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Objective: Nebulizer therapy is an effective and safe topical treatment for rhinosinusitis and is frequently used by otolaryngologists in Japan. However, treatment methods used vary among regions and according to doctors' preferences. In this study, we aimed to investigate the use of nebulizer therapy for rhinosinusitis. Administration of nebulizer therapy has been affected by the coronavirus disease 2019 (COVID-19) pandemic. Thus, we also investigated the difference in the prevalence of nebulizer use before and during the pandemic., Methods: Between February and September 2016 and in January 2021, we administered questionnaire surveys on nebulizer treatment for rhinosinusitis to otorhinolaryngologists, who were members of the Oto-Rhino-Laryngological Society of Japan, in Aomori, Saitama, Mie, Fukui, Shiga, Okayama, and Kagoshima prefectures., Results: More than 90% of the otorhinolaryngologists performed nebulizer treatment for rhinosinusitis in 2016. In April 2020 (the first wave of the COVID-19 pandemic), the use rate decreased to 20%, but in January 2021, the use rate increased to 60%. Jet nebulizers were the most frequently used type. One-third of the otolaryngologists enlarged the natural opening of the paranasal sinuses in more than half of their patients by using vasoconstrictors. Cefmenoxime and betamethasone were the most commonly used antibiotics and steroids, respectively., Conclusion: Because it is important to perform nasal pretreatment and strict disinfection of nebulizer equipment, it is clear that education of otorhinolaryngologists as well as paramedical personnel is required to ensure safe and effective use of nebulizer therapy in Japan., Competing Interests: Conflict of interest The authors have no conflict of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis (CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy., Methods: Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200mg/day) alone (monotherapy group) or CAM (200mg/day) in combination with SCMC (1500mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score., Results: Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P=0.001). In addition, objective findings, including characteristics of nasal discharge (P=0.008) and post-nasal discharge (P=0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 (P<0.001), and were not significantly different between groups., Conclusion: The results indicated that long-term combination therapy with SCMC at a dose of 1500mg/day and CAM at a dose of 200mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: The objective of this study was to assess the reliability and validity of a Japanese version of the 20-Item Sino-Nasal Outcome Test SNOT-20, which is one of the quality-of-life (QOL) evaluation sheets for chronic rhinosinusitis (CRS), and assess its reliability and validity., Methods: The SNOT-20 was conducted in patients with CRS and in healthy volunteers. The response rate was evaluated as the feasibility of this test, and reliability and internal consistency were assessed as reliability. In addition, concurrent validity and discriminant validity were assessed as validity., Results: Regarding the feasibility of this test, the response rate for each question item in the SNOT-20 was nearly 100% for all 20 items. For reliability, test-retest reliability was r=0.890 and the internal consistency was alpha=0.903. For validity, the concurrent validity was r=0.162 when compared with objective findings in the nasal cavity, and was r=0.431 when compared with the score for general physical condition, which evaluate the patient's general condition. Discriminant validity was significantly higher in patients with CRS than in healthy volunteers (p<0.001). Moreover, when the discriminant validity was assessed using an ROC (receiver operating characteristic) curve, it was found that ROC-AUC (the area under the curve)=0.775., Conclusion: The reliability and validity of a Japanese version of the SNOT-20 were assessed in this study. It is thought that the SNOT-20 serves as a useful QOL evaluation sheet for CRS., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS., Methods: We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-alpha, and endotoxin on their production of VEGF using ELISA and PCR., Results: The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-alpha or endotoxin., Conclusion: VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-alpha and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition.

Purpose: YAMIK sinus catheter (YAMIK) has already been reported to be a useful therapeutic device for sinusitis cases. The purpose of this study was to compare the effectiveness of YAMIK in sinusitis cases with and without nasal allergy in order to contribute toward establishing its indication., Methods: YAMIK was tried in 10 chronic sinusitis cases complicated with nasal allergy and 20 cases without nasal allergy. Clinical symptoms, endoscopic findings and pathological opacification in X-ray photographs were compared in these cases with and without nasal allergy., Results: No significant differences were seen in the effectiveness of YAMIK between cases with and without nasal allergy., Conclusion: These findings suggest that YANIK is useful and applicable even in sinusitis cases complicated with nasal allergy.

Sinusitis was induced in six rabbits in order to evaluate its influence on the proliferation of cells in the olfactory epithelium compared with the respiratory epithelium during conservative antibiotic therapy. Then 1% ofloxacin was injected into the paranasal sinuses. Three normal rabbits were not administered any treatment and served as controls. The rabbits were sacrificed under intravenous anesthesia and the olfactory and respiratory mucosa was excised 24 hours after intravenous administration with the labeling reagent 5-bromo-2'-deoxyuridine (BrdU). The extent of cell proliferation in these tissues was estimated by immunohistochemical staining with BrdU-specific antibody. The uptake of BrdU was significantly increased (p = 0.0099) in the respiratory mucosa, but not in the olfactory mucosa. Furthermore, in olfactory epithelium, 79.2% and 16.7% of all BrdU-positive cells were olfactory and basal, respectively. Thus, turnover of epithelial cells due to sinusitis was not as accelerated in the olfactory mucosa as in the respiratory mucosa during antibiotic treatment.

The ability of Streptococcus pyogenes to adhere to nasal mucosal cells was investigated by an in vitro assay system in order to clarify the actual role of secretory IgA in mucosal immunity in the nose. The number of bacteria adhering to isolated mucosal cells was significantly larger in patients with chronic sinusitis than in normal control subjects. The ability of bacteria to adhere, however, was significantly lower in the group of subjects having specific secretory IgA antibody activity to the M protein than in those having no secretory IgA activity. Findings demonstrated that mucosal immunity preventing or blocking the adherence of bacteria is impaired in patients with chronic sinusitis.