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This study aimed to investigate the impact of different types of nasal inflammation on the regulation of entry-associated genes of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and influenza virus, in the nasal epithelium. Subjects were classified into three groups: control, eosinophilic chronic rhinosinusitis (ECRS), and noneosinophilic CRS (NECRS) groups. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), alanyl aminopeptidase (ANPEP), dipeptidyl peptidase 4 (DPP4), and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), and beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) were selected as key entry-associated genes for SARS-CoV-2, HCoV-229E, MERS-CoV, and influenza, respectively, and were evaluated. Brushing samples obtained from each group and human nasal epithelial cells cultured using an air-liquid interface system were treated for 7 days with typical inflammatory cytokines and analyzed using real-time polymerase chain reaction. Western blot analysis and confocal microscopy were performed. The entry-associated genes showed distinct regulation patterns in response to each interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-α and IFN-γ). ANPEP significantly decreased in both types of cytokines. Remarkably, DPP4 significantly increased in type 2 cytokines and decreased in type 1 cytokines. Moreover, ST6GAL1 and ST3GAL4 significantly increased in type 2 cytokines and decreased in type 1 cytokines, particularly IFN-γ. These findings were supported by western blot analysis and confocal imaging results, especially for ACE2 and DPP4. The findings regarding differential regulation suggest that patients with ECRS, primarily mediated by type 2 inflammation, may have lower susceptibility to SARS-CoV-2 and HCoV-229E infections but higher susceptibility to MERS-CoV and influenza infections., (© 2024 Wiley Periodicals LLC.)

Patients with chronic rhinosinusitis (CRS) may have concerns regarding their potential for an increased likelihood of contracting Covid-19, given baseline inflammatory disease and utilization of topical or oral immunosuppressive therapies for disease treatment. In the present study, we utilize matched cohort sampling of over 12,000 CRS patients and 12,000 controls seen between June of 2020 and January of 2021, examining rates of Covid-19 testing and positivity during that time period. We found no difference in Covid-19 contraction between CRS patients and matched non-CRS patients, despite an almost twofold significant increase in testing among those with CRS. This suggests that CRS patients are likely not inherently more vulnerable to Covid-19 infection at a rate above that of the general population. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:257-258, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To evaluate and compare the prevalence of high-risk HPV and low-risk HPV types in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and healthy controls., Materials and Methods: A prospective cohort study was conducted in a tertiary care hospital on the patients of CRSwNP undergoing surgical management. All patients underwent preoperative endoscopic evaluation and radiological assessment using NCCT of the nose and paranasal sinuses. The severity of the disease was graded using the Lund-Mackay score on NCCT. All patients underwent endoscopic polypectomy and the sample of tissues was sent for HPV DNA detection using Hybrid Capture II® technique. The clinicopathological characteristics of HPV positive and negative patients were compared., Results: Sixty cases and 20 controls were included in the study. All controls were negative for HPV DNA. 27 patients (45%) had the presence of HPV DNA, out of which 23 had only LR-HPV and 1 had only HR-HPV types. Three patients had both HR-HPV and LR-HPV subtypes. There was a significant difference between the cases and controls for the presence of HPV DNA (p < 0.001). However, the patients with HPV-positive DNA in the nasal specimen did not differ significantly from HPV-negative patients in age, gender, or severity of the disease., Conclusions: Human papillomaviruses may play a significant role in the etiopathogenesis of CRSwNP, however, do not impact the degree of sinus involvement., (Copyright © 2021. Published by Elsevier Inc.)

Background: SARS-CoV-2, the COVID-19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT-PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding amongst patient's basal clinical conditions., Methods: We have evaluated all 513 patients attended in our hospital between 1 March and 1 July. We have selected all 18 patients with prolonged viral shedding and compared them with 36 sex-matched randomly selected controls. Demographic, treatment and clinical data were systematically collected., Results: Global median duration of viral clearance was 25.5 days (n = 54; IQR, 22-39.3 days), 48.5 days in cases (IQR 38.7-54.9 days) and 23 days in controls (IQR 20.2-25.7), respectively. There were not observed differences in demographic, symptoms or treatment data between groups. Chronic rhinosinusitis and atopy were more common in patients with prolonged viral shedding (67%) compared with controls (11% and 25% respectively) (P < 0.001 and P = 0.003). The use of inhaled corticosteroids was also more frequent in case group (P = 0.007). Multivariate analysis indicated that CRS (odds ratio [OR], 18.78; 95% confidence interval [95%CI], 3.89-90.59; P < 0.001) was independently associated with prolonged SARS-CoV-2 RNA shedding in URT samples, after adjusting for initial PCR Ct values., Conclusion: We found that chronic rhinosinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)

