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There are 4 subtypes of chronic rhinosinusitis (CRS): eosinophilic CRS with nasal polyps (ECRSwNP), ECRS without NPs (ECRSsNP), non-ECRSwNP, and non-ECRSsNP. Most ECRS cases are categorized as ECRSwNP, and the number of patients with ECRSwNP has recently increased. ECRS is associated mainly with helper T-cell type 2 inflammation and eosinophils. Recently, Interleukin-25, -33, or TSLP, helper T-cell type 17, and Group 2 innate lymphoid cells have also been shown to be involved in the molecular mechanism of ECRS. ECRS can lead to several complications including bronchial asthma and/or aspirin intolerance. Conventionally, surgery and corticosteroids have been used to treat ECRS, but biologics have since been applied. Mepolizumab, benralizumab, and tezepelumab have been reported to improve asthma complicated by NPs more than asthma uncomplicated by NPs. Omalizumab, mepolizumab, benralizumab, and dupilumab have been reported to significantly improve Sinonasal Outcome Test-22 scores, nasal polyp scores, and nasal congestion severity in phase III trials. Benralizumab, dupilumab, and tezepelumab have been reported to improve both ECRS and complicated bronchial asthma., Competing Interests: Decalaration of competing interest Tatsuya Nagano has received lecture fees from AstraZeneca, Japan, GlaxoSmithKline, Japan, and Sanofi, Japan., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Background: Rhinosinusitis and intracranial hemorrhage are prevalent conditions within their respective medical specialties. While rhinosinusitis is predominantly an inflammatory disease confined to the paranasal sinuses, it can, in exceedingly rare circumstances, lead to intracranial hemorrhage with potentially fatal outcomes. Despite the gravity of this rare association, the literature remains sparse regarding its pathophysiological mechanisms, natural history, management principles, and clinical outcomes., Methods: We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of epitural hematoma arising from rhinosinusitis., Results: A systematic review of the literature identified 20 published cases of intracranial hemorrhage induced by rhinosinusitis; plus the case presented herein, the total number of cases is 21. Nineteen epidural hematomas (EDHs) and 2 subdural hematomas were identified. The frontal region (14/19, 74%) was the most prevalent location for EDH, corresponding to sinusitis related to the frontal sinus (12/14, 86%). Common symptoms included headache (n = 18, 86%), fever and impaired consciousness (n = 13, 62%), and periorbital swelling/pain (n = 8, 38%). Interventions included hematoma removal/drainage, rhinosinus surgery, and antibiotic therapies. One fatality and 3 residual neurological impairments occurred. Multiple hypotheses exist regarding the mechanisms of intracranial hemorrhage in rhinosinusitis., Conclusions: Intracranial hemorrhagic complications, primarily EDH and subdural hematomas, are rare and potentially fatal consequences of rhinosinusitis. It should be cognizant of the potential existence of such a possibility during clinical practice., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We investigated the characteristics of the microbial community of the nasal sinuses in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and identified the correlations of the nasal microbiome with the inflammatory microenvironment of the nasal cavity., Methodology: We collected matched nasal secretion and polyp tissue samples from 77 CRSwNP patients. Then, we extracted microbial DNA from cotton swabs, used high-throughput sequencing technology based on 16S ribosomal RNA (rRNA) to detect the bacterial community composition, and detected cytokines such as interleukin (IL)-5, IL-8, IL-17a, IL-17e, IL-18, IL-27 and interferon (INF)-gamma in the polyp tissue samples using Luminex. Eosinophils and neutrophils in the peripheral blood and polyp tissue were counted, and the relationships between inflammatory factors or inflammatory cell counts and nasal microbial diversity were analyzed., Results: Among the inflammatory factors evaluated, IL-5 had a positive rate of 32.47%, IFN-γ had a positive rate of 84.42%, IL-17A and IL-17E had positive rates of 75.32%, IL-18 had a positive rate of 94.81%, IL-27 had a positive rate of 68.83%, and IL-8 had a positive rate of 100%. IL-17a and IL-27 were negatively correlated with both Enterobacter and Anaerococcus, IL-8 was negatively correlated with both Enterobacter and Staphylococcus, IL-18 was positively correlated with Candidatus Arthromitus and negatively correlated with Haemophilus, and IL-27 was positively correlated with Faecalibaculum. Lactobacillus and Enterococcus were positively correlated with the degree of neutrophil infiltration in nasal polyp tissue., Conclusions: In Southwest China, inflammation of the nasal polyps exhibits a variety of patterns. Enterobacteria and anaerobic bacteria may be correlated with the inflammatory pattern of nasal polyps. The neutrophil-mediated inflammatory response plays an important role in patients with CRSwNP in Southwest China., Competing Interests: Declaration of competing interest Weigang Gan declares that he has no conflict of interest. Yu Xiang declares that she has no conflict of interest. Bo Wei declares that she has no conflict of interest. Shixi Liu declares that he has no conflict of interest. Feng Liu declares that he has no conflict of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Eosinophilic otitis media (EOM) is a refractory condition associated with eosinophilic chronic rhinosinusitis and bronchial asthma. EOM is characterized by type-2 inflammation and is refractory to various treatments. We investigated the efficacy of dupilumab, interleukin-4 receptor alpha antagonist, for patients with EOM complicated by eosinophilic chronic rhinosinusitis (ECRS)., Methods: Between April 2017 and April 2022, we treated 124 patients with dupilumab for refractory CRS or bronchial asthma. Of these, 14 had EOM concurrently, and 10 of them who had been treated for >6 months were included in our study. We retrospectively evaluated the efficacy of dupilumab by the amount of systemic corticosteroid used, the frequency of exacerbations, severity score of EOM, computed tomography (CT) score of temporal bones, and pure tone audiometry. We also enrolled 8 EOM patients without dupilumab treatment as a control group., Results: Dupilumab significantly improved the amount of systemic corticosteroid used and the frequency of exacerbation and compared with before dupilumab was used (p = 0.01 and <0.01, respectively). All patients could be weaned from systemic-corticosteroid therapy by 54 weeks of dupilumab use. The severity score of EOM and CT score for temporal bones were significantly lower than before the treatment (p = 0.01 and 0.01, respectively). Compared to the control group, the systemic corticosteroid used and severity scores were improved in the dupilumab group (p = 0.02 and < 0.01, respectively)., Conclusions: Dupilumab could be used to wean patients from systemic corticosteroids with the improvement of severity score in EOM associated with ECRS and bronchial asthma., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Solutions containing Ag 0 nanoclusters, Ag +1 , and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection. Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution. Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission. Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes., Competing Interests: Conflict of interest RB was a consultant for Smith&Nephew from 2011 to 2013 and lectured for the same on wound care until 2017. RB is a founder of Kheprion, Inc., a University of Alberta start-up for biomedical devices. The remaining authors do not have a commercial or other association that might pose a conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic sinus surgery (ESS) is a common operation for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) when medical therapy alone is insufficient. No randomised controlled trials on the efficacy of ESS have been published. We aimed to assess the efficacy of ESS plus medical therapy versus medical therapy alone in patients with CRSwNP., Methods: We performed an open-label, multicentre, pragmatic, randomised, controlled trial in three tertiary care centres and 12 secondary care centres in 11 cities in the Netherlands (Almere, Amstelveen, Amsterdam, Blaricum, Den Haag, Deventer, Haarlem, Hoofddorp, Hoorn, Leiderdorp, and Rotterdam). Adults (aged ≥18 years) with CRSwNP and an indication for ESS were randomly assigned (1:1) using block randomisation (block sizes of six), stratified by study centre, to receive either ESS plus medical therapy or medical therapy. ESS was performed according to local practice, although anterior ethmoidectomy was mandatory. Medical therapy was prescribed at the patient's otorhinolaryngologist's discretion, and could be, but was not limited to, nasal corticosteroids, nasal rinsing, systemic corticosteroids, or systemic antibiotics. The primary outcome was disease-specific health-related quality of life (HRQoL) at 12 months of follow up, measured with the validated Sinonasal Outcome Test 22 (SNOT-22; where each item is scored from 0 to 5, where 0 indicated no problems and 5 indicates problems as bad as can be, with a total score of 0-110 points), and the minimal clinically important difference of the SNOT-22 is 9·0 points. Primary and safety analyses were performed on an intention-to-treat (ITT) basis. The ITT population comprised all patients who were randomly assigned to treatment according to their randomisation group and without any protocol violation. This study is registered with the Netherlands Trial Register, NTR4978, and is ongoing., Findings: Between Feb 15, 2015, and Aug 27, 2019, 371 patients were screened for eligibility, of whom 238 were eligible, willing to participate, and randomly assigned to ESS plus medical therapy (n=121) or medical therapy (n=117) and 234 were included in the baseline ITT population (n=118 ESS plus medical therapy; n=116 medical therapy). 142 (61%) of 234 patients at baseline were men and 92 (39%) were women, and the mean age was 50·4 years (SD 12·7). 206 participants were analysed at 12 months for the primary outcome (n=103 in the ESS plus medical therapy group; n=103 in the medical therapy group). At 12 months follow-up, the mean SNOT-22 score in the ESS plus medical therapy group was 27·9 (SD 20·2; n=103) and in the medical therapy group was 31·1 (20·4; n=103), with an adjusted mean difference of -4·9 (95% CI -9·4 to -0·4), favouring ESS plus medical therapy. Adverse events were similar between the groups. The most common adverse events were minor epistaxis or gastrointestinal problems. No treatment-related deaths occurred, but one patient died due to congestive heart failure., Interpretation: ESS plus medical therapy is more efficacious than medical therapy alone in patients with CRSwNP, although the minimal clinically important difference was not met. Long-term follow-up data are needed to determine whether the effect persists. The current results are a basis for further development of evidence-based guidelines., Funding: The Netherlands Organisation for Health Research and Development (ZonMw)., Competing Interests: Declaration of interests ESL, SR, MV, and WJF report a grant from the Netherlands Organisation for Health Research and Development (ZonMw) to do the study. WJF further reports receiving grants from Sanofi and Novartis; receiving consulting fees and speaker honoraria from Sanofi and GSK; participating on a data safety monitoring board for Lyra; is Secretary General of the European Rhinologic Society, chairperson of EPOS, founding member of EUFOREA, and a member of the Medical Advisory Board of the Dutch Patient Society for CRSwNP (all unpaid). SR reports grants, consulting fees, and honoraria from Sanofi and Novartis, and roles as a steering committee member (unpaid) for EPOS and for the European Chronic Rhinosinusitis Outcome Registry, and as being member (unpaid) of the Medical Advisory Board of the Dutch Patient Society for CRSwNP. All other authors report no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) improves pulmonary health and chronic rhinosinusitis (CRS) for people with cystic fibrosis (PwCF), however its impact on olfaction has not been investigated. Olfactory dysfunction impairs quality-of-life (QOL). This study evaluated the impact of ETI on multiple olfactory metrics., Methods: Adult PwCF/CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. Endpoints included changes after 6 months of ETI in quantitative olfactory function (Smell Identification Test, SIT), olfactory QOL (Questionnaire of Olfactory Disorders, QOD) and percent olfactory cleft opacification (%OCO), representing superior nasal cavity inflammation where afferent olfactory neurons are concentrated., Results: 30 PwCF/CRS met inclusion criteria; 25 completed the study. Mean ETI adherence was 93%. At baseline, participants were hyposmic (mean SIT 31.3), had significant %OCO (mean 65.6%), yet reported non-impaired olfactory QOL (mean QOD 6.1). At follow-up, mean SIT worsened mildly (p=0.009), mean %OCO remained stable (p=0.46), and mean QOD improved modestly (p=0.008). No outcomes were impacted by prior modulator use, genotype, nasal polyps, or CF-related diabetes. Prior sinus surgery was associated with QOD improvement (p=0.04). Increased (worse) baseline QOD scores and %OCO were associated with greater improvements (p<0.003), but not SIT (p=0.44)., Conclusions: ETI was not associated with improvement in quantitative olfaction or olfactory cleft opacification after 6 months. PwCF/CRS have hyposmia but do not report impairment in olfactory QOL. Further study to investigate mechanisms explaining olfactory dysfunction and whether olfaction improves with greater duration of ETI or in younger age groups is warranted., Competing Interests: Declaration of Competing Interest DMB: Medtronic, consultant, not affiliated with this work; SMH: Boehringer Ingelheim, Parexel and Imidex, consultant not affiliated with this work; CDB: none; MS: none; EKV: none; VRR: Medtronic and Optinose, consultant, not affiliated with this work; JLTC: received grants from Vertex Pharmaceuticals Incorporated, Gilead, N30, Celtaxsys, Proteostasis, and Bayer; has received fees from Vertex Pharmaceuticals Incorporated related to consultation on clinical research design, participation on advisory boards, and speaking engagements; has received speaking fees from Celtaxsys; and has served on advisory boards and/or provided consultation for Novartis, Genentech, Gilead, Protalix, Santhera, 4DMT, Abbvie and Proteostasis., (Copyright © 2021. Published by Elsevier B.V.)

