Chronic Sinonasal Inflammation Research Articles

The intra-host evolutionary landscape and pathoadaptation of persistent Staphylococcus aureus in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common chronic sinonasal mucosal inflammation associated with Staphylococcus aureus biofilm and relapsing infections. This study aimed to determine rates of S. aureus persistence and pathoadaptation in CRS patients by investigating the genomic relatedness and antibiotic resistance/tolerance in longitudinally collected S. aureus clinical isolates. A total of 68 S. aureus paired isolates (34 pairs) were sourced from 34 CRS patients at least 6 months apart. Isolates were grown into 48 h biofilms and tested for tolerance to antibiotics. A hybrid sequencing strategy was used to obtain high-quality reference-grade assemblies of all isolates. Single nucleotide variants (SNV) divergence in the core genome and sequence type clustering were used to analyse the relatedness of the isolate pairs. Single nucleotide and structural genome variations, plasmid similarity, and plasmid copy numbers between pairs were examined. Our analysis revealed that 41 % (14/34 pairs) of S. aureus isolates were persistent, while 59 % (20/34 pairs) were non-persistent. Persistent isolates showed episode-specific mutational changes over time with a bias towards events in genes involved in adhesion to the host and mobile genetic elements such as plasmids, prophages, and insertion sequences. Furthermore, a significant increase in the copy number of conserved plasmids of persistent strains was observed. This was accompanied by a significant increase in biofilm tolerance against all tested antibiotics, which was linked to a significant increase in biofilm biomass over time, indicating a potential biofilm pathoadaptive process in persistent isolates. In conclusion, our study provides important insights into the mutational changes during S. aureus persistence in CRS patients highlighting potential pathoadaptive mechanisms in S. aureus persistent isolates culminating in increased biofilm biomass.

The Role of Human Papilloma Virus in the Pathogenesis of Sinonasal Inverted Papilloma; A Metanalytical Study

Abstract Background Sinonasal inverted papilloma (SNIP) is a benign and relatively rare tumor of the nasal cavity and paranasal sinuses, most commonly originates from the lateral nasal wall or maxillary sinus from the schneiderian sinonasal epithelium. There is a male predominance with a male-to-female ratio of 3.4:1. Sinonasal Squamous Cell Carcinoma (SCC) associated with IP has an incidence of approx. 0.38 cases/million persons/year. Patients with carcinoma in IP are older than those IP patients without carcinoma. Some authors assume an influence of Human Papilloma Virus (HPV) subtyping. Transcripts of HPV DNA were found in malignant IP. Objective To perform a meta-analytical study to determine the relationship between human papilloma virus and the occurrence of sinonasal inverted papilloma. Patients and Methods The review will be restricted to RCTs, clinical trials, and comparative studies, either prospective or retrospective, which studied the outcome of Negative HPV group versus Positive HPV group of patients. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Data Extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, and adequate information and defined assessment measures. Results In our study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). HPV positive cases among malignant SNIP patients was (51.02%) (25/49). Conclusion In this meta-analytical study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). Though the etiology of SNIP remains controversial, the studies reviewed in this study indicate a role for HPV infection. Further studies in the future regarding the impact of other risk factors on the occurrence of SNIP would be of value, these factors include angiogenic factors, environmental factors, genetic, viral and chronic sinonasal inflammation.

Expert Opinion on Biological Treatment of Chronic Rhinosinusitis with Nasal Polyps in the Gulf Region.

Chronic rhinosinusitis (CRS) is defined as the inflammation of nose and paranasal sinuses, affecting the patients’ quality of life and productivity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a principal clinical entity confirmed by the existence of chronic sinonasal inflammation and is characterized by anterior or posterior rhinorrhea, nasal congestion, hyposmia and/or facial pressure or facial pain. Several epidemiologic studies have revealed wide variations in the incidence of CRS among regions globally ranging from 4.6% to 12%. The Gulf countries are also witnessing an unprecedented burden of CRSwNP. According to the current clinical guidelines, glucocorticosteroids and antibiotics are the principal pharmacotherapeutic approaches. Endoscopic sinus surgery is recommended for those who have failed maximal pharmacotherapy. Recently, biologics are considered as an alternative best approach due to the complications associated with medical therapy and surgery. However, precise data on the clinical position of biologic agents in the management of CRSwNP in the Gulf region is not available. The present review article addresses the current diagnostic and management approaches for CRSwNP and also emphasizes the role of emerging biologics in the current treatment strategies for CRSwNP in the Gulf region. Further, a consensus protocol was convened to rationalize the guideline recommendations, strategize the best practices with biologics, and develop clinical practice guidelines for all primary-care specialists in the Gulf region. The consensus-based report will be a useful reference tool for primary-care physicians in primary-healthcare settings, regarding the appropriate time for the initiation of biological treatment in the Gulf region.