With the ongoing development of the COVID-19 pandemic, research continues to emerge regarding the pathophysiology, characteristics, and treatment considerations for patients with COVID-19. No reports have highlighted the specific challenges posed in the management of pediatric patients with COVID-19 who present with complicated rhinosinusitis. In this report, we discuss our preoperative, intraoperative, and postoperative multidisciplinary treatment strategy for these cases and provide two examples of complicated rhinosinusitis cases in COVID-19 patients, treated with two different approaches. Pearls, insights, and a brief review of the literature are discussed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Acute rhinosinusitis (ARS) can be characterized as bacterial (ABRS) and require antibiotic therapy only in 0.5-5% of cases. In most cases, the disease is in a viral and post-viral form, which requires pathogenetic and symptomatic treatment. The study objective was to determine the efficacy of BNO 1012 extract in the technology of delayed antibiotic prescribing in children with acute rhinosinusitis., Methods: 292 children aged 6 to 11 years with ARS were randomized in the multicenter, comparative study. They received an extract of five medicinal plants in addition to standard symptomatic therapy or standard therapy only. EVALUATION CRITERIA: reduction of the sinusitis severity according to a 4-point medical assessment scale (nasal congestion, severity of anterior and posterior rhinorrhea) at each visit, dynamics of self-scoring of rhinorrhea and headache (according to a 10-point visual analogue scale), "therapeutic benefit" in days, frequency of antibiotic prescriptions due to the use of an extract of five plants., Results: The use of the 5-plant extract BNO 1012 in addition to the standard symptomatic treatment of acute rhinosinusitis provides a clinically significant, adequate reduction in the severity of rhinorrhea, nasal congestion and post-nasal drip, assessed by a physician at V2 (p < 0.005). Significant differences are noted in the patient's self-scoring of rhinorrhea on the second or third day in viral RS, and from the fourth to the eighth day in post-viral RS. Symptoms of similar intensity in control group were observed at V3. Thus, in the first week of treatment, the treatment group compared to the control one showed a "therapeutic benefit" of three days. The use of BNO 1012 in patients with acute rhinosinusitis can 1.81-fold reduce the prescription of antibacterial drugs., Conclusion: The combination of five medicinal plants is effective for the treatment of acute rhinosinusitis in children aged 6 to 11 years. Its use provides a significant "therapeutic benefit" when administered in addition to standard symptomatic therapy, reducing the need for antibiotic use., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Postviral olfactory loss is a common cause of olfactory impairment, affecting both quality of life as well as overall patient mortality. It is currently unclear why some patients are able to recover fully after a loss while others experience permanent deficit. There is a lack of research on the possible association between postviral olfactory loss and other cranial neuropathies., Objective: To evaluate the incidence of other cranial nerve deficits in patients with postviral olfactory loss and determine if there is an association with neurologic injury in this group. This study also sought to determine if other known risk factors were associated with postviral olfactory loss., Design, Setting, and Participants: A case-control study was conducted at a tertiary care rhinology clinic from January 2015 to January 2018 to review the incidence of cranial neuropathies in 2 groups of patients, those with postviral olfactory loss and those with chronic rhinosinusitis without olfactory loss used as a control group., Exposures: The Stanford Translational Research Integrated Database Environment (STRIDE) system was used for patient identification and data extraction. Patients with a history of olfactory loss or chronic rhinosinusitis as well as incidence of cranial neuropathies were identified by using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes., Main Outcomes and Measures: This study reviewed incidence of postviral or idiopathic cranial neuropathies in both patient groups, while also evaluating for any difference in demographic characteristics, comorbidities, or other patient-related factors., Results: There were 91 patients in the postviral olfactory loss group and 100 patients in the control group, which were age and sex matched as closely as possible. Of the 91 patients with postviral olfactory loss, mean (SD) age was 56.8 (15.3), and 58 (64%) were women; for the control group, the mean (SD) age was 57.5 (15.6) years, and 63 (63%) were women. Racial breakdown was similar across cases and controls, with white individuals making up 59% to 65%; Asian individuals, 20% to 24%; black individuals, approximately 3%; Hispanic individuals, approximately 1%; and the remaining patients being of other race/ethnicity. The incidence of other cranial neuropathies in the postviral olfactory loss group was 11% compared with 2% within the control group (odds ratio, 6.1; 95% CI, 1.3-28.4). The study also found 2 cases of multiple cranial neuropathies within a single patient within the olfactory group. Family history of neurologic disease was associated with more than 2-fold greater odds of cranial nerve deficit (odds ratio, 3.05; 95% CI, 0.59-15.68)., Conclusions and Relevance: Postviral olfactory loss appears to be associated with a higher incidence of other cranial neuropathies. It is possible that there is an inherent vulnerability to nerve damage or decreased ability for nerve recovery in patients who experience this disease process.

This is the first reported case of necrotizing nasal and sinus herpes infection with orbital involvement. A 94-year-old male with a past medical history of hypertension, congestive heart failure, and chronic kidney disease presented with necrotic nasal cellulitis and a red left eye with blurry vision. Onset was 2 weeks prior with an upper lip fever blister. He was admitted to medicine and started on antimicrobials. Maxillofacial computed tomography scan revealed pansinusitis with involvement of bilateral medial orbital walls. Initial nasal biopsy was negative. Repeat biopsy was positive for herpes simplex virus 1. His nose was debrided with full-thickness skin grafting. While there are reports of necrotizing herpes simplex, none were to the extent of our patient nor raised suspicion for invasive fungal sinusitis. Differentiating is important as this patient made a full recovery in comparison to patients with mucormycosis where mortality is often as high as 80%.

Tight junctions (TJs) alteration is commonly seen in airway inflammatory diseases. Oncostatin M (OSM) is an inflammatory mediator associated with chronic rhinosinusitis with nasal polyps (CRSwNP). We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for influenza A virus (IAV). However, its role in TJs alteration and the effects of IAV on inducing OSM expression in nasal epithelium remains to be further investigated. In this study, OSM and TJs expression was measured and compared between inferior turbinate from healthy controls and nasal polyps from CRSwNP. Additionally, hNECs cultured at air-liquid interface (ALI) were infected with H3N2 influenza virus to study the role of influenza virus in inducing epithelial OSM expression as a possible means of exacerbation. The expression of ZO-1, claudin-1, and occludin was markedly decreased and correlated negatively with that of OSM in CRSwNP. By using the in vitro hNEC model, H3N2 infection resulted in significantly increased OSM expression (2.2-, 4.7- and 3.9-fold higher at 8, 24, and 48 h post-infection vs. mock infection). Furthermore, OSM is found to co-localize with ciliated and goblet cells in hNECs infected with H3N2 influenza virus. Our findings demonstrated that increased OSM expression is implicated in CRSwNP as a possible mechanism of TJs' impairment, which can be further augmented following influenza infection via epithelial OSM expression, possibly contributing to exacerbations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The objective of the present study was to elucidate the peculiar features of acute viral and bacterial sinusitis in the children and to elaborate the algorithm for their treatment based on the results of the primary clinical and laboratory examination. As many as 224 children at the age varying from 1-17 years suffering from acute sinusitis were enrolled in the study. The following methods were employed for the purpose of the study; the analysis of the medical histories of the patients, general examination by an otorhinolaryngologist, diagnostic endoscopy of the nasal cavity and nasopharynx, radiological studies and computed tomography of the paranasal sinuses, echosinusoscopy, the comprehensive microbiological and virological investigation, and evaluation of the peripheral blood characteristics. The study allowed to elucidate the main clinical specific features of acute sinusitis of different etiology including the virological one. The scoring system for the estimation of the risk of development of acute bacterial sinusitis was proposed and the algorithm was developed for the treatment of the children suffering from acute sinusitis to be used in the practical work by general practitioners and otorhinolaryngologists.

Background: The objective of this clinical trial (CRS-02) was to assess the efficacy, safety and tolerability of two dosages of the herbal medicinal product BNO 1016 (Sinupret extract) in patients with chronic rhinosinusitis (CRS)., Methodology: 929 patients suffering from CRS were enrolled in this randomised placebo-controlled trial with a treatment period of 12 weeks. The primary endpoint was the mean Major Symptom Score (MSS) in week 8 and week 12 compared to placebo. Secondary endpoints included further MSS related parameters and responder rates over time. Pharmacoeconomic endpoints were also analysed. Finally, safety and tolerability were evaluated., Results: Sinupret extract was not superior over placebo regarding the primary endpoint. However, the results of the secondary endpoints showed a clear trend towards superior efficacy. Therefore, additional post-hoc sensitivity analyses were performed in patients with a baseline MSS over 9 and persistence of disease more than 1 year diagnosed by specialists in otorhinolaryngology. Those patients significantly benefited from Sinupret extract. Therapy was superior for the primary endpoint analysis. Patients were less impaired with respect to work and daily activities. A good safety and tolerability of Sinupret extract was assured in all patients., Conclusions: Sinupret extract can safely be administered in patients with CRS. Although the primary endpoint of the study was not significant, a post-hoc subgroup analysis in patients whose disease was diagnosed by a specialist revealed a pronounced treatment effect. Effects in that subgroup were even stronger with longer disease persistence and stronger severity.