The aim of this work was to present a practical management algorithm for orbital and brain complications of sinusitis. According to the inclusion criteria, a sample of 68 patients was collected between 2008 and 2018 (39 males and 29 females). Among them, 44 were adults, with a mean age of 50.46 years, and 24 were pediatric patients, with a mean age of 10.33 years. Oral or intravenous antibiotic therapy was administered to all patients. Pharmacological resolution was observed in 14 cases. Early surgical treatment within 48 hours was necessary in 10 cases. Surgery consisted of abscess drainage, associated or not with functional endoscopic sinus surgery. Delayed surgery within 15-30 days was performed in 44 patients. The core procedure was functional endoscopic sinus surgery. Subsidiary procedures were abscess drainage, tooth extraction or cranial base repair. The combination of two or more of these procedures was case selected. Median follow-up was of 46.36 months. Sinusitis complications necessitate rapid diagnosis and prompt treatment. Antibiotic therapy alone is enough for mistreated rhinosinusitis with no anatomical predisposing factor. Surgery is mandatory for altered nasal and paranasal sinus anatomy or odontogenic infections., Competing Interests: Declaration of competing interest The authors declare that there are no source of funds or financial interest or any commercial associations that might pose or create a conflict of interest with information presented in this manuscript., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Rhinosinusitis without nasal polyps (RSsNP) is prevalent in COPD. Previous studies on its association with health-related quality of life (HRQoL) have limitations, and RSsNP is currently not recognized as a comorbidity. This study investigates HRQoL in COPD including a focus on RSsNP. Generic HRQoL was assessed with the Short Form-36 (SF-36v2) questionnaire and compared between 90 COPD and 93 control subjects and in subgroups with and without RSsNP. The association between RSsNP and COPD versus not and generic HRQoL was assessed by multivariable linear regression with adjustments for age, education, and body mass index (BMI). Disease-specific HRQoL was assessed by Sinonasal outcome test-22 (SNOT-22), St. Georges Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT) and compared between COPD with and without RSsNP, and their association to RSsNP was assessed by multivariable linear regression with adjustments for age, BMI, and FEV 1 % predicted. RSsNP was associated with poorer disease-specific HRQoL, with higher SNOT-22 total score (14.67 points; 95% CI, 7.06-22.28; P < .001) and psychological subscale score (3.24 points; 95% CI, 0.37-6.11; P = .03), SGRQ symptom score (13.08 points; 95% CI, 2.73-23.4; P = .014), and CAT score (4.41 points; 95% CI, 1.15-7.66; P = .009). Generic HRQoL was poorer in COPD patients than in the control subjects. In addition to COPD, concomitant RSsNP was associated with poorer physical functioning, general health, vitality, and physical component summary. RSsNP in COPD is associated with poorer disease-specific HRQoL that is clinically relevant and, as it is amenable for treatment, should be recognized as a comorbidity of COPD., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Epidemiology and potential risk factors for cystic fibrosis arthropathy (CFA) were studied in a relevant cystic fibrosis (CF) patient cohort., Methods: Cohort study of patients included in the German CF registry in 2016-2017. Descriptive analysis, exploratory tests and multivariable logistic regression were used to assess prevalence of CFA and associated potential risk factors for adult patients with/without chronic Pseudomonas aeruginosa infection., Results: 6069 CF patients aged from 0 to 78 years were analysed. CFA was observed in 4.9% of the patients. Prevalence was significantly higher in adult patients (8.4%) compared to patients <18 years (0.7%; p<0.0001). Logistic regression analyses in adult patients (n=3319) showed that CFA was significantly associated with increasing age (OR=1.04; 95% CI: 1.02-1.05; p<0.0001), female gender (OR=2.10; 95%CI:1.52-2.90; p<0.0001), number of hospitalizations (OR=1.24; 95%CI:1.12-1.36; p<0.0001), chronic P. aeruginosa infection (OR=1.83; 95%CI:1.28-2.61; p=0.0009), CF-related diabetes (OR=1.69; 95%CI:1.23-2.33; p=0.0013), pancreatic insufficiency (OR=2.39; 95%CI:1.28-4.46; p=0.0060) and sinusitis/polyps (OR=1.91; 95%CI:1.39-2.62; p<0.0001). In a subgroup analysis of adults without chronic P. aeruginosa infection (n=1550) CFA was also significantly associated with increasing age, female gender, increasing number of hospitalizations, pancreatic insufficiency as well as sinusitis/polyps; antimycotic treatment associated only in this subgroup while association with CF-related diabetes was not significant., Conclusion: CFA is a frequent and clinically relevant co-morbidity particularly in adult CF patients. CFA is significantly more common in patients with chronic P. aeruginosa colonization but associations with other indicators for a more severe disease course were identified regardless of P. aeruginosa colonization status., Competing Interests: Declaration of conflict of interest The authors have no conflict of interest related to this manuscript., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: GGB has received honoraria for lectures or advisory boards, or both, from Amgen, AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi-Genzyme, and Teva. PG has received consulting fees, honoraria for lectures or research funding, or both, from 3NT Medical, ALK, Argenx, AstraZeneca, Genentech, Hall Allergy, Novartis, Regeneron Pharmaceuticals, Roche, Sanofi-Genzyme, Stallergenes Greer, and Teva.

