzymatic digestion. DNPCs were cultured with SEB in the presence or absence of COX inhibitors (diclofenac and indomethacin) for 72 hours; then the levels of IL-5, IL-13, RANTES, and eotaxin in the supernatants were measured. The effect of PGE(2) on SEB-induced responses by diclofenac-treated DNPCs was examined, especially in terms of receptor specificity. RESULTS: DNPCs produced significant amounts of IL-5, IL-13, and RANTES in response to SEB. COX inhibitors significantly increased the production of these cytokines. The degree of local eosinophilia was significantly and positively correlated with the changes in IL-5 production induced by diclofenac treatment. PGE(2) significantly and dose-dependently inhibited SEB-induced IL-5, IL-13, and RANTES production by diclofenac-treated DNPCs. E-prostanoid (EP) 2 receptor-selective agonist strongly inhibited the production of all 3 cytokines. EP3 and EP4 receptor-selective agonists partially suppressed these responses, whereas EP1 receptor-selective agonist did not. Interestingly, all of the combined treatments with 2 of the 4 EP receptor-selective agonists significantly inhibited the SEB-induced responses by diclofenac-treated DNPCs. CONCLUSIONS: These results suggest that PGE(2) inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis.

DOI： 10.1016/j.jaci.2009.01.047

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BACKGROUND: Prostaglandin D(2) (PGD(2)) participates in airway inflammation. We reported that levels of hematopoietic-type PGD(2) synthase (h-PGDS) in sinonasal tissues may play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Two PGD(2) receptors have been isolated, DP and CRTH2, but whether they participate in CRS remains unclear. We sought to determine the expression and characterization of DP and CRTH2 in CRS. METHODS: Expression of DP and CRTH2 in nasal polyps (NP) and uncinate process mucosae (UPM) was examined by in situ hybridization and immunohistochemistry and evaluated by real-time quantitative PCR. h-PGDS, IL-5, eotaxin and RANTES expression was also determined. In addition, the effect of PGD(2) on the expression of both receptors in UPM was assessed. RESULTS: DP was widely expressed, not only in infiltrating inflammatory cells but also in constitutive cells such as vascular endothelial cells and ciliated columnar epithelia. CRTH2 was selectively expressed in inflammatory cells and some glands. Significantly greater levels of DP mRNA and conversely decreased levels of CRTH2 mRNA were observed in NP compared with UPM. DP and CRTH2 mRNA levels were not only positively and inversely correlated with levels of h-PGDS but also with eotaxin, respectively. Furthermore, addition of PGD(2) significantly increased DP expression and conversely reduced CRTH2 expression in UPM. CONCLUSIONS: These results suggest that distinct expression of DP and CRTH2 is associated with the pathophysiology of CRS, including NP formation, and the expression of these receptors may be regulated by h-PGDS and PGD(2).

DOI： 10.1159/000155743

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BACKGROUND: Nasogastric tubes (NGT) are used widely for feeding and decompressions of stomach, but they are associated with several complications and discomfort. When prolonged use of NGT is required, percutaneous endoscopic gastrostomy (PEG) should be considered. However, PEG is not feasible for patients with previous gastrectomy. We have performed tube cervical esophagostomy (TCE) for such difficult cases of PEG. METHODS: The current study focused on 7 patients requiring TCE for feeding or decompression from 2004 to 2005 at Tottori Municipal Hospital in Japan. RESULTS: The procedure is relatively simply to perform under local anesthesia and significant complications were not experienced. CONCLUSIONS: Feeding or decompressive TCE is useful alternative procedure in patients where PEG is not feasible or unacceptable.