Rhinosinusitis (RS) is a symptomatic disease classification of many causes and is a major economic burden worldwide. It is widely accepted that RS is further classified into acute (ARS) and chronic (CRS) rhinosinusitis based on the duration of the symptoms, and that viral infection plays a large role in initiating or potentiating the disease. In this review, we examine the role of respiratory virus infection in the exacerbation of ARS and CRS. We explore the epidemiology of viral exacerbation of ARS and CRS and highlight key viruses that may cause exacerbation. We also review the current understanding of viral infections in the upper airway to further explain the putative underlying mechanisms of inflammatory events in ARS and CRS exacerbation. Advances in accurate diagnosis of the etiologic respiratory viruses of ARS and CRS symptoms which can lead to better disease management are also surveyed. In addition to the current treatments which provide symptomatic relief, we also explore the potential of harnessing existing antiviral strategies to prevent ARS and CRS exacerbation, especially with improved viral diagnostic tools to guide accurate prescription of antivirals against causative respiratory viruses.

Chronic rhinosinusitis (CRS) encompasses a heterogeneous group of debilitating chronic inflammatory sinonasal diseases. Despite considerable research, the etiology of CRS remains poorly understood, and debate on potential roles of microbial communities is unresolved. Modern culture-independent (molecular) techniques have vastly improved our understanding of the microbiology of the human body. Recent studies that better capture the full complexity of the microbial communities associated with CRS reintroduce the possible importance of the microbiota either as a direct driver of disease or as being potentially involved in its exacerbation. This review presents a comprehensive discussion of the current understanding of bacterial, fungal, and viral associations with CRS, with a specific focus on the transition to the new perspective offered in recent years by modern technology in microbiological research. Clinical implications of this new perspective, including the role of antimicrobials, are discussed in depth. While principally framed within the context of CRS, this discussion also provides an analogue for reframing our understanding of many similarly complex and poorly understood chronic inflammatory diseases for which roles of microbes have been suggested but specific mechanisms of disease remain unclear. Finally, further technological advancements on the horizon, and current pressing questions for CRS microbiological research, are considered., (Copyright © 2016 American Society for Microbiology.)

Sinusitis in immunocompromised patients can be caused by a wide variety of pathogens, primarily bacterial and fungal in nature. Tissue invasion can extend into the orbital apex and result in ophthalmoplegia and blindness. We report the first histologically proven case, to our knowledge, caused by cytomegalovirus infection., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The common cold is one of the most frequent human inflammatory diseases caused by viruses and can facilitate bacterial superinfections, resulting in sinusitis or pneumonia. The active ingredient of the drug Soledum, 1,8-cineole, is commonly applied for treating inflammatory diseases of the respiratory tract. However, the potential for 1,8-cineole to treat primary viral infections of the respiratory tract remains unclear. In the present study, we demonstrate for the first time that 1,8-cineole potentiates poly(I:C)-induced activity of the antiviral transcription factor interferon regulatory factor 3 (IRF3), while simultaneously reducing proinflammatory nuclear factor (NF)-κB activity in human cell lines, inferior turbinate stem cells (ITSCs) and in ex vivo cultivated human nasal mucosa. Co-treatment of cell lines with poly(I:C) and 1,8-cineole resulted in significantly increased IRF3 reporter gene activity compared with poly(I:C) alone, whereas NF-κB activity was reduced. Accordingly, 1,8-cineole- and poly(I:C) treatment led to increased nuclear translocation of IRF3 in ITSCs and a human ex vivo model of rhinosinusitis compared with the poly(I:C) treatment approach. Nuclear translocation of IRF3 was significantly increased in ITSCs and slice cultures treated with lipopolysaccharide (LPS) and 1,8-cineole compared with the LPS-treated cells mimicking bacterial infection. Our findings strongly suggest that 1,8-cineole potentiates the antiviral activity of IRF3 in addition to its inhibitory effect on proinflammatory NF-κB signalling, and may thus broaden its field of application., (© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.)

Most sinus infections are viral and only a small percentage develop bacterial infection. Rhino-, influenza, and para-influenza viruses are the most frequent viral causes of sinusitis. The most common bacterial isolates from children and adult patients with community-acquired acute bacterial sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic organisms (Prevotella and Porphyromonas, Fusobacterium, and Peptostreptococcus spp.) are the commonest isolates in chronic rhinosinusitis (CRS). Aerobic and anaerobic beta lactamase-producing bacteria (BLPB) were recovered from over a third of these patients. Methicillin-resistant S. aureus (MRSA) accounted for over 60 % of S. aureus isolates. Pseudomonas aeruginosa and other aerobic and facultative Gram-negative rods are frequently recovered in nosocomial sinusitis, the immunocompromised host, individuals with human immunodeficiency virus infection, and in cystic fibrosis. The CRS infection evolves the formation of a biofilm that might play a significant role in the pathogenesis and persistence of CRS. The microbiology of sinusitis is influenced by previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens. Recognition of the unique microbiology of CRS and their antimicrobial susceptibility is of great importance when selecting antimicrobial therapy.

There is increasing evidence to suggest that the sinus microbiome plays a role in the pathogenesis of chronic rhinosinusitis (CRS). However, the concentration of these microorganisms within the sinuses is still unknown. We show that flow cytometry can be used to enumerate bacteria and virus-like particles (VLPs) in sinus flush samples of CRS patients. This was achieved through trialling 5 sample preparation techniques for flow cytometry. We found high concentrations of bacteria and VLPs in these samples. Untreated samples produced the highest average bacterial and VLP counts with 3.3 ± 0.74 x 10(7) bacteria ml(-1) and 2.4 ± 1.23 x 10(9) VLP ml(-1) of sinus flush (n = 9). These counts were significantly higher than most of the treated samples (p < 0.05). Results showed 10(3) and 10(4) times inter-patient variation for bacteria and VLP concentrations. This wide variation suggests that diagnosis and treatment need to be personalised and that utilising flow cytometry is useful and efficient for this. This study is the first to enumerate bacterial and VLP populations in the maxillary sinus of CRS patients. The relevance of enumeration is that with increasing antimicrobial resistance, antibiotics are becoming less effective at treating bacterial infections of the sinuses, so alternative therapies are needed. Phage therapy has been proposed as one such alternative, but for dosing, the abundance of bacteria is required. Knowledge of whether phages are normally present in the sinuses will assist in gauging the safety of applying phage therapy to sinuses. Our finding, that large numbers of VLP are frequently present in sinuses, indicates that phage therapy may represent a minimally disruptive intervention towards the nasal microbiome. We propose that flow cytometry can be used as a tool to assess microbial biomass dynamics in sinuses and other anatomical locations where infection can cause disease.

