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Introduction: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS)., Methods: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment., Results: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced., Discussion/conclusion: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms., (© 2021 S. Karger AG, Basel.)

Objectives/hypothesis: Dupilumab, which blocks the shared receptor component for interleukin-4 and interleukin-13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers., Methods: Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co-primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund-Mackay CT (LMK-CT) scores. Symptoms, sense of smell, health-related quality of life, and safety were assessed during the 52-week treatment period., Results: Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: -3.1, P < .0001; Arm B: -2.1, P = .0011); NC score (Arm A: -1.2, P < .0001; Arm B: -0.9, P < .0001); and LMK-CT (Arm A: -5.1, P = .0005; Arm B: -2.8, P = .0425). The most common treatment-emergent adverse event in dupilumab and placebo-treated patients was nasopharyngitis., Conclusion: Dupilumab provided rapid, significant, and clinically meaningful improvements for patients with CRSwNP in Japan. Dupilumab was well tolerated, and safety and efficacy were consistent with the overall study population., Level of Evidence: 2 Laryngoscope, 131:E1770-E1777, 2021., (© 2020 Sanofi. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Previous studies have evaluated the risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the biomarkers of AAV for predicting relapse. However, little is known about the association between the presence of sinusitis and relapse and changes in the ANCA levels in AAV. This single-center, retrospective cohort study included 104 consecutive patients who were newly diagnosed with myeloperoxidase (MPO)-ANCA-positive microscopic polyangiitis (MPA) between 2006 and 2018 and were treated at the Aichi Medical University Hospital in Japan. The relationships between sinusitis and relapse of vasculitis and elevated MPO-ANCA levels were assessed using multivariate Cox proportional hazards models that were adjusted for clinically relevant factors. During the entire follow-up period (median, 24 months; interquartile range, 7-54 months), 93 (89.4%) patients achieved remission. After achieving remission, 38 (40.9%) patients experienced at least one relapse (13 [65.0%] in the sinusitis group; 25 [34.3%] in the non-sinusitis group). Sinusitis was identified as a significant predictor of relapse (adjusted hazard ratio: 2.41, 95% confidence interval [CI]: 1.19-4.88; P = 0.015). Furthermore, sinusitis was more likely to be associated with elevated MPO-ANCA levels (adjusted hazard ratio: 2.59, 95% CI: 1.14-5.92; P = 0.024). In conclusion, sinusitis was associated with a higher risk of relapse and elevated MPO-ANCA levels in MPA patients, suggesting that careful management may be required to reduce the risk of relapse in patients with sinusitis. Further studies are needed to elucidate the optimal treatment strategy for these patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice., Objective: To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma., Methods: From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations., Results: The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [- 71.3 ± 37.0% vs - 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [- 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5-336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14)., Conclusion: Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

Objective: To provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society., Methods: Seven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were "smell disorder," "olfactory dysfunction," "olfactory loss," "olfactory disturbance," "olfactory impairments," "olfaction disorder," "smell disorder," "anosmia," "cacosmia," and "dysosmia." Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A-strongly recommended to D-not recommended, were adopted for the management of olfactory dysfunction., Results: Both oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by randomized-controlled trials (RCTs) or placebo-controlled trials, olfactory training using odorants has been reported to be effective for improving olfactory function. There is considerable evidence that olfactory testing is useful for differential diagnosis, prediction of disease progression, and early detection of cognitive decline in neurodegenerative diseases., Conclusion: The Clinical Practice Guideline has developed recommendations for the management of various aspects of olfactory dysfunction., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease., Methods: We studied 783 patients (283 men, 500 women; mean age 77.0 ± 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of ≥ 4 was classified as positive and a score of ≤ 3 was classified as negative., Results: The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups., Conclusion: The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population.

Background: The relationship between chronic rhinosinusitis (CRS) and asthma has been known for a long time. However, no large studies on the relationship between CRS and lower airway diseases have been reported to date in Japan. Additionally, eosinophilic chronic rhinosinusitis (ECRS) in Japan is considered to be a subgroup of CRS with nasal polyps (CRSwNP) characterized by eosinophil-dominant inflammation. However, the diagnostic criteria of ECRS have not been established., Methods: To investigate clinical and epidemiological features of patients with CRS from the aspect of their associations with lower airway diseases, 553 patients with CRS who visited one of six local university hospitals were examined and interviewed. Local eosinophilic infiltration was evaluated pathologically by examining NPs., Results: The prevalences of olfactory dysfunction (OD) in the patients with nasal polyps (NPs) and those without NPs were 57.0% and 13.7%, respectively (p < 0.0001). The prevalence of asthma in all patients was 23.1%. Furthermore, the prevalences of NPs and OD in the patients with asthma and those without asthma were 81.0% and 50.1% (p < 0.0001) and 64.2% and 35.7% (p < 0.0001), respectively. 97.4% of the patients with asthma had ≥ 15% mucosal eosinophils, and 87.9% of the patients without asthma had <15% mucosal eosinophils., Conclusions: Similar to the relationship between nasal allergy and asthma, CRSwNP may be applicable to the concept of "one airway, one disease".