Effects of Nasal and Paranasal Sinus Variations on Chronic Otitis Media Development in Pediatric Patients.

Chronic otitis media is an inflammatory disease of the middle ear. The airflow in the nasal passage affects the development of mastoid air cells through the eustachian tube.Nasal and paranasal pathologies and their anatomical variations cause chronic sinonasal inflammation and affect the middle ear mucosa. This study aims to reveal whether the nasal and paranasal sinus variations in pediatric patients are a factor in developing chronic otitis media. Eighty patients, with unilateral chronic otitis media, who were admitted to the otorhinolaryngology clinic between May 2015 and July 2019, were included in this retrospective study. The control group (Group 2) consisted of a total of 51 patients. None of the patients in Group 2 had otorrhea history and no signs of chronic otitis in their otoscopic examination, middle ear pathologies. The patient's anatomical variations of the nasal cavity and sinuses were evaluated with CT by a radiologist Results: Nasal septum deviation was found to be 53% in children with chronic otitis media. It was found 31.4% in the control group. Since the P value was found to be .04, this rate was considered as significant. Inferior concha hypertrophy was found to be 17.6% in the control group and 38.8% in the group with chronic otitis media, and this rate was considered significant since the P value was .035 Conclusion: We detected that septum deviation and inferior concha hypertrophy increased chronic otitis media formation in children. All these studies show that cases causing nasal obstruction, such as septum deviation, have a negative effect on middle ear pressure and increase the rate of ear diseases.

Endogenous cannabinoids may regulate chronic inflammation in aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyposis, adult-onset asthma and non-IgE mediated reactions to aspirin and other cyclooxygenase-1 (COX-1) inhibitors. Patients with AERD are dependent on COX-1 activity to maintain production of prostaglandin (PG) species, such as PGE2, which maintain physiologic levels of inflammation and limit the production of pro-inflammatory cysteinyl leukotrienes. The endogenous cannabinoid system is a family of immunomodulatory lipids and their innate g-protein coupled receptors that are closely related to arachidonic acid and may modulate inflammation via several pathways, including the direct production of metabolically active prostaglandin glycerol-esters. A recent pilot study has identified the significant up-regulation of the peripherally expressed, type-2 cannabinoid receptor (CB2) in AERD nasal polyps versus control tissues from patients with either allergic fungal rhinosinusitis or no history of chronic sinonasal inflammation. These early findings suggest the involvement of increased endogenous cannabinoid activity in prostaglandin deficient states such as AERD. Future study is needed to explore the significance of these findings, with specific investigation of the impact of CB2 activation on markers of airway inflammation, as well as the potential to measure CB2 expression as a screening biomarker for the evaluation of unrecognized disease.

Nasal polyps in eosinophilic granulomatosis with polyangiitis: Structured histopathology and CD105 expression.

Distinguishing the prodromal nasal polyposis of eosinophilic granulomatosis with polyangiitis (EGPA) from chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenge for rhinologists and rheumatologists. It has recently been reported that angiogenesis and CD105 expressed on vascular endothelial cells could have a role in the pathogenesis and development of nasal polyps. This exploratory study examined the structured histopathology of nasal polyps in patients with EGPA and CRSwNP, comparing CD105 expression in their nasal tissue with that of a control group with no chronic sinonasal inflammation. A structured histopathological study was performed on surgical specimens of nasal tissue from 32 adults (13 with EGPA, 14 with CRSwNP, 5 controls), considering CD105 as a marker to determine microvessel density (MVD). The mean eosinophil count was higher in EGPA patients with tissue inflammation (p=.002), and in CRSwNP patients with sub-epithelial edema (p=.009). Neutrophil infiltration was significantly associated with severe tissue inflammation in EGPA patients (p=.04), but with the absence of fibrosis in CRSwNP patients (p=.04). In the EGPA group, CD105-MVD correlated with tissue eosinophil count (p=.05). Mean CD105-MVD was significantly higher in EGPA patients with mucosal ulceration (p=.004). In the CRSwNP group, a CD105-MVD correlated positively and significantly with tissue eosinophil count (p=.01). Alongside the known abundance of eosinophils, other cells might contribute to inflammatory processes. Neutrophils may amplify inflammation, eosinophil recruitment and tissue damage. CD105 expression in CRSwNP and EGPA nasal polyps supports the hypothesized involvement of angiogenesis in the pathogenesis and development of nasal polyps.

