Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term.

Intranasal Application of Is Safe in Chronic Rhinosinusitis Patients With Previous Sinus Surgery.

Modulation of the dysbiotic gut microbiome with "healthy" bacteria via a stool transplant or supplementation is increasingly practiced, however this approach has not been explored in the nasal passages. We wished to verify whether ( bacteria could be safely applied via irrigation to the nasal and sinus passages in individuals with chronic rhinosinusitis (CRS) with previous undergone endoscopic sinus surgery, and whether this was accompanied by bacterial community flora modification. Prospective open-label pilot trial of safety and feasibility.

Azithromycin in high-risk, refractory chronic rhinosinusitus after endoscopic sinus surgery and corticosteroid irrigations: a double-blind, randomized, placebo-controlled trial.

Background: Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low-morbidity, long-term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low-dose, long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS).

An Evaluation of SPARC Protein as a Serum Biomarker of Chronic Rhinosinusitis.

Objective: Precision medicine initiatives for chronic rhinosinusitis (CRS) management suggest tailoring treatment to the patient's individual disease profile; however, serum biomarkers for evaluation of disease activity or predicting response to therapy are lacking in CRS. Epithelial-to-mesenchymal transition (EMT) has been described as a component of barrier dysfunction in CRS. SPARC (secreted protein acidic and rich in cysteine) is a marker of EMT that has previously been identified in sinus epithelium by gene expression profiling.

on Sinus Culture Is Associated With Recurrence of Chronic Rhinosinusitis After Endoscopic Sinus Surgery.

Identify whether identification of on conventional culture is a predictor of success or failure after ESS followed by budesonide nasal irrigations (BUD) in chronic rhinosinusitis (CRS) patients at high risk of recurrence. Prospective clinical trial including 116 patients from a tertiary care center at high-risk of disease recurrence following ESS+BUD. Blood samples, microbial swabs, and SNSS/SNOT-22 were taken on the day of surgery (Visit-1) and 4 months postoperatively (Visit-2).

Do Aging Factors Influence the Clinical Presentation and Management of Chronic Rhinosinusitis?

Objective/Hypothesis Chronic rhinosinusitis (CRS) is a complex inflammatory disease of the upper respiratory airways resulting from the dysregulation of immunity and epithelial defenses. More recently, the contribution of an altered nasal microbiome to the development of CRS has also been proposed. However, the impact of aging on the development of CRS has been long overlooked.

Topical probiotics as a therapeutic alternative for chronic rhinosinusitis: A preclinical proof of concept.

Introduction: Patients with chronic rhinosinusitis (CRS) have been shown to manifest a high inflammatory phenotype, with a sinus microbiome deficient in gram-positive bacteria. Gram-positive bacteria are capable of downregulating proinflammatory host responses via an interleukin (IL) 10 mediated response and may represent a potential therapeutic alternative for CRS. We wanted to (i) immunoprofile the IL-10 induction capacity of two gram-positive probiotic strains and (ii) verify the tolerance of these strains by the sinus epithelium.

Dietary modifications for refractory chronic rhinosinusitis? Manipulating diet for the modulation of inflammation.

Background: An endotype of chronic rhinosinusitis (CRS) refractory to medical and surgical management is characterized by persistent T-helper 1/T-helper 17 inflammation of the sinus mucosa, which potentially facilitates colonization with dysbiotic microbial flora. Dietary interventions that target reduction of systemic inflammation are increasingly recommended as adjuncts to ongoing medical therapy in chronic disorders with a strong inflammatory component, such as cardiac disease, diabetes, and metabolic syndrome. Inflammation-reducing dietary modifications may thus be of benefit in patients with refractory CRS (RCRS).

Gram-negative bacterial carriage in chronic rhinosinusitis with nasal polyposis is not associated with more severe inflammation.