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

COVID-19の流行下における当院での鼻科手術実施にあたっての対策と現状について報告した。2020年4月から5月にかけて緊急症例や悪性腫瘍関連の症例以外は新規手術の予約の停止、予定の手術の延期等を行った。2020年6月以降は術前にPCR検査を施行することが可能となり、経鼻手術は術前に原則としてPCR施行の上で再開した。手術再開後、2020年8月から11月にかけて経鼻手術はほぼ例年同様の手術症例数となったが、流行の第3波の影響を受け2020年12月から2021年2月にかけて大きく手術数が減少した。手術を含めたすべての診療に関連して、新型コロナウイルスの感染リスクに関する問題が生じた場合は院内の感染制御部と連携し、助言を受けることが可能な体制となっている。

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

アレルギー性鼻炎は,非常に一般的な疾患であり,耳鼻咽喉科医にとって診断と治療は日常茶飯事と言っても良い.しかし,本邦におけるアレルギー性鼻炎は年々罹患率が上昇し,低年齢化が進みより大きな健康上の問題となっている.アレルギー性鼻炎の診療においては「鼻アレルギー診療ガイドライン」が2020年版に改訂され種々のupdateがなされた.これまで行ってきた治療法に関する新しい情報と,新規に利用できるようになった治療法を整理することでより質の高い診療ができると考えられる.アレルギー性鼻炎は報告によっては全体で49.2%,スギ花粉症で38.8%の有病率に達することが明らかにされており,過去20年で著増した.また,10歳代の若年層でスギ花粉症患者が急増しており,将来的により大きな問題になってくることが予想される.典型例が増加する中,一方では診断や抗原の同定に苦労する局所アレルギー性鼻炎も指摘されており,専門家の耳鼻咽喉科医としては種々のタイプのアレルギー性鼻炎に対応できる必要がある.アレルギー性鼻炎の治療で最も重要である薬物治療に関しては,抗ヒスタミン薬の増量についてガイドラインでも触れられるようになった.初期療法の有効性については各種エビデンスについて述べる.また,重症の花粉症における新規薬剤となる抗IgEモノクローナル抗体であるOmalizumabが登場した.通常治療でコントロール不良な患者にとって貴重な選択肢となる可能性がある.有病率の上昇が問題となっている中では,唯一アレルギー性鼻炎を根本的に改善させ得るアレルゲン免疫療法の重要性が高まる.近年,舌下免疫療法が定着しつつあるが,その有効性について紹介する.耳鼻咽喉科医は保存的加療とともに外科的治療について理解することで治療効果を向上させることができる.アレルギーは手術で改善する疾患ではないが,鼻腔形態を改善させる鼻中隔手術や下鼻甲介手術で患者のQOLの改善を図ることができる.(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J07551&link_issn=&doc_id=20210930310003&doc_link_id=%2Fdz0tokei%2F2021%2F012408%2F003%2F1144-1149%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0tokei%2F2021%2F012408%2F003%2F1144-1149%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー感染症学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：一般社団法人 日本耳鼻咽喉科頭頸部外科学会  

<p> アレルギー性鼻炎は, 非常に一般的な疾患であり, 耳鼻咽喉科医にとって診断と治療は日常茶飯事と言っても良い. しかし, 本邦におけるアレルギー性鼻炎は年々罹患率が上昇し, 低年齢化が進みより大きな健康上の問題となっている. アレルギー性鼻炎の診療においては「鼻アレルギー診療ガイドライン」が2020年版に改訂され種々の update がなされた. これまで行ってきた治療法に関する新しい情報と, 新規に利用できるようになった治療法を整理することでより質の高い診療ができると考えられる.</p><p> アレルギー性鼻炎は報告によっては全体で49.2%, スギ花粉症で38.8%の有病率に達することが明らかにされており, 過去20年で著増した. また, 10歳代の若年層でスギ花粉症患者が急増しており, 将来的により大きな問題になってくることが予想される. 典型例が増加する中, 一方では診断や抗原の同定に苦労する局所アレルギー性鼻炎も指摘されており, 専門家の耳鼻咽喉科医としては種々のタイプのアレルギー性鼻炎に対応できる必要がある.</p><p> アレルギー性鼻炎の治療で最も重要である薬物治療に関しては, 抗ヒスタミン薬の増量についてガイドラインでも触れられるようになった. 初期療法の有効性については各種エビデンスについて述べる. また, 重症の花粉症における新規薬剤となる抗 IgE モノクローナル抗体である Omalizumab が登場した. 通常治療でコントロール不良な患者にとって貴重な選択肢となる可能性がある.</p><p> 有病率の上昇が問題となっている中では, 唯一アレルギー性鼻炎を根本的に改善させ得るアレルゲン免疫療法の重要性が高まる. 近年, 舌下免疫療法が定着しつつあるが, その有効性について紹介する.</p><p> 耳鼻咽喉科医は保存的加療とともに外科的治療について理解することで治療効果を向上させることができる. アレルギーは手術で改善する疾患ではないが, 鼻腔形態を改善させる鼻中隔手術や下鼻甲介手術で患者の QOL の改善を図ることができる.</p>