Background: Orbital findings such as cellulitis, ophthalmoplegia, and proptosis are possible complications of sinusitis. Acute sinusitis can also cause a conjunctival cyst-like lesion induced by severe chemosis; however, it is an uncommon complication., Case Report: We report the case of a 53-year-old man who presented to our facility's emergency department. The patient complained of orbital discomfort resulting from an inability to close both eyes, and orbital discharge, accompanied by general weakness. On physical examination, cyst-like-appearing lesions with erythema of the eyelids were identified bilaterally and initially misdiagnosed as inflammatory lesions of the orbital area. However, orbital pathology was excluded by the ophthalmologist, and it was found that the patient had bilateral pansinusitis on the imaging studies. It was suspected that the sinusitis was responsible for the ocular symptoms. The patient was treated with emergent endoscopic sinus surgery, and the symptoms were promptly relieved. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although it is well known that orbital complications of sinusitis can occur, a conjunctival cyst-like-appearing lesion induced by severe chemosis is uncommon and is difficult to diagnose at first sight. Emergent surgical drainage is needed to prevent permanent orbital damage and other sinusitis-related complications. Therefore, recognizing the unique clinical presentation of a conjunctival cyst-like lesion resulting from severe chemosis is the key to appropriate diagnosis and management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic rhinosinusitis (CRS) affects nearly all individuals with cystic fibrosis (CF) and is thought to serve as a reservoir for microbiota that subsequently colonize the lung. To better understand the microbial ecology of CRS, we generated a 16S rRNA gene sequencing profile of sinus mucus from CF-CRS patients. We show that CF-CRS sinuses harbor bacterial diversity not entirely captured by clinical culture. Culture data consistently identified the dominant organism in most patients, though lower abundance bacteria were not always identified. We also demonstrate that bacterial communities dominated by Staphylococcus spp. were significantly more diverse compared to those dominated by Pseudomonas spp. Diversity was not significantly associated with clinical factors or patient age, however, younger subjects yielded a much wider range of bacterial diversity. These data mirror bacterial community dynamics in the lung and provide additional insight into the role of sinus microbiota in chronic airway disease progression., Competing Interests: Declaration of Competing Interest The authors declare no conflicts., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: There have been few investigations examining the benefits, consequences, and patterns of use for prophylactic antibiotics for nasal packing in the emergency department setting. Given the frequency of epistaxis in the emergency department, it is an ideal setting to study the efficacy and utilization patterns of prophylactic antibiotics in nasal packing., Objective: Our aim was to assess both rates of utilization and evidence of benefit for prophylactic antibiotics in patients with nasal packing for epistaxis., Methods: A single-institution retrospective review of 275 cases of anterior nasal packing in an urban emergency department between September 2013 and April 2017 was performed. Chi-square statistical analysis was used to evaluate results., Results: Among 275 cases studied, there were no instances of toxic shock syndrome. Roughly 73% of patients with nonabsorbable packing received prophylactic antibiotics. Only one (1.1%) case of sinusitis was noted among the nonabsorbable packing with prophylaxis group, with no such complication in the nonprophylaxis group. In contrast, 95% of patients with absorbable nasal packing were not given prophylactic antibiotics. Analysis of all cases given prophylactic antibiotics vs. no prophylaxis, regardless of packing type, revealed no statistically significant difference in the development of acute sinusitis (1% vs. 0.56%; p = 0.6793)., Conclusions: There was no observed advantage or disadvantage to using prophylactic antibiotics in anterior nasal packing in the emergency department, regardless of whether patients received absorbable or nonabsorbable packing. However, patients who receive nonabsorbable nasal packing were more likely to receive antibiotic prophylaxis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Schizophyllum commune, a basidiomycete fungus, is a quite rare cause of invasive sinusitis for which no standard treatment has yet been established. We report herein a 59-year-old woman who developed S. commune rhinosinusitis after remission induction chemotherapy for her acute myeloid leukemia. No causative microorganisms were identified in the sinus lavage fluid culture, whereas nucleotide sequencing of the internal transcribed spacer region using endoscopic sinus biopsy specimen could confirm the pathogen as S. commune. Liposomal amphotericin B and voriconazole (VRCZ) treatment ameliorated both her clinical symptoms and laboratory findings. The patient was successfully treated with allogeneic stem cell transplantation, under continuous VRCZ administration, without aggravation of S. commune sinusitis. Molecular diagnosis and prompt intervention with suitable antifungal drugs may be crucial to manage this rare infectious complication., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To qualitatively explore patient experiences of severe, recurrent, bilateral nasal polyps (NP)., Methods: A targeted literature review of published qualitative studies and online blogs describing patient experiences of NP was conducted. Semistructured concept elicitation interviews were conducted in the United States and Germany with participants ≥18 years with severe, recurrent, bilateral NP to explore their symptom experience and impacts on health-related quality of life (HRQoL; NCT03221192). A subset of 10 participants reported symptoms and impacts using a smartphone or tablet application (app) over a 10-day period., Results: A paucity of qualitative evidence regarding patient experience of NP was identified from the literature or blog review. Twenty-seven participant interviews were conducted. Thirty-six symptoms were identified, including 7 primary symptoms (nasal congestion [n = 27 of 27], breathing difficulties [n = 27 of 27], postnasal drip [n = 25 of 27], runny nose [n = 24 of 27], head/facial pressure [n = 23 of 27], loss of smell [n = 23 of 27], loss of taste [n = 22 of 27]) and 29 secondary symptoms (the most common were mucus/catarrh and nose bleeds [both n = 20 of 27]). Most symptoms were reported to vary both within and between days. Sixty impacts of severe NP were reported, including impacts on sleep (n = 22 of 27), physical functioning (n = 21 of 27), activities of daily living (n = 21 of 27), emotional well-being (n = 27 of 27), treatment (n = 23 of 27), social life (n = 26 of 27), and work (n = 19 of 27). Symptoms/impacts reported using the app were consistent with interview findings, although new symptoms were identified (ear pain, throat pain, nasal scabs, and nasal burning). These results supported the development of a conceptual model outlining concepts related to symptoms, impacts, and treatment of NP., Conclusions: Severe, recurrent, bilateral NP are associated with a range of symptoms that have significant detrimental impact on HRQoL., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Asthma often coexists with chronic rhinosinusitis (CRS). Recent studies revealed that sinus inflammation in asthmatic patients was related to eosinophilic inflammation. However, the relationship between the severity of CRS and four different sputum inflammatory phenotypes as defined by the proportion of eosinophils and neutrophils is unknown. The aim of this study was to examine the impact of the severity of CRS on lower airway and systemic inflammation in asthmatic patients., Methods: We enrolled 57 adult asthmatic patients who underwent sinus computed tomography (CT). The severity of CRS was evaluated by the Lund-Mackay score (LMS). The induced sputum inflammatory phenotype was defined by eosinophils (≥/<2%) and neutrophils (≥/<60%). Peripheral blood mononuclear cells (PBMC) were collected to examine cytokine productions., Results: The median LMS of subjects was 6 (interquartile range, 0-11.5). The sputum inflammatory cell phenotype was categorized as paucicellular (n = 14), neutrophilic (n = 11), eosinophilic (n = 20), or mixed (n = 12). LMS was positively correlated with the percentage of blood eosinophils, sputum eosinophils, and mean fluorescence intensity (MFI) of IL-5 on CD4 + T cells. In the severe CRS group (LMS, 12-24), the number of mixed cellular phenotypes was higher than that in the group without CRS (LMS, 0-4) and mild-to-moderate CRS group (LMS, 5-11)., Conclusions: In asthmatic patients with severe CRS, the proportion of the mixed cellular inflammatory phenotype was increased as well as eosinophilic inflammation., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Invasive sinonasal aspergillosis is rarely seen in immunocompetent individuals. It may involve adjacent intracranial and intraorbital structures causing high morbidity and mortality., Case Description: We report a rare case of invasive Aspergillus sinusitis in a young, immunocompetent woman causing headache and vision loss. Endoscopic débridement under general anesthesia was complicated by rupture of a mycotic cavernous carotid artery aneurysm. This was managed by packing with muscle and fascia followed by endovascular coiling. Subsequently, the aneurysm extended intradurally and caused fatal subarachnoid hemorrhage., Conclusions: This case emphasizes the need for early diagnosis of invasive fungal sinusitis to prevent intracranial complications and fatal outcome. When the diagnosis is made, aggressive treatment with surgical débridement and adjuvant antifungal therapy is required. Internal carotid artery involvement is a rare but life-threatening complication of invasive fungal sinusitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Management of chronic cough relies on the recognition of cough background disorders. It is not known whether certain cough triggers are associated with specific background disorders., Methods: This was an e-mail study to public service employees of two towns in Finland. The questionnaire included twelve triggers. Current asthma was defined as doctor's diagnosis of asthma and current wheezing. Chronic rhinosinusitis was defined as either nasal blockage or nasal discharge and either facial pain/pressure or reduction/loss of smell for more than three months. Gastroesophageal reflux disease was defined as heartburn and/or regurgitation on at least one day a week during the last three months. Idiopathic cough was defined as absence of any of them., Results: There were 421 subjects with current cough that had lasted at least eight weeks. Subfreezing air as a cough trigger was associated with an adjusted odds ratio (aOR) of 7.27 (4.09-12.9), (p < 0.001), for current asthma. The number of cough triggers was largest in asthma, followed by chronic rhinosinusitis, gastroesophageal reflux, and idiopathic cough (7.05 (6.14-7.96), 4.94 (4.35-5.54), 4.60 (3.77-5.43), and 3.44 (3.02-3.86), respectively, p < 0.001). Presence of five or more triggers was associated with an aOR of 7.49 (3.96-14.2), (p < 0.001) for current asthma. Absence of any cough triggers increased the probability of idiopathic cough (aOR 2.71 (1.54-4.77), p = 0.001)., Conclusions: Subfreezing air as a cough trigger and multiple triggers are strongly associated with the presence of current asthma in chronic cough. Absence of any cough triggers increases the probability of idiopathic cough., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The airway is the major entry route of pathogens due to continuous gas exchange with the environment. In particular, the nasal epithelial layer is the common site of airborne mucotropic virus infections. The inflammatory response to such infections must be tightly controlled due to its non-specific nature. Unrestrained inflammation breaks down the physiological mucosal defense system and leads to secondary bacterial or fungal infections. Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease that compromises quality of life. In spite of its importance in the initiation of inflammation, the role of interferon signaling in nasal airway epithelial cells is largely unknown. We analyzed the expression of interferon signaling genes using clinical lavage specimens and nasal airway epithelial cells collected from CRS patients and controls. Basal expression of IFNAs, IKBKE, STAT1, and some CXC chemokines was elevated in samples from CRS patients. In subsequent in vitro studies, we found IKKε to be the key molecule and augmented CXCL10 secretion. Based on our findings and review of the literature, we hypothesized that high levels of IKKε might induce intractable inflammation via CXCL10. We tested the hypothesis in an animal model and found not only that IKKε induced severe eosinophilic inflammation with CXCL10 over-production, but also that inhibition of IKKε resolved the inflammation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: By definition bronchiectasis (BE) means destructed structure of normal bronchus as a consequence of frequent bacterial infections and inflammation. In many senses, BE is a neglected orphan disease. A recent pan-European registry study, EMBARC, has been set up in order to better understand its pathophysiology, better phenotype patients, and to individualize their management., Aim: To examine the aetiology and co-morbidity of BE in the capital area in Finland., Methods: Two hundred five patients with BE diagnosis and follow up visits between 2016 and 2017 in Helsinki University Hospital were invited to participate in the study. Baseline demographics, lung functions, imaging, microbiological, and therapeutic data, together with co-morbidities were entered into EMBARC database. Clinical characteristics, aetiologic factors, co-morbidities, and risk factors for extensive BE were explored., Results: To the study included 95 adult patients and seventy nine percent of the BE patients were women. The mean age was 69 years (SD ± 13). Asthma was a comorbid condition in 68% of the patients but in 26% it was estimated to be the cause of BE. Asthma was aetiological factor for BE if it had been diagnosed earlier than BE. As 41% BE were idiopathic, in 11% the disorder was postinfectious and others were associated to rheumatic disease, Alpha-1-antitrypsin deficiency, IgG deficiency and Kartagener syndrome. The most common co-morbidities in addition to asthma were cardiovascular disease (30%), gastroesophageal reflux disease (26%), overweight (22%), diabetes (16%), inactive neoplasia (15%), and immunodeficiency (12%). Extensive BE was found in 68% of BE patients in whom four or more lobes were affected. Risk factors for extensive BE were asthma (OR 2.7), asthma as aetiology for BE (OR 4.3), and rhinosinusitis (OR 3.1)., Conclusions: Asthma was associated to BE in 68% and it was estimated as aetiology in every fourth patient. However, retrospectively, it is difficult to exclude asthma as a background cause in patients with asthma-like symptoms and respiratory infections. We propose asthma as an aetiology factor for BE if it is diagnosed earlier than BE. Asthma and rhinosinusitis were predictive for extensive BE., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Both asthma and rhinosinusitis are complex and heterogeneous diseases and, importantly, they often coexist: these diseases can be concomitant in 35-65% of affected children, according to different studies. Thus, evaluating this comorbidity in the clinical practice should be paramount. In this review, we focused our discussion on the multiple pathophysiological aspects that may link rhinosinusitis and asthma in the pediatric population. Although rhinosinusitis may exacerbate asthma through several mechanisms occurring by contiguity, actually this aspect seems to be only one component of the complex interplay between upper and lower airways. In particular, the onset of an important and persistent Th2-driven inflammatory process dominated by eosinophils presence at one site of the airways, may release into the bloodstream several cytokines; in their turn, those can lead to the stimulation of the bone marrow, which may function as a systemic amplifier of such an eosinophilic inflammation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Sinusitis is a common clinical condition, but sphenoid sinusitis is a less common form and even rarer is hypophysitis as a complication of the latter. Clinically, hypophysitis may mimic a pituitary neoplasm in presenting with mass effect and pituitary hormone dysfunction., Case Description: We present 5 cases of sinusitis-related hypophysitis treated at the Royal Care International Hospital in Khartoum, Sudan. Clinical symptoms at presentation included headache, fever, ptosis, ophthalmoplegia, and history of sinusitis with running nose (nasal discharge). None of the patients were immunocompromised or showed signs of meningitis. Laboratory tests indicated neutrophilia and elevated inflammatory indices, namely C-reactive protein and erythrocyte sedimentation rate. There was also a disturbance of the hypothalamic-pituitary hormone axis, particularly impaired cortisol level. Magnetic resonance imaging scans on all patients revealed swollen masses in the pituitary fossa and enhancement of the sellar region and paranasal sinuses, especially the sphenoid sinus. All cases were empirically treated with hydrocortisone and amoxicillin-clavulanate, resulting in reversal of symptoms., Conclusions: Sinusitis is common in tropical regions where the climate is usually warm and often hot and dry. Here, the condition is considered a common incidental finding in magnetic resonance imaging examinations done for various indications. Hence it is not considered to be a serious health problem. Though our cohort of cases is small, we emphasize the importance of keeping a high index of suspicion for the diagnosis of hypophysitis in relevant case settings. This would help make an early diagnosis and ensure appropriate medical, perhaps nonsurgical, management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

MicroRNAs represent a component of the innate immune responses that can restrain inflammatory signaling, miR124 is an important member of inflammation-associated miRNAs, and abnormal miR124 expression is observed in many inflammatory diseases and immune disorders. However, the role and signaling pathways of miR124 in chronic rhinosinusitis with nasal polyps (CRSwNPs) have not been studied in detail. The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is highly conserved in evolution and plays important roles in the inflammatory response process. In our study, we describe the role of miR124 in the inflammatory response of CRS with nasal polyps. We found that the expression of miR124 was decreased in nasal polyps, and negatively correlated with the expression of AHR. MiR124 can inhibit AHR expression by directly target 3' untranslated region (3'-UTR) of AHR. To further investigate the relationship between miR124, AHR and CRS inflammatory response, we transfect HNEpC cells with miR124 mimic, miR124 inhibitors or siRNA of AHR, then all the results showed that miR124 could regulates cellular inflammatory response through negatively regulating AHR expression. This study demonstrated that the regulation of AHR expression by miR124 is critical to the development of inflammatory response in CRSwNPs., (Copyright © 2018. Published by Elsevier Inc.)