Chronic Rhinosinusitis and Allergy: Increased Allergen Sensitization Versus Real Allergic Rhinitis Multimorbidity: a Systematic Review.

The objective of this article is to provide a recent update of the association between allergic inflammation and chronic rhinosinusitis. The systematic approach of this review article critically evaluates the literature published over the past few years and summarizes the specific pathophysiologic pathway of chronic sinonasal inflammation that has been postulated. From a systematic search of the Ovid Medline and Embase, 11 studies were included in a qualitative analysis of the association between systemic allergy and chronic rhinosinusitis (CRS). Of the 11 studies, four showed an association, three were inconclusive, and four did not show any association. From the systematic search, 50 studies suggested four possible pathophysiologic pathways that may explain the association of allergic inflammation and CRS, namely, (1) staphylococcal enterotoxin, (2) the innate immunity pathway, (3) mast cell-associated inflammation, and (4) dysbiosis of microbiota. The association of systematic allergy and CRS remains inconclusive. The recent advances in the study of the pathophysiologic pathway of CRS may lead to the possibility of a targeted treatment option for CRS.

Predictors of long-term success and failure in primary and revision endoscopic dacryocystorhinostomy.

Although endoscopic dacryocystorhinostomy (endo-DCR) is a common treatment of nasolacrimal duct obstruction, little is known about the determinants of surgical success and failure. The purpose of this study was to identify patient- and technique-specific factors that may influence surgical outcomes of primary and revision endo-DCR. A retrospective review was conducted of 596 patients who underwent endo-DCR over a 30-year period (1989-2018). Patients' demographics and surgical techniques were assessed. Among the cohort of patients (n = 478) who underwent primary endo-DCR, 10% (n = 48) required revision surgery. Patients who failed primary DCR tended to be younger (p = 0.015) and were less likely to have chronic sinonasal inflammation on histopathology (p = 0.047) than the successful surgery group. After adjusting for patient demographics and comorbidities, the occurrence of a postoperative complication was significantly associated with primary DCR failure (odds ratio [OR], 2.2; p = 0.032). Among the cohort of patients (n = 118) who underwent revision endo-DCR, 8.5% (n = 10) required additional revision surgery. Patients who failed revision DCR tended to be younger (p = 0.022), more likely to have had intraoperative laser usage (p = 0.031), and more likely to have had an intraoperative complication (p = 0.013) than the successful revision surgery group. Endo-DCR failure was not associated with smoking status, middle turbinate resection, or intraoperative visualization of the internal common punctum (p > 0.05). An understanding of factors associated with primary and revision endo-DCR failure can help to inform preoperative counseling, intraoperative surgical technique, and postoperative care in the treatment of patients with nasolacrimal duct obstruction.

Understanding and clinical relevance of chronic rhinosinusitis endotypes

Chronic rhinosinusitis (CRS) is the downstream manifestation of heterogeneous pathophysiologic mechanisms leading to chronic sinonasal inflammation. Traditional grouping of patients by symptoms or clinical findings/phenotypes is being replaced by classification of CRS patients based on the underlying pathophysiologic mechanisms: endotypes. To provide an up-to-date review on the current knowledge of CRS endotypes with a focus on how the pathophysiologic mechanisms defined by each endotype may be targeted therapeutically. Special emphasis is placed on the clinical relevance of the material and how it may inform the current practice of otolaryngologists. A systematic review of contemporary literature review focusing on the latest studies examining the role of endotypes in the management and treatment of CRS. A MEDLINE and PubMed Central search were undertaken to perform this review using the keywords "Endotype" and "Sinusitis." Articles containing the keywords, as well as the references of those articles, were then examined for relevance. The endotypes for CRS are often defined based on the balance of T-helper cell patterns of inflammation and can be grouped into Th2 and non-Th2 inflammation. These groups have shown a variable response to medical and surgical therapy, demonstrating that existing mainstream treatments can be tailored to patients with specific endotypes. The inflammatory mediators of Th2 inflammation, IL-4, IL-5 and IL-13 as well as IgE, are targeted by available biologic drugs that can be used for treatment of refractory disease. Increased understanding of CRS endotypes has led to the identification of biomarkers that define these endotypes and act as targets for potential therapeutics. Increasing knowledge about characteristics associated with these endotypes and their responses to treatments, including both established mainstream CRS treatments and novel biologic medications, has allowed incorporation of CRS endotypes into the current clinical decision-making. Treatment of CRS patients based on consideration of their endotypes is therefore not only presently possible but may improve clinical outcomes of those patients as well.