Objective: To determine the rate of sinusitis complicating upper respiratory tract illnesses (URIs) in children. We prospectively identified the clinical, virologic, and epidemiologic characteristics of URIs in a population of 4- to 7-year-old children followed for 1 year., Study Design: This was an observational cohort study in 2 primary care pediatric practices in Madison, Wisconsin. Nasal samples were obtained during 4 asymptomatic surveillance visits and during symptomatic URIs. A polymerase chain reaction-based assay for 9 respiratory viruses was performed on nasal samples. A diagnosis of sinusitis was based on published criteria., Results: Two hundred thirty-six children ages 48-96 months were enrolled. A total of 327 URIs were characterized. The mean number of URIs per child was 1.3 (range 0-9) per year. Viruses were detected in 81% of URIs; rhinovirus (RV) was most common. Seventy-two percent of URIs were resolved clinically by the 10th day. RV-A and RV-C were detected more frequently at URI visits; RV-B was detected at the same rate for both asymptomatic surveillance visits and URI visits. Sinusitis was diagnosed in 8.8% of symptomatic URIs. Viruses were detected frequently (33%) in samples from asymptomatic children., Conclusions: Sinusitis occurred in 8.8% of symptomatic URIs in our study. The virus most frequently detected with URIs in children was RV; RV-A and RV-C detection but not RV-B detection were associated with illness. Viruses, especially RV, are detected frequently in asymptomatic children. Most URIs have improved or resolved by the 10th day after onset. Children experienced a mean of 1.3 URIs per year, which was lower than expected., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The role of viruses in chronic rhinosinusitis (CRS) is poorly understood. In part, this is secondary to difficulty in isolating viruses. Although traditional detection methods for respiratory viruses have had little clinical utility, modern viral screening techniques that use molecular sequencing are now both rapid and feasible, which makes analysis of the paranasal sinus microbiome more accessible., Objective: To detect respiratory viruses in the paranasal sinuses of patients with CRS and of healthy controls as well as to correlate clinical and radiographic measures of CRS with viral presence., Methods: In this prospective study, 13 patients with CRS with nasal polyposis (CRSwNP) and 8 patients without nasal polyposis (CRSsNP) were enrolled and compared with 14 healthy controls. Samples were obtained from the paranasal sinuses and were screened for viral DNA with polymerase chain reaction--based sequencing techniques. Typical symptoms of CRS, the Sinonasal Questionnaire, and objective measures, including the modified Lund-Mackay and modified Lund-Kennedy scores were obtained., Results: Eighty percent of the positive screens (4/5) were found in patients with CRSsNP, whereas 20% of the positive tests (1/5) were in the CRSwNP group, and none of the controls tested positive (p = 0.0029). Coronavirus was the most common virus detected. Sinonasal Questionnaire scores of the patients with CRS who tested positive for viruses were higher but not statistically different than those without a positive screen (p = 0.31). Radiographic and endoscopic measures of disease were not significantly different in the setting of a positive viral screen (p = 0.12 and 0.11 respectively)., Conclusion: Although traditionally difficult, advances in molecular sequencing enhance detection of viruses in the sinonasal tract. In this study, respiratory viruses were more commonly isolated from patients with CRS compared with healthy controls. Moreover, viral infection may play a greater role in symptom exacerbation in CRSsNP than in CRSwNP. These findings warrant further investigation into the role of the viral microbiome in CRS.

Introduction: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis., Objective: To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls., Methods: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls., Results: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11)., Conclusion: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis., (Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

We report a patient with newly diagnosed late-stage HIV presenting with fever, rhinosinusitis and cognitive impairment. Analysis of cerebrospinal fluid and nasal turbinate tissue confirmed cytomegalovirus (CMV) infection. CMV pp65 antigen assay conducted on peripheral blood leukocytes revealed large CMV infected mononuclear cells (diameter ∼ 50 μm) with an unusual cytoplasmic pattern of pp65 staining. These large cells were also seen in buffy coat Wright's stained smears; their size, morphology and pp65 antigen uptake pattern were consistent with CMV infected cytomegalic endothelial cells. While CMV sinus infections are occasionally encountered in AIDS patients, this is the first report to document CMV infection of the nasal mucosa with secondary sinusitis and chronic suppurative otitis media. Furthermore, the detection of circulating cytomegalic cells is described--a rare finding with pathological and clinical significance in immunocompromised patients with CMV disease., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) can be aggravated by viral upper respiratory infections. We aimed to investigate whether any specific human rhinovirus (HRV) serotype is more common in the mucosa of CRS patients, and to find any defining clinical characteristics, according to the various HRV serotypes., Methods: A prospective case-control study was conducted to determine HRV serotypes in 111 CRS patients and 51 non-CRS controls. No participant had a history of upper respiratory infection over a 4-week period. Nasal lavage fluids and turbinate epithelial cells were collected prospectively. When HRV was detected with multiplex polymerase chain reaction (PCR), strains were further characterized by sequencing the VP4/VP2 region of the HRV genome., Results: HRV was detected in 40 CRS subjects (36%) and 11 non-CRS controls (21%). The overall detection rates of HRV in CRS patients were higher than in non-CRS controls (p < 0.05). Of the 8 serotypes detected in CRS patients, 5 belonged to HRV-A and 3 belonged to HRV-B; HRV-C was not detected. In non-CRS controls, only HRV-A was identified, with only 2 serotypes detected (HRV-A13 and HRV-A16). HRV-B and C were not detected., Conclusion: The high prevalence of HRV in CRS patients was confirmed in our study. However, we were unable to determine whether certain HRV serotypes are more predominant in CRS patients than non-CRS controls. HRV-A13 was the most common serotype in both CRS patients and non-CRS controls. We could not find any differences in the clinical characteristics according to the HRV serotypes in CRS patients., (© 2014 ARS-AAOA, LLC.)