Background: Bronchial hypersecretion is a poorly studied symptom in asthma. The aim of the study was to determine the specific characteristics of asthmatics with bronchial hypersecretion., Methods: A total of 142 asthmatics (21.8% men; mean age 49.8 years) were prospectively followed for one year. Mucus hypersecretion was clinically classified into two severity categories: daily sputum production and frequent expectoration but not every day. Clinical and pulmonary function variables associated with mucus hypersecretion were assessed by multiple logistic regression analysis., Results: Daily cough was recorded in 28.9% of patients and sputum production daily or most of the days in 52.1%. Patients with mucus hypersecretion had more dyspnoea, poorer asthma control and quality of life, had suffered from more exacerbations and showed anosmia associated with chronic rhinosinusitis and nasal polyposis more frequently. Factors associated to mucus hypersecretion were anosmia, one exacerbation or more in the previous year and FEV1/FVC <70% (AUC 0.75, 95% CI 0.66-0.85) for the first definition of hypersecretion, and anosmia, poor asthma control and age (AUC 0.75, 95% CI 0.67-0.83) for the second definition., Conclusions: Mucus hypersecretion is frequent in patients with asthma, and is associated with chronic upper airways disease, airway obstruction, poor asthma control and more exacerbations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 (FEV 1 )/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., (Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

We report a case of cryptococcal sinusitis, a rare presentation of Cryptococcus neoformans infection in a patient with multiple myeloma. The objective of this case report is to highlight the utility of structural and functional imaging modalities in the differential diagnosis of sinonasal soft tissue masses in the immunocompromised patient population. PET-CT was the first imaging modality in this patient, who presented for routine follow-up staging of multiple myeloma, and was asymptomatic at the time of his presentation. PET-CT findings prompted further evaluation with MRI, to aid in the differential diagnosis with respect to a neoplastic versus infectious etiology. Ultimately, surgical excision with histopathology was required to provide definitive diagnosis. Final histopathology displayed yeast-organism staining consistent with Cryptococcus neoformans/gatti. The patient subsequently underwent treatment for this infection, along continued treatment for multiple myeloma. To our knowledge this is the first known case of cryptococcal sinusitis in a patient with neoplastic disease. Imaging represents an important tool to differentiate fungal infection from neoplasm in the immunocompromised patient population. As the population of immunocompromised patients continues to grow, the relevance of this diagnosis as well as the use of alternative imaging modalities is becoming more important in clinical practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Sinonasal pathology in adults with Cystic Fibrosis (CF) is common but the extent of CT-abnormalities and symptoms of sinonasal disease in children with CF and the age of onset are less frequently studied., Methods: In this observational, cross-sectional study 58 children with CF from two CF centres were included. All subjects completed a questionnaire regarding sinonasal symptoms, underwent a CT scan of the paranasal sinuses, and in each subject a culture of the upper airways was performed. Subjects were divided in 6 age cohorts (0-2, 3-5, 6-8, 9-11, 12-14 and 15-17years) and were divided into severe and mild CF based on their CFTR mutation. Opacification of the sinonasal system of the subjects was compared with opacification on MRI-scans of an age-matched control group without CF., Results: Most frequently reported symptoms were nasal obstruction and posterior/anterior nasal discharge. Opacification was abundant in every age cohort of the study group and was significantly more compared to the control group. In patients with severe CF the opacification was higher than subjects with mild CF. Upper airway cultures showed predominantly Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa., Conclusion: CT-abnormalities indicating sinonasal disease and symptoms are present from shortly after birth which may argue for a thorough examination of the upper airways in children with CF., (Copyright © 2016. Published by Elsevier B.V.)

Background: Few epidemiologic population-based data are available to describe the wide range of health conditions that affect children with asthma. We conducted this study to identify common comorbidities of asthma during childhood and compare the prevalences of selected comorbidities among children with and without asthma., Methods: We analyzed weighted data from the 2012 National Health Interview Survey child sample, a sample of 10,954 U.S. children aged 3-17 years. Information about each child's health, including history of asthma and other health conditions, was provided by an adult proxy respondent. We conducted binomial regression to compare the prevalences of 41 selected health conditions among children with and without current asthma., Results: An estimated 10.4% of children aged 3-17 years (n = 1202) were identified as having current asthma. Nearly all conditions considered were more common among children with than without asthma. Compared to children without asthma, children with asthma had higher prevalences of hay fever or respiratory allergies (prevalence difference [PD]: 30.5%; 95% CI: 26.6, 34.4), eczema or skin allergies (PD: 14.1%; 95% CI: 10.7, 17.5), sinusitis (PD: 11.3%; 95% CI: 8.4, 14.1), food or digestive allergies (PD: 10.4%; 95% CI: 7.7, 13.1), and difficulty with emotions, concentration, behavior, or getting along (PD: 7.9%; 95% CI: 4.7, 11.1)., Conclusions: These results highlight the burden of comorbidities among children with asthma. Improved understanding of the impact of comorbidities among children with asthma may help develop best practices for the assessment, treatment, and control of coexisting health conditions., (Published by Elsevier Ltd.)