Classification of chronic rhinosinusitis with nasal polyps based on eosinophilic inflammation

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disorder characterized by chronic sinonasal mucosal inflammation. CRSwNP can be subdivided into two types based on eosinophilic inflammation: eosinophilic CRSwNP (Eos CRSwNP) and non-eosinophilic CRSwNP (Non-Eos CRSwNP). Eos CRSwNP and Non-Eos CRSwNP demonstrate distinct clinical manifestations, treatment outcomes, and cellular and immunopathologic characteristics. However, currently, there is no unified and generally accepted standard to define the Eos CRSwNP. The aim of this review is to compare the advantages and disadvantages of current methods used to classify Eos CRSwNP, in order to lay foundation for further study.

Tissue and Exosomal Serine Protease Inhibitors Are Significantly Overexpressed in Chronic Rhinosinusitis With Nasal Polyps.

Background The fibrinolysis pathway has been previously implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Objective The purpose of this study was (1) to explore protein derangements of selected protease inhibitors of the serpin superfamily in CRSwNP and (2) to correlate the protease inhibitor derangements of the fibrinolysis pathway in tissue with exosomal samples to evaluate the potential of an exosomal noninvasive “liquid biopsy” for CRSwNP. Methods Institutional review board approved study in which matched tissue and mucus exosomal proteins (SerpinB2, SerpinF2, SerpinG1, and SerpinE1) were compared between control and CRSwNP patients using Western Blot analysis (n = 6/group) and immunohistochemistry (IHC). Transcriptome analysis (n = 10/group) on the same proteins was performed using whole transcriptome sequencing. Semiquantitative analysis of the Western Blots was performed using the Whitney–Mann U test. Results The transcriptomic data set showed multiple differentially expressed genes including SerpinB2 (fold changes [FC] 7.38), SerpinE1 (FC 1.42), SerpinF2 (FC 2.03), and SerpinG1 (FC 0.72). Western Blot and IHC analysis showed an overexpression of the Serpin protease inhibitors in tissue (SerpinB2, P < .01; SerpinE1, P < .01; SerpinF2, P < .01; and SerpinG1, P < .01) indicating a downregulation of the fibrinolysis cascade. The mucus exosomal serpin proteins exhibited similar findings. Conclusion Our analysis supported that protease inhibitors of the fibrinolysis pathway, especially SerpinB2, SerpinF2, and SerpinG1, are highly deranged in patients with CRSwNP. These findings suggest a downregulation of the fibrinolysis pathway via proteolytic cascade imbalance leading to excessive polyp fibrin deposition. Our data further supported our hypothesis that exosomal proteomic analyses may be used as noninvasive “liquid biopsy” for CRSwNP and a novel method to study chronic sinonasal inflammation.

Exosomes and chronic rhinosinusitis.

The objective of this manuscripts to review current knowledge regarding exosomes as they relate to the physiology and pathology of the human nose as well as their role as biomarkers of chronic rhinosinusitis with nasal polyps (CRSwNP).Exosomes are 30–150 nm membrane-bound vesicles secreted by virtually all cell types. Exosomes contribute to the rapid inter-epithelial transfer of proteins and mediate innate immunosurveillance and defense mechanisms in the human nasal cavity. Exosomes also protect their cell specific cargo from degradation by nucleases and proteases and mirrorCRS related tissue protein perturbations more effectively than whole mucus. Thus, exosomal isolation and analysis may be used to non-invasively monitor disease severity, prognosis, and potentially even treatment response.Recent studies of exosomes in CRS suggest they can be used to study the immunopathology of chronic sinonasal inflammation. Furthermore, their relative accessibility suggests that exosomal proteomescan be used as non-invasive, serial, and quantitative biosignatures for rhinosinusitis that can be sampled in clinic in order to predict disease severity, prognosis, and treatment response. Exosomal research has also led to important revelations regarding their physiologic function as they seem to play an important role in innate immunosurveillance and defense. However, exosomal research is still nascent and cost-effectiveness as well as feasibility of implementation in the routine workup for CRS have to be further explored.