Conclusion: Daily intake of 480 mg of BNO 1016 for 15 days is an effective treatment in acute viral rhinosinusitis., Objectives: The pooled efficacy data of two similar randomized placebo-controlled clinical trials were analyzed. Safety was evaluated on the basis of the individual trials., Methods: The efficacy analysis was based on 589 patients. Treatment was performed orally with either 3 × 160 mg BNO 1016 (n = 294) or 3 × placebo (n = 295) for 15 days. In both trials patients underwent five visits to the investigational sites. Symptoms were evaluated according to the EPOS 2012 guideline. Ultrasonography was used to confirm the diagnosis at onset of treatment and the remission of symptoms at the last visit. Efficacy was evaluated by the investigator as the mean major symptom score (MSS) at the end of treatment (visit 5, day 14). Patients reported symptoms and social/emotional consequences of rhinosinusitis using a quality of life questionnaire (SNOT-20 GAV)., Results: MSS improved during the treatment period by a mean of 10.02 ± 1.61 score points to 2.47 ± 2.55 for BNO 1016 and of 9.87 ± 1.52 to 3.63 ± 3.63 for placebo. Differences between treatment groups at end of therapy (1.16 ± 3.14 score points; p < 0.0001) and patient-assessed quality of life (p = 0.0015) were statistically significant in favor of BNO 1016.

Background: Chronic rhinosinusitis (CRS) is a common illness, yet little is known about its pathogenesis, including the role played by respiratory viruses., Methods: A transversal prospective study was conducted to analyze the seasonality of CRS using real-time polymerase chain reaction to detect respiratory virus genomes in secretions and tissue samples from patients with CRS with and without nasal polyps., Results: The frequency of viral detection was 41% (31/75). The respiratory virus most frequently detected was human rhinovirus, found in 18 patients (24%), followed by human metapneumovirus, human enterovirus, human respiratory sincicial virus, human adenovirus, human bocavirus, human coronavirus, and human influenza virus, detected in 12 (16%), five (6.6%), four (5.3%), four (5.3%), two (2.6%), two (2.6%), and one (1.3%) patient(s), respectively. Although none of the patients presented symptoms when the samples were collected, there was a peak in detection of the most prevalent virus in the autumn and winter seasons of both years, similar to the pattern that occurs in acute conditions., Conclusions: The pattern of respiratory virus seasonality found in nasal mucosa, polyps, and paranasal sinus samples in patients with CRS reinforces the possibility of asymptomatic respiratory viral infections.

Background: Acute bacterial sinusitis (ABS) is a common complication of viral upper respiratory tract infections (URI). Clinical characteristics of URIs complicated by ABS in young children have not been well studied., Methods: We identified ABS episodes in a prospective, longitudinal cohort study of 294 children (6-35 months of age at enrollment), who were followed up for 1 year to capture all URI episodes and complications. At the initial URI visit seen by the study personnel (median day = 4 from symptoms onset), nasopharyngeal samples were obtained for bacterial cultures and viral studies., Results: Of 1295 documented URI episodes, 103 (8%) episodes (in 73 children) were complicated by ABS, 32 of which were concurrent with acute otitis media. The majority (72%) of ABS episodes were diagnosed based on persistent symptoms or a biphasic course. Average age at ABS diagnosis was 18.8 ± 7.2 months; White children were more likely to have ABS episodes than Blacks (P = 0.01). Hispanic/Latino ethnicity (P < 0.0001) was negatively associated, and adequate 7-valent pneumococcal conjugate vaccine immunization status (P = 0.001) appeared to increase the risk of ABS. Girls had more ABS episodes than boys (0.5 ± 0.8 vs. 0.3 ± 0.6 episodes/yr, respectively, P = 0.03). Viruses were detected in 63% during the initial URI visit; rhinovirus detection was positively correlated with ABS risk (P = 0.01). Bacterial cultures were positive in 82/83 (99%) available samples obtained at the initial URI visit; polymicrobial (56%), Moraxella catarrhalis (20%) and Streptococcus pneumoniae (10%) were the most common cultures. Presence of pathogenic bacteria overall and presence of M. catarrhalis during URI were positively correlated with the risk for ABS (P = 0.04 for both)., Conclusions: ABS complicates 8% of URI in young children. Girls have more frequent ABS episodes than boys. Presence of rhinovirus and M. catarrhalis during URI are positively correlated with the risk for ABS complication.

In this study, we review our current knowledge of the autoimmune etiopathogenesis of chronic rhinosinusitis with nasal polyps including bacterial infections, viral infections and immunomediated mechanisms and to discuss pathogenesis with relevance for pharmacotherapy. Relevant publications on the etiopathogenesis and treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) from 1977 to 2013 were analyzed. The characteristic signs and symptoms include appearance of relapsing nasal polyps, with typical symptoms such as nasal obstruction, nasal discharge and, usually, loss of the sense of smell. The etiology and pathogenesis remain unknown. Proposed theories of causation include bacterial or viral infections and immunomediated mechanisms. The autoimmune aetiology of unknown origin or failure to respond to classic pharmacological treatments with nasal and oral steroids is now suspected. At present, the nature of the antigen trigger, the exact role played by B/T cells and anti-dsDNA autoantibodies in the pathogenesis of nasal polyposis remains unclear. Corticosteroids and surgery are the first line of treatment in CRSwNP. In the case of corticosteroid treatment failure, other drugs can be used such as rituximab, belimumab or omalizumab which have demonstrated clinical efficacy in the treatment of nasal polyposis with comorbid asthma. Immunosuppressive drugs such as methotrexate, and cyclophosphamide have also been used with varying degrees of success.

Objective: To evaluate the diagnostic value of symptom duration and purulent rhinorrhea in adults suspected of having acute bacterial rhinosinusitis., Data Sources: PubMed, EMBASE, and the Cochrane Library., Review Methods: We performed a comprehensive systematic search on March 28, 2013. We included studies on the diagnostic value of duration of symptoms and purulent rhinorrhea in patients suspected of having acute bacterial rhinosinusitis. We assessed study design of included articles for directness of evidence and risk of bias. We extracted prevalence and positive and negative predictive values., Results: Of 4173 unique publications, we included 1 study with high directness of evidence and moderate risk of bias. The prior probability of bacterial rhinosinusitis was 0.29 (95% confidence interval [CI], 0.24-0.35); we could not extract posterior probabilities. Odds ratios (95% CI) from univariate analysis were 1.03 (0.78-1.36) for duration of symptoms and 2.69 (1.39-5.18) for colored discharge on the floor of the nasal cavity., Conclusion and Recommendation: We included 1 study with moderate risk of bias, reporting data in such a manner that we could not assess the value of symptom duration and purulent rhinorrhea in adults suspected of having acute bacterial rhinosinusitis. Recommendations to distinguish between a viral and a bacterial source based on purulent rhinorrhea are not supported by evidence, and the decision to prescribe antibiotic treatment should not depend on its presence. Based on judgment driven by theory and subsidiary evidence of a greater likelihood of bacterial rhinosinusitis after 10 days, antibiotic therapy may seem a reasonable empirical option.