DOI： 10.3950/jibiinkotokeibu.124.8_1144

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Language：Japanese   Publisher：Japan Rhinologic Society  

<p>Extraosseous plasmacytomas are localized plasma cell neoplasms that arise in tissues other than bone, and are most commonly located in the head and neck. The patient was a 83-year-old man who complained of left nasal bleeding and left nasal obstruction. He consulted a nearby doctor and a left nasal mass was discovered. A tumor with a smooth surface filled the left nasal cavity, and was observed from the left nasal cavity to the ethmoid sinus on sinus computed tomography (CT) and magnetic resonance imaging (MRI). Left nasal polypotomy under local anesthesia was performed for improvement of left nasal obstruction. A pathological examination revealed plasma cell neoplasms. However, blood M protein and urinary Bence-Jones protein were not present, and the bone marrow was found to be normal by biopsy; thus, findings of myeloma were not observed. The patient was diagnosed with extraosseous plasmacytoma and underwent left endoscopic sinus surgery under general anesthesia. The tumor had not infiltrated the surrounding tissues and was completely removed under visual inspection. However, the safety margin was not secured, which led to addition of radiotherapy after surgery. There has been no recurrence in two and a half years postoperatively. Since extraosseous plasmacytoma may shift to multiple myeloma after several years, there is a need to follow-up the patient regularly and carefully over a long period to monitor possible local recurrence and distant metastasis.</p>

DOI： 10.7248/jjrhi.60.13

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00083&link_issn=&doc_id=20201019080437&doc_link_id=%2Fcl8isoke%2F2020%2Fs055s1%2F194%2F0387-0387%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl8isoke%2F2020%2Fs055s1%2F194%2F0387-0387%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01099&link_issn=&doc_id=20200925570126&doc_link_id=130007921011&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007921011&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(株)北隆館  

好酸球性副鼻腔炎は難治性副鼻腔炎として知られている。副腎皮質ステロイド投与が有効であるが、手術や薬物療法に対して抵抗性である。JESREC Studyにより診断基準が確立され、重症度分類で中等症以上か好酸球性中耳炎の合併で厚生労働省の指定難病の対象となっている。治療に関して抗IL-4/IL-13受容体モノクローナル抗体のデュピルマブが既存治療で効果不十分な鼻茸を伴う慢性副鼻腔炎で適応となり、その他の抗体療法についても現在、臨床研究が進められている。(著者抄録)

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Language：Japanese   Publisher：(株)北隆館  

アレルギー性鼻炎では、症状が発症する前にMinimal Persistent Inflammation(MPI)というごく軽い炎症が生じている。花粉症の初期療法は、MPIの抑制により効果を発揮することが考えられている。マウスの鼻炎モデルを用いてMPIの存在と、初期療法について検討を行った。(著者抄録)

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Language：Japanese  

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Other Link： http://search.jamas.or.jp/link/ui/2021101901

Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>症例は65歳男性。糖尿病性腎症による末期腎不全に対する腎移植術前CTにて右蝶形骨洞に真菌を疑う軟部影を認めたが、無症候性であった。しかしながら、移植後の免疫抑制状態で劇症型になる可能性を考慮し、移植3カ月前に内視鏡下副鼻腔手術ESSにて糸状菌塊を除去（粘膜への真菌浸潤なし）、追加治療することなく経過は安定していた。 生体腎移植については妻をドナーとしたABO不適合（術前減感作療法としてRituximab 200mg/body×1、DFPP×2、PE×1を実施、免疫抑制剤はTac-ER、MMF、PSL、Basiliximabを使用）、経過は良好でPOD18に退院となった（ Cr 1.28mg/dl ）。 移植後2カ月が経過し、右顔面痛・頭痛が出現、近医で副鼻腔洗浄や抗菌薬投与を受けるも改善せず。β-Dグルカン 53pg/mlと異常高値、副鼻腔MRIでは一部骨への浸潤を疑う軟部影を認め、再度ESSを施行、紙様板は腐骨化を認めたが真菌塊を可及的に除去した。VRCZも併用・継続し、術後1カ月でβ-Dグルカンも正常化、現在、再燃を認めていない。 浸潤性副鼻腔真菌症は副鼻腔から眼窩，海綿状静脈洞，頭蓋内へ浸潤し致死的となり、全生存率は概ね50%と、予後不良とされる。今回、予防的にESSを先行したが、腎移植後、急性浸潤性に再燃した症例を経験したので、若干の文献的考察を加えて報告する。 </p>

DOI： 10.11386/jst.55.Supplement_387_3

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Language：Japanese   Publisher：Japanese Society of Allergology  

DOI： 10.15036/arerugi.69.897

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Other Link： http://search.jamas.or.jp/link/ui/2021111343

Language：Japanese   Publisher：Japan Rhinologic Society  

<p>The anterior ethmoidal artery (AEA) arises from the ophthalmic artery and enters the paranasal cavity through the anterior ethmoidal canal. An accidental injury to the AEA during endoscopic sinus surgery (ESS) can cause bleeding and orbital hematoma. This should be avoided because it may result in severe complications such as blindness. The course of the AEA can mostly be determined on CT, and it is important to identify where the artery runs before an operation. Herein, we report a case of a 75-year-old man with an isolated AEA in an ethmoidal sinus cyst. The patient suffered from left ocular proptosis, ophthalmalgia and diplopia. CT and MRI revealed an ethmoid cyst without signs of cellulitis or abscess formation. A blood test showed elevations of leukocyte count and CRP, raising a concern of possible orbital complications. Therefore, we performed an emergency ESS. In view of flow-void sign at the preoperative MRI imaging, we suspected that AEA run through a cyst. During an ethmoid cyst fenestration with purulent drainage, we identified the AEA floating in the cyst, and thus determined to preserve it to complete the surgery. The patient recovered without any complications or postoperative bleeding. The location of the AEA can vary greatly among individuals, and this case underscores the importance of preoperative imaging to localize the AEA as a preventive measure against complications.</p>

DOI： 10.7248/jjrhi.59.358

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Language：Japanese   Publisher：(株)北隆館  

アレルギー性真菌性鼻副鼻腔炎(Allergic Fungal Rhinosinusitis:AFRS)は真菌に対するアレルギー機序により生じる難治性の副鼻腔炎として知られている。以前は欧米からの報告が中心であったが、本邦でも昨今増加傾向であるがまだ不明な点も多い。真菌が副鼻腔に寄生、増殖し、副鼻腔でアレルギー反応が起こることで副鼻腔粘膜に好酸球が浸潤する。その結果、難治性の鼻ポリープおよび好酸球性ムチンが生じ、手術を行なっても再発しやすく、臨床的にも問題となることが多い、耳鼻咽喉科医にとって注意を要する疾患である。今回、AFRSについて解説するとともに、AFRSに対する術後のアレルゲン免疫療法について紹介する。(著者抄録)

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Language：Japanese   Publisher：(株)北隆館  