Highly multiplexed proteomic analysis reveals significant tissue and exosomal coagulation pathway derangement in chronic rhinosinusitis with nasal polyps.

The coagulation pathway has been previously implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) through analysis of individual proteins within the cascade. The purpose of this study was to: (1) apply a large-scale proteomic approach to confirm these previous findings; and (2) correlate the protein aberrations between tissue and exosomes to establish exosomal proteomics as a method to probe the pathophysiology of CRSwNP. This investigation was an internal review board-approved study in which matched tissue and mucus exosomal proteomes were compared between control and CRSwNP (n = 10/group) using an aptamer-based proteomic array and confirmed using whole transcriptome sequencing. Protein expression and the correlation between samples were calculated using Student's t-test and Benjamini-Hochberg procedures followed by the application of Ingenuity Pathway and MetaCore™ bioinformatics analyses. Among all protein pathways, the coagulation cascade was the most significantly associated with CRSwNP (p = 2.85e-8). Among the 13 significantly altered coagulation-related tissue proteins, fibronectin and fibrinogen gamma chains were the most overexpressed in CRSwNP relative to control (fold change [FC], 2.59; p = 0.006; and FC, 2.38; p < 0.001, respectively), whereas von Willebrand factor was the most underexpressed (FC, -3.06; p < 0.001). The exosomal fibrinolysis and coagulation pathway proteomes exhibited strong inverse and significant correlations with the tissue findings (r = -0.86; p = 0.013; and r = -0.79; p = 0.007, respectively). Our proteomic analysis confirmed that the coagulation pathway is highly significantly deranged within nasal polyp tissue. The correlation between tissue- and mucus-derived exosomal fibrinolysis and coagulation protein alterations were strong, inverse, and highly significant. This lends further support to the emerging concept of exosomal proteomic analysis as a method to study chronic sinonasal inflammation.

Rhinogenic Contact Point Headache: Surgical Treatment Versus Medical Treatment

Rhinogenic contact point headache (RCPH) is a headache syndrome secondary to mucosal contact points in the sinonasal cavities, in the absence of inflammatory signs, hyperplastic mucosa, purulent discharge, sinonasal polyps, or masses. It may result from pressure on the nasal mucosa due to anatomic variations among which the septal deviation, septal spur, and concha bullosa, are the most commonly observed. In recent years, RCPH has remained a subject of controversy regarding both its pathogenesis and treatment. This study aimed to investigate the effect of surgical and medical treatment of pain relief in patients with RCPH, evaluating the intensity, duration, and frequency of headaches, and the impact of different treatments on quality of life. Ninety-four patients with headache, no symptoms or signs of acute and chronic sinonasal inflammation and who present with intranasal mucosal contact points positive to the lidocaine test were randomized into 2 equal groups and given medical or surgical treatment. The authors used visual analog scale, number of hours, and days with pain to characterize the headache and Migraine Disability Assessment score (MIDAS) to assess the migraine disability score before and 3 to 6 months after treatment. After treatment the severity, duration, and frequency of the headache decreased significantly (P < 0.001, P < 0.001, and P = 0.031, respectively) as well as the MIDAS in the surgical group compared with medical group. Our results suggest that surgical removal of mucosal contact points is more effective than local medical treatment improving the therapeutic outcomes in patients with contact point headache.

Chronic sinonasal tract inflammation as a precursor to nasopharyngeal carcinoma and sinonasal malignancy in the United States.