The objective of the present study was to elucidate the role of respiratory viruses in etiology of acute rhinosinusitis (ARS) in the children and adolescents. We analysed the results of a microbiologial study of 50 aspirates from the paranasl sinuses. It was shown that acute rhinosinusitis had bacterial and viral-bacterial etiology in 8% and 24% of the cases respectively. In 42% of the cases the pathogen could not be identified by any of the methods used in the study.

Objective: To evaluate the prevalence of human herpesviruses (HHV) 1-6 and community-acquired respiratory viruses (CARVs) in specimens from patients with nasal polyposis undergoing functional endoscopic sinus surgery (FESS) and investigate the potential clinical role., Methods: Viral occurrence was evaluated by molecular methods in polyp, turbinate mucosa, and pre- and postoperative scraping specimens from 35 consecutive patients at different time points in relation to FESS., Results: Overall, 21 patients (60%) were positive to at least one virus in at least one specimen; in particular, 12.1% of all specimens for HHV-6 (3/35 polyps, 11/31 turbinates, 1 presurgical scraping) and 10.5% for Epstein-Barr virus (EBV) (8/35 polyps, 3/31 turbinates, 1/29 pre- and 1/29 postsurgical scraping), followed by CMV and HSV-1 (both 1.6%; 1/35 polyps, 1/29 postsurgical scraping and 2/35 polyps, respectively). EBV positivity tended to be higher in polyps, as well as HHV-6 in adjacent healthy turbinate mucosa, although no significant association was found. Only one preoperative cytological specimen was positive to parainfluenza virus-1., Conclusion: No association between the development of nasal polyps, herpesviruses and CARVs seems to exist. However, the higher EBV frequency in polyps could suggest a causative role or persistence in the inflammatory lymphoid tissue.

Background: Staphylococcus aureus is the most common organism in recalcitrant chronic rhinosinusitis (CRS) and is often resistant to traditional antibiotic therapy. Bacteriophages ("phages") are a potential candidate for a new, effective therapy. For phages to be useful in the setting of CRS, two minimum requirements must be presented: (1) phages must be effective against S. aureus biofilms and (2) phages must have a broad spectrum of activity. This study aimed to assess the in vitro activity of a phage cocktail (CockTail of Staphylococcus aureus specific bacteriophage [CT-SA]) against S. aureus biofilms and a broad panel of strains isolated from patients with CRS., Methods: The study examined 66 clinical isolates (CIs) of S. aureus. All isolates were tested for the susceptibility to phage lysis by spotting CT-SA onto bacterial lawns. To measure its effect on S. aureus biofilms, a minimum biofilm eradication concentration assay was used, using five S. aureus isolates. Biofilms of these isolates were grown, treated with CT-SA for 48 hours, fluorescently stained, and viewed using confocal scanning laser microscopy., Results: CT-SA lysed 62 of 66 (94%) CIs of S. aureus. CT-SA treatment yielded significant reductions in biofilm mass for 4/5 CIs tested and for ATCC 25923. Challenge of S. aureus with a single phage resulted in the emergence of bacteriophage-insensitive mutants (BIM) with a frequency of 10(-7), and challenge with CT-SA completely prevented their development., Conclusion: This study indicates that phage cocktail CT-SA can effectively eliminate S. aureus, in planktonic and biofilm forms, from the great majority of CIs from this hospital setting. In addition, its potential effect in preventing the emergence of BIMs was also established. Thus, CT-SA has the potential to treat S. aureus infection and biofilm in CRS patients.

Acute rhinosinusitis is a common illness in children. Viral upper respiratory tract infection is the most common presentation of rhinosinusitis. Most children resolve the infection spontaneously and only a small proportion develops a secondary bacterial infection. The proper choice of antibiotic therapy depends on the likely infecting pathogens, bacterial antibiotic resistance, and pharmacologic profiles of antibiotics. Amoxicillin-clavulanate is currently recommended as the empiric treatment in those requiring antimicrobial therapy. Isolation of the causative agents should be considered in those who failed the initial treatment. In addition to antibiotics, adjuvant therapies and surgery may be used in the management of acute bacterial rhinosinusitis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Respiratory viral infections are often implicated as triggers of chronic rhinosinusitis (CRS) flare-ups. However, there is a paucity of respiratory viral surveillance studies in CRS patients, and such studies could elucidate the potential role of viruses in promoting symptoms and aggravating mucosal inflammation. Therefore, a prospective case-control study was conducted to determine the prevalence of respiratory viruses in CRS patients and non-CRS controls. Nasal lavage fluids and turbinate epithelial cells were collected prospectively from 111 CRS patients and 50 controls. Multiplex PCR was used to identify common respiratory viruses in both sample types and the infection rate was compared between groups. Respiratory viruses were detected in 50.5% of lavage samples and in 64.0% of scraping samples from CRS patients. The overall infection rate was significantly different in CRS patients and controls (odds ratio, 2.9 in lavage and 4.1 in scraping samples). Multiple viral infections were detected more frequently in lavage samples from CRS patients than those from controls (P < 0.01; odds ratio, 7.7). Rhinovirus was the most prevalent virus and the only virus with a significantly different infection rate in CRS patients and controls in both samples (odds ratio, 3.2 in lavage and 3.4 in scraping samples). This study detected a higher prevalence of respiratory viruses in CRS patients than controls, suggesting that there may be significant associations between inflammation of CRS and respiratory viruses, particularly rhinovirus. Further studies should investigate the exact role of highly prevalent respiratory viruses in CRS patients during symptomatic aggravation and ongoing mucosal inflammation.

Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs.

Objective: A herbal drug combination (Dry Extract BNO 1016) has been assessed for efficacy and tolerability in patients with acute viral rhinosinusitis., Methodology: In this randomised, controlled trial patients with symptom duration of up to 3 days, mild to moderate facial pain and a Major Symptom Score (MSS) between 8 and 12 were treated for 15 days with BNO 1016 or placebo (coated tablets administered orally). Primary efficacy endpoint was mean MSS at end of treatment. Secondary outcome measures included treatment response and changes in paranasal sinuses assessed by ultrasonography., Results: Treatment resulted in clinically relevant, significant differences in mean MSS for BNO 1016 versus placebo. BNO 1016 provided symptom relief two days earlier than placebo. The number needed to treat for healing is 8. BNO 1016 was superior regarding responder rates at Day 10 and Day 14 and percentage of patients without signs of acute viral rhinosinusitis assessed by ultrasonography at end of treatment. BNO 1016 was well tolerated; no serious adverse events were reported., Conclusion: The herbal dry extract BNO 1016 is efficacious and well tolerated in patients with acute viral rhinosinusitis., Trial Registration: ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01146860; EudraCT: 2009-016682-28).

Background: This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP)., Methods: HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group)., Results: The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration., Conclusions: HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.