Background: We have previously demonstrated that persistent symptoms following functional endoscopic sinus surgery for chronic rhinosinusitis (CRS) is associated with Gram-negative bacterial carriage. Mechanisms for this remain unknown. We wished to determine whether Gram-negative carriage in patients with CRS with nasal polyposis is associated with a more severe inflammatory phenomenon.

Clinical features of cytotoxic CD8+ T-lymphocyte deficiency in chronic rhinosinusitis patients: a demographic and functional study.

Background: Identification of Staphylococcus aureus intracellularly in chronic rhinosinusitis (CRS) suggests an underlying cellular immunodeficiency. Supporting this, we have previously reported low CD8+ (cytotoxic) T-lymphocyte levels in a subpopulation of CRS patients and identified polymorphisms in the CD8A gene associated with CRS. In order to better understand the role of low CD8+ in CRS, we wished to determine the phenotype for CRS/Low CD8+ in comparison to that of conventional CRS.

Active smoking status in chronic rhinosinusitis is associated with higher serum markers of inflammation and lower serum eosinophilia.

Background: Smoking negatively affects postoperative evolution in patients with chronic rhinosinusitis (CRS); however, the mechanism remains incompletely described. In the lung, smoking increases expression of proinflammatory genes and is associated with an elevation of inflammatory serum markers. Our objective is to determine the impact of smoking on these biomarkers in CRS.

A pooling-based genomewide association study identifies genetic variants associated with Staphylococcus aureus colonization in chronic rhinosinusitis patients.

Background: Staphylococcus aureus (S. aureus) has been implicated in the pathogenesis of chronic rhinosinusitis (CRS). However, host factors contributing to susceptibility to S.

Genetic variations in taste receptors are associated with chronic rhinosinusitis: a replication study.

Background: Recent evidence implicates polymorphisms of the bitter taste receptor TAS2R38 as defining characteristics in respiratory innate defense that may contribute to the complex genetic and environmental interactions predisposing to chronic rhinosinusitis (CRS). The purpose of this study was to (1) verify whether identified polymorphisms associated with respiratory infection in taste receptors replicate within our existing population of patients with CRS and (2) identify other taste receptors potentially associated with CRS.

Methods: Pooling-based genomewide association studies (pGWAS) were previously performed on 2 populations of Canadian CRS patients (genetics of chronic rhinosinusitis 1, refractory CRS [GCRS1]; and genetics of chronic rhinosinusitis 2, CRS with nasal polyposis [GCRS2]) using the Illumina HumanHap 1-M chip.

CD8A gene polymorphisms predict severity factors in chronic rhinosinusitis.

Background: A genetic basis to chronic rhinosinusitis (CRS) is postulated, but remains elusive. We have recently identified low levels of circulating CD8 lymphocytes as a frequent finding in difficult-to-treat or refractory CRS. In major histocompatibility complex 1 class 1 (MHC1) deficiency, low circulating levels of CD8 lymphocytes secondary to mutations in the cluster of differentiation 8a (CD8A), tapasin 1 (TAP1), tapasin 2 (TAP2), or tapasin binding-protein (TAPBP) genes lead to a clinical syndrome, which is associated with severe CRS.

Polymorphisms in RYBP and AOAH genes are associated with chronic rhinosinusitis in a Chinese population: a replication study.

Background: The development of CRS is believed to be the result of combined interactions between the genetic background of the affected subject and environmental factors.

Objectives: To replicate and extend our recent findings from genetic association studies in chronic rhinosinusitis (CRS) performed in a Canadian Caucasian population in a Chinese population.

Methods: In a case-control replication study, DNA samples were obtained from CRS with (n  = 306; CRSwNP) and without (n = 332; CRSsNP) nasal polyps, and controls (n = 315) in a Chinese population.

Expression of the extracellular matrix gene periostin is increased in chronic rhinosinusitis and decreases following successful endoscopic sinus surgery.