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., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to evaluate patients who underwent endoscopic sphenoid sinus surgery for isolated sphenoid sinus disease. We also investigated the impact of sphenoid sinus surgery on headache intensity., Material and Methods: Twenty-one consecutive patients who underwent endoscopic sphenoidotomy for isolated sphenoid sinus disease were included in the study. Diagnosis of isolated sphenoid sinus pathology was based on history, physical examination, and radiologic evaluation. All patients had headache with various localizations. Pre- and postoperative headache intensity of patients was scored using a visual analogue scale (VAS)., Results: The most common location of headache was the vertex (24%). The preoperative and postoperative mean VAS scores for headache were 8.24 ± 0.94 and 2.67 ± 1.49, respectively. Statistical comparison revealed a significant improvement in headache intensity (p < 0.01). Polyps (33.3%) were the most common pathology, followed by inflammation (23.8%)., Conclusions: The most common presenting symptom of isolated sphenoid sinus disease is headache. In this study, we demonstrated that headache induced by isolated sphenoid disease can be relieved by endoscopic sphenoidotomy. Sphenoid sinus disease should be considered in the differential diagnosis of patients presenting with subacute or chronic headache., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

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.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized as a Th2-driven disease. Activated dendritic cells (DCs) are the main T-cell activators; their role in the chronic inflammatory process of nasal polyposis is still unclear., Methods: The regulation of DC subsets was analyzed in nasal polyp tissue from CRSwNP patients and compared to inferior turbinate tissue from healthy subjects. Tissue localization and expression of both plasmacytoid and myeloid DCs were assayed by means of immunohistochemistry and flow cytometry. Plasmacytoid DCs were also assayed by PCR, and tissue homogenates were assayed for various inflammatory markers., Results: The number of plasmacytoid (pDCs) and myeloid (mDCs) dendritic cells was significantly increased in nasal polyp tissue when compared to non-inflamed nasal mucosa. The number of pDCs, but not mDCs, was down-regulated in more severe cases (nasal polyps with asthma) and varied with the cytokine milieu. The amount of pDCs was significantly decreased in IL5+IFNγ - nasal polyp tissue compared to tissues with high IFNγ levels (IL5+IFNγ+). Furthermore, levels of indoleamine 2,3-dioxygenase were increased in nasal polyp compared to inferior turbinate tissue and correlated negatively with the number of pDCs., Conclusions: There is an altered balance of pDC and mDC numbers in nasal polyp tissue. pDCs seem to be more susceptible to an inflammatory cytokine milieu and may play a crucial role in disease severity., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: Orbitocranial complications (OCCs) of sinusitis are uncommon but potentially life threatening. OCCs carry high morbidity, mortality, and significant long-term sequelae. Late recognition leads to even worse outcomes., Objective: To present four case reports showing that aggressive management of complications of sinusitis-like OCC decreases long-term sequelae and mortality in pediatric patients., Case Reports: Four pediatric patients diagnosed with OCC were treated at our institution from April 2012 to March 2013. Three were boys and one was a girl; ages ranged from 4-14 years. Magnetic resonance imaging and computed tomography were the most useful imaging modalities. All patients received broad-spectrum antibiotics. Additional interventions consisted of endoscopic sinus surgery, subdural empyema drainage, and orbital decompression., Conclusion: The difficult complications of acute sinusitis in the pediatric age group should be anticipated, recognized early, and aggressively managed to prevent morbidity and a fatal outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis is common in cystic fibrosis (CF), as CFTR defects equally affect the airway and sinonasal mucosa. However, therapeutic strategies for CF-associated chronic rhinosinusitis lag behind current approaches for pulmonary disease., Objective: To assess the tolerability and efficacy of a nasal spray formulation containing 0.2% sodium hyaluronate and 3% tobramycin compared to a control formulation containing 0.2% sodium hyaluronate alone in the treatment of bacterial rhinosinusitis in patients with CF., Methods: In a double-blind controlled study, 27 patients with an established diagnosis of CF and a documented nasal infection with Pseudomonas aeruginosa and/or Staphylococcus aureus [22 males (81%), median age of 15 years (range 5-26 yrs)], were randomized to receive the nasal spray formulation containing hyaluronate and tobramycin (N=14) or hyaluronate alone (N=13) for 14 days. Efficacy and local tolerability of the treatments were assessed by ear, nose and throat (ENT) examination and related symptoms., Results: The formulation containing hyaluronate and tobramycin was more effective than hyaluronate alone in improving the status of the nasal mucosa, in reducing the mucopurulent secretion at the level of the osteomeatal complex and in improving ENT symptoms (hyposmia/anosmia and headache/facial pain). The treatment was well tolerated without relevant side effects., Conclusions: The present study suggests that the combination therapy with hyaluronate plus tobramycin was more effective than hyaluronate alone in the treatment of bacterial rhinosinusitis in CF., Trial Registration Number: EudraCT 2007-003628-39., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Headache is a common complaint in emergency department (ED) patients. Nearly 15% of ED headache patients will have brain computed tomography (CT) done. One frequent finding on these scans is "chronic sinusitis." Assuming that "chronic sinusitis" is the cause of the patient's headache is a potential source of mis-diagnosis., Study Objective: We hypothesized that CT findings of chronic sinusitis occur with equal frequency in patients with atraumatic headache as in control patients with minor head injury., Methods: This is a retrospective, single-center medical record review of consecutive discharged patients who received noncontrast head CT scans in an urban ED for either minor closed head injury or atraumatic headache. Each patient's head CT radiologic report was reviewed for findings of sinusitis and classified as chronic sinusitis, indeterminate for sinusitis, air-fluid levels, or no findings of sinusitis., Results: We enrolled 500 patients (234 in the atraumatic headache group, 266 in the minor head injury group). The two groups were similar except that more women were enrolled in the atraumatic headache group. CT findings of chronic sinusitis in the atraumatic headache group (22.2%) and the minor head injury group (17.7%; difference 4.5%; 95% confidence interval of -2.5-11.6%)., Conclusion: Prevalence of CT findings of sinusitis in ED patients with atraumatic headaches and mild head injury are similar. This strongly suggests that CT findings of chronic sinusitis in patients with atraumatic headache may be incidental, and are rarely the cause of a patient's acute headache., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the correlation between quality of the surgical field, intraoperative bleeding during endoscopic sinus surgery (ESS) and the density of microvasculature of the nasal mucosa., Material/methods: Nasal mucosa of 30 patients, operated for chronic rhinosinusitis, was biopsied to assess expression of CD34 antigen on vascular endothelium. Quality of surgical field was evaluated with Fromm-Boezaart scale at mean arterial pressure (MAP) of 70-80 mmHg. If at this MAP surgical field quality was not satisfactory further reduction of hemodynamic parameters was performed until 'bloodless surgical field' (grade 2 or lower) was achieved. The rate of intraoperative bleeding was calculated from the ratio of total blood loss and the operative time. The extent of the disease was assessed according to computed tomography findings using Lund-Mackay staging system., Results: Significant positive correlation (Spearman correlation test; p<0.05) was found between CD34 antigen expression and quality of surgical field at MAP between 70 and 80 mmHg as well as the rate of intraoperative bleeding. More intense reduction of MAP was necessary to achieve 'bloodless surgical field' in patients with high CD34 expression than in those with moderate and low expression. Lund-Mackay score correlated with quality of surgical field but not with the rate of intraoperative bleeding., Conclusion: During ESS, it is microvascular density of the nasal mucosa rather than the extent of the disease that contributes to the intensity of intraoperative bleeding, although both factors negatively influence the quality of surgical field., (Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)