The examination was applied to 81 children aged 5-15 years, including 64 children with diagnosis of rhinosinusitis. The control group consisted of 17 healthy children. The set of laboratory clinical diagnostic techniques was applied to detect the causes of pathology. It is established that children with rhinosinusitis suffered from concurrent bacterial and virus infections. The morphologic presentation of mucous membrane of nasal cavity reflects the etiologic factor and the stage of inflammatory process. The detection of concentration of IL-4, IL-6 and IL-8 of blood serum gives a possibility to diagnose children with combined mechanisms of development of rhinosinusitis.

Background: Many chronic rhinosinusitis (CRS) patients recall an upper respiratory tract infection as the inciting event of their chronic illness. Viral infections have been shown to cause obstruction of the osteomeatal complex, which is likely to be a critical step in the development of CRS. There is clear overlap between the pathogenesis of CRS and asthma. Infections with respiratory viruses in childhood increase the risk of subsequently developing asthma. Viral infections in established asthmatics are associated with acute exacerbations. We sought to determine whether respiratory viruses could be detected within the sinonasal mucosa of CRS patients using polymerase chain reaction (PCR) techniques., Methods: Sinus mucosa was sampled from 13 patients with CRS and 2 patients with normal sinuses. PCR was used to look for common respiratory viruses (parainfluenza 1, 2, and 3; respiratory syncytial virus [RSV]; human metapneumovirus [hMPV]; adenovirus [ADV]; rhinovirus; coronavirus; bocavirus [BoV]; cytomegalovirus [CMV]; and influenza A and B)., Results: No respiratory viruses were detected in any of the samples., Conclusion: Persistence of respiratory viruses within the sinonasal mucosa is unlikely to be a cause of ongoing inflammation in CRS. The possibility remains that a transient viral infection provides the initial inflammatory stimulus., (Copyright © 2011 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.)

Most sinus infections are viral, and only a small proportion develops a secondary bacterial infection. Rhinoviruses, influenza viruses, and parainfluenza viruses are the most common causes of sinusitis. The most common bacteria isolated from pediatric and adult patients with community-acquired acute purulent sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic bacteria (Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp.) are the main isolates in chronic sinusitis. Pseudomonas aeruginosa and other aerobic and facultative gram-negative rods are commonly isolated from patients with nosocomial sinusitis, the immunocompromised host, those with HIV infection, and in cystic fibrosis. Fungi and Pseudomonas aeruginosa are the most common isolates in neutropenic patients. The microbiology of sinusitis is influenced by the previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens.

Aim: The aim of this study was to assess the validity of Narhinel method in the prevention of recurrences of viral rhinitis and of any associated sequelae, in particular acute otitis of the middle ear (AOM) and acute rhinosinusitis (AR)., Methods: This was a prospective observational study, in children aged from two months to two years, observed for five months during the cold season and carried out by family pediatricians (FIMP association) in Friuli Venezia Giulia, Italy. The study enrolled 435 patients. The observed population consisted of two groups: the first one of 238 children treated with Narhinel method and the second one of 197 patients treated only with the physiological saline solution. In compliance with the guidelines of an observational trial, the children were prescribed the therapeutic treatments used as a routine. The patients were recruited for the trial after the responsible parent had signed the informed consent form. The study protocol had been approved by the Ethics Committee of the area of Pordenone. In order to be recruited, patients had to comply with the following criteria: symptoms suggestive of the common cold; age > or =2 months < or =2 years; male and female. Patients presenting one or more of the following characteristics were not included: systemic diseases; congenital nasal obstruction (choanal atresia); infections of the upper and lower respiratory tracts other than common cold; systemic and/or topical use of antibiotics and/or corticosteroids at the moment of recruitment. During the five months of the observation period, all the therapies that the investigators had decided it was necessary to administer had been included and recorded in the CRF. Patients evaluations were carried out for five months. The clinical assessment was performed at baseline (B), in the first week (Fw) and monthly and described as M1 to 5; several clinical parameters were analyzed (anterior and posterior rhinorrhoea, oral respiration, noisy nasal respiration, and nasally transmitted thoracic sounds) and measured by the pediatrician at all examinations from B to M5. Other parameters were derived from the parents' daily observations, recorded in a diary and made note of the quality of sleep, diet and respiration, and the use of any drug during any relapse of acute rhinitis (common cold episode). Recurrence of AOM and AR was assessed by the pediatrician at M1-2-3-4-5. Safety of use was determined using the Italian Health Ministry incident/near incident report sheets for Medical Device and based on diaries where the parents took note of any events which occurred during the observation period. Parental satisfaction and compliance were assessed through a questionnaire given to the parents at the end of the last visit (M5)., Results: In the Narhinel group, the mean age was inferior (statistically significant): 8.9 compared to 11.4 months in the physiological saline solution group. The frequency of recurrences from viral rhinitis was very similar in the two groups and a decrease (statistical significant) was observed from M3 through M5 in both groups. Rhinorrhea, oral breathing, and other upper respiratory symptoms, improved in the two groups even if in the Narhinel one the improvement was more prominent during the first two months of observation. There was no difference in the frequency of AR between the groups: at M4 and M5, there was a statistically significant decrease in the frequency of episodes. The frequency of AOM varied in the two groups considering a comparison intra-groups: at M5 the decrease of episodes was statistically significant in the Narhinel group. In Narhinel group, AR and acute AOM seem to be more markedly controlled (frequency) especially for AOM. The frequency of adverse events (AEs) did not vary in the two groups: in the Narhinel one there was a difference (not statistically significant and not clinically relevant) in the number of patients with AEs, especially crying and nasal bleeding. One serious AE was reported in the physiological saline solution group. A 14-month-old child developed laryngospasm which recovered completely after hospital treatment with adrenaline. This event was not related to treatment with saline solution and causality was assessed as "unlikely" by the investigator. In the Narhinel group, one serious event of moderate convulsion febrile in a male patient (age of 0.9) was reported. The causality relationship was assessed by the investigator as improbable. Parents' satisfaction was higher (statistically significant) in the Narhinel group compared to the physiological saline solution alone group., Conclusion: In acute rhinites (common cold) both medical devices are effective nevertheless Narhinel method is valid and shows better results in AOM and AR. Moreover Narhinel method was also more appreciated by parents than physiological saline solution. According to authors' experience, the Narhinel method is safe and its performance is valid in the prevention of AOM and AR in children.

At present, many authors accept the many-factor theory of development of polypous rhinosinusitis associated with bronchial asthma according to which this condition should be regarded as an inflammatory syndrome in subjects predisposed to a specific tissue reaction. Inflammation induced by an infection is accompanied by the release of protease-inhibiting enzymes that turn inflammation into a chronic process thereby contributing to tissue disintegration, remodeling of mucous membranes, and development of polyps.