Background: The extracellular matrix (ECM) is a potentially important component of mucosal immunity. ECM dysregulation in chronic rhinosinusitis (CRS) is suggested by genomewide association studies identifying ECM genes as top candidates. Further support is afforded by the demonstration of increased expression of periostin (POSTN) in CRS biopsy samples compared to controls, and by reported roles in eosinophilic inflammation and steroid responsiveness.

Polymorphisms in the nitric oxide synthase 1 gene are associated with severe chronic rhinosinusitis.

Background: Nitric oxide (NO), is a biological messenger molecule and a component of innate immunity, with important roles in the regulation of inflammation and in defense against bacterial biofilms. Polymorphisms in genes regulating NO production have the potential for a role in the development of chronic rhinosinusitis (CRS). The purpose of this study was to determine whether polymorphisms in genes regulating NO synthesis are associated with CRS.

Genetics of rhinosinusitis.

Suggestion for a potential genetic basis to chronic rhinosinusitis (CRS) is afforded by degree of inheritability suggested from family and twin studies, existence of CRS in simple mendelian diseases, and development of sinusitis as part of the phenotype of certain gene "knockout" murine models. Genetic association studies are expected to identify novel genes associated with CRS and suggest novel mechanisms implicated in disease development. Although these studies are subject to methodologic difficulties, associations of CRS and polymorphisms in more than 30 genes have been published, with single nucleotide polymorphisms in 3 (IL1A, TNFA, AOAH) replicated.

c-MET pathway involvement in chronic rhinosinusitis: a genetic association analysis.

Objective: The c-MET receptor and its ligand hepatocyte growth factor (HGF) has been shown to be overexpressed in tissue from chronic rhinosinusitis (CRS) patients with nasal polyps compared with that from controls. We assessed the genetic association of polymorphisms in the met proto-oncogene (MET) gene with CRS.

Study Design: Case-control genetic association study.

Association of IL1A, IL1B, and TNF gene polymorphisms with chronic rhinosinusitis with and without nasal polyposis: A replication study.

Objective: To replicate and extend recent findings in a Turkish population of associations between chronic rhinosinusitis (CRS) with nasal polyposis and single-nucleotide polymorphisms (SNPs) in the IL1A (rs17561 and Ser114Ala), IL1B (rs16944), and TNF (rs361525 and rs1800629) genes.

Design: In a case-control replication study, DNA samples were obtained from 206 patients with severe CRS (cases) and from 196 postal code-matched controls. For IL1A and TNF, the 3 reported SNPs were complemented with tagging SNPs using an International HapMap genotyping data set to ensure complete genetic coverage.

Polymorphisms in the SERPINA1 (Alpha-1-Antitrypsin) gene are associated with severe chronic rhinosinusitis unresponsive to medical therapy.

Background: Alpha-1-antitrypsin (AAT) is a serine protease inhibitor that blocks the protease, neutrophil elastase. Previous population studies have suggested that heterozygote status for the AAT gene (SERPINA1) is a risk factor for chronic rhinosinusitis with nasal polyposis (CRSwNP). This implies a potential genetic predisposition to CRS tied to AAT deficiency.

Evidence of association of interleukin-1 receptor-like 1 gene polymorphisms with chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is a common complex respiratory disease, with a potential genetic component to its development. The protein encoded by the Interleukin-1 receptor-like 1 (IL1RL1) gene is an important effector molecule of T-helper type 2 responses and may potentially be involved in the persistent inflammatory process observed in CRS. We investigated whether certain polymorphisms in the IL1RL1 gene are differentially present in patients with surgery-unresponsive CRS and in control subjects.

Polymorphisms in the interleukin-22 receptor alpha-1 gene are associated with severe chronic rhinosinusitis.

Rationale: Stimulation of interleukin-22 receptor alpha-1 (IL22RA1) was reported to increase the innate immune responses in inflammatory diseases. Moreover, a reduced level of IL22RA1 was found in patients with recalcitrant CRS with nasal polyps.

Objective: To explore association between single nucleotide polymorphisms (SNPs) in IL22RA1 and severe CRS.