Chronic inflammatory states have been linked to the development of malignancy. Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) have been associated with nasopharyngeal carcinoma (NPC) in population-based studies in Asia. A similar association with NPC and paranasal sinus malignancy (PSM) has not been defined in a North American population. Our purpose was to investigate the impact of CRS and AR on the risk of NPC and PSM. The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was queried as a case-control study of adults ≥65 years of age. The study cohort included 2009 patients diagnosed with NPC and/or PSM diagnosed between 2003 and 2011, and 2009 propensity-score-matched controls selected from a 5% random sample of Medicare beneficiaries without cancer. CRS and AR were examined as exposures. Multivariable unconditional logistic regression was employed. Overall, NPC and PSM patients were more likely to have previous CRS diagnosis than the controls (9.2% vs 3.0% and 11.1% vs 2.7%, respectively). CRS was associated with greater odds of developing NPC (odds ratio [OR], 3.51; 95% confidence interval [CI], 2.12-5.79) and PSM (OR, 5.30; 95% CI, 3.55-7.92). AR was associated with greater odds of developing NPC (OR, 4.23; 95% CI, 2.96 to 6.06) and PSM (OR, 3.35; 95% CI, 2.49-4.49). The number needed to harm in the exposed population was 311. CRS and AR are associated with the presence of NPC and PSM in the elderly population of United States. This epidemiologic association will need to be examined for causative pathophysiologic mechanisms and utility in clinical diagnosis.

Chronic Rhinosinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an important clinical entity diagnosed by the presence of both subjective and objective evidence of chronic sinonasal inflammation. Symptoms include anterior or posterior rhinorrhea, nasal congestion, hyposmia, and/or facial pressure or pain that last for a duration of more than 12 weeks. Nasal polyps are inflammatory lesions that project into the nasal airway, are typically bilateral, and originate from the ethmoid sinus. Males are more likely to be affected than females, but no specific genetic or environmental factors have been strongly linked to the development of this disorder to date. CRSwNP is frequently associated with asthma and allergic rhinitis, but the cellular and molecular mechanisms that contribute to the clinical symptoms are not fully understood. Defects in the sinonasal epithelial cell barrier, increased exposure to pathogenic and colonized bacteria, and dysregulation of the host immune system are all thought to play prominent roles in disease pathogenesis. Additional studies are needed to further explore the clinical and pathophysiological features of CRSwNP so that biomarkers can be identified and novel advances can be made to improve the treatment and management of this disease.

Innate immunity and chronic rhinosinusitis: What we have learned from animal models.

ObjectiveChronic rhinosinusitis (CRS) is a heterogeneous and multifactorial disease characterized by dysregulated inflammation. Abnormalities in innate immune function, including sinonasal epithelial cell barrier function, mucociliary clearance, response to pathogen‐associated molecular patterns (PAMPs) via pattern recognition receptors, and the contribution of innate immune cells, will be highlighted in this review.Data SourcesPubMed literature review.MethodsA review of the literature was conducted to determine what we have learned from animal models in relation to innate immunity and chronic rhinosinusitis.ResultsDysregulation of innate immune mechanisms, including sinonasal barrier function; mucociliary clearance; PAMPs; and innate immune cells such as eosinophils, mast cells, and innate lymphoid cells, may contribute to CRS pathogenesis. Sinonasal inflammation has been studied using mouse, rat, rabbit, pig, and sheep explant or in vivo models. Study using these models has allowed for analysis of experimental therapeutics and furthered our understanding of the aforementioned aspects of the innate immune mechanism as it relates to sinonasal inflammation. These include augmenting mucociliary clearance through activation of the cystic fibrosis transmembrane conductance regulator and study of drug toxicity on ciliary beat frequency. Knockout models of Toll‐like receptors (TLR) have demonstrated the critical role that these pattern recognition receptors play in allergic inflammation because loss of TLR2 and TLR4 leads to decreased lower airway inflammation. Mast cell deficient mice are less susceptible to ovalbumin‐induced sinonasal inflammation.ConclusionAnimal models have shed light as to the potential contribution of dysregulated innate immunity in chronic sinonasal inflammation.

Nasal lavage levels of granulocyte‐macrophage colony‐stimulating factor and chronic nasal hypereosinophilia