耳鼻咽喉科領域におけるアレルギー検査は主にアレルギー性鼻炎の診断のため行われる。主な検査としては鼻汁好酸球検査、血液による血清特異的IgE抗体測定、抗原による皮膚テストが広く行われている。また、抗原で直接鼻粘膜を刺激し鼻粘膜の過敏性を評価する誘発テストもある。アレルギー性鼻炎の診断はこれらの検査結果と問診の結果を総合して行う。詳細で的確な問診と、適切な検査の選択により患者の負担を最小限にとどめた正しい診断を行う事ができる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publisher：JAPAN SOCIETY OF IMMUNOLOGY AND ALLERGOLOGY IN OTOLARYNGOLOGY  

DOI： 10.5648/jjiao.37.253

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Language：Japanese   Publisher：Japanese Society of Allergology  

<p>Background: Baker's rhinitis is a kind of occupational allergic rhinitis mainly caused by intranasal exposure to wheat and/or rye flour in bakery workers. Continuous exposure to flour may induce the onset of asthma in these patients.</p><p>Method: We experienced a case of 34-year-old male with baker's rhinitis without asthma, and investigated responses of IgE and peripheral blood mononuclear cells (PBMCs) to flour extracts used in the bakery in practice.</p><p>Result: In the immunoblotting, the patient's IgE reacted with 18 and 30kDa molecules in the extracts of 6 flours used in the bakery. The patient's PBMC produced a substantial amount of IL-5 and IL-13 in response to these flour extracts.</p><p>Conclusion: It is suggested that water/salt soluble components of wheat flour selectively induce type 2 cytokines production in baker's rhinitis.</p>

DOI： 10.15036/arerugi.68.35

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Other Link： http://search.jamas.or.jp/link/ui/2019129202

Language：Japanese   Publisher：日本鼻科学会  

DOI： 10.7248/jjrhi.58.114

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：日本鼻科学会  

DOI： 10.7248/jjrhi.57.301

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本職業・環境アレルギー学会  

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Language：Japanese   Publisher：医薬ジャーナル社  

鼻噴霧用ステロイド薬はアレルギー性鼻炎に対して強力な抗炎症作用を示す。花粉症の本格発症前の最小持続炎症の制御という観点から,これまで,鼻噴霧用ステロイド薬は花粉症初期治療薬としての有用性が議論されていたが,最新版の鼻アレルギー診療ガイドライン(2016年版)からは,鼻噴霧用ステロイド薬は初期療法の1つとして記載されるようになった。自験例も含めいくつかのプラセボ対照二重盲検比較試験において,鼻噴霧用ステロイド薬によるスギ・ヒノキ花粉症に対する初期治療は,プラセボと比較して症状およびQOLの増悪を有意に抑制した。一方,安全性に関しては実薬とプラセボとの間に有意な差を認めなかった。さらに発症後治療と比較しても花粉の本格飛散後の鼻眼症状の増悪を有意に抑制した。以上の結果からは鼻噴霧用ステロイド薬による初期治療は有効かつ安全な治療法であることが明らかとなった。しかし,初期治療の適切な開始時期や飛散花粉数による効果の変化など今後の検討も必要である。(著者抄録)

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Language：Japanese   Publisher：Japan Rhinologic Society  

<p>A meningoencephalocele is the herniation of intracranial tissue, including brain and meninges, through a defect in the skull. The condition is typically congenital and is frequently associated with midfacial, ocular, and brain anomalies. Cranial meningoencephalocele is usually classified into occipital, frontal, ethmoidal, naso-orbital, and transsphenoidal types, according to the location. The aim of this study is to identify the clinical and surgical factors involved in treatment of frontal meningoencephalocele. A 40-year-old man was admitted to hospital complaining of impaired consciousness. Magnetic resonance imaging (MRI) revealed a mass in the left frontoethmoidal sinus and nasal cavity, and also showed marked bilateral ventricular enlargement. Computed tomography (CT) detected a bone defect in the posterior wall of the frontal sinus, and the patient had cerebrospinal rhinorrhea. Histological examination of biopsy specimens from the nasal mass led to diagnosis of meningoencephalocele. The patient was referred to our hospital because of prolonged disturbance of consciousness, from which he recovered after administration of phenobarbital sodium and meropenem trihydrate. Frontal craniotomy in conjunction with endoscopic sinus surgery (ESS) was performed to remove the meningoencephalocele. Ventriculoperitoneal shunt placement was used to treat idiopathic hydrocephalus. The postoperative course was uneventful and there has been no recurrence of meningoencephalocele in 2 years of follow-up.</p>