Conclusion: The results of the present study indicate the existence of natural immunity mechanisms via which viruses are eliminated from nasal and paranasal sinus mucosa., Objectives: Acute sinusitis and acute aggravation of chronic sinusitis are often caused by bacteria, which are secondary to viral infection of the nose. Antiviral molecules are considered to be expressed and protect the host after viral infection. We investigated the expression of antiviral molecules after viral infection of the nose., Materials and Methods: We assessed the expression of antiviral molecules, defensin and interferon mRNA, by the real-time polymerase chain reaction (PCR) technique after stimulating cultured nasal polyp cells with polyinosine-polycytidylic acid (poly(I:C)), which is an analog of double-stranded (ds) RNA., Results: The expression of beta-defensin mRNA significantly increased after the stimulation. On the other hand, expression of both interferon-alpha mRNA and interferon-beta mRNA was recognized, but only the expression of interferon-beta mRNA increased after the stimulation.

Conclusion: The significant up-regulation of matrix metalloproteinase (MMP)-9 mRNA, which is not modulated by tissue inhibitor of metalloproteinase (TIMP)-1, is an additional source of increased proteolytic activity in virus-infected upper airways that might contribute to the exacerbation of chronic rhinosinusitis with nasal polyps., Objectives: Chronic rhinosinusitis is often exacerbated by viral infection. We hypothesized that a disruption of the mechanisms that regulate the activity of MMPs during viral infection is one possible mechanism responsible for the exacerbation. In the present study we attempted to achieve a better understanding of MMP expression in nasal epithelial cells after viral infection., Materials and Methods: Human nasal epithelial cells were isolated from nasal polyp specimens obtained during endoscopic endonasal surgery in chronic rhinosinusitis patients. We investigated the expression of MMP-2, MMP-9, and TIMP-1 mRNA in primary human nasal polyp epithelial cells after dsRNA stimulation., Results: Among the genes whose expression was evaluated, only expression of MMP-9 mRNA increased significantly after dsRNA stimulation.

Background: T-cell infiltration of the epithelium is a key feature of chronic rhinosinusitis and asthma. Viral infections are an important cause of disease exacerbations. We have found virus-induced expression of T cell-interacting ligands, B7 homolog costimulatory molecules, on airway epithelium., Objective: We tested the ability of human rhinovirus (HRV) 16 and double-stranded RNA (dsRNA) to alter the expression of B7 homologs on human airway epithelial cells., Methods: BEAS2B and primary human airway epithelial cells were exposed in vitro to dsRNA (25 microg/mL) or HRV-16, and then expression of cell-surface protein and mRNA for B7 homologs was assessed by means of flow cytometry and real-time PCR, respectively. Additionally, human subjects were infected with HRV-16 in vivo, and mRNA for B7 homologs was assessed by means of real-time PCR in fresh nasal epithelial cell scrapings obtained before and daily up to 4 days after infection., Results: dsRNA exposure of BEAS2B and human primary bronchial epithelial cells resulted in increased levels of cell-surface and mRNA expression of B7-H1 and B7-DC but not B7-H2 or B7-H3. Exposure of primary cells to HRV-16 resulted in induction of cell-surface expression of B7-H1 and B7-DC. Pretreatment with fluticasone propionate failed to suppress the induction of B7-H1 and B7-DC. Nasal scrapings taken at the time of peak symptom scores (3 days) after infection of 6 human subjects with HRV-16 displayed selective induction of levels of mRNA for B7-H1 and B7-DC., Conclusion: These data show that HRV-16 infection or exposure to dsRNA induces epithelial B7-H1 and B7-DC.

Objective: To investigate the difference in susceptibility to rhinovirus (RV) infection and RV-induced inflammatory response between the nasal mucosae from patients with chronic rhinosinusitis with nasal polyps (CRS/NP) and subjects without CRS/NP (hereinafter, normal subjects)., Design: In vitro study., Setting: Tertiary care rhinology clinic., Patients: We conducted RV infection experiments on the organ cultures of NPs and inferior turbinate mucosae from 16 patients with CRS/NP and sphenoid sinus and inferior turbinate mucosae from 19 patients who underwent transsphenoidal pituitary surgery., Main Outcome Measures: Successful RV-16 infection was determined by positive identification of RV on the surface fluid of organ culture using seminested reverse transcriptase-polymerase chain reaction. Effects of RV on interleukin 6 (IL-6) and IL-8 secretion were measured by enzyme-linked immunosorbent assay., Results: The successful RV infection was achievable in 9 of 16 NP samples (56.3%) and 9 of 16 turbinate samples (56.3%) from patients with CRS/NP compared with 11 of 19 sphenoid sinus samples (57.9%) and 15 of 19 turbinate samples (78.9%) from normal subjects. The RV infection increased IL-6 and IL-8 secretion 236% and 173%, respectively, in NP samples, and 218% and 178%, respectively, in turbinate samples from patients with CRS/NP; compared with 231% and 145%, respectively, in sphenoid mucosa samples, and 181% and 148%, respectively, in turbinate samples from normal subjects. However, there were no statistical differences among the 4 groups., Conclusion: These in vitro findings suggest that subjects with CRS/NP mucosa might not be more susceptible to RV infection, and did not secrete more cytokines in response to rhinovirus infection, than those with normal mucosa.

Swollen head syndrome (SHS) associated with avian metapneumovirus (aMPV) subtype A or subtype B in broilers and broiler breeders has been reported worldwide. Data about pathogenesis of aMPV subtypes A and B in broilers are scarce. It has been difficult to reproduce swollen sinuses in chickens with aMPV under experimental conditions. In the field, SHS in broilers is suspected to be induced by combined infections with different respiratory pathogens. The objectives of the present study were to compare the pathogenesis of subtypes A and B aMPV in commercial broilers and to investigate the reproducibility of clinical disease. In two repeat experiments, commercial broilers free of aMPV maternal antibodies were inoculated with aMPV subtypes A and B of turkey origin. The clinical signs such as depression, coughing, nasal exudates, and frothy eyes appeared at 4 days post inoculation, followed by swelling of periorbital sinuses at 5 days post inoculation. Higher numbers of broilers showed clinical signs in subtype-B-inoculated compared with subtype-A-inoculated groups. Seroconversion to aMPV was detectable from 10 to 11 days post inoculation. The appearance of serum aMPV enzyme-linked immunosorbent assay antibodies and the clearance of the aMPV genome coincided. Subtype B aMPV showed a broader tissue distribution and longer persistence than subtype A. Histopathological changes were observed in the respiratory tract tissues of aMPV-inoculated broilers, and also in paraocular glands, such as the Harderian and lachrymal glands. Overall, our study shows that representative strains of both aMPV turkey isolates induced lesions in the respiratory tract, accompanied by swelling of infraorbital sinuses, indicating the role of aMPV as a primary pathogen for broilers.