Objective: Chronic rhinosinusitis is a heterogeneous disease. Most cases of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) in Western countries show a strong tendency for recurrence after surgery and pronounced eosinophil infiltration in the nasal polyps. The prevalence of CRSwNP with pronounced eosinophilic inflammation is steadily increasing and is classified as eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, less than 50% of CRSwNP patients in Japan and East Asia show such features. Since the treatment strategy of ECRS differs from that of non-ECRS, clinical diagnostic criteria that distinguish ECRS from non-ECRS are needed., Methods: A total of 124 patients with CRSwNP patients who underwent endonasal sinus surgery were classified as ECRS or non-ECRS according to their clinical characteristics and the clinical features of the two groups were compared. Computed tomography (CT) images of the sinuses were graded according to the Lund-Mackay system. We also graded CT images of the olfactory cleft. Blood examination findings, sinus CT images and asthma complications were analyzed by multivariate logistic regression. Clinical findings that were significantly different between ECRS and non-ECRS were analyzed by receiver operating characteristic curves to determine optimal predictors of ECRS., Results: Blood eosinophilia, asthma complications and CT image scores were significantly different between ECRS and non-ECRS. In particular, increased blood eosinophil percentage and CT image scores for the posterior ethmoid and the olfactory cleft showed good accuracy as predictors of ECRS. A combination of the cut-off values for three predictors (increased blood eosinophil percentage above the normal range, olfactory cleft score ≥1 and posterior ethmoid score ≥1) indicated high accurate diagnostic ability (sensitivity, 84.6%; specificity, 92.3%)., Conclusion: A set of three clinical findings can differentiate ECRS from non-ECRS with high accuracy, even when these findings are assessed in regular outpatient clinics., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The University of Pennsylvania Smell Identification Test (UPSIT) and a smell ability questionnaire were administered to 167 Japanese volunteers ranging in age from 20 to 59 years. Of these subjects, 80 also received the T&T olfactometer threshold test. Of the latter subjects, 36 were patients tested before endoscopic nasal surgery for sinusitis and polyposis. The patients exhibited decreased smell function, as measured by the T&T olfactometer, the UPSIT, and a 30-item version of the UPSIT in which the 10 least familiar items were removed (ps < 0.001). Spearman correlations ranging from 0.53 to 0.70 were found between (i) scores on the 30- and 40-item UPSITs and (ii) the T&T detection and recognition threshold values. Significant correlations were found between scores on the smell ability questionnaire and the olfactory test measures (UPSIT30 r = 0.56; UPSIT40 r = 0.58; T&T detection r = 0.56; T&T recognition r = 0.69, p < 0.001), indicating that subjects are relatively accurate in assessing their olfactory ability. This study suggests that the 30 and 40-item UPSITs correlate well with measures derived from the T&T olfactometer, and that all three tests are sensitive to the smell loss of Japanese sinusitis/polyposis patients.

A 56-year-old man was admitted for the evaluation of recurrent pulmonary infections. Since the patient presented with the combination of diffuse cystic bronchiectasis, chronic sinusitis and obstructive azoospermia, the diagnosis of Young's syndrome was made. Because the sweat chloride value, pancreatic function and ciliary ultrastructure were normal, this case could be clearly differentiated from cystic fibrosis and primary ciliary dyskinesia. There have been only a few reported cases of Young's syndrome in Japan.

Diffuse panbronchiolitis is a type of chronic bronchiolitis associated with chronic sinusitis and infection of the lower respiratory tract. The cause of this disease is unknown, and it is being seen with increasing prevalence among the Japanese population. This article discusses treatment in light of recent studies.

In the period 1983 to 1985, 66 patients presented to six Japanese university hospitals with squamous cell carcinoma of the maxillary sinus. Using self-administered questionnaires, a case-control study was conducted to examine history of nasal diseases, occupational exposures, and other possible risk factors for this disease. For each patient, two controls were selected from the general population, matched to the patient by sex, age (+/- 5 years), and district of residence. A history of chronic sinusitis was associated with a 2.3-fold increase in risk (p = 0.05). A high relative risk was also observed in males with an occupational history of woodworking or joinery, particularly when these jobs involved sanding or lathing practices (RR = 7.5, p = 0.02). No association between cigarette smoking and maxillary sinus cancer was observed in this study and no evidence was found that indoor air pollution in the home is involved in cancer development.