DOI： 10.7248/jjrhi.56.564

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Language：Japanese   Publisher：Japan Rhinologic Society  

<p>Reactive lymphoid hyperplasia (RLH) is histologically defined as reactive hyperplasia of lymphoid follicles with germinal centers, few variants of individual lymphocytes, and polyclonal proliferation. Here, we present a case of RLH with accumulation of IgG4-positive plasma cells in the nasal floor. The patient was a 69-year-old woman who complained of a left nasal mass and right hearing loss. She did not have swelling of the salivary glands or nasal symptoms. Her serum IgG4 concentration of 45.5mg/dl was within the normal range. Two biopsies could not rule out the possibility of malignant lymphoma; therefore, surgical resection was performed. A pathological examination revealed infiltration of abundant IgG4-positive plasma cells, but no fibrosis. The lesion was not diagnosed as IgG4-related disease based on comprehensive diagnostic criteria for this disease. There has been no recurrence in the 1 year after surgery, but the patient is under careful observation for recurrence and malignant conversion.</p>

DOI： 10.7248/jjrhi.56.619

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Language：Japanese   Publisher：日本耳鼻咽喉科感染症・エアロゾル学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：日本鼻科学会  

DOI： 10.7248/jjrhi.55.99

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：(株)全日本病院出版会  

鼻噴霧用ステロイド薬はアレルギー性鼻炎に対して強力な抗炎症作用を示すことが知られている。鼻アレルギー診療ガイドラインでは、花粉症に対して、鼻噴霧用ステロイド薬は主に症状の増悪時や重症例に対して用いることが推奨されている。一方、本格発症前の最小持続炎症を制御するという観点から、初期治療における鼻噴霧用ステロイド薬の可能性が議論されている。自験例も含めて、いくつかのプラセボ対照二重盲検比較試験において、鼻噴霧用ステロイド薬を用いたスギ・ヒノキ花粉症に対する初期治療は、プラセボと比べて症状増悪およびQOL増悪を有意に抑制するという報告がある。一方、安全性については実薬とプラセボとの間に有意な差を認めなかった。さらには、発症後治療と比較しても本格飛散後の鼻症状および眼症状の増悪を有意に抑制した。以上の結果より、鼻噴霧用ステロイド薬を用いた花粉症初期治療は有効かつ安全な治療法である可能性が示唆された。今後は、初期治療の至適開始時期や飛散する花粉数による効果の変化などの検討も望まれる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：Japan Rhinologic Society  

Acute invasive fungal sinusitis is the most aggressive form of fungal sinusitis. It is seen in patients who are immunocompromised, and has a bad prognosis. The key to successful management is early and aggressive medical and surgical treatment. We report a case of rhinocerebral mucormycosis involving acute invasive fungal sinusitis with acute lymphocytic leukemia. After starting remission induction therapy for acute lymphocytic leukemia, a 74-year-old female started to have symptoms of visual loss in the left eye, left eyelid swelling, pain on the left side of the face and diplopia. CT scan demonstrated opacification of sinuses and left-eye proptosis. There was black eschar of the left nasal mucosa, and the biopsy of this mucosa showed mucormycosis. After diagnosis, she started to use liposomal amphotericin B as the systemic antifungal agent. We recommended extensive debridement of all infected and necrotic tissue, and orbital exenteration, but she and her family refused. She underwent endoscopic sinus debridement of necrotic tissue except for left orbital tissue, and local irrigation of sinus by amphotericin B was started. After the surgery, black eschar and perforation of her palate and saddle-nose deformity occurred. Finally, she died of bacterial pneumonia. Even if she had undergone extensive debridement of all infected and necrotic tissue, orbital exenteration and received systemic antifungal therapy, it would still have been very difficult to control this disease. We should make a prompt correct diagnosis of mucormycosis, and initiate appropriate therapies urgently.