The aim of the present study was to measure levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in nasal lavage of patients affected by chronic eosinophilic sinonasal inflammation to clarify the relationship with eosinophilic tissue infiltration and clinical features. Between November 2012 and June 2013, we selected 70 patients with chronic eosinophilic inflammation (average age 41.8 years) who were classified into the following groups: persistent allergic rhinitis (group 1), noninfectious non-allergic rhinitis with eosinophilia syndrome (group 2) and chronic rhinosinusitis with polyps (group 3). Finally, we enrolled 20 healthy subjects as controls (group 4). All patients underwent symptoms score questionnaire based on a visual analogue scale, nasal endoscopy and/or computed tomography (CT) scan, and allergy testing. Nasal cytology by scraping of the mucosa and GM-CSF assays in nasal lavage were performed in all subjects. Detectable levels of GM-CSF were found in 34 of 70 (48.57%) patients, with an average concentration of 2.67± 0.8 pg/mL, whereas in controls only 1 of 20 individuals showed detectable GM-CSF levels. Eosinophil infiltration was significantly higher in patients with detectable GM-CSF compared to those with undetectable levels (49.4% vs 39.2%, respectively; p < 0.05). Furthermore, significant weakly-moderate correlation was found between GM-CSF levels and percentage of eosinophil infiltration in tissue (p < 0.05). Correlation between symptom scores and GM-CSF levels was significant only in group 2, which showed higher average concentrations of GM-CSF compared to groups 1 and 3 (2.9 pg/mL vs 1.6 pg/mL and 1.8 pg/mL, respectively; p < 0.05). Our data confirm that GM-CSF is more frequently detectable in nasal lavages of patients affected by chronic sinonasal eosinophilic inflammation than in controls. Statistical analyses revealed a significant weakly-moderate correlation between GM-CSF levels in nasal lavage of all patients and percentage of eosinophil infiltration of nasal mucosa.

Nasal fluid release of eotaxin-3 and eotaxin-2 in persistent sinonasal eosinophilic inflammation.

The aim of the present study was to measure eotaxin-3 (CCL26) and eotaxin-2 (CCL24) in nasal lavage fluid of patients with different forms of chronic sinonasal eosinophilic inflammation to evaluate their role in the pathophysiology of nasal hypereosinophilia. The study was an analytic cross-section study, level of evidence 3b. Patients (n = 80) with nasal hypereosinophilia were randomly recruited and grouped in the following categories: persistent allergic rhinitis (AR) (n = 25), nonallergic rhinitis with eosinophilia syndrome (NARES) (n = 30), and chronic rhinosinusitis with polyps (CRSwNP) (n = 25). Non-rhinitic volunteers (n = 20) were recruited as controls. CCL24 and CCL26 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) Quantikine Human Immunoassays (R&D Systems, Minneapolis, MN) in nasal lavage fluids. Differential cell counts were performed by microscopic cytological examination of nasal tissue scraped from the inferior turbinate. Mean CCL26 levels were significantly higher (p < 0.05) in AR and in NARES (132.0 pg/mL and 187.63 pg/mL, respectively) than in the control group (13.5 pg/mL); in patients with CRSwNP, CCL26 values were increased compared to controls even though the difference was not statistically significant (58.9 pg/mL vs 16.5 pg/mL). Mean CCL24 levels measured in AR, NARES, and CRSwNP were significantly increased (p < 0.05) compared to controls (96.7 pg/mL, 135.4 pg/mL, and 107.0 pg/mL, respectively, vs 32.2 pg/mL). Moreover, we observed a significant correlation between CCL24 and CCL26 levels, evaluating them intraindividually by Spearman's rank correlation test. Finally, a significant correlation was found between CCL24 and CCL26 levels and the percentage of eosinophilic infiltration of nasal mucosa. Our data suggest that CCL26 and CCL24 are likely involved in the pathogenesis of chronic nasal hypereosinophilia, with a complex cooperation and different involvement of the various members of eotaxin family. Further studies are necessary to better understand the actual physiopathologic mechanism, possible clinical relevance, and therapeutic implications.

Sinonasal symptoms in adults with ear disease.

The association between eustachian tube dysfunction and middle-ear effusion is well established. Studies have also demonstrated pathological changes affecting the middle-ear mucosa associated with chronic sinonasal inflammation. No previous studies have evaluated symptoms related to sinonasal inflammatory disease in different ear diseases. To assess the presence of sinonasal symptoms in ear diseases using the Dundee Rhinogram. Data were collected prospectively in the period February-October 2011. Sinonasal symptoms were graded using the Dundee Rhinogram. Student's t-test analyses were performed to identify any statistically significant associations. In total, 164 patients were assessed. There was a statistically significant association between sinonasal symptoms and mucosal middle-ear diseases (p < 0.005). The mean sinonasal symptoms score for mucosal middle-ear disease patients was 5.94 (range, 0-32). Assessment of sinonasal symptoms is paramount in patients presenting with an ear symptom; inflammatory sinonasal disease treatment may become necessary in the management of middle-ear mucosal disease for better patient outcome.