DOI： 10.7248/jjrhi.54.31

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.63.396

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Language：Japanese   Publisher：日本鼻科学会  

DOI： 10.7248/jjrhi.53.39

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DOI： 10.7248/jjrhi.53.399

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DOI： 10.15036/arerugi.63.526_2

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.62.1294_4

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Publishing type：Book review, literature introduction, etc.  

In Japan, pollen from Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), species that have been planted in approximately 4.5 and 2.6 million ha, respectively, is spread wide through aerial dispersion in spring. Consequently, Japanese cedar/cypress pollinosis (JCCP) is the major phenotype of allergic rhinitis (AR) in Japan, and significantly impairs the quality of life (QOL). Compared with Japanese cedar pollinosis, the pathogenesis and management of Japanese cypress pollinosis remain unclear. Cha o 1 and Cha o 2 are major allergens in Japanese cypress pollen, and have considerable homology with Cry j 1 and Cry j 2, respectively, in Japanese cedar pollen. Several other components were recently identified in Japanese cypress pollen, and may facilitate allergic inflammation via IgE-independent mechanisms. Allergen-specific CD4 + Th2 cells producing interleukin (IL)-4, IL-5, IL-13 and IL-31 are believed to play central roles in the pathogenesis of AR. The major human T cell epitopes in Cha o 1 and Cha o 2 have been identified. Compared with those in Cry j 1 and Cry j 2, both common and unique T cell epitopes in the cypress allergens have been characterized. Peripheral blood mononuclear cells (PBMCs) produced these Th2-type cytokines in response to a crude extract of Japanese cypress pollen. Among these cytokines, induction of antigen-specific IL-5 and IL-31 production is closely associated with the onset and exacerbation of Japanese cypress pollinosis, respectively. Allergen-specific immunotherapy using a standardized extract of Japanese cedar pollen is effective in controlling both naso-ocular symptoms and QOL during the period of cedar pollen dispersion, although the significant efficacy tends to be reduced during the period of cypress pollen dispersion, especially when the pollen dispersion is high. IL-5 production by PBMCs in response to the crude extract of Japanese cypress pollen did not differ significantly between patients with and without the immunotherapy, suggesting that unique component(s) in Japanese cypress pollen can induce IL-5 production, which is not fully suppressed by immunotherapy with the standardized extract of cedar pollen. The Practical Guideline for Management of Allergic Rhinitis in Japan recommends that patients who experience severe symptoms of pollinosis every year should receive early interventional treatment. Although early interventional treatment with a histamine H1 receptor antagonist (H1RA) is effective for Japanese cedar pollinosis, especially at the beginning of the season, this treatment has limitations for Japanese cypress pollinosis when exposure to the pollen is high. Combined therapy with a leukotriene receptor antagonist and/or intranasal corticosteroids may be required to fully control the worsening of JCCP during the cypress pollen season. © 2012 Blackwell Publishing Ltd.

DOI： 10.1111/j.1472-9733.2011.01156.x

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.61.1440_1

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DOI： 10.7248/jjrhi.51.38

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DOI： 10.15036/arerugi.61.1541_4

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DOI： 10.15036/arerugi.61.1536_3

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DOI： 10.15036/arerugi.60.437_1

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DOI： 10.7248/jjrhi.49.51

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DOI： 10.15036/arerugi.59.430_4

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DOI： 10.15036/arerugi.59.1398_1

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DOI： 10.15036/arerugi.59.1343_2

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DOI： 10.15036/arerugi.58.423_4

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DOI： 10.15036/arerugi.58.1288_2

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DOI： 10.15036/arerugi.58.1287_1

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DOI： 10.15036/arerugi.58.424_3

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.57.361_2

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Language：Japanese   Publisher：一般社団法人 日本アレルギー学会  

DOI： 10.15036/arerugi.57.424_1

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(公社)鳥取県医師会  

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